bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-6 Promotes Osteogenic Differentiation of Rat Tendon Stem Cells through the STAT3/Wnt5a Signalling Pathway
Authors: Liu Xiangzhou , Jin Ying , Liu Xiuqi , Peng Jiachen 
Published: May 2021

Abstract
Background: Tendinopathy is currently the common clinical condition related to sports injury. The main pathological change in tendinopathy is ectopic ossification in tendon tissue, but the mechanisms have remained elusive. Studies have found that interleukin-6 (IL-6) is a major inflammatory mediator in chronic tendinopathy, and osteogenic differentiation of tendon stem cells (TSCs) is believed to be closely related to ectopic ossification of tendons. Methods: Rat tendon-derived stem cell (rTDSC) culture model, Lentivirus transfection, Alkaline phosphatase staining, Real-time PCR and Western blotting were performed in this study.Results: We showed that after IL-6 induction, the mRNA expression of Runx2, Alpl, Dlx5, and Wnt5a and the protein expression of phosphorylated STAT3, Runx2, and Wnt5a were increased in rTDSCs. Wnt5a shRNA and cDNA induced silencing and overexpression of Wnt5a inhibited and promoted osteogenic differentiation of rTDSCs, respectively. The addition of a STAT3 inhibitor inhibited osteogenic differentiation and Wnt5a mRNA and protein expression in rTDSCs, and this inhibition was reversed by cDNA induced Wnt5a overexpression. Conclusion: We concluded that IL-6 promotes osteogenic differentiation of rTDSCs through the STAT3/Wnt5a signalling pathway.
Thinking Outside the Field: Two Cases of RT+ICI Synergy in Melanoma
Authors: Davidson Tara , Zhang Henan , Dong Haidong , Grams Michael P. , Park Sean S. , Yan Yiyi 
Published: May 2021

Abstract
While combination radiotherapy (RT) and immunotherapy is not novel there is still much to learn about this approach. Some initial pre-clinical and clinical evidence suggests triple therapy with RT and dual immune checkpoint blockade (anti-CTLA-4 + anti-PD-1/PD-L1) is a complimentary technique. We present two cases using the same novel regime of combination RT plus nivolumab and ipilimumab to treat metastatic melanoma. In both cases the burden of disease was significant within a lower extremity. Additionally, in both cases using this treatment plan, we were able establish sustained local disease control with additional systemic benefit which allowed both patients to avoid significant debility from surgical amputation. Given the response and safety we observed, this technique could be used as a potentially safe approach for future patients who are not eligible for traditional RT palliation or clinical trials.
NAP1L1 Interacts with Hepatoma-Derived Growth Factor to Recruit C-Jun Inducing Breast Cancer Growth
Authors: Liu Shu , Zhang Yewei , Cui Shien , Li Bo , Chen Qian , Yao Guangyu , GONG BIN 
Published: May 2021

Abstract
Background：Breast cancer is the top cancer in women in the world. However, its pathogenesis is still to be determined. The role and molecular mechanism of NAP1L1 in breast cancer have not been reported. Elucidation of molecular mechanism might provide a novel therapeutic target for glioma treatment.Methods：A bioinformatics analysis was conducted to determine the differential expression of NAP1L1 in breast cancer and find the potential biomarker that interacts with NAP1L1 and HDGF. The expression of NAP1L1 in tissues was detected by using immunohistochemistry. Breast cancer cells were transfected with the corresponding lentiviral particles and siRNA. Then, MTT, Edu, plate clone formation, and subcutaneous tumorigenesis in nude mice were used to detect the cell proliferation in breast cancer. Furthermore, coimmunoprecipitation (Co-IP) assay and confocal microscopy were performed to explore the detailed molecular mechanism of NAP1L1 in breast cancer.Results：In this study, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) protein was upregulated based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Consistent with the prediction, immunohistochemistry staining showed that NAP1L1 protein expression was significantly increased in breast cancer tissues. Its elevated expression was an unfavorable factor for breast cancer clinical progression and poor prognosis. Stably or transiently knocking down NAP1L1 reduced the cell growth in vivo and in vitro via repressing the cell cycle signal in breast cancer. Furthermore, the molecular basis of NAP1L1-induced cell cycle signal was further studied. NAP1L1 interacted with the hepatoma-derived growth factor (HDGF), an oncogenic factor for tumors, and the latter subsequently recruited the key oncogenic transcription factor c-Jun, which finally induced the expression of cell cycle promoter CCND1 and thus the cell growth of breast cancer. Conclusions：Our data demonstrated that NAP1L1 functions as a potential oncogene via interacting with HDGF to recruit c-Jun in breast cancer.
Tight–Binding Analysis of Electronic Structure of Germanene Sheet and Nanoribbons Including Stone-Wales Defect
Authors: Rahmani Komeil , Mohammadi Saeed 
Published: May 2021

