bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic characterization of aggressive breast cancer cells exhibiting invasive phenotype: impact of non-cytotoxic doses of 2-DG on diminishing invasiveness
Authors: Fujita Mayumi , Imadome Kaori , Somasundaram Veena , Kawanishi Miki , Karasawa Kumiko , Wink David A. 
Published: September 2020

Abstract
Background
Metabolic reprogramming is being recognized as a fundamental hallmark of cancer, and efforts to identify drugs that can target cancer metabolism are underway. In this study, we used human breast cancer (BC) cell lines and established their invading phenotype (INV) collected from transwell inserts to compare metabolome differences and evaluate prognostic significance of the metabolome in aggressive BC invasiveness.

Methods
The invasiveness of seven human BC cell lines were compared using the transwell invasion assay. Among these, INV was collected from SUM149, which exhibited the highest invasiveness. Levels of metabolites in INV were compared with those of whole cultured SUM149 cells (WCC) using CE-TOFMS. The impact of glycolysis in INV was determined by glucose uptake assay using fluorescent derivative of glucose (2-NBDG), and significance of glycolysis, or tricarboxylic acid cycle (TCA) and electron transport chain (ETC) in the invasive process were further determined in aggressive BC cell lines, SUM149, MDA-MB-231, HCC1937, using invasion assays in the presence or absence of inhibitors of glycolysis, TCA cycle or ETC.

Results
SUM149 INV sub-population exhibited a persistent hyperinvasive phenotype. INV were hyper-glycolytic with increased glucose (2-NBDG) uptake; diminished glucose-6-phosphate (G6P) levels but elevated pyruvate and lactate, along with higher expression of phosphorylated-pyruvate dehydrogenase (pPDH) compared to WCC. Notably, inhibiting of glycolysis with lower doses of 2-DG (1 mM), non-cytotoxic to MDA-MB-231 and HCC1937, was effective in diminishing invasiveness of aggressive BC cell lines. In contrast, 3-Nitropropionic acid (3-NA), an inhibitor of succinate dehydrogenase, the enzyme that oxidizes succinate to fumarate in TCA cycle, and functions as complex II of ETC, had no significant effect on their invasiveness, although levels of TCA metabolites or detection of mitochondrial membrane potential with JC-1 staining, indicated that INV cells originally had functional TCA cycles and membrane potential.

Conclusions
Hyper-glycolytic phenotype of invading cells caters to rapid energy production required for invasion while TCA cycle/ETC cater to cellular energy needs for sustenance in aggressive BC. Lower, non-cytotoxic doses of 2-DG can hamper invasion and can potentially be used as an adjuvant with other anti-cancer therapies without the usual side-effects associated with cytotoxic doses.
Does high and intensive care reduce coercion? Association of HIC model fidelity to seclusion use in the Netherlands
Authors: Van Melle A. L. , Noorthoorn E. O. , Widdershoven G. A. M. , Mulder C. L. , Voskes Y. 
Published: September 2020

Abstract
Background
A new inpatient care model has been developed in the Netherlands: High and Intensive Care (HIC). The purpose of HIC is to improve quality of inpatient mental healthcare and to reduce coercion.

Methods
In 2014, audits were held at 32 closed acute admission wards for adult patients throughout the Netherlands. The audits were done by trained auditors, who were professionals of the participating institutes, using the HIC monitor, a model fidelity scale to assess implementation of the HIC model. The HIC model fidelity scale (67 items) encompasses 11 domains including for example team structure, team processes, diagnostics and treatment, and building environment. Data on seclusion and forced medication was collected using the Argus rating scale. The association between HIC monitor scores and the use of seclusion and forced medication was analyzed, corrected for patient characteristics.

Results
Results showed that wards having a relatively high HIC monitor total score, indicating a high level of implementation of the model as compared to wards scoring lower on the monitor, had lower seclusion hours per admission hours (2.58 versus 4.20) and less forced medication events per admission days (0.0162 versus 0.0207). The HIC model fidelity scores explained 27% of the variance in seclusion rates (p < 0.001). Adding patient characteristics to HIC items in the regression model showed an increase of the explained variance to 40%.

