bluuebunny/crossref_metadata_2025_split huggingface dataset:
USP14 Haploinsufficiency Ameliorates Alzheimer’s Disease-Like Pathology in APP/PS1 Mice
Authors: Xu Hua , Wu Xueheng , Liang Lu , Chen Haoyu , Xu Jia , Hu Wanyan , Li Xinci , Liu Qin , Wang Xuejun , Zhang Chang-E , liu jinbao 
Published: September 2020

Abstract
Background: Alzheimer's disease (AD) is the most common cause of dementia; its main pathological features are neurofibrillary tangles (NFTs) consisting of hyperphosphorylated microtubule-associated protein (Tau) in the cell and extracellular beta-amyloid protein (Aβ)-based senile plaques (SP). The ubiquitin-proteasome system (UPS) is the main pathway for protein degradation in cells. Proteasome malfunction exists in AD patients and may promote the progression of the disease. USP14 is a deubiquitinating enzyme associated with the 19S proteasome. Functional inhibition of USP14 was shown to enhance proteasome proteolytic function, but no reported study has investigated the impact of genetic inhibition of USP14 on AD.Methods: Mice with heterozygous knockout of the Usp14 gene (USP14+/-) were generated and cross-bred with the APP/PS1 transgenic mice, the resultant offspring littermates were subjected to basal survival and growth analyses, and comparison of AD-like pathologies as detected with biochemical and histopathological methods and of cognitive function as assessed with the Morris water maze tests. Results:USP14 mRNA and protein levels in USP14+/- mice were decreased by ~50% compared with USP14+/+mice. The increases of total, K48 or K63 linked ubiquitinated proteins in APP/PS1 mouse brains were abolished in APP/PS1::USP14+/- mice. The increases in Aβ deposition and AD-associated phosphorylated Tau, senile plagues and neurofibrillary tangles, as well as spatial learning and memory decline induced by APP/PS1 were significantly attenuated in APP/PS1 mice. Conclusions: This study demonstrates that global knocking down USP14 protein expression by 50% is tolerable by mice and exhibits marked protection against AD-like pathologies in a widely used AD mouse model, favoring the exploration of moderate inhibition ofUSP14 as a potentially novel and viable therapy against AD.
Sirt2-SUMOylation is essential for its tumor-suppressor&nbsp;function in neuroblastoma
Authors: Lu Wenmei , Wang Qian , Xu Ci , Yuan Haihua , Fan Qiang , Chen Biying , Cai Renjie , Wu Danhong , Xu Ming 
Published: September 2020

Abstract
Background

SUMOylation is an important post-translational modification and participates in a variety of cellular physiological and pathological processes in eukaryotic cells. Sirt2, as a NAD+-dependent deacetylase, usually exerts tumor-suppressor function. However, its SUMOylation roles in cancer cells have not been illustrated.
Methods

Ni2+-NTA, GST-pull down and immunoprecipitation in vitro and in vivo were used for the Sirt2-SUMOylation or P38-Acetylation assay. Immunofluorescence and Nuclear/Cytosol Fractionation Kit were performed to identify the localization of Sirt2 with or without SUMOylation. The proliferation, soft-agar colony formation, migration and invasion were performed to detect the phenotypes of neuroblastoma cells in vitro, and the xenograft tumor model was conducted to verify Sirt2-SUMOylation role in tumorigenesis in vivo. R2 online database were used for the clinical analysis, including expression, survival curve and pathology stage.
Results

SUMOylation can occur in Sirt2 protein at both lysine 183 and lysine 340 sites. SUMOylation of Sirt2 does not affect its localization or stability, but involves in the P38-mTORC2-AKT cellular signal transduction via the direct deacetylation on P38. SUMOylation-deficient Sirt2 losses the capability of suppressing tumor processes and neuroblastoma cell shows a resistance to Sirt2-specific inhibitor AK-7.
Conclusion

We revealed an important function of SUMOylation on Sirt2, which is closely associated with the cellular signal transduction and is essential for suppressing the tumorigenesis in neuroblastoma.
Corporate Ownership and Firm Value: A Gmm-Based Dynamic Panel Data Approach
Authors: PANDEY KRISHNA DAYAL , SAHU TARAK NATH 
Published: September 2020

