bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helminthostachys zeylanica alleviates hepatic steatosis and insulin resistance in diet-induced obese mice
Authors: Chang Ting-Chen , Chiang Hao , Lai Yu-Heng , Huang Yu-Ling , Huang Hsiu-Chen , Liang Yu-Chih , Liu Hui-Kang , Huang Cheng 
Published: December 2019

Abstract
Background
Obesity and its associated health conditions, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are worldwide health problems. It has been shown that insulin resistance is associated with increased hepatic lipid and causes hepatic steatosis through a myriad of mechanisms, including inflammatory signaling.

Methods
Helminthostachys zeylanica (HZ) is used widely as a common herbal medicine to relieve fever symptoms and inflammatory diseases in Asia. In the present study, we evaluated whether HZ has therapeutic effects on obesity, NAFLD and insulin resistance. The protective effects of HZ extract were examined using free fatty acid-induced steatosis in human HuS-E/2 cells and a high-fat diet-induced NAFLD in mice.

Results
The major components of the HZ extract are ugonins J and K, confirmed by HPLC. Incubation of human hepatocytes, HuS-E/2 cells, with palmitate markedly increased lipid accumulation and treatment with the HZ extract significantly decreased lipid deposition and facilitated AMPK and ACC activation. After 12 weeks of a high-fat diet with HZ extract treatment, the HFD mice were protected from hyperlipidemia and hyperglycemia. HZ extract prevented body weight gain, adipose tissue expansion and adipocyte hypertrophy in the HFD mice. In addition, fat accumulation was reduced in mice livers. Moreover, the insulin sensitivity-associated index, which evaluates insulin function, was also significantly restored.

Conclusions
These results suggest that HZ has a promising pharmacological effect on high-fat diet-induced obesity, hepatic steatosis and insulin resistance, which may have the potential for clinical application.
Prediction of health care expenditure increase: how does pharmacotherapy contribute?
Authors: Jödicke Annika M. , Zellweger Urs , Tomka Ivan T. , Neuer Thomas , Curkovic Ivanka , Roos Malgorzata , Kullak-Ublick Gerd A. , Sargsyan Hayk , Egbring Marco 
Published: December 2019

Abstract
Background
Rising health care costs are a major public health issue. Thus, accurately predicting future costs and understanding which factors contribute to increases in health care expenditures are important. The objective of this project was to predict patients healthcare costs development in the subsequent year and to identify factors contributing to this prediction, with a particular focus on the role of pharmacotherapy.

Methods
We used 2014–2015 Swiss health insurance claims data on 373′264 adult patients to classify individuals’ changes in health care costs. We performed extensive feature generation and developed predictive models using logistic regression, boosted decision trees and neural networks. Based on the decision tree model, we performed a detailed feature importance analysis and subgroup analysis, with an emphasis on drug classes.

Results
The boosted decision tree model achieved an overall accuracy of 67.6% and an area under the curve-score of 0.74; the neural network and logistic regression models performed 0.4 and 1.9% worse, respectively. Feature engineering played a key role in capturing temporal patterns in the data. The number of features was reduced from 747 to 36 with only a 0.5% loss in the accuracy. In addition to hospitalisation and outpatient physician visits, 6 drug classes and the mode of drug administration were among the most important features. Patient subgroups with a high probability of increase (up to 88%) and decrease (up to 92%) were identified.

Conclusions
Pharmacotherapy provides important information for predicting cost increases in the total population. Moreover, its relative importance increases in combination with other features, including health care utilisation.
Targeted regulation of fibroblast state by CRISPR-mediated CEBPA expression
Authors: Liu Wei , Meridew Jeffrey A. , Aravamudhan Aja , Ligresti Giovanni , Tschumperlin Daniel J. , Tan Qi 
Published: December 2019

Abstract
Background
Fibroblasts regulate tissue homeostasis and the balance between tissue repair and fibrosis. CCAAT/enhancer-binding protein alpha (CEBPA) is a key transcription factor that regulates adipogenesis. CEBPA has been shown to be essential for lung maturation, and deficiency of CEBPA expression leads to abnormal lung architecture. However, its specific role in lung fibroblast regulation and fibrosis has not yet been elucidated.

Methods
Lung fibroblast CEBPA expression, pro-fibrotic and lipofibroblast gene expression were assessed by qRT-PCR. CEBPA gain and loss of function experiments were carried out to evaluate the role of CEBPA in human lung fibroblast activation with and without TGF-β1 treatment. Adipogenesis assay was used to measure the adiopogenic potential of lung fibroblasts. Finally, CRISPR activation system was used to enhance endogenous CEBPA expression.