Conclusions
This study showed that higher HIC model fidelity was associated with less seclusion and less forced medication at acute closed psychiatric wards in the Netherlands.
Burden of viral hepatitis caused by specific aetiologies in China, 1990–2016: findings from the GBD 2016
Authors: Li Man , Wang Zhuo-qun , Zhang Lu , Zheng Hao , Zhou Mai-geng , Liu Dian-wu 
Published: September 2020

Abstract
Background
The aim of this study is to quantify the burden caused by viral hepatitis in China from 1990 to 2016.

Methods
Data from the GBD 2016 study were extracted to calculate incidence, prevalence and disability-adjusted life years (DALYs). Trends in DALYs were assessed in 33 provinces/regions.

Results
From 1990 to 2016, the total incidence of hepatitis decreased by 88.5%. However, the prevalence of hepatitis (counts in thousands), increased by 37.6% from 153,856 (95% UI: 136,047-172,319) in 1990 to 211,721 (95% UI: 179,776-240,981) in 2016, with age-standardized prevalence rates changing slightly. The number and age-standardized rates of prevalence increased by 35.9 and 1.6% for hepatitis B, respectively, and by 81.8 and 30.4% for hepatitis C. Guangxi, Guangdong and Hainan had the highest age-standardized prevalence rates (≥16,500 per 100,000). Tibet, Qinghai and Gansu had the highest age-standardized DALYs rates (≥40 per 100,000). The largest absolute number of DALYs was observed in the 15–49 year age group in 2016. The highest rate of DALYs occurred in males aged 50–69 years and in females aged ≧70 years.

Conclusion
The incidence and DALYs of viral hepatitis decreased dramatically from 1990 to 2016. However, the prevalence still remains at a high level, which may result in heavy burdens in the future.
External validation of three atherosclerotic cardiovascular disease risk equations in rural areas of Xinjiang, China
Authors: Jiang Yunxing , Ma Rulin , Guo Heng , Zhang Xianghui , Wang Xinping , Wang Kui , Hu Yunhua , Keerman Mulatibieke , Yan Yizhong , Ma Jiaolong , Song Yanpeng , Zhang Jingyu , He Jia , Guo Shuxia 
Published: September 2020

Abstract
Background
To externally validate the Prediction for ASCVD Risk in China (PAR) risk equation for predicting the 5-year atherosclerotic cardiovascular disease (ASCVD) risk in the Uyghur and Kazakh populations from rural areas in northwestern China and compare its performance with those of the pooled cohort equations (PCE) and Framingham risk score (FRS).

Methods
The final analysis included 3347 subjects aged 40–74 years without CVD at baseline. The 5-year ASCVD risk was calculated using the PAR, PCE, and FRS. Discrimination, calibration, and clinical usefulness of the three equations in predicting the 5-year ASCVD risk were assessed before and after recalibration.

Results
Of 3347 included subjects, 1839 were female. We observed 286 ASCVD events in within 5-year follow-up. All three risk equations had moderate discrimination in both men and women. C-indices of PAR, PCE, and FRS were 0.727 (95% CI, 0.725–0.729), 0.727 (95% CI, 0.725–0.729), and 0.740 (95% CI, 0.738–0.742), respectively, in men; the corresponding C-indices were 0.738 (95% CI, 0.737–0.739), 0.731 (95% CI, 0.730–0.732), and 0.761 (95% CI, 0.760–0.762), respectively, in women. PCE, PAR and FRS substantially underestimated the 5-year ASCVD risk in women by 70, 23 and 51%, respectively. However, PAR and FRS fairly predicted the risk in men and PAR was well calibrated. The calibrations of the three risk equations could be changed by recalibration. The decision curve analyses demonstrated that at the threshold risk of 5%, PCE was the most clinically useful in both men and women after recalibration.

Conclusions
All three risk equations underestimated the 5-year ASCVD risk in women, while PAR and FRS fairly predicted that in men. However, the results of predictive performances for three risk equations are inconsistent, more accurate risk equations are required in the primary prevention of ASCVD aiming to this Uyghur and Kazakh populations.
Extraordinarily long-inactive solitary fibrous tumor transformed to produce big insulin-like growth factor-2, leading to hypoglycemia and rapid liposarcoma growth: a case report
Authors: Kaneko Keizo , Sawada Shojiro , Satake Chihiro , Kondo Keiichi , Izumi Tomohito , Tanaka Mamiko , Imai Junta , Yamada Tetsuya , Katsushima Hiroki , Fujishima Fumiyoshi , Katagiri Hideki 
Published: September 2020

Abstract
Background
A high-molecular-weight form of insulin-like growth factor-2 (IGF-2), known as “big” IGF-2, is occasionally produced by various tumor types, leading to hypoglycemia. Although solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, it has been estimated that 4–6% of SFT patients develop hypoglycemia due to circulating big IGF-2. The mean time elapsed from tumor detection until the onset of hypoglycemia is reportedly less than one year (8.5 ± 1.9 months).