Abstract
To establish the relationship between corporate ownership and firm value, static as well as Arellano-Bond dynamic panel model based on Generalised Method of Moments (GMM) are applied on a set of panel data consisting 112 Indian manufacturing firms listed in BSE 200 Index of Bombay Stock Exchange for the period of 2011-18. A significant and positive effect of domestic promoters, foreign promoters and institutional ownership on Tobin’s Q is established. Regarding ownership concentration, a U-shaped relationship between ownership of large shareholders and ownership of largest shareholder and firm value is evidenced. At lower level of concentration, the effect on firm value is found to be negative indicating joint effect of ‘expropriation of minority shareholders’ and ‘misaligned interests’ of majority owners with the firm. For ownership concentration by large owners and the largest one owner, the effect on firm value is found to be positive after a threshold of 70 and 52 percent respectively. This signifies improved alignment of interests and efficient monitoring of managerial opportunistic behaviour and dismantling of owners-managers agency problem at higher level of concentration. Stricter external regulatory mechanism is suggested as a complimentary force to internal governance to ensure protection of minority shareholders’ interest and improved firm valuation.
Cerebaral Hyperperfusion in General Paralysis Patients
Authors: Wu Yali , li jingjing , wu wenqing 
Published: September 2020

Abstract
Objective This study aimed to identify the cerebral blood flow (CBF) in patients with general paralysis (GP). Methods Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) imaging was performed to measure the CBF in twenty patients with GP and twenty healthy subjects(NC). CBF was normalized to reduce variations among subjects. CBF was compared between the groups. Results Compared with the healthy subjects, the patients with GP exhibited increased CBF in the frontal lobe, temporal lobe, insular lobe, limbic lobe, and parietal lobe(all P<0.05). There was no difference in CBF of the occipital lobe between the GP group and the NC group(all P>0.05). Conclusions Our results suggest that the patients with GP may exhibit regional increased CBF, which may be one of the pathogenesis of general paralysis.
Models for Predicting Bulinids Species Habitats in Southwestern Nigeria Using Geographic Information System
Authors: Oso Opeyemi G. , Odaibo Alex 
Published: September 2020

Abstract
Background: Schistosomiasis prevalence is high in southwestern Nigeria and planorbids of the genus Bulinus had been implicated in the transmission of the disease in the area. The knowledge of species distribution in relation to environmental variables will be auspicious in planning control strategies. Methods: Satellite imagery and geographic information system (GIS) were used to develop models for predicting the habitats suitable for bulinid species. Monthly snail sample collection was done in twenty-three randomly selected water contact sites using standard method for a period of two years. Remotely sensed variables such as Land Surface Temperature (LST), Normalized Difference Vegetation Index (NDVI) were extracted from Landsat TM, ETM+; Slope and Elevation were obtained from digital elevation model (DEM) while Rainfall was retrieved from European Meteorology Research Program. These environmental factors and snail species were integrated into GIS to predict the potential habitats of different bulinid species using exploratory regression models. Results: The following environmental variables: flat-moderate slope (0.01-15.83), LST (21.1oC-23.4oC), NDVI (0.19-0.52), spatial rainfall (> 1,569.34 mm) and elevation (1-278 meters) all contributed to the model used in predicting habitat suitable for bulinids snail intermediate hosts. Exploratory regression models showed that LST, NDVI and slope were predictors of B. globosus and B. jousseaumei; elevation, LST, Rainfall and slope were predictors of B. camerunensis; spatial rainfall, NDVI and slope were predictors of B. senegalensis while NDVI and slope were predictors of B. forskalii in the area. Bulinids in the forskalii group showed clustering in middle belt and south. The predictive risk map of B. jousseaumei was similar to the pattern described for B. globosus, but with a high R-square value of 81%. Conclusion: The predictive risk models of bulinid species in this study provided a robust output for the study area which could be used as base-line for other areas in that ecological zone. It will be useful in appropriate allocation of scares resources in the control of schistosomiasis in that environment.
Detection of circulating genetically abnormal cells using 4-color fluorescence in situ hybridization for the early detection of lung cancer
Authors: Feng Mingxiang , Ye Xin , Lin Miao , Zhou Haining , Huang Meng , Chen Yanci , Zhu Yunhe , Xiao Botao , Chen Baishen , Huang Chuoji , Zhang Juncheng , Katz Ruth L. , Bai Chunxue 
Published: September 2020