Results
We found that CEBPA gene expression is significantly decreased in IPF-derived fibroblasts compared to normal lung fibroblasts. CEBPA knockdown in normal human lung fibroblasts enhanced fibroblast pro-fibrotic activation and ECM production. CEBPA over-expression by transient transfection in IPF-derived fibroblasts significantly reduced pro-fibrotic gene expression, ECM deposition and αSMA expression and promoted the formation of lipid droplets measured by Oil Red O staining and increased lipofibroblast gene expression. Inhibition of the histone methyl transferase G9a enhanced CEBPA expression, and the anti-fibrotic effects of G9a inhibition were partially mediated by CEBPA expression. Finally, targeted CRISPR-mediated activation of CEBPA resulted in fibroblasts switching from fibrogenic to lipofibroblast states.

Conclusions
CEBPA expression is reduced in human IPF fibroblasts and its deficiency reduces adipogenic potential and promotes fibrogenic activation. CEBPA expression can be rescued via an inhibitor of epigenetic repression or by targeted CRISPR activation, leading to reduced fibrogenic activation.
Abiraterone acetate and docetaxel with androgen deprivation therapy in high-volume metastatic hormone-sensitive prostate cancer in China: an indirect treatment comparison and cost analysis
Authors: Hu Xin , Qu Shuli , Yao Xingxing , Li Chaoyun , Liu Yanjun , Wang Jianye 
Published: December 2019

Abstract
Background
To conduct an indirect treatment comparison of patients with high-volume mHSPC and a cost analysis between Abi-ADT and Doc-ADT therapies in China.

Methods
The Bucher technique for indirect treatment comparison was used. A cost analysis was conducted from both healthcare and patient perspectives.

Results
The indirect treatment comparison demonstrated no significant difference in PFS for Abi-ADT versus Doc-ADT (HR: 0.84, 95% CI 0.66–1.07). Doc-ADT therapy costs less than Abi-ADT, with potential savings of up to RMB 887,057 per patient from the healthcare perspective and RMB 226,210 per patient from the patient perspective.

Conclusions
No significant differences in PFS between Doc-ADT and Abi-ADT therapy for patients with high-volume mHSPC. Doc-ADT therapy is a cost-saving alternative to Abi-ADT in China.
Veterinary use of bacteriophage therapy in intensively-reared livestock
Authors: Gigante Adriano , Atterbury Robert J 
Published: December 2019

AbstractZoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals asymptomatically, which may lead to contamination of the food chain and public health hazards. Moreover, routine sampling of carcasses at retail by government authorities over the past 20 years suggests the prevalence of antibiotic resistance in foodborne pathogens has increased. If this continues, antibiotics may be ineffective against such pathogens in the future and alternative approaches, such as phage therapy, may be necessary. Intensive livestock farming is the only realistic way of meeting the demand for meat from an increasing global population and growth in middle class consumers in developing countries, particularly in Asia. This review elaborates on the use of phages to control zoonotic pathogens in intensively-reared livestock (poultry and pigs).
Total cross-sectional area of the femoral neck nutrient foramina measured to assess arterial vascular beds in the femoral head
Authors: Mei Jiong , Quan Kun , Wang Hua , Dai Yahui , Zhang Fangfang , Ni Ming 
Published: December 2019

Abstract
Background
A detailed understanding of the blood supply to the femoral head is required to plan the surgery in the femoral neck and head area. However, information about the blood vessel networks in the femoral head is inadequate.

Methods
The surface of the femoral neck of 100 dry cadaveric adult femur specimens was scanned using a 3D scanner. The scanning distance was 200 mm, precision 0.01 mm, and measuring point 0.04 mm. The images were acquired at a resolution of 1,310,000 pixels. Digital imaging data were recorded from the femoral neck surface. The diameters of the nutrient foramina of the superior, inferior and anterior retinacular arteries, and the ligamentum teres arteries were determined and divided into five groups.

Results
The mean cumulative cross-sectional area of the nutrient foramina was as follows: canals of the superior, inferior, anterior, and ligamentum retinacular arteries were 15.59 mm2, 3.63 mm2, 4.32 mm2, and 1.58 mm2, respectively. Next, we analyzed the canals of the superior, inferior, anterior and ligamentum retinacular arteries, respectively, via 3D scanner. We found that the canals of the superior retinacular arteries appear to supply more blood to the femoral head than the canals of the other three types of arteries.

Conclusions
Our results demonstrated that surgeries of the femoral neck and femoral head will be improved with prior 3D scanning and lead to better outcomes in surgeries involving the hip area.
A prenatal diagnosis and genetics study of five pedigrees in the Chinese population with Xp22.31 microduplication
Authors: Zhuang Jianlong , Wang Yuanbai , Zeng Shuhong , Lv Chunling , Lin Yiming , Jiang Yuying 
Published: December 2019

Abstract
Background
Copy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored.

