bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis Reveals A Six-Gene Signature and Associated Drugs in Alzheimer Disease
Authors: Jiang Zhengye , Tan Guowei , Wang Zhanxiang 
Published: May 2020

Abstract
Background: Alzheimer disease (AD) is a progressive neurodegenerative disease caused by many factors. The essential genes and signaling pathways involved in the pathogenesis of AD are still unknown. The purpose of our research is to analyze and screen out potential molecular biomarkers and related signaling pathways.Methods: We obtained the gene expression profile of GSE18309 from the gene expression Omnibus website. Then, we used the Limma package in Rstudio to screen out differentially expressed genes (DEGs), followed by the corresponding cell signal pathway enrichment using DAVID analysis. Finally, STRING used to obtain the protein-protein interaction (PPI) network and the corresponding hub gene obtained through MCODE of Cytoscape software.Results: The results showed that a total of 119 upregulated genes and 160 downregulated genes were identified, which met the criteria of |log2 changes| ≥2, adjusted P value <0.01. Through the PPI network, the hub gene module we obtained shows that genes such as GNG13, EDNRB, CHRM3, CCKAR, FFAR4 and TRIO are closely related to AD. The signaling pathway is about signal transducer activity, G-protein coupled receptor activity and transmembrane signaling receptor activity. Conclusions: In summary, the above-obtained hub gene and the identified signaling pathway will help explore the pathogenesis of AD; and provide new therapeutic targets and prognostic assessment for AD.
Effect of Different Bacterial Composition of Fermented Cow Milk and Soy Milk on Epidermal Growth Factor and Epidermal Thickness in Female Wistar Rats
Authors: Lesmana Ronny , Adriani Lovita , Haryawan Zahran , Goenawan Hanna , Pratiwi Yuni Susanti , Sylviana Nova , Supratman Unang 
Published: May 2020

Abstract
Background Skin aging stimulates higher regression of proliferation and architecture of the skin tissue. Isoflavone has been used for countering aging and shown its effect to alter the progression of skin aging, while probiotics have an ability to boost the absorption of nutrient and also have its own ability to maintain the skin tissue. However, there is limited information about the difference of effect between various formulation of fermented cow milk and soy milk towards the skin regeneration via epidermal growth factor (EGF) signalling.Results Our data showed that there are differences characteristic of stool and its macroscopic appearance after different fermented formula of cow milk and soy milk treatment. Histology results showed that skin epidermal thickness was found thicker in every group tthe same trend as the EGF protein levels.Composition of milk and soy milk fermented by Bifidobacterium bifidum potentially stimulate EGF protein levels. This finding inline withConclusions Milk fermented by Bifidobacterium bifidum showed the greatest effect for the skin tissue regeneration and it might prevent the skin aging process compared to the other formulations. Compared to conventional fermented milk, the composition of soy milk might enhance this positive effect of fermented milk to the skin.
Effects of Dietary N-Carbamylglutamate Supplementation on Milk Production Performance, Nutrient Digestibility and Blood Metabolomics of Lactating Holstein Cows Under Heat Stress
Authors: Ma Ning , Li Yan , Ren Liyuan , Hu Linqi , Xu Ruiting , Cao Yufeng , Gao Yanxia , Li Jianguo 
Published: May 2020