Abstract
Background
Available biomarkers lack sensitivity for early lung cancer. Circulating genetically abnormal cells (CACs) occur early in tumorigenesis. To determine the diagnostic value of CACs in blood detected by 4-color fluorescence in situ hybridization (FISH) for lung cancer.
Methods
This was a prospective study of patients with pulmonary nodules ≤ 30 mm detected between 10/2019 and 01/2020 at four tertiary hospitals in China. All patients underwent a pathological examination of lung nodules found by imaging and were grouped as malignant and benign. CACs were detected by 4-color FISH. Patients were divided into the training and validation cohorts. Receiver operating characteristics analysis was used to analyze the diagnosis value of CACs.
Results
A total of 205 participants were enrolled. Using a cut-off value of ≥ 3, blood CACs achieved areas under the curve (AUCs) of 0.887, 0.823, and 0.823 for lung cancer in the training and validation cohorts, and all patients, respectively. CACs had high diagnostic values across all tumor sizes and imaging lesion types. CACs were decreased after surgery (median, 4 vs. 1, P < 0.001) in the validation set. The CAC status between blood and tissues was highly consistent (kappa = 0.909, P < 0.001). The AUC of CAC (0.823) was higher than that of CEA (0.478), SCC (0.516), NSE (0.506), ProGRP (0.519), and CYFRA21-1 (0.535) (all P < 0.001).
Conclusions
CACs might have a high value for the early diagnosis of lung cancer. These findings might need to be validated in future studies. Evidence suggested homology in genetic aberrations between the CACs and the tumor cells.
STOML2 Interacts with PHB through Activating MAPK Signaling Pathway to Promote Colorectal Cancer Proliferation.
Authors: Ma Wenhui , Chen Yuehong , Li Wenyi , Xu Zhuoluo , Wei Zhigang , Mou Tingyu , Wu Zhaokun , Cheng Mingzhen , Zou Yini , Zhu Yu , Zhou Weijie , Geng Yan 
Published: September 2020

Abstract
BackgroundOverexpression of STOML2 has been widely reported in a variety of cancer, yet few has detailed its function and regulatory mechanism. This study aims to reveal the clinicopathologic significance and oncologic function of STOML2 in colorectal cancer, explore its specific mechanism by means of yeast two-hybrid assay and bioinformatics.MethodsExpression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay was conducted to screen interacting proteins of STOML2, followed by bioinformatics to predict biological process and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.ResultsSTOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, ERK1/2 and ELK1 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.ConclusionsThis study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.
A Modified Shuffling Method to Reduce Decoding Complexity of QC-LDPC Codes
Authors: Hasani Alireza , Lopacinski Lukasz , Kraemer Rolf 
Published: September 2020

Abstract
Layered decoding (LD) of Low-Density Parity-Check (LDPC) codes is a decoding schedule that facilitates partially parallel architectures for performing Belief Propagation (BP)-based iterative algorithms. It has reduced implementation complexity and memory overhead compared to fully parallel architectures and higher convergence speed compared to both serial and parallel architectures. In this paper, we introduce a modified form of shuffling of the Parity-Check Matrices (PCMs) of Quasi-Cyclic LDPC (QC-LDPC) codes, which is basically an interleaving operation of the rows of the PCM. The modified shuffling method just like the conventional shuffling method results in a PCM in which each layer can be produced by the circulation of its above layer one symbol to the right. However, it additionally guarantees the weights of the columns in each layer to be either zero or one. Then, we show that due to these two properties, the number of occupied Look-Up Tables (LUTs) on a Field Programmable Gate Array (FPGA) is reduced by about 93% and consumed on-chip power by nearly 80%. Nevertheless, shuffling doesn’t degrade Bit Error Rate (BER) performance compared with the non-shuffled case. Additionally, decoding throughput is not sacrificed for low SNR values and its degradation is negligible until the BER of 1e-6.
A QoS-driven Service Selection Optimization Algorithm for Internet of Things
Authors: Zhang Xiaofei , Geng Juncheng , Ma Jianwei , Liu Hao , Niu Shuangxia 
Published: September 2020

Abstract
Currently, the smart devices have been widely deployed in Internet of Things (IoT). With the scale of IoT continues to increase, it brings big challenges for service composition in a large-scale IoT. For solving this problem, a QoS-driven service selection method based on the enhanced Genetic algorithm (EGS ~ QoS) is proposed in this paper. To decrease the scale of service composition, we use the lexicographic optimization approach and QoS constraint relaxation technique to find the candidate service with height QoS. Then, the IoT service composition problem is transformed into a single-objective optimization problem adopting a simple weighting method, and the final composite service meeting the user's QoS needs is found from the candidate service. Compared with the related algorithm, the simulation results show that EGS ~ QoS can efficiently and quickly select a composite service satisfying user's QoS needs, and is more suitable for solving the service composite problem in large-scale IoT services.
Insecticide Treated Net Ownership, Utilization and Knowledge of Malaria in Children Residing in Batoke-Limbe, Mount Cameroon Area: Effect on Malariometric and Haematological Indices
Authors: Teh Rene Ning , Sumbele Irene Ule Ngole , Meduke Derick Ndelle , Nkeudem Gillian Asoba , Ojong Samuel Takang , Teh Akwa Exodus , Kimbi Helen Kuokuo 
Published: September 2020

