bluuebunny/crossref_metadata_2025_split huggingface dataset:
A stratification method based on clustering for the minimization of data masking effect in signal detection
Authors: Wei Jian-Xiang , Ding Yue , Li Ming , Sun Jun 
Published: February 2020

AbstractBackgroundData masking is an inborn defect of measures of disproportionality in adverse drug reactions (ADRs) signal detection. Many previous studies can be roughly classified into three categories: data removal, regression and stratification. However, frequency differences of adverse drug events (ADEs) reports, which would be an important factor of masking, were not considered in these methods. The aim of this study is to explore a novel stratification method for minimizing the impact of frequency differences on real signals masking.MethodsReports in the Chinese Spontaneous Reporting Database (CSRD) between 2010 and 2011 were selected. The overall dataset was stratified into some clusters by the frequency of drugs, ADRs, and drug-event combinations (DECs) in sequence.K-meansclustering was used to conduct stratification according to data distribution characteristics. The Information Component (IC) was adopted for signal detection in each cluster respectively. By extracting ADRs from drug product labeling, a reference database was introduced for performance evaluation based onRecall,PrecisionandF-measure. In addition, some DECs from the Adverse Drug Reactions Information Bulletin (ADRIB) issued by CFDA were collected for further reliability evaluation.ResultsWith stratification, the study dataset was divided into 21 clusters, among which the frequency of DRUGs, ADRs or DECs followed the similar order of magnitude respectively.Recallincreased by 34.95% from 29.93 to 40.39%,Precisionreduced by 10.52% from 54.56 to 48.82%, whileF-measure increased by 14.39% from 38.65 to 44.21%. According to ADRIB after 2011, 5 DECs related toPotassium Magnesium Aspartate, 61 DECs related toLevofloxacin Hydrochlorideand 26 DECs related toCefazolinwere highlighted.ConclusionsThe proposed method is effectively and reliably for the minimization of data masking effect in signal detection. Considering the decrease ofPrecision, it is suggested to be a supplement rather than an alternative to non-stratification method.
Emergency department and inpatient utilization among U.S. older adults with multiple chronic conditions: a post-reform update
Authors: Ahn SangNam , Hussein Mustafa , Mahmood Asos , Smith Matthew Lee 
Published: February 2020

AbstractBackgroundThe Affordable Care Act (ACA) was enacted to enhance access to care primarily among nonelderly and low-income populations; however, several provisions addressed key determinants of emergency department (ED) and inpatient visits among Medicare beneficiaries over age 65 years. We take stock of the overall changes in these visits among older Medicare beneficiaries, focusing on those with multiple chronic conditions (MCCs), and provide a nationally representative post-reform update.MethodsWe analyzed a sample of 32,919 older adults (65+) on Medicare from the 2006–2015 Medical Expenditure Panel Survey (MEPS). Using a survey-weighted two-part model, we examined changes in ED visits, inpatient visits, and length of stay (LOS) by MCC status, before (2006–2010), during (2011–2013), and after the ACA (2014–2015).ResultsPrior to the ACA, 18.1% of Medicare older adults had ≥1 ED visit, whereas 17.1% had ≥1 inpatient visits, with an average of 5.1 nights/visit. Following ACA reforms, among those with 2+ chronic conditions, the rate of ever having an ED visitincreasedby 4.3 percentage points [95% confidence intervals [CI]: 2.5, 6.1,p < 0.01], whereas the rate of inpatient visits decreased by 1.4 percentage points [95%CI: − 2.9, 0.2,p < 0.1], after multivariable adjustment.ConclusionsWe found sizable increases in ED visits and nontrivial decreases in inpatient visits among older Medicare beneficiaries with MCCs, underscoring the continuing need for improving access to and quality of care among older adults with MCCs to decrease reliance on the ED and reduce preventable hospitalizations.
Anti-cancer effect of gallic acid in presence of low level laser irradiation: ROS production and induction of apoptosis and ferroptosis
Authors: Khorsandi Khatereh , Kianmehr Zahra , hosseinmardi Zohreh , Hosseinzadeh Reza 
Published: February 2020

Abstract
Background
There are different treatments for breast cancer and melanoma that mostly have some side effects. One of the therapeutic strategies is the use of natural components. Phenol components are a class of antioxidants in plants that have many biological functions like anticancer effects. Gallic acid (GA) is a natural polyhydroxy phenolic compound and commonly found in various foods. In the present study, GA effects alone and in combination with low-level laser irradiation on human dermal fibroblast cell line (HDF), human non-tumorigenic breast epithelial cell line (MCF10A), breast cancer cell line (MDA-MB-231) and melanoma cancer cell line (A375) was under the investigation.