Abstract
Background: Heat stress (HS) becomes a serious threat to dairy cow industry in certain circumstances, N-carbamylglutamate (NCG) is a novel feed additive that may be used to alleviate HS. However, the effects and mechanisms of NCG on dairy cows under HS are still unknown. A total of 48 Holstein dairy cows with similar days in milk (154.37±13.56 d), parity (1-3), and body condition score (BCS) were randomly divided into 4 groups of 12 animals each. Under HS, the cows were fed a TMR diet supplemented with 0 (control), 15, 20, 25 g of NCG/d per cow for 60 days. Milk production performance was recorded and serum parameters were examined. Meanwhile, metabolomics study of plasma based on liquid chromatography–mass spectrometry (LC-MS) was also applied to investigate metabolites and pathways in response to NCG supplementation.Results: Milk yield (MY) was increased but milk urine nitrogen (MUN) was reduced by the NCG treatment. Addition of 15 g of NCG/d increased the milk protein percentage (MPP) compared with the control. No effect of NCG was observed on dry matter intake (DMI), lactose percentage (LP), milk fat percentage (MFP) and somatic cell count (SCC). Serum glucose (GLU) levels in cows fed with 15, 20, 25 g of NCG/d were increased by 14.35%, 19.34% and 18.63% in comparison with the control. Meanwhile, the concentrations of blood urea nitrogen (BUN) and blood ammonia (BA) were decreased with the addition of NCG. Results for antioxidant capacity and immune function showed beneficial effects of NCG, such as the increases in total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), IgG, IgM and IgA. Clear separations of plasma metabolic profiles between control and NCG groups were observed in the score plots. Sixteen different metabolites involved in metabolisms of amino acids, ketone bodies, butanoate and energy, as well as gut microbiome-derived metabolism were regulated by NCG supplementation.Conclusions: This study found that NCG treatment improved antioxidant capacity, immune function, production performance, and metabolic profile of dairy cows under HS and provided new evidence for the better utilization of NCG.
Mapping Geologic Structures from Gravity and Digital Elevation Model in the Ziway-Shala Lakes Basin; central Main Ethiopian Rift
Authors: Kebede Hailemichael , Alemu Abera , Nedaw Dessie 
Published: May 2020

Abstract
This study attempts to delineate subsurface lineaments for the tectonically and volcanically active region of the Ziway-Shala Lakes basin, central Main Ethiopian rift. Most of the previously mapped subsurface structures in the region under consideration focus on delineating crustal structures thicknesses and Moho depths undulations. Moreover, near-surface structures in the same region were mapped using analysis of Digital Elevation Model image data. On the other hand, there are few studies that have targeted in mapping geologic structures lying at intermediate depth levels between the shallower and deeper Earth. The objective of this research is thus to map the subsurface geologic structures/lineaments to an average depth of 3 km (crystalline basement layer depth) from surface using gravity data. These investigation results are validated by Digital Elevation Model extracted lineaments. Filtering techniques including derivative filters, upward-continuation and line module algorithm of PCI Geomatica are used to extract the gravity and topographic lineaments of the region. Orientation analyses of these subsurface and surface lineaments are made using line direction histogram of the QGIS software. Accordingly, the gravity subsurface lineaments mapped in this study are found to be dominantly oriented in the NNW-SSE to NW-SE and E-W direction on average. These results appear to be contrary to the NNE-SSW to NE-SW trending surface geologic structure mapped on the bases of actual field observation carried out by previous researchers and automatically extracted lineaments based on Digital Elevation Models data considered in this research. The subsurface lineaments mapped using gravity data coincide with the orientation of pre-existing subsurface structures crossing the rift orthogonally. These structural lineaments which are considered to be masked in the subsurface coincide with the orientation of the Mesozoic Ogaden rift as compared to the overlying surface structures which appear to coincide with the orientation of the Cenozoic Main Ethiopian rift.
Prototype of Disc Brake Dynamometer
Authors: Kraisoda Pakkip 
Published: May 2020

Abstract
This paper presents the design and test of prototype of Disk Brake Dynamometer of Single-cylinder engine performance standard Brake horsepower with water using the Honda GX-200 four-stroke 196 cm3 gasoline engine, 1-cylinder gasohol 95 fuel. The experiment result showed that the Prototype of Disk brake Dynamometer maximum engine torque was 11.58 N m at 2500 rpm. The maximum power of engine was 3.29 kW at 3000 rpm and maximum thermal efficiency of engine brake was 25.36% at 2500 rpm. When being compared the performance of a standard single-cylinder engine performance test with the all-purpose gasoline engine Honda GX-200 1-stroke 4-stroke 196 cm3 gasohol 95, it was found that Maximum engine torque was less than 5.39%, the maximum engine power was higher than 2.49%, the maximum fuel consumption of the engine was higher than 10% and the maximum thermal efficiency of the engine was higher than 2.39%.
Knockdown of LincRNA PADNA Promotes Bupivacaine-Induced Neurotoxicity by miR-194/FBXW7 Axis
Authors: Yuning Fan , Liang Chen , Tenghuan Wang , Zhenhua Nan , Gong Shengkai 
Published: May 2020