Abstract
Background: Insecticide treated nets (ITNs) are the most widely used interventions for malaria control in Africa. The aim of this study was to assess the ownership and utilization of ITNs and the knowledge of malaria and their effects on malariometric and haematological indices in children living in the Mount Cameroon area.Methods: A community-based cross-sectional study involving a total of 405 children aged between 6 months and 14 years living in Batoke-Limbe was carried out between July and October 2017. A semi-structured questionnaire was used to document demographic status, knowledge on malaria and ITN ownership and usage. Venous blood sample was collected from each child to determine the prevalence and intensity of malaria parasitaemia by Giemsa-stained microscopy and full blood count by auto haematology analysis to obtain white blood cell (WBC) and red blood cell (RBC) counts, haemoglobin (Hb) level, haematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). A multilinear regression model was used to determine the relationship between haematological parameter as dependent variable and the independent variables. Results: The overall prevalence of malaria parasitaemia (MP), anaemia, knowledge about malaria, ITN ownership, usage and effective usage was 46.7%, 54.7%, 40.7%, 78.8%, 50.9% and 29.9% respectively. The prevalence of MP was significantly higher (P<0.001) in children who ineffectively utilized ITNs (54.9%) than effective users (27.3%). Having knowledge of malaria, negatively correlated with WBC counts (P = 0.005) but positively correlated with Hb levels (P < 0.001), RBC counts (P < 0.001), Hct (P < 0.001), MCV (P < 0.001) and MCH (P < 0.001). ITN use positively correlated with WBC counts (P = 0.005) but negatively with Hb levels (P = 0.004), RBC counts (P = 0.006), and MCH (P < 0.001). Meanwhile, MP negatively correlated with Hb levels (P = 0.004), RBC counts (P = 0.01), Hct (P = 0.04) and MCHC (P = 0.015). Conclusion: There is need for more sensitization on the benefits of using the ITNs to meet up with the intended and expected impact of the free distribution of ITNs.
Analysis of Technical Efficiency and Its Potential Determinants among Smallholder Tomato Farmers in Siltie Zone, Southern Ethiopia
Authors: chefebo Derebe Ermias , Tefera Gosaye Eshetu , Tefera Gosaye Eshetu 
Published: September 2020

Abstract
Background: In developing world including Ethiopia, agricultural productivity was very low; especially where production is common on fragile lands and characterized by smallholder subsistence farming. One of the main reasons for low productivity is the inability of farmers to fully exploit available technologies and production techniques. Considering this in to account, this study analyzes the technical efficiency and its possible source of inefficiency in smallholder tomato farming in Siltie Zone Southern Ethiopia. Methods: By using three stage sampling, 175 randomly selected smallholder tomato farmers were sampled and stochastic frontier Cobb Douglas production model was applied. Results and Conclusion: The results indicate that the mean technical efficiency among smallholder tomato farmers is 81.7%, implying a potential to increase tomato production by 19.3% with the current level of resources and technology. The study further revealed that output responds positively to increases in technological factors of production. According to estimates of the inefficiency model among various factors sex of household head, frequency of weeding, diseases incidence and type of variety used were found to significantly affect the level of technical efficiency of tomato crop producers. Thus, development policies in the tomato sub sector might focus more on empowering women in resource allocation, adoption of high-yielding and disease-resistant tomato varieties and better management of tomato plantations might reduce technical inefficiency among tomato farmers in the study area.
GW4064 Enhances the Chemosensitivity of Colorectal Cancer to Oxaliplatin by Inducing Pyroptosis
Authors: Guo Jing , Zheng Jianbao , Xu Zhengshui , Zhao Chenye , Yang Kui , Sun Xuejun , Yu Junhui 
Published: September 2020

Abstract
Background Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment.Methods A series of in vitro and in vivo experiments were conducted to assess the antitumor effect of the combination of oxaliplatin and FXR agonist GW4064 in CRC. The synergistic mechanism involved was explored.Results A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression.Conclusions Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.