bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Connexin43 provides anti-inflammatory effects after intracerebral hemorrhage injury by regulating YAP signaling
Authors: Yu Hailong , Cao Xiang , Li Wei , Liu Pinyi , Zhao Yuanyuan , Song Lilong , Chen Jian , Chen Beilei , Yu Wenkui , Xu Yun 
Published: June 2020

Abstract
Background: In the central nervous system(CNS),Connexin43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Like Cx43 overexpression,abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies.However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear.Methods: Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH modals in vitro and vivo.Cx43 mimetic peptide Gap19 was treated after ICH injury. Ethidium bromide (EtBr) uptake assays was used to measure the opening of Hcs. Western blot and immunofluorescence were used to measure the expression of protein. qRT-PCR and ELISA were used to determine the level of cytokines. Co-immunoprecipitation(Co-IP) and Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins.Results: In this study,Cx43 expression was upregulated, and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition,Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo, as determined by GFAP staining. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture.However,Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased YAP nuclear translocation, which upregulated SOCS1 and SOCS3 expression, and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor verteporfin (VP) reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury.Conclusions: This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs.Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 plays anti-inflammatory and neuroprotective roles after ICH injury.
Management of patients with suspected COVID-19 who underwent emergency surgery
Authors: Tan Yanzhe , Yan Chengwei , guo chunbao 
Published: June 2020

Abstract
Background: Since the outbreak of COVID-19, no official guidelines for urgent surgical management of patients with the COVID-19 concern have been recommended. The current study provides our experience about the management for the patients with suspected or confirmed COVID-19 who required urgent surgical intervention.Methods: From February 5, 2019, to May 26, 2020, there were 5 cases of patients with suspected or confirmed COVID-19 infection managed with urgent surgical intervention in two hospitals in Chongqing. Results: The five cases with COVID-19 concern were admitted with different diseases, including acute intussusception, strangulated inguinal indirect hernia, acute purulent appendicitis, femoral fracture and onset to delivery. Finally, four patients obtained negative results afterwards. One pregnant woman with confirmed COVID-19 infection underwent caesarean section. All medical staff involved in the patients management were well, and no in-hospital transmission occurredConclusion:Suspected COVID-19 patients must be managed as positive patients until proven or denied in order to minimize the spread and transmission of infection. The current protocol carried out in our practice might be plausible and technically feasible for hospitals when dealing with COVID-19 infection.
Brain Imaging Big Data Mining and Fusion Method Based on Cognitive Intelligence
Authors: Li Xiao-Yan , Zhang Feng , Zhang Yong-Heng 
Published: June 2020

Abstract
In order to improve the utilization rate of brain imaging big data and solve the fusion problem of multi-source and heterogeneous brain imaging big data, an improved brain imaging big data ant colony optimization algorithm (BigDataACO) is proposed to complete the multi-source brain imaging big data information in the feature layer and decision-making and the problem of multi-source data fusion was solved. The swarm intelligence algorithm is a process of simulating the complex problem of populations in nature through the mutual cooperation between individuals. The algorithm has potential parallelism and strong robustness, and the algorithm does not depend on specific problems. The definition, principle and implementation method of brain imaging big data fusion problem are studied. Then the insufficiency of big data fusion modeling algorithm is analyzed. Finally, the source and core steps of ant colony big data fusion algorithm are studied. The experimental results show that the improved BigDataACO algorithm is verified by the measured data. Compared with K-means, D-S evidence theory and Bayesian algorithm, the uncertainty of data fusion is greatly reduced by the improved algorithm proposed in this paper.
Lung Function Decline and Other Physiological Changes in Health Workers after Working in COVID-19 Isolation Wards: An Observational Study
Authors: Chen Kailei , Zhu Peipei , Wang Liyuan , Zuo Siting , Wu CuiPing , Hu Ying , Wang YiSi , Wu Feng , Tang Xin 
Published: June 2020