Abstract
In this paper, we investigate the electronic characteristics of germanene using the tight binding approximation. Germanene as the germanium-based analogue of graphene has attracted much research interest in recent years. Our analysis is focused on the pristine sheet of germanene as well as defective monolayer. The Stone-Wales defect, which is one of the most common topological defects in such structures, is considered in this work. Not only the infinite sheet of germanene but also the germanene nanoribbons in different orientations are analyzed. The obtained results show that applying the Stone–Wales defect into the germanene monolayer changes the energy band structure; the E-k curves around the Dirac point are no longer linear, a band gap is opened, and the Fermi velocity is reduced to half of that of defect-free germanene. In the case of nanoribbon structures, the armchair germanene nanoribbons with nanoribbon widths of 3p and 3p+1 reveal the semiconductor behaviour. However, armchair germanene nanoribbon with width of 3p+2 is semi-metal. After applying the Stone–Wales defect, the band gap of armchair germanene nanoribbons with widths of 3p and 3p+1 is reduced and it is increased for the width of 3p+2. Furthermore, there is no band gap in the energy band structure of zigzag germanene nanoribbon and the metallic behaviour is obvious.
How Do Energy Demand and Socioeconomic Factors Drive Localities Towards Deforestation and Carbon Emissions in Pakistan?
Authors: Tufail Muhammad , Alvi Shahzad , Khayam Umer , Ahmed Ather Maqsood 
Published: May 2021

Abstract

Pakistan, the 6th most populous country in the world is also classified as the 7th most-affected by climate change. To blame is the ever-rising population growth, leading to higher energy demand that is dragging the rural communities towards forest resource depletion in order to meet household energy needs. It is impacting an already limited 4% of the country’s forest reserves and excessive carbon emissions. This research has analyzed deforestation rate, biomass and carbon losses, and CO2 emissions in the Malakand Division, Pakistan. The data sources and models used were Landsat (8), GIS, and Remote Sensing, coupled with self-administered 521 household questionnaires deployed in 23 villages in the proximity of forest land. The results confirmed deforestation at the rate of 0.74%yr-1, corresponding to the total emission of 1352055.64 MgCO2eqyr-1 over a period of 17 years (2000-17). The risk of losing forest resources stands at 8141 species yr-1. The drivers behind deforestation found were fuelwood collection up-to 8501720 kg to meet the energy needs of households and commercial activities. The reasons behind this exhaustive deforestation and carbon emissions as per the household survey were abridged formal sector, low off-farm wages, and non-availability of credits to shift to other sources of income which has also affected the affordability of the social services. The study calls for the provision of alternative livelihood opportunities and effective forest management on the REDD+ mechanism to protect forest resources and address global warming.
Functional Architecture of Executive Control and Associated Event-Related Potentials
Authors: Sajad Amirsaman , Errington Steven , Schall Jeffrey 
Published: May 2021

