bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-admission CHADS2 and CHA2DS2-VASc scores predict long-term outcomes after first spontaneous intracranial hemorrhage
Authors: HUANG Duo , ZHOU Mi , CHAN Koon-Ho , LUI Wai-Man , ZUO Ming-Liang , LUO An-Guo , YUE Wen-Sheng , YIN Li-Xue , PU Jenny Kan-Suen , LEUNG Gilberto Ka-Kit , Wah David SIU Chung 
Published: February 2020

Abstract
Background: Spontaneous intracranial hemorrhage (ICH) results in significant morbidity and mortality. Approximately 50% patients die within the first 30 days of the index hemorrhage, and of those who survive, only a minority is expected to be functionally independent. The ability to predict long-term functional outcomes may facilitate decision making in early management of ICH. This study aim to evaluate for the first time whether CHADS 2 score and CHA 2 DS 2 -VASc developed to stratify the risk of ischemic stroke among patients with AF is useful in predicting the functional outcomes among patients surviving their first spontaneous ICH. Methods: This single-centered observational registry was carried out between 1996 and 2010 and included 691 consecutive patients with the first spontaneous ICH. Results: Amongst these, 427 patients (60.1 ± 15.2 years, male: 62.5%) surviving the 30 days after the first ICH fulfilling the inclusion criteria were studied. At 1 year and 2 years, 52.9% and 54.8% patients had unfavorable outcome as defined as modified Rankin score of ≥3. In both univariate and multivariate analysis, increasing age, a higher pre-admission CHADS 2 and CHA 2 DS 2 -VASc scores surgical intervention for the ICH were associated with unfavorable outcomes. The c statistic of the CHADS 2 score as a predictor of favorable outcome was 0.59 (95% CI: 0.54-0.64, p <0.0001) with the optimal cutoff to predict favorable outcome at CHADS 2 ³1 with sensitivity of 73.9% and specificity of 39.4%. On the other hand, the C statistic of the CHA 2 DS 2 -VASc score to predict favorable outcome was similar to that of the CHADS 2 score (C-statistic: 0.58, 95% CI: 0.53-0.63, p =0.003) with the optimal cutoff at CHA 2 DS 2 -VASc ³3. The sensitivity and specificity were 67.7% and 46.3% respectively. Conclusion: The outcome of ICH patients surviving the first 30 days was poor. CHADS 2 and CHA 2 DS 2 -VASc appeared to be a reasonable score to predict long-term ICH outcomes.
Overexpression of MATN3 predicts poor prognosis of gastric adenocarcinoma: based on TCGA database
Authors: Zheng GuoLiang , Zhao Yan , Zheng Zhichao 
Published: February 2020

Abstract
Background Matrilin-3 (MATN3) was previously reported to in the cartilage extracellular matrix and had a role in the development and homeostasis of cartilage and bone. We evaluated the role of MATN3 in gastric adenocarcinoma (GAC) using publicly available data from The Cancer Genome Atlas (TCGA). Methods The relationship between clinicapathologic features and MATN3 were analyzed with the Wilcoxon signed-rank test and logistic regression. Clinicopathologic variables associated with overall survival (OS) in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set Enrichment Analysis (GSEA) was performed using TCGA cohort. Results MATN3 overexpressed in GAC than that in normal tissues (p﹤0.05), and MATN3 overexpression was significantly associated with TNM stage (p= 0.012), and T stage (p﹤0.01). Kaplan-Meier survival analysis showed that GAC with MATN3 - high had a worse prognosis than that with MATN3- low (p﹤0.01). The univariate analysis revealed that MATN3- high correlated significantly with a poor OS (HR: 1.86; 95% confidence interval [CI]: 0.82- 2.01; p = 0.014). The multivariate analysis revealed that MATN3 remained independently associated with OS, with a HR of 2.68 (CI: 0.74- 2.13; p﹤0.01). GSEA showed that NOTCH, WNT, and MTOR signaling pathway were differentially enriched in MANT3 high expression phenotype. Conclusion Overexpression of MATN3 may be a potential prognostic biomarker of poor survival in gastric cancer, Moreover, NOTCH, WNT, and MTOR signaling pathway may be the key pathway regulated by MATN3 in GAC.
The digestive/reproductive tract microbiota dominates over host genetics in regulating chicken egg production
Authors: Li Diyan , Tian Shilin , Zhu Wei , Su Yuan , Wang Tao , Ma Tianyuan , Mishra Shailendra Kumar , Shi Lianzhe , Wei Ranlei , Xu Zhongxian , Ning Chunyou , Zhang Dejing , Lin Xuxu , Zhao Xiaoling , Wang Yan , Yin Huadong , Hu Yaodong , Fan Xiaolan , Zeng Bo , Yang Mingyao , Yang Deying , Ni Qingyong , Li Yan , Zhang Mingwang , Yao Yongfang , Xu Huailiang , Li Mingzhou , Zhu Qing 
Published: February 2020