Abstract
The aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Mouse DRG neurons were cultured in vitro and treated with bupivacaine to establish the neurotoxicity model. Caspase3 activity, cell viability, tunel assay were analyzed to assess the role of lincRNA PADNA. Dual-luciferase reporter assay was used to determine the binding target of lincRNA PANDA. The expression of lincRNA PADNA was significantly increased with the increasing concentration of bupivacaine. Functional analysis revealed that knockdown of lincRNA PADNA accelerated the caspase3 activity and inhibited the cell viability. Western blot showed that knockdown of lincRNA PADNA promoted the occurrence of cleaved-caspase3. We also proved that lincRNA PADNA may bind with miR-194. Overexpression of miR-194 could rescued the function of lincRNA PADNA, suggesting that lincRNA PADNA may sponge miR-194. In addition, we provided new evidences that lincRNA PADNA/miR-194/FBXW7 axis play an important role in the neurotoxicity process. We performed comprehensive experiments to verify the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Our study provided new evidences and clues for prevention of neurotoxicity.
Clinical Characteristics and Survival Associations of Pancreatic Neuroendocrine Tumor: Does Age Matter?
Authors: Liu Mengqi , Sun Xiaoyan , Zhang Zheng , Xu Xiaowu , Yu Xianjun , Zhuo Qifeng , Ji Shunrong 
Published: May 2020

Abstract
Background: Pancreatic neuroendocrine tumor (pNET) is the second most common epithelial neoplasm of pancreas. As in pancreatic adenocarcinoma, patients with different onset ages display different clinical features and prognosis, we divided pNET patients into early-onset pancreatic neuroendocrine tumor (EOpNET) and typical age-at-onset pancreatic neuroendocrine tumor (TOpNET) to investigate the effect of onset age on its clinical characteristics and prognosis. Methods: Data were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2015; cohort 1) and Fudan University Shanghai Cancer Center (FUSCC) (2005–2018; cohort 2) retrospectively. The clinical characteristics were compared using chi-squared tests. Cox proportional hazards regression was used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs), and overall survival were formulated by Kaplan–Meier curves.Results: In total 5,368 and 330 patients’ data were included from the SEER database and FUSCC. Gender had no effect on survival in EOpNET group. Tumors locating in the tail (HR: 0.721, 95%CI: 0.63-0.83, P < 0.001) and body (HR: 0.712, 95%CI: 0.60-0.85, P = 0.001) had lower risks of death compared to tumors in the head in TOpNET group. The overall survival of EOpNET (136 (3-143) months) was better than TOpNET (85 (3-143) months) ( P < 0.001) in SEER database. The results in FUSCC was similar with SEER cohort. Conclusions: EOpNET group had significantly better overall survival than TOpNET though their clinical characteristics were not significantly different. In the future personalized treatment of pNET, the onset age of patients will become another important factor for guiding the treatment and prognosis.
Cerebrospinal Fluid α-Synuclein Predicts Neurodegeneration and Clinical Progression in Prodromal Alzheimer's Disease
Authors: Li Jie-Qiong , Bi Yan-Lin , Shen Xue-Ning , Wang Hui-Fu , Xu Wei , Tan Chen-Chen , Dong Qiang , Wang Yan-Jiang , Tan Lan , Yu Jin-Tai 
Published: May 2020