Methods
G-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities.

Results
The fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups.

Conclusion
Our study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .
Pancreatic cancer-initiating cell exosome message transfer into noncancer-initiating cells: the importance of CD44v6 in reprogramming
Authors: Wang Zhe , Sun Hanxue , Provaznik Jan , Hackert Thilo , Zöller Margot 
Published: December 2019

Abstract

Background
Cancer-initiating cell (CIC) exosomes (CIC-TEX) are suggested reprogramming Non-CIC. Mode of message transfer and engagement of CIC-markers being disputed, we elaborated the impact of CD44v6 and Tspan8 on the response of Non-CIC.

Methods
Non-metastasizing CD44v6- and Tspan8-knockdown (kd) pancreatic cancer cells served as Non-CIC. CIC-TEX coculture-induced changes were evaluated by deep-sequencing and functional assays. Tumor progression was surveyed during in vivo CIC-TEX treatment.

Results
Deep-sequencing of CIC-TEX-cocultured CD44v6kd-Non-CIC revealed pronounced mRNA changes in signaling, transport, transcription and translation; altered miRNA affected metabolism, signaling and transcription. CIC-TEX coculture-induced changes in Tspan8kd-Non-CIC mostly relied on CIC-TEX-Tspan8 being required for targeting. CIC-TEX transfer supported apoptosis resistance and significantly promoted epithelial mesenchymal transition, migration, invasion and (lymph)angiogenesis of the kd Non-CIC in vitro and in vivo, deep-sequencing allowing individual mRNA and miRNA assignment to altered functions. Importantly, CIC-TEX act as a hub, initiated by CD44v6-dependent RTK, GPCR and integrin activation and involving CD44v6-assisted transcription and RNA processing. Accordingly, a kinase inhibitor hampered CIC-TEX-fostered tumor progression, which was backed by an anti-Tspan8 blockade of CIC-TEX binding.

Conclusions
This in depth report on the in vitro and in vivo impact of CIC-TEX on CD44v6kd and Tspan8kd Non-CIC unravels hub CIC-TEX activity, highlighting a prominent contribution of the CIC-markers CD44v6 to signaling cascade activation, transcription, translation and miRNA processing in Non-CIC and of Tspan8 to CIC-TEX targeting. Blocking CIC-TEX binding/uptake and uptake-initiated target cell activation significantly mitigated the deleterious CIC-TEX impact on CD44v6kd and Tspan8kd Non-CIC.
Drug screening approach combines epigenetic sensitization with immunochemotherapy in cancer
Authors: Facciotto Chiara , Casado Julia , Turunen Laura , Leivonen Suvi-Katri , Tumiati Manuela , Rantanen Ville , Kauppi Liisa , Lehtonen Rainer , Leppä Sirpa , Wennerberg Krister , Hautaniemi Sampsa 
Published: December 2019

Abstract
Background
The epigenome plays a key role in cancer heterogeneity and drug resistance. Hence, a number of epigenetic inhibitors have been developed and tested in cancers. The major focus of most studies so far has been on the cytotoxic effect of these compounds, and only few have investigated the ability to revert the resistant phenotype in cancer cells. Hence, there is a need for a systematic methodology to unravel the mechanisms behind epigenetic sensitization.

Results
We have developed a high-throughput protocol to screen non-simultaneous drug combinations, and used it to investigate the reprogramming potential of epigenetic inhibitors. We demonstrated the effectiveness of our protocol by screening 60 epigenetic compounds on diffuse large B-cell lymphoma (DLBCL) cells. We identified several histone deacetylase (HDAC) and histone methyltransferase (HMT) inhibitors that acted synergistically with doxorubicin and rituximab. These two classes of epigenetic inhibitors achieved sensitization by disrupting DNA repair, cell cycle, and apoptotic signaling. The data used to perform these analyses are easily browsable through our Results Explorer. Additionally, we showed that these inhibitors achieve sensitization at lower doses than those required to induce cytotoxicity.

Conclusions
Our drug screening approach provides a systematic framework to test non-simultaneous drug combinations. This methodology identified HDAC and HMT inhibitors as successful sensitizing compounds in treatment-resistant DLBCL. Further investigation into the mechanisms behind successful epigenetic sensitization highlighted DNA repair, cell cycle, and apoptosis as the most dysregulated pathways. Altogether, our method adds supporting evidence in the use of epigenetic inhibitors as sensitizing agents in clinical settings.
DNA methylation data by sequencing: experimental approaches and recommendations for tools and pipelines for data analysis
Authors: Rauluseviciute Ieva , Drabløs Finn , Rye Morten Beck 
Published: December 2019