Methods
The normal and cancerous cell lines were exposed to 660 nm low-level laser with 3 J/cm2 for 90 s. Then, the cells were treated with different concentrations of GA for 24 h. In another study, the cell lines firstly were treated with GA and then exposed to low-level laser irradiation. The effects of GA and low-level laser on cell survival and apoptosis were examined using MTT assay, light microscopy, ROS production assay, fluorescence microscopy (AO/EB double staining) and flow cytometry.

Results
The results showed that pre-treatment with low-level laser and then GA reduced the survival of breast cancer cells and melanoma more than the first treatment with GA and then low-level laser irradiation. Our findings showed that ROS production in cells treated with both low-level laser and GA was more than the cells treated with GA alone. The apoptosis and ferroptosis assays confirmed the MTT results which combination treatment with low-level laser and then GA increase the cell death probably via apoptosis and ferroptosis cell death mechanisms compared to GA alone.

Conclusions
This study suggests that low-level laser irradiation alone is not able to cause death in human normal and cancerous cells. Preirradiation followed by GA treatment did not change the cell viability in human normal significantly but reduces the cell survival of cancer cells more than GA alone.
Sexual forms obtained in a continuous in vitro cultured Colombian strain of Plasmodium falciparum (FCB2)
Authors: Ararat-Sarria Monica , Prado Cesar Camilo , Camargo Milena , Ospina Laura Tatiana , Camargo Paola Andrea , Curtidor Hernando , Patarroyo Manuel Alfonso 
Published: February 2020

Abstract
Background
The epidemiological control of malaria has been hampered by the appearance of parasite resistance to anti-malarial drugs and by the resistance of mosquito vectors to control measures. This has also been associated with weak transmission control, mostly due to poor control of asymptomatic patients associated with host-vector transmission. This highlights the importance of studying the parasite’s sexual forms (gametocytes) which are involved in this phase of the parasite’s life-cycle. Some African and Asian strains of Plasmodium falciparum have been fully characterized regarding sexual forms’ production; however, few Latin-American strains have been so characterized. This study was aimed at characterizing the Colombian FCB2 strain as a gametocyte producer able to infect mosquitoes.

Methods
Gametocyte production was induced in in vitro cultured P. falciparum FCB2 and 3D7 strains. Pfap2g and Pfs25 gene expression was detected in FCB2 strain gametocyte culture by RT-PCR. Comparative analysis of gametocytes obtained from both strains was made (counts and morphological changes). In vitro zygote formation from FCB2 gametocytes was induced by incubating a gametocyte culture sample at 27 °C for 20 min. A controlled Anopheles albimanus infection was made using an artificial feed system with cultured FCB2 gametocytes (14–15 days old). Mosquito midgut dissection was then carried out for analyzing oocysts.

Results
The FCB2 strain expressed Pfap2g, Pfs16, Pfg27/25 and Pfs25 sexual differentiation-related genes after in vitro sexual differentiation induction, producing gametocytes that conserved the expected morphological features. The amount of FCB2 gametocytes produced was similar to that from the 3D7 strain. FCB2 gametocytes were differentiated into zygotes and ookinetes after an in vitro low-temperature stimulus and infected An. albimanus mosquitoes, developing to oocyst stage.

Conclusions
Even with the history of long-term FCB2 strain in vitro culture maintenance, it has retained its sexual differentiation ability. The gametocytes produced here preserved these parasite forms’ usual characteristics and An. albimanus infection capability, thus enabling its use as a tool for studying sexual form biology, An. albimanus infection comparative analysis and anti-malarial drug and vaccine development.
MicroRNA-192 promotes the development of nasopharyngeal carcinoma through targeting RB1 and activating PI3K/AKT pathway
Authors: Huang Qingli , Hou Sen , Zhu Xiuqing , Liu Shouzhou 
Published: February 2020

Abstract
Background
The dysregulation of microRNAs (miRNAs) has been found in diseases and cancers, including microRNA-192 (miR-192). This study was designed to investigate the role of miR-192 in nasopharyngeal carcinoma (NPC) progression.

Methods
The expression levels of miR-192 and some genes were assessed by qRT-PCR and Western blot. The function of miR-192 was investigated through MTT, Transwell, and dual-luciferase reporter assays.