Abstract
Background:Global healthcare systems have been under huge pressure since Coronavirus Disease 2019 (COVID-19) was declared a pandemic. It is critical to prevent further spread of COVID-19 and to protect health workers from infection. This study aims to figure out short-term physiological impact on health workers induced by working in isolation wards for hours with personal protective equipment (PPE), so as to provide insights on reducing physiological impact and infection risk of health workers.Methods:Health workers who had worked in COVID-19 isolation wards for at least five weeks in Wuhan, China were recruited. Parameters including lung function, heart rate, oxygen saturation and weight were respectively measured before and after they worked in isolation wards. Comparison and regression analyses were conducted. Correlations between changing levels of measured parameters (lung function and heart rate) and baseline characteristics (body mass index, age, and working duration) were also analyzed. Results: After working in isolation wards for four to nine hours, the forced vital capacity (FVC) of health workers (74.32±17.59 versus 81.28±16.35, P<0.001) as well as weight (54.79 (48.50, 61.00) versus 55.50 (48.90, 61.00) P<0.01) showed significant decrease, while HR showed significant increase (110.31±14.65 versus 103.94±16.38, P=0.04). Correlation between BMI and the decline levels of FEV1/FVC (β=2.87, P=0.02) and correlation between BMI and the decline levels of FEF25-75 % predicted (β=1.80, P<0.05) were reported.Conclusions:After working in COVID-19 isolation wards with PPE for four to nine hours, the lung function of health workers declined. The decline levels were associated with BMI. HR increase and weight loss were reported. In order to reduce the potential infection risk of health workers, the balance between working duration and physiological changes should be considered when making shifting schedule.
Change of foulant concentration in an anaerobic membrane bioreactor
Authors: Hasegawa Susumu , Murakami Genki , Takagi Ryosuke , Matsuyama Hideto 
Published: June 2020

Abstract
Anaerobic membrane bioreactors (AnMBRs) have many advantages, such as producing methane gas for energy generation and little excess sludge. However, membrane fouling is a serious problem because the foulant, which causes the membrane to foul, may get rejected by the membrane and accumulate in the reactor, resulting in an acceleration of membrane fouling. However, there is no information related to a change in the foulant concentration in an AnMBR. Therefore, we examined the changes in the foulant concentration in the reactor, related to membrane fouling in an AnMBR. For the influent, reactor solution, and effluent, the concentration of each component of the foulant was analyzed by using a liquid chromatography-organic carbon detector (LC-OCD). It was found that fouling in the AnMBR was closely related to the components in the reactor, and the main foulant of the ultrafiltration (UF) membrane was biopolymers (BPs). BP accumulated in the reactor because of a high rejection by the UF membrane. However, once the BP accumulated in the reactor was biodegraded, the concentration of BP decreased with time even under a high organic loading rate of 1.9kg TOC/m3/day.
Adsorption onto MWCNTs Coupled with Cloud Point Extraction for Dye Removal from Aqueous Solutions: Optimization by Experimental Design
Authors: Safa Fariba , Osaghi Bahare 
Published: June 2020

Aims:
The main aim of the study was to examine the feasibility and benefits of
adsorption onto multi-walled carbon nanotubes (MWCNTs) coupled with cloud point extraction
(CPE) for the removal of Rhodamine B (RB) from aqueous solutions.

Background:
MWCNTs offer the particular features of the ideal adsorbents for the organic dyes
such as hollow tubular structure and specific surface area. Nevertheless, they suffer from the
drawbacks of low dispersion in the aqueous solutions and separation inconvenience from the
media. Cloud point extraction, combined with the adsorption onto MWCNTs can be a promising
method to overcome the problems.

Objective:
In the study, adsorption onto MWCNTs coupled with CPE was applied for RB removal
from aqueous solutions. The process was optimized by the response surface modeling method.
Moreover, the applicability of the proposed method in the real sample analyses was investigated.

Methods:
MWCNTs were used as adsorbent and Triton X-100 (TX-100) as the nonionic surfactant
for CPE process. The experiments were carried out based on a Box-Behnken design (BBD) with
the input variables of MWCNTs dosage (0.6-1.2 mg), solution pH (3–9), clouding time (20-40
min) and TX-100 concentration (10-20 v/v%) using 5 mg L-1 RB solutions.

Result:
Regression analyses resulted in a statistically significant quadratic model (R2=0.9718,
F=24.96, p#60;0.0001) by which the optimum levels of the variables were predicted as: MWCNTs
dosage of 0.7 mg, pH=3, clouding time of 39.9 minutes and TX-100 concentration of 19.91%
(v/v). The predicted conditions were experimentally validated by achieving an RB removal of
94.24%.

Conclusion:
Based on the results, the combination of the environmentally friendly technique of
CPE with adsorption onto MWCNTs allows the efficient removal of RB from water samples and
the method can be effectively optimized by the response surface modeling.
Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors
Authors: Güngör Emine Merve , Altıntop Mehlika Dilek , Sever Belgin , Çiftçi Gülşen Akalın 
Published: June 2020

Background:
Akt is overexpressed or activated in a variety of human cancers, including
gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction
of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted
to the discovery of potent antitumor drugs targeting Akt.

Objectives:
The objective of this work was to identify potent anticancer agents targeting Akt.

Methods:
New hydrazone derivatives were synthesized and investigated for their cytotoxic effects
on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast
cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were
evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric
assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME)
studies were also performed using Schrödinger’s Maestro molecular modeling package.

Results and Discussion:
Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells
(with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with
cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced
apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin-
2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared
with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed
good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the
compound also complies with Lipinski's rule of five and Jorgensen's rule of three.