AbstractSequencing technologies have changed not only our approaches to classical genetics, but also the field of epigenetics. Specific methods allow scientists to identify novel genome-wide epigenetic patterns of DNA methylation down to single-nucleotide resolution. DNA methylation is the most researched epigenetic mark involved in various processes in the human cell, including gene regulation and development of diseases, such as cancer. Increasing numbers of DNA methylation sequencing datasets from human genome are produced using various platforms—from methylated DNA precipitation to the whole genome bisulfite sequencing. Many of those datasets are fully accessible for repeated analyses. Sequencing experiments have become routine in laboratories around the world, while analysis of outcoming data is still a challenge among the majority of scientists, since in many cases it requires advanced computational skills. Even though various tools are being created and published, guidelines for their selection are often not clear, especially to non-bioinformaticians with limited experience in computational analyses. Separate tools are often used for individual steps in the analysis, and these can be challenging to manage and integrate. However, in some instances, tools are combined into pipelines that are capable to complete all the essential steps to achieve the result. In the case of DNA methylation sequencing analysis, the goal of such pipeline is to map sequencing reads, calculate methylation levels, and distinguish differentially methylated positions and/or regions. The objective of this review is to describe basic principles and steps in the analysis of DNA methylation sequencing data that in particular have been used for mammalian genomes, and more importantly to present and discuss the most pronounced computational pipelines that can be used to analyze such data. We aim to provide a good starting point for scientists with limited experience in computational analyses of DNA methylation and hydroxymethylation data, and recommend a few tools that are powerful, but still easy enough to use for their own data analysis.
Deviation from normative brain development is associated with symptom severity in autism spectrum disorder
Authors: Tunç Birkan , Yankowitz Lisa D. , Parker Drew , Alappatt Jacob A. , Pandey Juhi , Schultz Robert T. , Verma Ragini 
Published: December 2019

AbstractBackgroundAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. The degree to which the brain development in ASD deviates from typical brain development, and how this deviation relates to observed behavioral outcomes at the individual level are not well-studied. We hypothesize that the degree of deviation from typical brain development of an individual with ASD would relate to observed symptom severity.MethodsThe developmental changes in anatomical (cortical thickness, surface area, and volume) and diffusion metrics (fractional anisotropy and apparent diffusion coefficient) were compared between a sample of ASD (n = 247) and typically developing children (TDC) (n = 220) aged 6–25. Machine learning was used to predict age (brain age) from these metrics in the TDC sample, to define a normative model of brain development. This model was then used to compute brain age in the ASD sample. The difference between chronological age and brain age was considered a developmental deviation index (DDI), which was then correlated with ASD symptom severity.ResultsMachine learning model trained on all five metrics accurately predicted age in the TDC (r = 0.88) and the ASD (r = 0.85) samples, with dominant contributions to the model from the diffusion metrics. Within the ASD group, the DDI derived from fractional anisotropy was correlated with ASD symptom severity (r = − 0.2), such that individuals with the most advanced brain age showing the lowest severity, and individuals with the most delayed brain age showing the highest severity.LimitationsThis work investigated only linear relationships between five specific brain metrics and only one measure of ASD symptom severity in a limited age range. Reported effect sizes are moderate. Further work is needed to investigate developmental differences in other age ranges, other aspects of behavior, other neurobiological measures, and in an independent sample before results can be clinically applicable.ConclusionsFindings demonstrate that the degree of deviation from typical brain development relates to ASD symptom severity, partially accounting for the observed heterogeneity in ASD. Our approach enables characterization of each individual with reference to normative brain development and identification of distinct developmental subtypes, facilitating a better understanding of developmental heterogeneity in ASD.
ChemScanner: extraction and re-use(ability) of chemical information from common scientific documents containing ChemDraw files
Authors: Nguyen An , Huang Yu-Chieh , Tremouilhac Pierre , Jung Nicole , Bräse Stefan 
Published: December 2019

AbstractWe developed ChemScanner, a software that can be used for the extraction of chemical information from ChemDraw binary (CDX) or ChemDraw XML-based (CDXML) files and to retrieve the ChemDraw scheme from DOC, DOCX or XML documents. This can facilitate the reuse of chemical information embedded into diverse documents used as standard storage and communication instrument in chemical sciences (e.g. for student’s theses, PhD theses, or publications). The extracted information is processed to reactions, molecules, as well as additional text and values and can be accessed via the ChemScanner UI. ChemScanner supports the export to Excel and CML, the direct import of the extracted data to the Open Source ELN Chemotion or the use via “copy and paste” of selected information. The software was designed with a focus on the processing of documents with embedded molecular structure information as CDX or CDXML as these are the most common file formats for chemical drawings. The project aims to support the chemists in their efforts to re-use chemistry research data by providing them missing tools for an automated assembly of reaction data.