Abstract
Background: The microbiota of the digestive and reproductive systems has a prominent role in animal health and performance, but the extent of its contribution is difﬁcult to determine. In chickens, the effect of host genetics on the reproductive and digestive tract microbiota is unclear, and the means by which digestive/reproductive microbiomes help improve egg production in chicken are unknown.
Results: To gain insight into this, we examined genomes from 128 chickens reared under identical conditions and described their digestive (crop, gizzard and small intestine) and reproductive tract (vagina, uterus and isthmus) microbiota. Although the diversity, composition and predicted function of the digestive and reproductive tract microbiota exhibited notable microbiota variation substantially between different parts, host genetics had limited effects on the reproductive and digestive tract microbial community. The digestive and reproductive tract microbiota had a significant effect on egg production (accounting for 52.31% - 98.86% of the variance), after correcting for host genetic effects; in particular, the uterus and isthmus microbiota accounted for an average of 93.59% and 98.86%, respectively, of variance in egg production. We further identiﬁed four reproductive tract microbial species which were related to immune system, Bacteroides fragilis , Bacteroides salanitronis , Bacteroides barnesiae and Clostridium leptum , that were signiﬁcantly positively correlated with egg production. Chickens with a lower abundance of these species had produced signiﬁcantly fewer eggs at 300 days of age (37.13 vs. 113.75) than those with a higher abundance of these microorganisms. We speculated that these microorganisms regulate chicken reproductive activity by mediating its immune system.
Conclusions: Host genetics has limited effect on digestive/reproductive microbiome composition. The distinct site-associated chicken microbiome may be determined by the differences of their physical function. These ﬁndings may help design strategies for controlling and altering the digestive/reproductive tract microbiota in chickens to improve egg production.
DPepH3, an Improved Peptide Shuttle for Receptor-independent Transport Across the Blood-Brain Barrier
Authors: Cavaco Marco , Valle Javier , da Silva Ruben , Correia João D.G. , Castanho Miguel A. R. B , Andreu David , Neves Vera 
Published: February 2020

Background:The use of peptides as drug carriers across the blood-brain barrier (BBB) has increased significantly during the last decades. PepH3, a seven residue sequence (AGILKRW) derived from the α-helical domain of the dengue virus type-2 capsid protein, translocates across the BBB with very low toxicity. Somehow predictably from its size and sequence, PepH3 is degraded in serum relatively fast. Among strategies to increase peptide half-life (t1/2), the use of the enantiomer (wholly made of D-amino acid residues) can be quite successful if the peptide interacts with a target in non-stereospecific fashion.Methods:The goal of this work was the development of a more proteolytic-resistant peptide, while keeping the translocation properties. The serum stability, cytotoxicity, in vitro BBB translocation, and internalization mechanism of DPepH3 was assessed and compared to the native peptide.Results:DPepH3 demonstrates a much longer t1/2 compared to PepH3. We also confirm that BBB translocation is receptor-independent, which fully validates the enantiomer strategy chosen. In fact, we demonstrate that internalization occurs trough macropinocytosis. In addition, the enantiomer demonstrates to be non-cytotoxic towards endothelial cells as PepH3.Conclusion:DPepH3 shows excellent translocation and internalization properties, safety, and improved stability. Taken together, our results place DPepH3 at the forefront of the second generation of BBB shuttles.
Manipulation of Pharmaceutical Polymorphic Transformation Process Using Excipients
Authors: Tian Beiqian , Ding Zhiyong , Zong Shuyi , Yang Jinyue , Wang Na , Wang Ting , Huang Xin , Hao Hongxun 
Published: February 2020

Background:
In the pharmaceutical field, it is vital to ensure a consistent product containing a single
solid-state form of the active pharmaceutical ingredient (API) in the drug product. However, some APIs are suffering
from the risk of transformation of their target forms during processing, formulation and storage.