Abstract
BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in prodromal AD stage Chinese elders. The predictive values of CSF α-synuclein in longitudinal change in clinical outcomes and conversion risk of prodromal AD stage subjects were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsAmong individuals in prodromal AD stage, we detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.
Incidence of Huntington disease in a northeastern Spanish region: A 13-year retrospective study at tertiary care centre
Authors: Bailo Paula Sienes , Lahoz Raquel , Marín Juan Pelegrín Sánchez , Álvarez Silvia Izquierdo 
Published: May 2020

Abstract
Background
Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant.
Methods
Descriptive retrospective study with 188 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per million inhabitants per year during the period 2007–2019 in Aragon (Spain).
Results
50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (73.4%) were HD negative (CAG repeat length < 36). Male to female ratio was 1:1,4; with 29 (58.0%) females and 21 (42.0%) males confirmed HD cases. The overall incidence was 6.48 per million patient-years. 12/50 positive HD cases (24,0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 10 and the most common CAG length among HD negative individuals was 16.
Conclusions
Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.
Combined forced oscillation and fractional-order modeling in patients with work-related asthma: a case-control study analyzing respiratory biomechanics and diagnostic accuracy
Authors: Tuza Fábio Augusto d´Alegria , de Sá Paula Morisco , Castro Hermano , Lopes Agnaldo José , de Melo Pedro Lopes 
Published: May 2020

Abstract
Background Fractional-order (FrOr) models have a high potential to improve pulmonary science. These models could be useful for biomechanical studies and diagnostic purposes, offering accurate models with an improved ability to describe nature. This paper evaluates the performance of the Forced Oscillation (FO) associated with integer (InOr) and FrOr models in the analysis of respiratory alterations in work-related asthma (WRA). Methods Sixty-two individuals were evaluated: 31 healthy and 31 with WRA with mild obstruction. Patients were analyzed pre and post bronchodilation. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). To evaluate how well do the studied models correspond to observed data, we analyzed the mean square root of the sum (MSEt) and the relative distance (Rd) of the estimated model values to the measured resistance and reactance measured values. Results and discussion Initially, the use of InOr and FrOr models increased our understanding of the WRA physiopathology, showing increased peripheral resistance, damping, and hysteresivity. The FrOr model (AUC=0.970) outperformed standard FO (AUC=0.929), as well as InOr modeling (AUC=0.838) in the diagnosis of respiratory changes, achieving high accuracy. FrOr improved the curve fitting (MSEt=0.156±0.340; Rd=3.026±1.072) in comparison with the InOr model (MSEt=0.367±0.991; Rd=3.363±1.098). Finally, we demonstrated that the bronchodilator use increased dynamic compliance, as well as reduced damping and peripheral resistance. Conclusions Taken together, these results show clear evidence of the utility of FO associated with fractional-order modeling in patients with WRA, improving our knowledge of the biomechanical abnormalities and the diagnostic accuracy in this disease.
Estimating transmission dynamics and serial interval of the first wave of COVID-19 infections under different control measures: A statistical analysis in Tunisia from February 29 to May 5, 2020
Authors: Talmoudi Khouloud , Safer Mouna , Letaief Hejer , Hchaichi Aicha , Harizi Chahida , Dhaouadi Sonia , Derouiche Sondes , Bouaziz Ilhem , Gharbi Donia , Najar Nourhene , Osman Molka , Cherif Ines , Mlallekh Rym , Ben-Ayed Oumaima , Ayedi Yosr , Bouabid Leila , Bougatef Souha , Ben-Alaya Nissaf Bouafif ép , Chahed Mohamed Kouni 
Published: May 2020