Results
The expression of miR-192 was increased in NPC tissues, and high miR-192 expression predicted poor prognosis in NPC patients. Functionally, upregulation of miR-192 promoted NPC cell migration, invasion, and growth. Furthermore, miR-192 activated EMT and PI3K/AKT pathway to regulate NPC progression. In addition, miR-192 directly targeted RB1 and suppressed its expression in NPC. Moreover, overexpression of RB1 weakened the promoted effect of miR-192 in NPC.

Conclusion
miR-192 promoted cell viability and metastasis in NPC through suppressing RB1 expression and activating PI3K/AKT pathway.
Angiocrine endothelium: from physiology to cancer
Authors: Pasquier Jennifer , Ghiabi Pegah , Chouchane Lotfi , Razzouk Kais , Rafii Shahin , Rafii Arash 
Published: February 2020

AbstractThe concept of cancer as a cell-autonomous disease has been challenged by the wealth of knowledge gathered in the past decades on the importance of tumor microenvironment (TM) in cancer progression and metastasis. The significance of endothelial cells (ECs) in this scenario was initially attributed to their role in vasculogenesis and angiogenesis that is critical for tumor initiation and growth. Nevertheless, the identification of endothelial-derived angiocrine factors illustrated an alternative non-angiogenic function of ECs contributing to both physiological and pathological tissue development. Gene expression profiling studies have demonstrated distinctive expression patterns in tumor-associated endothelial cells that imply a bilateral crosstalk between tumor and its endothelium. Recently, some of the molecular determinants of this reciprocal interaction have been identified which are considered as potential targets for developing novel anti-angiocrine therapeutic strategies.
Characterization of a recombinant pseudorabies virus expressing porcine parvovirus VP2 protein and porcine IL-6
Authors: Zheng Hui-Hua , Wang Lin-Qing , Fu Peng-Fei , Zheng Lan-Lan , Chen Hong-Ying , Liu Fang 
Published: February 2020

Abstract
Background
Porcine parvovirus (PPV) and pseudorabies virus (PRV) are the important etiological agents of swine infectious diseases, resulting in huge economic losses to the Chinese swine industry. Interleukin-6 (IL-6) has the roles to support host immune response to infections as a pleiotropic cytokine. It is essential to construct a live attenuated vaccine-based recombinant PRV that expresses PPV VP2 protein and porcine IL-6 for prevention and control of PRV and PPV.

Methods
The recombinant plasmid, pGVP2-IL6, was constructed by porcine IL-6 gene substituting for EGFP gene of the PRV transfer plasmid pGVP2-EGFP containing VP2 gene of PPV. Plasmid pGVP2-IL6 was transfected into swine testicle cells pre-infected with the virus rPRV-VP2-EGFP strain through homologous recombination and plaque purification to generate a recombinant virus rPRV-VP2-IL6. The recombinant PRV was further identified by PCR and DNA sequencing, and the expression of the VP2 protein and porcine IL-6 was analyzed by reverse transcription-PCR (RT-PCR) and Western blot. The virus titer was calculated according to Reed and Muench method. The immunogenicity of the recombinant virus was preliminarily evaluated in mice by intramuscular administration twice with the rPRV-VP2-IL6 at 4-week intervals.

Results
A recombinant virus rPRV-VP2-IL6 was successfully constructed and confirmed in this study. The properties of rPRV-VP2-IL6 were similar to the parental virus HB98 in terms of growth curve, morphogenesis and virus plaque sizes, and rPRV-VP2-IL6 was proliferated in different cell types. It induced specific antibodies against PPV as well as a strong increase of PPV-specific lymphocyte proliferation responses in mice immunized with rPRV-VP2-IL6, and provided partial protection against the virulent PPV challenge. rPRV-VP2-IL6 also induced a high level of neutralizing antibodies against PRV, and significantly reduced the mortality rate of (1 of 10) following virulent PRV challenge compared with the control (10 of 10).

Conclusions
The recombinant rPRV-VP2-IL6 might be a potential candidate vaccine against PRV and PPV infections in pigs.
The effect of cisatracurium infusion on the energy expenditure of critically ill patients: an observational cohort study
Authors: Koekkoek W. A. C. , Menger Y. A. , van Zanten F. J. L. , van Dijk D. , van Zanten A. R. H. 
Published: February 2020

Abstract
Background
Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes. A reliable estimation of the energy expenditure (EE) of ICU patients may help to avoid these phenomena. Several factors that influence EE have been studied previously. However, the effect of neuromuscular blocking agents on EE, which conceptually would lower EE, has not been extensively investigated.