Conclusion:
Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis
inducer targeting Akt.
Classifying Cognitive Normal and Early Mild Cognitive Impairment of Alzheimer’s Disease by Applying Restricted Boltzmann Machine to fMRI Data
Authors: Pei Shengbing , Guan Jihong 
Published: June 2020

Background:
Neuroimaging is an important tool in early detection of Alzheimer’s disease
(AD), which is a serious neurodegenerative brain disease among the elderly subjects. Independent
component analysis (ICA) is arguably one of the most widely used algorithm for the analysis of
brain imaging data, which can be used to extract intrinsic networks of brain from functional
magnetic resonance imaging (fMRI).

Method:
Witnessed by recent studies, a more flexible model known as restricted Boltzmann
machine (RBM) can also be used to extract spatial maps and time courses of intrinsic networks from
resting state fMRI, moreover, RBM shows superior temporal features than ICA. Here, we seek to
employ RBM to improve the performance of classifying individuals. Experiments are performed on
healthy controls and subjects at the early stage of AD, i.e., cognitive normal (CN) and early mild
cognitive impairment participants (EMCI), and two types of data, i.e., structural magnetic resonance
imaging (sMRI) and fMRI data.

Results:
(1) By separately employing ICA for sMRI and fMRI, the features extracted from fMRI
improve classification accuracy by 7.5% for CN and EMCI; (2) instead of applying ICA to fMRI,
using RBM further improves classification accuracy by 7.75% for CN and EMCI; (3) the lesions at
the early stage of AD are more likely to occur in the regions around slices 4, 6, 10, 14, 19, 51 and 59
of the whole brain in the longitudinal direction.

Conclusion:
By using fMRI instead of sMRI and RBM instead of ICA, we can classify CN and
EMCI more efficiently.
Metabolic Adjustments by LncRNAs in Peripheral Neutrophils Partly Account for the Complete Compensation of Asymptomatic MMD Patients
Authors: Han Ziping , Li Lingzhi , Liu Ping , Huang Yuyou , Zhang Sijia , Li Guangwen , Li Fangfang , Zhao Haiping , Tao Zhen , Wang Rongliang , Ma Qingfeng , Luo Yumin 
Published: June 2020

Backgrounds:
Due to the recent development of non-invasive examinations, more asymptomatic
patients with Moyamoya Disease (MMD) have been diagnosed than ever. However, its underlying
molecular mechanisms and clinical intervention guidelines are all still obscure.

Methods:
Microarray was used to explore those differentially expressed mRNAs and lncRNAs in peripheral
neutrophils of asymptomatic MMD patients. Then enrichment analyses based on Gene Ontology
(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for those differentially expressed
mRNAs and lncRNA associated mRNAs were performed for underlying molecular mechanisms.

Results:
Here, we identified a total of 2824 differentially expressed lncRNAs and 522 differentially
expressed mRNAs (fold change > 2 and P<0.05) in peripheral neutrophils of asymptomatic MMD patients,
compared with healthy controls. Then enrichment analyses based on GO and KEGG showed
that the neighboring protein-coding mRNAs of those up-regulated and down-regulated lncRNAs were
mainly involved in distinct metabolic processes respectively, which may act as a complementary response
to insufficient blood supplies in MMD. Further enrichment analyses of those differentially expressed
mRNAs preferentially listed essential physiological processes such as peptide cross-linking,
chromatin assembly among others. Moreover, altered mRNAs also revealed to be enriched in renin secretion,
platelet activation, inflammation and others.

Conclusion:
We demonstrated for the first time that metabolic adjustments by dysregulated lncRNAs
in peripheral neutrophils might partially account for the complete compensation of asymptomatic
MMD patients. In addition, more attention should be paid on renin secretion and platelet activation in
order to better understand the pathogenesis and guide clinical intervention for asymptomatic MMDs.
Implementation of Genetic Algorithms and Momentum Backpropagation in Classification of Subtype Cells Acute Myeloid Leukimia
Authors: Mustikaningrum Dian , Wardoyo Retantyo 
Published: June 2020

