bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of RAS and PI3-AKT pathway by Stavudine (d4T) in PBMC of Alzheimer’s Disease Patients
Authors: Rosa Francesca La , Zoia Chiara Paola , Bazzini Chiara , Bolognini Alessandra , Marina Saresella , Conti Elisa , Ferrarese Carlo , Piancone Federica , Marventano Ivana , Fenoglio Chiara , Galimberti Daniela , Scarpini Elio , Clerici Mario 
Published: May 2020

Abstract
Background

Aβ42-deposition plays a pivotal role in AD-pathogenesis by inducing the activation of microglial cells and neuroinflammation. This process is antagonized by microglia-mediated clearance of Aβ plaques. Activation of the NLRP3 inflammasome is involved in neuroinflammation and in the impairments of Aβ-plaques clearance. Stavudine (d4T) on the other hand down-regulates the NLRP3 inflammasome and stimulates autophagy-mediated Aβ-clearing in a TPH-1 cell line model.
Methods

We explored the effect of d4T on Aβ- autophagy using PBMC of AD patients that were primed with LPS and stimulated with Aβ in the absence/presence of d4T. We analyzed the NLRP3 inflammasome activity by measuring NLRP3-ASC complexes formation by AMNIS Flow-sight and pro-inflammatory cytokines (IL-1β, IL-18 and Caspase-1) production by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were used to measure phosphorylation and protein expression of p38, CREB, ERK and AKT, p70, LAMP 2A, beclin-1 and Bax.
Results

data showed that d4T: 1) down regulates NLRP3 inflammasome activation and the production of down-stream proinflammatory cytokines even in PBMC; 2) stimulates the phosphorylation of AKT, ERK, p70 as well as LAMP2A production, but does modulate beclin-1, suggesting a selective effect of this compound on chaperone-mediated autophagy (CMA); 3) up regulates p-CREB and BAX, possibly diminishing Aβ–mediated cytotoxicity; and 4) reduces the phosphorylation of p-38, a protein involved in the production of proinflammatory cytokines.
Conclusions

d4T reduces the activation of the NLRP3 inflammasome and stimulates CMA autophagy as well as molecular mechanisms that modulate cytotoxicity and reduce inflammation in cells of AD patients. It might be interesting to verify the possibly beneficial effects of d4T in the clinical scenario.
Clinical Characteristics and CT Manifestations of 143 Patients With 2019 Novel Coronavirus Disease (COVID-19) in Taizhou City, Zhejiang, China
Authors: Kuang Yani , He Susu , Lin Shuangxiang , Zhu Rui , Zhou Rongzhen , Ying Shuying , Li Renzhan , Lin Haiyong , Zhang Zhibang , Pang Peipei , Ji Wenbin 
Published: May 2020

Abstract
Background In December 2019, the first case of pneumonia associated with the SARS-CoV-2 was found in Wuhan and rapidly spread throughout China, so data are needed on the affected patients. The purpose of our study was to find the clinical manifestations and CT features of COVID-19.Methods All patients with COVID-19 in Taizhou city were retrospectively included and divided into non-severe group and severe group according to the severity of the disease. The clinical manifestations, laboratory examinations and imaging features of COVID-19 patients were analyzed, and the differences between the two groups were compared.Results A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 (range 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. Between two groups of cases, the results of aspartate transaminase, creatine kinase and lactate dehydrogenase, serum albumin, CPR, glomerular filtration rate, amyloid protein A, fibrinogen, calcitonin level and oxygen partial pressure, red protein, IL – 10, absolute value of CD3, CD4, CD8 were different, and the difference was statistically significant (P < 0.05). On admission, the CT showed that the lesions were mostly distributed in the external lung or under the pleura (135 cases (98%)), and most of lesions presented as patchy (81%), heterogeneous (73%) and mixed density (63%) shadow. Consolidation (68% vs 41%), bronchial inflation signs (59% vs 41%), and bronchiectasis (71% vs 39%) were more common in the severe group.Conclusions Most of the cases of COVID-19 in Taizhou have mild symptoms and no death. In addition to clinical symptoms, some laboratory tests (such as absolute values of CD4 and CD8) and CT findings can be used to assess the severity of the disease.
Reputation-Based Dynamic Contract Incentive Mechanism in Mobile Crowdsourcing Network
Authors: Wu Minghu , Wan Qixuan , Zheng Xuan , Jiang Yuhan , Zhao Nan 
Published: May 2020