Methods
We studied a cohort of adult critically ill patients requiring invasive mechanical ventilation and treatment with continuous infusion of cisatracurium for at least 12 h. The study aimed to quantify the effect of cisatracurium infusion on EE (primary endpoint). EE was estimated based on ventilator-derived VCO2 (EE in kcal/day = VCO2 × 8.19). A subgroup analysis of septic and non-septic patients was performed. Furthermore, the effects of body temperature and sepsis on EE were evaluated. A secondary endpoint was hypercaloric feeding (> 110% of EE) after cisatracurium infusion.

Results
In total, 122 patients were included. Mean EE before cisatracurium infusion was 1974 kcal/day and 1888 kcal/day after cisatracurium infusion. Multivariable analysis showed a significantly lower EE after cisatracurium infusion (MD − 132.0 kcal (95% CI − 212.0 to − 52.0; p = 0.001) in all patients. This difference was statistically significant in both sepsis and non-sepsis patients (p = 0.036 and p = 0.011). Non-sepsis patients had lower EE than sepsis patients (MD − 120.6 kcal; 95% CI − 200.5 to − 40.8, p = 0.003). Body temperature and EE were positively correlated (Spearman’s rho = 0.486, p < 0.001). Hypercaloric feeding was observed in 7 patients.

Conclusions
Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE, although the magnitude of the effect is small. Sepsis and higher body temperature are associated with increased EE. Cisatracurium infusion is associated with overfeeding in only a minority of patients and therefore, in most patients, no reductions in caloric prescription are necessary.
Genotype-free demultiplexing of pooled single-cell RNA-seq
Authors: Xu Jun , Falconer Caitlin , Nguyen Quan , Crawford Joanna , McKinnon Brett D. , Mortlock Sally , Senabouth Anne , Andersen Stacey , Chiu Han Sheng , Jiang Longda , Palpant Nathan J. , Yang Jian , Mueller Michael D. , Hewitt Alex W. , Pébay Alice , Montgomery Grant W. , Powell Joseph E. , Coin Lachlan J.M 
Published: February 2020

AbstractA variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We introduce scSplit which utilizes genetic differences inferred from scRNA-seq data alone to demultiplex pooled samples. scSplit also enables mapping clusters to original samples. Using simulated, merged, and pooled multi-individual datasets, we show that scSplit prediction is highly concordant with demuxlet predictions and is highly consistent with the known truth in cell-hashing dataset. scSplit is ideally suited to samples without external genotype information and is available at: https://github.com/jon-xu/scSplit
Analysis of Galileo signal-in-space range error and positioning performance during 2015–2018
Authors: Wu Weiwang , Guo Fei , Zheng Jiazhu 
Published: February 2020

AbstractA long-term analysis of signal-in-space range error (SISRE) is presented for all healthy Galileo satellites, and the first pair of full operational capability satellites in wrong elliptical orbits. Both orbit and clock errors for Galileo show an obvious convergence trend over time. The annual statistical analyses show that the average root mean squares (RMSs) of SISRE for the Galileo constellation are 0.58 m (2015), 0.29 m (2016), 0.23 m (2017), and 0.22 m (2018). Currently, the accuracy of the Galileo signal-in-space is superior to that of the global positioning system (GPS) Block IIF (0.35 m). In addition, the orbit error accounts for the majority of Galileo SISRE, while the clock error accounts for approximately one-third of SISRE due to the high stability of the onboard atomic clock. Single point positioning results show that Galileo achieves an accuracy of 2–3 m, which is comparable to that of GPS despite the smaller number of satellites and worse geometry. Interestingly, the vertical accuracy of Galileo, which uses the NeQuick ionospheric model, is higher than that of GPS. Positioning with single frequency E1 and E5 show a higher precision than E5a and E5b signals. Regarding precise point positioning (PPP), the results indicate that a comparable positioning accuracy can be achieved among different stations with the current Galileo constellation. For static PPP, the RMS values of Galileo-only solutions are within 1 cm horizontally, and the vertical RMSs are mostly within 2 cm horizontally. For kinematic PPP, the RMSs of Galileo-only solutions are mostly within 4 cm horizontally and 6 cm vertically.
Main insights of genome wide association studies into HCV-related HCC
Authors: Moaz Inas Maged , Abdallah Ayat Rushdy , Yousef Marwa Fekry , Ezzat Sameera 
Published: February 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-mortality globally. Hepatocarcinogenesis is a complex multifactorial process. Host genetic background appeared to play a crucial role in the progression of HCC among chronic hepatitis C patients, especially in the era of Genome Wide Association Studies (GWAS) which allowed us to study the association of millions of single nucleotide polymorphisms (SNPs) with different complex diseases. This article aimed to review the discovered SNPs associated with the risk of HCV-related HCC development which was reported in the published GWA studies and subsequent validation studies and also try to explain the possible functional pathways.