Case presentation
A 68-year-old man was hospitalized for exacerbation of recurring hypoglycemic episodes. He had been diagnosed with an SFT 17 years before the onset of hypoglycemia, and the SFT had already been very large at that time. The tumor, which was non-resectable and refractory to chemotherapies, had slowly increased in size since the initial diagnosis. Half a year before the hypoglycemic episodes manifested, another tumor, adjacent to the left kidney, was newly identified. Fluorodeoxyglucose positron emission tomography-computed tomography scanning, revealed the left peri-renal tumor to show much higher fluorodeoxyglucose uptake than the preexisting SFT, suggesting that it was unlikely to be a metastasis from the SFT. Abundant serum big IGF-2 was detected by western immunoblot analysis, indicating it to be the cause of the hypoglycemia. Since the 17 years between SFT detection and the onset of IGF-2-induced hypoglycemia was an extremely long period as compared with those in previous reports, we initially suspected that the new, peri-renal tumor had produced big IGF-2, but transcatheter arterial embolization of its feeding arteries did not suppress hypoglycemia. Notably, by measuring the tumor volume doubling time, the peri-renal tumor growth was shown to be markedly accelerated in parallel with exacerbation of the hypoglycemia. The patient died of heart failure 21 months after the onset of hypoglycemia. Unexpectedly, autopsy revealed that big IGF-2 had been produced only by the preexisting SFT, not the peri-renal tumor, and that the peri-renal tumor was a dedifferentiated liposarcoma.

Conclusions
We should keep in mind that even a long-inactive SFT can undergo transformation to produce big IGF-2, which then acts on both insulin and IGF-1 receptors, possibly leading to both hypoglycemia and the development/growth of another tumor, respectively.
Hospitalization costs among immobile patients with hemorrhagic or ischemic stroke in China: a multicenter cross-sectional study
Authors: Liu Hongpeng , Zhu Chen , Cao Jing , Jiao Jing , Song Baoyun , Jin Jingfen , Liu Yilan , Wen Xianxiu , Cheng Shouzhen , Wu Xinjuan 
Published: September 2020

Abstract
Background
In this study, we aimed to analyze the hospitalization costs for immobile patients with hemorrhagic stroke (IHS) or ischemic stroke (IIS) in China and to determine the factors associated with hospitalization costs.

Methods
We evaluated patients with IHS and IIS hospitalized between November 2015 and July 2016 in six provinces or municipality cities of China. Linear regression analysis was used to examine the association with hospitalization costs and predictors.

Results
In total, 1573 patients with IHS and 3143 with IIS were enrolled and analyzed. For IHS and IIS, the average length of stay (LoS) was 17.40 ± 12.3 and 14.47 ± 11.55 days. The duration of immobility was 12.11 ± 9.98 and 7.36 ± 9.77 days, respectively. Median hospitalization costs were RMB 47000.68 (interquartile range 19,827.37, 91,877.09) for IHS and RMB 16578.44 (IQR 7020.13, 36,357.65) for IIS. In both IHS and IIS groups, medicine fees accounted for more than one-third of hospitalization costs. Materials fees and medical service fees accounted for the second and third largest proportions of hospital charges in both groups. Linear regression analysis showed that LoS, hospital level, and previous surgery were key determinants of hospitalization costs in all immobile patients with stroke. Subgroup analysis indicated that hospital level was highly correlated with hospitalization costs for IHS whereas pneumonia and deep vein thrombosis were key factors associated with hospitalization costs for IIS.