Abstract
Mobile crowdsourcing network is a promising technology utilizing the mobile ter- minal’s sensing and computing capabilities to collect and process data. However, because the mobile users (MUs) have selfish characteristics, the MUs only aim at maximizing their benefits. Therefore, how to design an appropriate long-term incentive mechanism for the service provider (SP) in dynamic environments is an urgent problem. In this work, we investigate the reputation-based dynamic contract for mobile crowdsourcing network. A two-period dynamic contract is first investi- gated to deal with the asymmetric information problem in the long-term crowd- sourcing tasks. Reputation strategy is introduced to attract the MUs to complete the long-term tasks. The incentives of the contract and the implicit incentives of the reputation strategy are used together to encourage MUs to complete the long-term crowdsourcing tasks. The optimization strategy is formulated by adjust- ing the reputation coefficient to maximize the SP’s utility. The impact of MUs’ risk attitude and reputation impact factors on the incentive mechanism is studied through experiments. Numerical simulation results demonstrate that the optimal reputation-based contract design scheme is efficient in the Mobile crowdsourcing networks.
Elevated Circulating Levels of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline ( AcSDKP) Involved in Pancreatic Cancer Development
Authors: Susanto Hendra , Purnomo Jerry Dwi Trijoyo , Chen Chang-Chiang , Wang Chih-Hong 
Published: May 2020

Abstract
Background: Pancreatic cancer is the fourth leading cause of patient mortality with poor early prognosis. Lack of symptoms as early detection of this cancer has become the major problem for its clinical investigation. Thymosin β-4 (Tβ4) has been associated with angiogenesis and metastasis in pancreatic cancer. Recently, N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP), a cleavage and active form of Tβ4, is suggested related to systemic alteration to patients and involve in the Pancreatic Ductal Adenocarcinoma (PDAC) progression. However, the way this systemic change affected PDAC development is still not fully elucidated. This case-control study was conducted to evaluate the level of AcSDKP in health and pancreatic cancer patients during the progression of pancreatic cancer development. Methods: We analyzed 105 patients, including 15 healthy subjects and 90 pancreatic cancer subjects. The levels of AcSDKP were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) kit. Proliferation rate analysis was conducted using MTS assay in AsPC, HPAC, and PANC-1 cell line pre-treated by prolyl oligopeptidase (POP) inhibitor and AcSDKP polypeptide. Results: Compared to healthy patients (0.73 ± 0.13), the levels of AcSDKP significantly increased in pancreatic cancer subjects (1.34 ± 0.14). AcSDKP induced pancreatic cell proliferation while inversely inhibited with POP inhibitor by in vitro analysis. Moreover, levels of AcSDKP were strongly positively correlated with pancreatic cancer status (r = 0.278, p = 0.026), betatrophin (r = 0.270, p = 0.025), ALP (r = 0.267, p = 0.034), ALT (r = 0.336, p = 0.007), and AST (r = 0.255, p = 0.042), while inversely correlated with cholesterol levels (r = - 0.250, p = 0.046). Furthermore, in univariate and multivariate binary logistic regression analysis, the levels of AcSDKP showed a strong association with pancreatic cancer [(p = 0.031, OR±95%CI = 3.342 (1.117-10.002)] and [(p = 0.024, OR±95%CI = 4.324 (1.030-18.148)]. Quintile analysis showed that the level of AcSDKP has a strong association with betatrophin [(p = 0.033, OR±95%CI = 5.623 (1.142-24.266)]. Conclusions: AcSDKP can contribute to the progression of pancreatic cancer incidence and may indirectly be associated with liver lipid metabolism hormone as well as tumor cell proliferation. AcSDKP might be a potential additional predictor for pancreatic cancer.
Exploring the zoonotic potential of Mycobacterium bovis using variant calling approaches
Authors: Banerjee Ruma , Balamurugan Muthukumar , Joshi Rajendra 
Published: May 2020