Methods:
The purpose of this review is to summarize the relevant category of excipients and demonstrate the
availability and importance of using excipients as a key strategy to manipulate pharmaceutical polymorphic transformation.

Results:
The excipient effects on solvent-mediated phase transformations, solid-state transitions and amorphous
crystallization are significant. Common pharmaceutical excipients including amino acids and derivatives, surfactants,
and various polymers and their different manipulation effects were summarized and discussed.

Conclusion:
Appropriate use of excipients plays a role in manipulating polymorphic transformation process of
corresponding APIs, with a promising application of guaranteeing the stability and effectiveness of drug dosage
forms.
Comprehensive in silico Study of GLUT10: Prediction of Possible Substrate Binding Sites and Interacting Molecules
Authors: Hosen Mohammad J. , Hasan Mahmudul , Chakraborty Sourav , Abir Ruhshan A. , Zubaer Abdullah , Coucke Paul 
Published: February 2020

Objectives:The Arterial Tortuosity Syndrome (ATS) is an autosomal recessive connective tissue disorder, mainly characterized by tortuosity and stenosis of the arteries with a propensity towards aneurysm formation and dissection. It is caused by mutations in the SLC2A10 gene that encodes the facilitative glucose transporter GLUT10. The molecules transported by and interacting with GLUT10 have still not been unambiguously identified. Hence, the study attempts to identify both the substrate binding site of GLUT10 and the molecules interacting with this site.Methods:As High-resolution X-ray crystallographic structure of GLUT10 was not available, 3D homology model of GLUT10 in open conformation was constructed. Further, molecular docking and bioinformatics investigation were employed.Results and Discussion:Blind docking of nine reported potential in vitro substrates with this 3D homology model revealed that substrate binding site is possibly made with PRO531, GLU507, GLU437, TRP432, ALA506, LEU519, LEU505, LEU433, GLN525, GLN510, LYS372, LYS373, SER520, SER124, SER533, SER504, SER436 amino acid residues. Virtual screening of all metabolites from the Human Serum Metabolome Database and muscle metabolites from Human Metabolite Database (HMDB) against the GLUT10 revealed possible substrates and interacting molecules for GLUT10, which were found to be involved directly or partially in ATS progression or different arterial disorders. Reported mutation screening revealed that a highly emergent point mutation (c. 1309G>A, p. Glu437Lys) is located in the predicted substrate binding site region.Conclusion:Virtual screening expands the possibility to explore more compounds that can interact with GLUT10 and may aid in understanding the mechanisms leading to ATS.
Inhibitory Effect of Sesamolin on Melanogenesis in B16F10 Cells Determined by In Vitro and Molecular Docking Analyses
Authors: Baek Seung-Hwa , Kang Myung-Gyun , Park Daeui 
Published: February 2020

Background:Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition.Objective:The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation.Methods:Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina.Results:Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol).Conclusion:Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.
Overview of Gene Regulatory Network Inference Based on Differential Equation Models
Authors: Yang Bin , Chen Yuehui 
Published: February 2020

:
Reconstruction of gene regulatory networks (GRN) plays an important role in understanding
the complexity, functionality and pathways of biological systems, which could support the design of
new drugs for diseases. Because differential equation models are flexible androbust, these models have
been utilized to identify biochemical reactions and gene regulatory networks. This paper investigates
the differential equation models for reverse engineering gene regulatory networks. We introduce three
kinds of differential equation models, including ordinary differential equation (ODE), time-delayed
differential equation (TDDE) and stochastic differential equation (SDE). ODE models include linear
ODE, nonlinear ODE and S-system model. We also discuss the evolutionary algorithms, which are
utilized to search the optimal structures and parameters of differential equation models. This investigation
could provide a comprehensive understanding of differential equation models, and lead to the
discovery of novel differential equation models.
Automatic Detection of Cognitive Impairments through Acoustic Analysis of Speech
Authors: Nagumo Ryosuke , Zhang Yaming , Ogawa Yuki , Hosokawa Mitsuharu , Abe Kengo , Ukeda Takaaki , Sumi Sadayuki , Kurita Satoshi , Nakakubo Sho , Lee Sangyoon , Doi Takehiko , Shimada Hiroyuki 
Published: February 2020

Background:
Early detection of mild cognitive impairment is crucial in the prevention of
Alzheimer’s disease. The aim of the present study was to identify whether acoustic features can help
differentiate older, independent community-dwelling individuals with cognitive impairment from
healthy controls.