Abstract
Background
Describing transmission dynamics of the outbreak and impact of intervention measures are critical to planning responses to future outbreaks and providing timely information to guide policy makers decision. We estimate serial interval (SI) and temporal reproduction number (Rt) of SARS-CoV-2 in Tunisia.
Methods
We collected data of investigations and contact tracing between March 1, 2020 and May 5, 2020 as well as illness onset data during the period February 29-May 5, 2020 from National Observatory of New and Emerging Diseases of Tunisia. Maximum likelihood (ML) approach is used to estimate dynamics of Rt.
Results
491 of infector-infectee pairs were involved, with 14.46% reported pre-symptomatic transmission. SI follows Gamma distribution with mean 5.30 days [95% CI 4.66–5.95] and standard deviation 0.26 [95% CI 0.23–0.30]. Also, we estimated large changes in Rt in response to the combined lockdown interventions. The Rt moves from 3.18 [95% CI 2.73–3.69] to 1.77 [95% CI 1.49–2.08] with curfew prevention measure, and under the epidemic threshold (0.89 [95% CI 0.84–0.94]) by national lockdown measure.
Conclusions
Overall, our findings highlight contribution of interventions to interrupt transmission of SARS-CoV-2 in Tunisia.
The Prognostic Significance and Tumor-promoting Roles of MED30 in Pancreatic Cancer
Authors: Liu Liangwen , Han Myoung-Eun , Kim Ji-Young , Kim Ga Hyun , Park Si Young , Kim Yun Hak , Oh Sae-Ock 
Published: May 2020

Abstract
Background: MED30 is an evolutionarily new member of the mediator complex thatcan bridge transcription factors and preinitiation complexfor the transcription. Pancreatic cancer is highly chemo-resistant andis the fourth leading cause of cancer-related deaths. Rapid progression and poor prognosis of pancreatic cancer result in shortened survival rate following diagnosis.Methods: Expression of MED30 was investigated by the analysis of TCGA database and immunohistochemistry of patients tissues. Roles of MED30 were investigated by gain-of-function and loss-of-function studies.Results: Analysis of TCGA database and immunohistochemistry provedthe frequentamplification and overexpression of MED30 in the pancreatic cancer tissues compared with the normal pancreatic tissues at the chromosome, mRNA and protein levels. Notably its overexpression was association with poor prognosis of pancreatic cancer patients in the Kaplan-Meier curve analysis (P=0.00072) and multivariate analysis (P=0.027). Uno’s C-index values in the time-dependent Area Under the Curve (AUC) analysis and AUC valuein the receiver operating characteristics (ROC) curves showed its good performance as a prognostic marker. To reveal the functional roles of MED30 during the progression of pancreatic cancer, we overexpressed or knocked down MED30 using cDNA or siRNA, respectively. Gain-of-function and loss-of-function studies showed that MED30 can regulate proliferation, migration, and invasion of pancreatic cancer cells. Furthermore overexpression of MED30 promoted tumorigenicity in SCID mice significantly. Conclusions: MED30 is frequently amplified and overexpressed and its overexpression is associated with poor prognosis of pancreatic cancer patients. Moreover it has tumor-promoting roles in proliferation, migration, invasion and in vivo tumorigenicity of pancreatic cancer cells. Thus, MED30 could be a potent diagnostic and therapeutic target in pancreatic cancer.
Sars-Cov-2 Spike 1 protein control Natural killer cells activation via HLA-E/NKG2A pathway.
Authors: Bortolotti Daria , Gentili Valentina , Rizzo Sabrina , Rotola Antonella , Rizzo Roberta 
Published: May 2020

Abstract

Natural killer (NK) cells are important in the control of viral infections. However, the role of NK cells during Sars-Cov-2 infection has previously not been identified. Peripheral blood NK cells from Sars-Cov and Sars-Cov-2 naïve subjects were evaluated for their activation, degranulation, interferon-gamma expression in the presence of Sars-Cov and Sars-Cov-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune-fluorescence. Sars-Cov and Sars-Cov-2 spike proteins did not alter NK cell activation in K562 in vitro model. On the contrary, Sars-Cov-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of a SP1-derived HLA-E-binding peptide. Simultaneously, there was the up-modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 is expressed in lung epithelial cells. We ruled out GATA3 transcription factor as responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicate in NK cells exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells exhaustion might contribute to immunopathogenesis in Sars-Cov-2 infection.