Abstract
BackgroundMycobacterium tuberculosis var. bovis is one of the causative agents of Tuberculosis primarily known to infect cattle and is a member of the Mycobacterium Tuberculosis Complex. M.bovis is zoonotic and infects human and other animals resulting in immense economic losses globally. M.bovis is often misdiagnosed and becomes a challenge for treatment and recovery, as M.bovis is intrinsically resistant to certain antibiotics. Hence, the need for accurate diagnostics for zoonotic tuberculosis. ResultsIn order to discern the differences which lie between M.tuberculosis and M.bovis isolates we collected a global collection of M.bovis isolates from NCBI and carried out variant identification studies keeping M.tuberculosis as the reference. Clustering approaches like Principal component analysis and distance-based UPGMA methods helped to segregate isolates into different clusters of homogeneous and heterogeneous populations, which were further analyzed for variant identification. Methods like Joint Variant Calling using population-based studies was adopted for the M.bovis strains, which helped to discern high confidence polymorphisms for each set of populations. Four different variant callers were used to predict SNPs present in their genomic regions. Based on the predicted SNPs, M.bovis samples isolated from New-Zealand were identified as a heterogeneous fast evolving population, whereas the UK samples were identified as a slow evolving homogeneous population. The core-SNP identified for each population revealed the “fixed” mutations present within the populations, whereas, the total-SNP for heterogeneous population indicated presence of clonal subpopulations. A methodology for assignment of genomic coordinates to the reference SNP cluster id of M.tuberculosis entries in dbSNP was also developed and implemented, which helped to identify the percentage of known variants in a population. ConclusionsPopulation-specific studies for global collection of M.bovis samples aided in identification of SNPs responsible for zoonosis. The core-SNP set identified across global M.bovis isolates provide a rationale for further studies to the underlying host-tropism along with aiding in as a robust genetic biomarker for distinguishing M.bovis form M.tuberculosis in addition to the already known RDs. The variation profile reported in this study can serve as potential biomarkers for identification of M.bovis isolates and provide a rationale for further studies to the underlying host-tropism.
Differences in radiological and functional outcomes between cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament after multi-level laminoplasty
Authors: Yu Dongwoo , Kim Sang Woo , Jeon Ikchan 
Published: May 2020

Abstract
Objective

The purpose of this study was to compare the radiological and functional outcomes between patients with cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) after multi-level laminoplasty.
Methods

This study included 75 patients (32 with CSM and 43 with OPLL) with preserved cervical sagittal balance who underwent multi-level laminoplasty for cervical myelopathy. The radiological outcomes were analyzed using the following parameters: C2–C7 Cobb angle in neutral (C27AN), flexed (C27AF), and extended (C27AE) neck postures; C2–C7 range of motion (C27ROM); T1 slope (T1S); and C2–C7 sagittal vertical axis (C27SVA). The functional outcomes were analyzed using the modified Japanese Orthopedic Association (mJOA) score, Nurick grade, and recovery rate. The radiological and functional outcomes between the two groups were evaluated 12-months postoperatively.
Results

C27AF, C27ROM, and C27SVA in the CSM group and C27ROM in the OPLL group decreased significantly (p < 0.05). There was a significant difference in ΔC27SVA between the two groups (9.41 ± 17.06 mm vs. 1.10 ± 17.15 mm, p < 0.05). However, there were no significant intra- or intergroup changes and differences in C27AN (p > 0.05). The functional outcomes including mJOA score (p = 0.251), Nurick grade (p = 0.316), and recovery rate (p = 0.435) showed no significant intergroup differences.
Conclusions