Conclusions
We found that hospitalization costs were notably higher in IHS than IIS, and medicine fees accounted for the largest proportion of hospitalization costs in both patient groups, perhaps because most patients ended up with complications such as pneumonia thereby requiring more medications. LoS and hospital level may greatly affect hospitalization costs. Increasing the reimbursement ratio of medical insurance for patients with IHS is recommended. Decreasing medicine fees and LoS, preventing complications, and improving treatment capability may help to reduce the economic burden of stroke in China.
Gut microbiota and fecal metabolites in captive and wild North China leopard (Panthera pardus japonensis) by comparsion using 16 s rRNA gene sequencing and LC/MS-based metabolomics
Authors: Hua Yan , Cao Heqin , Wang Jiao , He Fengping , Jiang Guangshun 
Published: September 2020

AbstractBackgroundGut microbes significantly contribute to nutrient digestion and absorption, intestinal health and immunity, and are essential for the survival and environmental adaptation of wild animals. However, there are few studies on the gut microbiota of captive and wild North China leopard (Panthera pardus japonensis).ResultsA total of 10 mainly bacterial phyla were identified in the fecal microbiota of North China leopard,Lachnoclostridium(p = 0.003),Peptoclostridium(p = 0.005),Bacteroides(p = 0.008),Fusobacterium(p = 0.017) andCollinsella(p = 0.019) were significantly higher than those of wild North China leopard. Distinct differences in the fecal metabolic phenotypes of captive and wild North China leopard were found, such as content of l-methionine, n-acetyl-l-tyrosine, pentadecanoic acid and oleic acid. Differentially abundant gut microbes were associated with fecal metabolites, especially the bacteria in Firmicutes and Bacteroidetes, involved in the metabolism of N-acetyl-L-alanine and D-quinovose.ConclusionThis study reports for the first time the differences in gut microbiota abundance between captive and wild North China leopard, as well as significant differences in fecal metabolic phenotypes between two groups.
Optimal regimens based on PK/PD cutoff evaluation of ceftiofur against Actinobacillus pleuropneumoniae in swine
Authors: Sun Da , Mi Kun , Hao Haihong , Xie Shuyu , Chen Dongmei , Huang Lingli 
Published: September 2020

AbstractBackgroundActinobacillus pleuropneumoniaeformerly known asHaemophilus pleuropneumoniae, can cause pleuropneumoniae in pigs, which lead to significant mortality. Ceftiofur was the first cephalosporin antibiotic used in animals, which was effective against gram-negative and gram-positive bacterium. This study aimed to formulate a rational dosage strategy and review the preceding recommended dosage based on PK/PD modeling and Establish Clinical breakpoint of ceftiofur againstActinobacillus pleuropneumoniaebased on the pharmacodynamic-pharmacokinetic cutoff.ResultsThe epidemiologic cutoff value was 0.125 μg/mL. The results of the pharmacodynamic study showed that the MICs of BW39 were 0.5 μg/mL and 1 μg/mL in vitro and ex-vivo, respectively. The minimal bactericidal concentrations (MBCs) under in vitro and ex vivo conditions were both 1 μg/mL. The time-killing profiles of ceftiofur against BW39 were time-dependent with a partly concentration-dependent pattern. Based on the inhibitory sigmoid Emaxmodel, the AUC24 h/MIC values for the bacteriostatic, bactericidal, and elimination effects in serum were 45.73, 63.83, and 69.04 h for healthy pigs separately. According to the Monte Carlo simulation, the COPDwas calculated as 2 μg/mL, and the optimized dosage regimen of ceftiofur againstActinobacillus pleuropneumoniaeto achieve bacteriostatic, bactericidal, and elimination effects over 24 h was 2.13, 2.97, and 3.42 mg/kg for the 50% target attainment rate (TAR) and 2.47, 3.21, and 3.70 mg/kg for the 90% TAR respectively.ConclusionsIn conclusion, we reveal the EOFF and PK/PD cutoff values of ceftiofur against A. pleuropneumoniae in piglets. However, with the paucity of clinical data for ceftiofur to establish a clinical cutoff against A. pleuropneumoniae, the PK/PD cutoff value of 2 μg/mL will be recommended as surrogate. According to the PK/PD data and the MIC distribution in China, the single bactericidal dose was 3.21 mg/kg for the 90% target, which would be more able to cureActinobacillus pleuropneumoniaeand avoid the emergence of resistance for clinical ceftiofur use in piglet.
Hsa_circ_0000231 knockdown inhibits the glycolysis and progression of colorectal cancer cells by regulating miR-502-5p/MYO6 axis
Authors: Liu Yanhe , Li Hui , Ye Xiaoyi , Ji Anlong , Fu Xiangwei , Wu Haishan , Zeng Xiangyong 
Published: September 2020

Abstract
Background
Colorectal cancer (CRC) poses a heavy threat to human health owing to its high incidence and mortality. Circular RNAs (circRNAs) were investigated to participate in the progression of CRC, whereas there was no revenant data on the CRC process regulated by hsa_circ_0000231. This study aimed to explore the effects of hsa_circ_0000231 on CRC progression and underneath regulatory mechanism.