Abstract
Medial frontal cortex enables executive control by monitoring relevant information and using it to adapt behavior. In macaques performing a saccade countermanding (stop-signal) task, we recorded EEG over and neural spiking across all layers of the supplementary eye field (SEF). We report the laminar organization of concurrently activated neurons monitoring the conflict between incompatible responses and the timing of events serving goal maintenance and executive control. We also show their relation to coincident event-related potentials (ERP). Neurons signaling response conflict were largely broad-spiking found across all layers. Neurons signaling the interval until specific task events were largely broad-spiking neurons concentrated in L3 and L5. Neurons predicting the duration of control and sustaining the task goal until the release of operant control were a mix of narrow- and broad-spiking neurons confined to L2/3. We complement these results with the first report of a monkey homologue of the N2/P3 ERP complex associated with response inhibition. N2 polarization varied with error likelihood and P3 polarization varied with the duration of expected control. The amplitude of the N2 and P3 were predicted by the spike rate of different classes of neurons located in L2/3 but not L5/6. These findings reveal important, new features of the cortical microcircuitry supporting executive control and producing associated ERP.
Alteration of Gene Expression in Reactive Astrocytes Induced by Aβ1-42 Using Low Dose of Methamphetamine
Authors: Soltanian Bita , shasaltaneh marzieh dehghan , Riazi Gholam Hossein , Masoudian Nahid 
Published: May 2021

Abstract
Background: Alzheimer's disease (AD) is considered as a degenerative brain disorder. Since functional loss of astrocytes is associated with AD, therefore, we investigated the effects of low dose of methamphetamine (METH) on primary fetal human astrocytes under a stress paradigm as a possible model for AD. Methods and Results: Our assessed groups include Aβ (Group 1), METH (Group 2), Ab + METH (METH after adding Aβ for 24 h: Treated group; Group 3), METH + Ab (Aβ after adding METH for 24 h: Prevention group; Group 4), and control group. The gene expression of Bax, Bcl-X, PKCα, GSK3β, and Cdk5 was evaluated. Phosphorylated tau, p-GSK3β, GSK3β, and GSK3α proteins were assessed by western blotting. Cell cycle arrest and apoptosis were checked by flow cytometry and Hoechst staining. The expression of GSK3β, Cdk5, and PKCα genes decreased in the prevention group, while GSK3β and Cdk5 were amplified in the treatment group. The level of GSK3α and GSK3β proteins in the treatment group increased, while it decreased in the prevention group. A decrease occurred in the percentage of necrosis and early apoptosis in the treatment and prevention groups. The results of cell cycle indicated that G1 increased, while G2 decreased in the prevention group. Conclusions: The pure form of METH can prevent from activating GSK-3β and CDK-5, as well as enhanced activity of PKCa to inhibit phosphorylated tau protein. Therefore a low dose of METH may have a protective effect or reducing role in the pathway of tau production in reactive astrocytes.
Physiological, Photochemical and Antioxidant Responses of Wild and Cultivated Carthamus Species Exposed to Nickel Toxicity and Evaluation of Their Usage Potential in Phytoremediation
Authors: Baran Uğurcan , Ekmekci Yasemin 
Published: May 2021

Abstract
The responses of growth, photochemical and antioxidant defence of safflower species (Carthamus oxyacantha M. Bieb. and Carthamus tinctorius L. exposed to nickel (Ni) toxicity were investigated in the study. Fourteen-day-old seedlings were treated with excessive Ni levels [control, 0.50, 0.75 and 1.00 mM] for 7 days. The results of chlorophyll a fluorescence indicated that toxic nickel exposure led to changes in specific, phenomenological energy fluxes and quantum yields in thylakoid membranes, and activities of donor and acceptor sides of photosystems. These changes resulted in a significant decrease in the photosynthetic performance of the species, but these negative effects of Ni were not in a level to destroy the functionality of the photosystems. At the same time, toxic Ni affected membrane integrity and the amount of photosynthetic pigments in the antenna and active reaction centers. Additionally, the accumulation of Ni was higher in roots than in stem and leaves for both species. Depending on Ni accumulation, a significant reduction in dry biomass of root and shoot was observed in both species. Two species could probably withstand deleterious Ni toxicity with better upregulating own protective defence systems such as antioxidant enzymes. Among of them, SOD and POD activities were increased with increasing Ni concentrations. The POD activities of both species were most prominent and consistently increased in toxic Ni levels and may be protected them from damaging effect of H2O2. When all results are evaluated as a whole, Carthamus species produced similar responses to toxicity and also both species have Bioconcentration (BCF) and Bioaccumulation factors (BF) > 1 and Translocation factor (TF) < 1 under Ni toxicity may be regarded a good indication of Ni tolerance. Consequently, it is possible to use the Carthamus species in the remediation (phytostabilization) of soils contaminated with nickel, because of their roots accumulating more nickel.
Deep Learning Implementation of Autonomous Driving using Ensemble-M in Simulated Environment
Authors: Gupta Meenu , Upadhyay Vikalp , Kumar Prince , Al-Turjman Fadi 
Published: May 2021