Although there were no significant differences in functional outcomes between the two groups, the CSM group showed a greater deterioration in sagittal balance with an increase of C27SVA than the OPLL group after multi-level laminoplasty.
Construct validity and differential item functioning of the PHQ-9 among health care workers: Rasch Analysis approach
Authors: Jiraniramai Surin , Wongpakaran Tinakon , Angkurawaranon Chaisiri , Jiraporncharoen Wichuda , Wongpakaran Nahathai 
Published: May 2020

Abstract
Background The Patient Health Questionnaire (PHQ-9) is a widely used self-report questionnaire to screen depression. Its psychometric property has been tested in many populations including health care workers. We used Rasch measurement theory to examine the psychometric properties of PHQ-9 regarding item difficulty, item fit and the differences between subgroups of respondents classified by sex, age, education and alcohol user status, based on the same overall location of participants.Methods In total, 3,204 health care workers of Maharaj Nakorn Chiang Mai Hospital participated and were administered the PHQ-9. Rating scale Rasch measurement modeling was used to examine the psychometric properties of the PHQ-9.Results The data fitted well to the Rasch model and no violations of the assumption of unidimensionality were observed. All 9 items could form a unidimensional construct of overall depressive severity. Suicidal ideation was the least endorsed while sleep problem was the most. No disordered category and threshold of the rating response were observed. No locally dependent items were observed. No items were found to show differential item functioning across age, sex, education and alcohol consumption. The item-person Wright map showed that the PHQ-9 did not target well with the sample, and a wide gap suggesting few or no items exist to differentiate participants at a certain ability level among the PHQ-9 items.Conclusion The PHQ-9 can be used as a screening questionnaire for major depressive disorder as its psychometric property was verified based on Rasch measurement model. The findings are generally consistent with related studies in other populations. However, the PHQ-9 may be unsuitable for assessing depressive symptoms among health care workers who have low levels of depression.
Comparative genome analysis of Bacillus okhensis Kh10-101T reveals insights into adaptive mechanisms for halo-alkali tolerance
Authors: Krishna Pilla Sankara , Raghunathan Sarada , Jogadhenu Shyam Sunder Prakash 
Published: May 2020

Abstract
Background: Bacillus okhensis, isolated from saltpan near port of Okha, India, was initially reported to be a halo-alkali tolerant bacterium.We previously sequenced it’s 4.86 Mb genome, here we analyze its genome and physiological responses to high salt and high pH stress. Results: B. okhensis is a halo-alkaliphile with optimal growth at pH 10 and 5% NaCl. 16S rDNA phylogenetic analysis resulted in habitat based segregation of 106 Bacillus species into 3 major clades with all alkaliphiles in one clade clearly suggesting a common ancestor for alklaliphilic Bacilli. We observed that B. okhensis has been adapted to survive at halo-alkaline conditions, by acidification of surrounding medium using fermentation of glucose to organic acids. Comparative genome analysis revealed that the surface proteins which are exposed to external high pH environment of B. okhensis were evolved with relatively higher content of acidic amino acids than their orthologues of B. subtilis. It posess relatively more genes involved in the metabolism of osmolytes and sodium dependent transporters in comparison to B. subtilis. Growth of B. okhensis is Na+ dependent, with a minimum requirement of 4% NaCl at neutral pH but 0.5% NaCl is enough at pH 10. It tolerated sudden increase of salt concentration of its medium, and exhibited an elongated cellular phenotype. But, could not tolerate a sudden shift of pH from 7 to 11, and cell envelope got damaged, confirming the pH regulation through cell wall reinforcement is key to survival at high-pH condition. We observed that hydroxyl ions damage the cell, but not Na+ ions, becuase at high pH Na+ ions were not accumulated inside. Conclusion: B. okhensis uses acidification of the external medium and pH dependent cell wall reinforcement to survive sodic environments. Interestingly, its growth is highly Na+ dependent and the genome encodes for a high proportion of acidic amino acids in majority of surface proteins in comparison to their orthologues of B. subtilis, a direct evidence of adaptive evolution.
The worldwide contribution of medical students during the COVID-19 pandemic: quantitative and qualitative research
Authors: Blom Iris Martine , Whyatt Gemma , Viva Inês , Martin Anastasia 
Published: May 2020