Methods
The expression levels of hsa_circ_0000231, miR-502-5p, and Myosin VI (MYO6) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). Western blot was employed to determine the protein expression levels of MYO6 and proliferating cell nuclear antigen (PCNA). The effects of hsa_circ_0000231 on cell proliferation, apoptosis, migration, and invasive in CRC were determined by cell counting kit-8 proliferation (CCK-8) and colony formation assays, flow cytometry analysis, wound-healing assay, and transwell invasion assay, respectively. Glucose uptake and lactate production were severally illustrated by glucose assay kit and lactate assay kit. The relationship between miR-502-5p and hsa_circ_0000231 or MYO6 was predicted by circular RNA interactome or targetScan online databases, and identified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. In vivo tumor formation assay was carried out to determine the effects of hsa_circ_0000231 knockdown on tumor growth in vivo.

Results
Hsa_circ_0000231 expression was dramatically upregulated while miR-502-5p was obviously downregulated in CRC tissues and cells compared with control groups. Hsa_circ_0000231 knockdown repressed the expression levels of MYO6 and PCNA protein. Functionally, hsa_circ_0000231 knockdown repressed cell glycolysis, proliferation, migration and invasion, and induced cell apoptosis, whereas these effects were decreased by miR-502-5p inhibitor. Mechanistically, hsa_circ_0000231 acted as a sponge of miR-502-5p and miR-502-5p bound to MYO6. Furthermore, hsa_circ_0000231 knockdown decreased tumor volume and weight of CRC in vivo.

Conclusion
Hsa_circ_0000231 knockdown inhibited CRC progression and glycolysis by downregulating MYO6 expression through sponging miR-502-5p, which might provide a theoretical basis in further studying circ_0000231-directed therapy in CRC.
Effect of remifentanil-based fast-track anesthesia on postoperative analgesia and sedation in adult patients undergoing transthoracic device closure of ventricular septal defect
Authors: Xu Ning , Huang Shu-Ting , Sun Kai-Peng , Chen Liang-Wan , Chen Qiang , Cao Hua 
Published: September 2020

Abstract
Objective
To investigate the effect of remifentanil-based fast-track anesthesia on analgesia and sedation after transthoracic device closure of ventricular septal defects (VSDs) in adult patients.

Methods
A retrospective analysis was performed on 59 patients aged 21–53 years who underwent transthoracic device closure of VSDs from January 2019 to September 2019. According to the different anesthesia strategies, the patients were divided into the R group (using remifentanil-based anesthesia, n = 33) and the S group (using sufentanil-based anesthesia, n = 26). Patient-related clinical data, postoperative analgesia, and sedation scores were collected and analyzed.

Results
There was no significant difference in age, gender, body weight, and operation time between the group R and the group S (P > 0.05). There was also no significant difference in intraoperative hemodynamic changes, BIS scores, postoperative analgesia, and sedation scores between the two groups (P > 0.05). The duration of mechanical ventilation, the length of ICU stay, and hospital stay in the group R were significantly lower than those in the group S (P < 0.05).

Conclusion
Remifentanil-based fast-track anesthesia is effective for adult patients undergoing transthoracic device closure of VSDs, which may shorten the mechanical ventilation duration, the ICU and hospital stay of patients.
Integrated analysis of the aging brain transcriptome and proteome in tauopathy
Authors: Mangleburg Carl Grant , Wu Timothy , Yalamanchili Hari K. , Guo Caiwei , Hsieh Yi-Chen , Duong Duc M. , Dammer Eric B. , De Jager Philip L. , Seyfried Nicholas T. , Liu Zhandong , Shulman Joshua M. 
Published: September 2020

Abstract
Background
Tau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes.

Methods
Paired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutant form causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy.

Results
TauWT induced 1514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5494 transcripts and 697 proteins. There was a ~ 70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes.

Conclusions
Our results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.