Abstract
Making Autonomous Driving a safe, feasible and better alternative is one the core problems the world is facing today. The horizon of the applications of AI and Deep Learning has changed the perspective of the human mind. Initially, what used to be thought as subtle impossible task is applicable today and that too in the feasibly efficient way. Computer vision tasks powered with highly tuned CNNs are outperforming humans in many fields. Introductory implementations of autonomous vehicle were merely achieved using raw image processing and hard programmed rule-based logic systems along with machine/deep Learning used as secondary objective handlers. With the autonomous driving method proposed by NVIDIA, the usability of CNNs is more adequate, adaptable and applicable. In this paper, we propose, the ensemble implementation of CNN based regression models for autonomous-driving. We have taken simulator generated driving view image dataset along with mapped file of steering angle in radians. After applying image pre-processing and augmentation, we have used two CNN models along with their ensemble and compared their performance as to minimize the risks of unsafe driving. We have compared Nvidia proposed CNN, MobileNet-V2 as regression model and Ensemble-M results for comparison their respective performance, MSE scores and compute time to process. In result analysis, the MobileNet-V2 model performs better in densely-featured roads and Nvidia model performs better in sparsely-featured roads whereas Ensemble-M normalizes the performance of both models and efficiently result in the least MSE score (0.0201) with highest computation time utilization.
Phenylalanine Impairs Insulin Signaling and Inhibits Glucose Uptake by Modifying IRβ
Authors: Zhou Qian , Sun Wan-Wan , Chen Jia-Cong , Zhang Huilu , Liu Jie , Lin Yan , Lin Peng-Cheng , Wu Bai-Xing , An Yan-Peng , Huang Lin , Sun Wen-Xing , Zhou Xin-Wen , Li Yi-Ming , Yuan Yiyuan , Zhao Jian-Yuan , Xu Wei , Zhao Shi-Min 
Published: May 2021

Abstract
Although elevated circulating amino acids are associated with the onset of type 2 diabetes (T2D), how amino acids act on cell insulin signaling and glucose uptake remains unclear. Herein, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or overexpressing human phenylalanyl-tRNA synthetase (hFARS) developed insulin resistance and symptoms of T2D. Mechanistically, FARS phenylalanylated lysine 1057/1079 of IRβ (F-K1057/1079) inactivated IRβ and prevented insulin from generating insulin signaling to promote glucose uptake by cells. SIRT1 reversed F-K1057/1079 and counteracted the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels of white cells of T2D patients’ blood samples were positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitized insulin signaling and relieved T2D symptoms in hFARS-transgenic and db/db mice. We revealed mechanisms of how phenylalanylation inactivates insulin signaling that may be employed to control T2D.
Ecological Efficiency of Hog Scale Production under Environmental Regulation in China: Based on an Optimal Super Efficiency SBM-Malmquist–Tobit Model
Authors: Wu Qianrong , Xu Lanzhuang , Geng Xianhui 
Published: May 2021