Abstract
Background

One of the biggest concerns regarding the COVID-19 pandemic is the extreme demand for health care workers and health systems. Medical students possess a range of skills and attributes that can help the declining workforce. This paper aims to provide an overview of the roles medical students have taken during this pandemic worldwide and provide insights to work towards establishing safe, efficient and useful roles during the progression of the pandemic.
Methods

A comprehensive questionnaire was distributed through social media using platforms and networks that involved medical students worldwide. Analysis of the data included both quantitative and qualitative methods. Qualitative data of multiple-choice questions was done to calculate the percentage of countries in which students played a role during the pandemic, whether they were paid, and if medical education was suspended. Furthermore, we identified the different roles medical students had across the globe. Qualitative analysis was performed on blank space questions to gain more insights regarding the roles of medical students across different countries.
Results

144 responses were reported from 47 countries and 81 different universities, representing all United Nations Regions. The role of medical students was most reported as providing medical assistance, namely in 61.7% of countries. Other reported roles were helplines, no role, logistical assistance, testing, baby-sitting, awareness, triage and supporting a physician at home. In 7.5% of the countries where students are performing services, it is reported these are paid services. In 45.7% (n = 37) of all universities, medical schools have been suspended with no reported (online) alternative for classes or exams.
Conclusions

Our results show that medical students have the capability to contribute in many different ways during this pandemic. In most cases, roles are unpaid and many reports show that there is no clarity on whether their roles will count towards their educational credits. It is crucial to develop adequate protocols and statements, so medical students can contribute to the best of their capacity and in a safe, ethical and healthy manner during the pandemic, for which additional research and collaboration between institutions is needed.
Identification of a Four-miRNA Risk Score Model and Hub Genes as a Novel Potential Prognostic Biomarker in Patients with Glioma
Authors: xu jianguang , Li Si-Si , Lu Ye-Chen , Hua Xu-Yun , Wu Jia-Jia , Ding Dao-Fang , Ma Zhen-Zhen 
Published: May 2020

Abstract
Background Novel biomarkers for malignant glioma are urgently needed due to the poor prognosis of this cancer. Numerous discoveries have demonstrated that microRNAs (miRNAs) participate in the occurrence and progression of glioma. The objective of this study is to explore new biomarkers related to glioma prognosis by bioinformatic analysis.Methods The miRNA, mRNA expression profiles and relevant clinical information were extracted from TCGA database. Differently expressed miRNAs (DEMs) and differently expressed mRNAs/genes (DEGs) were screened, and a risk score comprising four miRNAs was constructed. We evaluated and tested the model accuracy through the ROC curve and a survival status analysis. Four-miRNA nomography were performed to quantitatively and visually evaluate the model. The potential biological functions of those network genes were performed through KEGG pathways and Gene Ontology (GO) terms analysis. Furthermore, survival analysis and the clinical information was used to verify whether the hub genes are associated with prognosis. The CGGA and GEPIA database were used to verified the accuracy of these analysis. To investigate the potential functions of those hub genes in glioma, we performed GSEA and GSVA.Results The results of univariate Cox regression showed that twenty miRNAs were significantly associated with overall survival of glioma. Multivariate Cox regression analyses were performed to screen four miRNAs (hsa-miR-744-5p, hsa-miR-1249-3p, hsa-miR-3677-3p and hsa-miR-10b-3p). The estimated area under the receiver operating characteristic (ROC) curve (AUC) were 0.902, 0.896 and 0.907 for groups train, test and entire, respectively, indicating that the model had a significant ability to predict survival in glioma patients. Furthermore, univariate and multivariate Cox regression were performed using relevant clinical factors associated with glioma, showed that the model could act as an independent prognostic factor. CGGA and GEPIA database were used to verified the accuracy of these hub genes. GSEA and GSVA revealed that the lower expressions of these hub genes were most closely associated with vascularization and tumor proliferation.Conclusions In conclusion, the four-miRNA risk score model and these hub genes may represent a novel prognostic marker to predict the survival of patients with glioma.