Main text
We reviewed the recent GWA studies which reported several new loci associated with the risk of HCV-related HCC, such as (SNPs) in MHC class I polypeptide-related sequence A (MICA), DEP domain-containing 5 (DEPDC5), Tolloid-like protein 1 (TLL1), and human leukocyte antigen (HLA) genes. We also explained the possible underlying biological mechanisms that affect the host immune response pathways. Additionally, we discussed the controversial results reported by the subsequent validation studies of different ethnicities.

Conclusions
Although GWA studies reported strong evidence of the association between the identified SNPs and the risk of HCV-related HCC development, more functional experiments are necessary to confirm the defined roles of these genetic mutations for the future clinical application in different populations.
pH-Responsive Tunable Mixed-Charge Polymers for pH-Selective Interaction with Anionic Biological Constituents
Authors: Hiruta Yuki , Sawada Kazuki , Mizui Yuki , Citterio Daniel 
Published: February 2020

Abstract
A pH-responsive mixed-charge polymer consists of uniformly distributed cationic and anionic units in the polymer chain. Carboxylic acid monomers are generally used as anionic monomers. The pH responsive range is confined to a relatively narrow pH of ∼5, which is limiting the biological application of pH-responsive polymers. Therefore, we investigated the effect of a series of carboxylic acid and neutral monomers on the pKa value of pH-responsive mixed-charge polymers. We synthesized the polymers using [2-(methacryloyloxy)ethyl]trimethylammonium chloride, carboxylic acid monomers, and neutral monomers as the spacer moiety. As the monomer hydrophobicity and the composition ratio of neutral monomers increased, the pKa shifted to higher values. Finally, the polymer pKa values were tuned from 4.6 to 6.1. We confirmed that the pH-dependent interaction between anionic tissue constituent and pH-responsive mixed-charge polymers depends on their pKa.
Spallation of 56Fe by 1.0 GeV Protons
Authors: Nicolis N. G. , Souliotis G. S. , Asimakopoulou A. 
Published: February 2020

Mass, charge and isotopic distributions observed in spallation reactions of 56Fe with 1 GeV protons are analysed in the framework of the intranuclear cascade code ISABEL coupled with the sequential binary decay code MECO. The code MECO provides a description of the equilibrated nuclear decay by the emission of gamma-rays, light-mass particles and clusters as well as intermediate mass fragments emitted in their ground, excited bound and excited unbound states (continuum) according to a generalized Weisskopf formalism. A good overall description of the experimental data is obtained with a global Fermi gas level density parameter and inverse cross sections based on the Christensen and Winther nuclear potential. Multifragmentation decay events are simulated with the code SMM and their influence on the above observables is discussed.
Application of radio-dating methods in marine areas of Greece
Authors: Pappa F. K. , Tsabaris C. , Patiris D. L. , Eleftheriou G. , Androulakaki E. G. , Kokkoris M. , Vlastou R. 
Published: February 2020

Chronology models based on radiotracers are useful for dating aquatic sediments influenced by industrialization. Among the many natural (e.g. 7Be, 234Th,210Pb) and artificial (e.g. 137Cs,238,239,240Pu) radiotracers, the proper ones to study the industrial impact and reconstruct past events during the last 100 years, are 210Pb and 137Cs. Mining belongs to the industries with great ecological impact in the aquatic environment, as mines are situated near environmental sensitive areas such as coasts, rivers and lakes. Additionally, the accurate historical reconstruction may provide information regarding the mine footprint in the aquatic environment so as to assess the previous or the remaining contamination, in case of on-going or abandoned mines. In the present study, the retrospective investigation in a coastal area of Lavrio, near an abandoned metallic mine is attempted, using the 210Pb and 137Cs methodologies and the emerged difficulties are discussed.