Acute Myeloid Leukimia (AML) is a type of cancer which attacks white blood cells from myeloid. AML subtypes M1, M2, and M3 are affected by the same type of cells called myeloblasts, so it needs more detailed analysis to classify.Momentum Backpropagation is used to classified. In its application, optimal selection of architecture, learning rate, and momentum is still done by random trial. This is one of the disadvantage of Momentum Backpropagation. This study uses a genetic algorithm (GA) as an optimization method to get the best architecture, learning rate, and momentum of artificial neural network. Genetic algorithms are one of the optimization techniques that emulate the process of biological evolution.The dataset used in this study is numerical feature data resulting from the segmentation of white blood cell images taken from previous studies which has been done by Nurcahya Pradana Taufik Prakisya. Based on these data, an evaluation of the Momentum Backpropagation process was conducted the selection parameter in a random trial with the genetic algorithm. Furthermore, the comparison of accuracy values was carried out as an alternative to the ANN learning method that was able to provide more accurate values with the data used in this study.The results showed that training and testing with genetic algorithm optimization of ANN parameters resulted in an average memorization accuracy of 83.38% and validation accuracy of 94.3%. Whereas in other ways, training and testing with momentum backpropagation random trial resulted in an average memorization accuracy of 76.09% and validation accuracy of 88.22%.
Budgetary Impact of Covering “Me-Too” Drugs from Social Security: Buenos Aires State Case Report
Authors: Marin Gustavo H. , Marin Lupe , Agüero Daniel , Pagnotta Mariana , Marin Gina , Blanco Luis 
Published: June 2020

The majority of new drugs that are register at Health Global Market are not considered real innovations and due to their chemical structure similarity of reference’s group drug, they are known as “me-too”. These “me too” drugs has no additional therapeutic benefits but greatly increasing treatment´s. PURPOSE: To demonstrate the economic impact in Social Security budget by covering “me too” medicines. METHODS: An epidemiological-descriptive-analytical study was performed in order to analyze the burden of anti-hypertensive prescription from patients under coverage by Buenos Aires State Social Security. Two types of medicines were compared: “pioneer” or “me-too”. Variables considered were: type of drug, class or therapeutical group of medicines, global costs, burden for social security and for patients. RESULTS: From 185865 patients that received medication; in 121748 of the cases the strategy was monotherapy while 64117 received at least two or more medicines. 189714 were reference drugs while 64393 of them were considered “me-too”. In average, “me-too” drugs were 41.23% more expensive than classical treatment. The percentage covered by IOMA varies according to the medicines (between 45 to 51%) and patients must complete the amount of money remaining from their pockets. Paradoxically, the percentage covered by IOMA some “me-too” were greater than the percentage paid for most classic medications of each group. CONCLUSIONS: By only choosing the drug of reference, with proven effectiveness, from each therapeutical group, the State Social Security could cover 100% of the cost of all anti-hypertensive treatment and all patients even saving almost 2 million dollars per year.
Keywords: Health, Policies, Medicines, Me too, Economical Burden, Coverage, anti-hypertensive
Development and Validation of UPLC-MS/MS Method for Rapid Simultaneous Determination of Levothyroxine and Liothyronine in Human Serum
Authors: Dutt Rohit , Malik Kailash Chander , Karwa Manoj , JAIN Gaurav Kumar 
Published: June 2020

A simple ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated to simultaneously determine levothyroxine (LT4) and liothyronine (LT3) in human serum. Sample preparation was done through protein precipitation with acetonitrile. HyPURITY C18 column was selected to achieve rapid separation for LT4 and LT3 within 4 min. Electrospray ionization (ESI) under multiple reaction monitoring (MRM) was used to monitor the ion transitions for LT4 (m/z 777.54→731.52), LT3 (m/z 651.64→ 605.65) and internal standard LT4-D3 (m/z 780.53 →734.19), operating in the positive ion mode. The method was proved to be accurate (82.35% to 113.56%) and precise (0.73% to 8.28%) over concentration range of 50.37 ng/ml – 300.13 ng/ml for LT4 and 0.5 ng/ml – 50.37 ng/ml for LT3. The validated method could be applied for pharmacokinetic study or bioequivalence testing of combination products of LT4 and LT3.
Keywords: Levothyroxine; Liothyronine; Ultra Performance Liquid Chromatographic; Mass Spectrometry; Human Serum
The Economic Effects of Earnings Management Pre- and Post-SOX
Authors: Mason Terry W. , Morton Richard M. 
Published: June 2020

ABSTRACT
Research suggests that following several high-profile accounting scandals and the passage of SOX legislation in 2002, firms substituted real earnings management strategies for accrual manipulation. However, the broader implications of this tradeoff from a public policy and financial oversight perspective are not well understood. Consistent with our expectations, we find that abnormal operating decisions are less informative about future ROA in the post-SOX period. We also find that the increase in real earnings management negatively impacts firm value, but investors appear slow to recognize and price the myopic behavior. We do not observe a corresponding increase in the quality of discretionary accruals after SOX, but market mispricing of abnormal accruals essentially disappears, consistent with greater investor scrutiny. Although the shift away from accrual manipulation to real earnings management should result in less distortion of underlying economic events, the net effect appears to be value destroying for the average firm.
Data Availability: Data are publicly available from sources identified in the paper.
JEL Classifications: G32; G38; M41; M48.