Abstract
China’s hog production is facing the dual pressures of the market and environment. A systematic analysis on the ecological efficiency (eco-efficiency) of hog cultivation is of great significance for the development of sustainability and distribution optimization in the industry. This paper investigates the eco-efficiency of hog production and the determinants of eco-efficiency in China using a panel data (2004–2018). An optimal Super Efficiency SBM-Malmquist–Tobit model is adopted for hog production analysis, and the empirical results show a great variation in eco-efficiency across provinces, ranging from 0.557 to 1.19 with a mean value of 0.937 in 2018. The predominant production area of hogs is found being transferred from north to south, with small- and medium-scale predominant production areas shifted from east China to southwest China, and large-scale predominant production areas shifted from north China to south-central China. Another finding is that eco-efficiency increased by the improvement of technical efficiency. In addition, the Tobit regression results show that, rural economic development, the government’s investment in environmental control, the market advantage index, and transportation conditions had positive effects on the eco-efficiency; meanwhile, the forbidden policy for livestock cultivation in certain areas, the structure of the hog-breeding industry, the density of slaughtered fattened hogs, and the prices of hogs had negative effects on the eco-efficiency.
Biological knowledge-slanted random forest approach for the classification of calcified aortic valve stenosis
Authors: Cantor Erika , Salas Rodrigo , Rosas Harvey , Guauque-Olarte Sandra 
Published: May 2021

Abstract
Background: Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with normal valves, using a knowledge-slanted random forest (RF). Results: This study implemented a knowledge-slanted random forest (RF) using information extracted from a protein-protein interactions network to rank genes in order to modify the selection probability of them to draw the candidate split-variables. A total of 1591 genes were assessed in 19 valves with CAVS (BAV, n=10; TAV, n=9) and 8 normal valves. The performance of the model was evaluated using accuracy, sensitivity, and specificity to discriminate cases with CAVS. A comparison with conventional RF was also performed. The performance of this proposed approach reported better accuracy in comparison with conventional RF to classify cases separately with BAV and TAV (Slanted RF: 59.3% versus 40.7%). When patients with BAV and TAV were grouped against patients with normal valves, the addition of prior biological information was not relevant with an accuracy of 92.6%.Conclusion: The knowledge-slanted RF approach reflected prior biological knowledge, leading to better precision in distinguishing between cases with BAV, TAV, and normal valves. The results of this study suggest that the integration of biological knowledge can be useful during difficult classification tasks.
A Novel Patient-Specific Model for Predicting Postoperative SIRS in Elderly Patients: A Retrospective Cohort Study
Authors: Chen Chaojin , Luo Tongsen , Li Xiaoyue , Lu Yaxin , Chen Jingjing , Zhang Qi , Liu Zifeng , Zhou Shaoli , Hei Ziqing 
Published: May 2021

Abstract
Background

Postoperative systemic inflammatory response syndrome (SIRS) is common in surgical ICU patients especially in elderly patients, and the geriatric population with SIRS is more susceptible to sepsis, MODS, and death. There have been no reliable and accurate methods to predict SIRS in the elderly. Therefore, we aimed to develop and validate a novel effective model for predicting postoperative SIRS in elderly patients.
Methods

Data of 16141 patients aged ≥ 65 years who underwent surgery in two centers of Third Affiliated Hospital of Sun Yat-sen University from January 2015 to September 2020 were retrieved and analyzed. We developed a predictive model for postoperative SIRS based on a retrospectively cohort study of 5904 patients spanning from January 2015 to December 2019. The discriminative performance of this model was determined by area under the receiver operating characteristics curve (AUC). We also used the model to validate outcomes in 1105 patients who underwent surgery at the same institutions from January 2020 to September 2020, and to perform a stratified analysis.
Results

A total of 5904 patients were enrolled in the training cohort and 1105 patients comprised the validation cohort, in which incidence rates of postoperative SIRS were 24.6% and 20.2%, respectively. Patients with SIRS had more postoperative complications and a worse in-hospital survival rate than patients without SIRS. Six feature variables including preoperative fever, preoperative serum albumin level, ASA classification, total intraoperative infusion volume, surgical duration, and postoperative intensive care unit admission were identified as valuable predictors to construct the nomogram, with high AUCs in both the training and validation cohorts (0.800 [0.787, 0.813] and 0.823 [0.791, 0.855], respectively).
Conclusions

We constructed an effective nomogram using 6 routinely obtained variables to assist clinicians to predict postoperative SIRS in elderly patients.