Methods:
A total of 8779 participants (mean age 74.2 ± 5.7 in the range of 65-96, 3907 males and 4872
females) with different cognitive profiles, namely healthy controls, mild cognitive impairment, global
cognitive impairment (defined as a Mini Mental State Examination score of 20-23), and mild cognitive
impairment with global cognitive impairment (a combined status of mild cognitive impairment and
global cognitive impairment), were evaluated in short-sentence reading tasks, and their acoustic features,
including temporal features (such as duration of utterance, number and length of pauses) and spectral
features (F0, F1, and F2), were used to build a machine learning model to predict their cognitive impairments.

Results:
The classification metrics from the healthy controls were evaluated through the area under the
receiver operating characteristic curve and were found to be 0.61, 0.67, and 0.77 for mild cognitive impairment,
global cognitive impairment, and mild cognitive impairment with global cognitive impairment,
respectively.

Conclusion:
Our machine learning model revealed that individuals’ acoustic features can be employed
to discriminate between healthy controls and those with mild cognitive impairment with global cognitive
impairment, which is a more severe form of cognitive impairment compared with mild cognitive impairment
or global cognitive impairment alone. It is suggested that language impairment increases in
severity with cognitive impairment.
Analysis of QTc Interval during Levofloxacin Prescription in Cardiac Patients with Pneumonia
Authors: Shojaei Lida , Ruzbahani Mohammad , Khajavian Shiva , Shahsavari Soodeh , Tamasoki Negin , Rajabian Mina , Moradi Farzaneh , Shahbazi Foroud 
Published: February 2020

Background:
Medications induced QT prolongation could cause ventricular arrhythmia,
torsade de pointes, and death.

Objective:
The purpose of this study was to evaluate the magnitude of QTc interval prolongation as
a result of levofloxacin treatment in patients admitted to cardiology wards.

Methods:
This was a cross-sectional study conducted in the coronary care units and general wards
of the Imam Ali Heart Hospital in Kermanshah, Iran. The QTc interval was determined at baseline
and after 72 hours of levofloxacin administration. Changes in the QTc interval before and after the
levofloxacin prescription were determined.

Results:
The mean age of recruited patients was 63.26 ± 14.56 years. More than 80% of patients
who received levofloxacin experienced QTc prolongation. The QTc interval was increased significantly
after levofloxacin administration (15.68 ± 26.84 milliseconds) (p<0.001). These changes remained
significant after excluding medications with QTc lengthening properties (p<0.001).

Conclusion:
Treatment with levofloxacin in patients with heart disease increases the risk of QT
prolongation.
Perturbation of HSP Network in MCF-7 Breast Cancer Cell Line Triggers Inducible HSP70 Expression and Leads to Tumor Suppression
Authors: Ergul Mustafa , Aktan Fugen , Yildiz Mehmet T. , Tutar Yusuf 
Published: February 2020

Background:
Heat shock protein 70 (HSP70) is constitutively expressed in normal cells but aberrantly
expressed in several types of tumor cells, helping their survival in extreme conditions. Thus, specific
inhibition of HSP70 in tumor cells is a promising strategy in the treatment of cancer. HSP70 has a variety of
isoforms in the cellular organelles and form different functions by coordinating and cooperating with cochaperones.
Cancer cells overexpress HSPs during cell growth and proliferation and HSP network provides
resistance against apoptosis. The present study aimed to evaluate quantitative changes in HSPs- and cancerassociated
gene expressions and their interactions in the presence of 2-phenylethyenesulfonamide (PES) in
MCF-7 cells.

Methods:
Antiproliferative activity of PES was evaluated using the XTT assay. Inducible HSP70 (HSP70i)
levels in the PES-treated cells were determined using the ELISA kit. PCR Array was performed to assess the
HSPs- and cancer-pathway focused gene expression profiling. Gene network analysis was performed using the
X2K, yEd (V.3.18.1) programs, and web-based gene list enrichment analysis tool Enrichr.

Results:
The results demonstrated that PES exposure increased the amount of both HSP70i gene and protein
expression surprisingly. However, the expression of HSP70 isoforms as well as other co-chaperones, and 17
cancer-associated genes decreased remarkably as expected. Additionally, interaction network analysis revealed a
different mechanism; PES induction of HSP70i employs a cell cycle negative regulator, RB1, which is a tumor
suppressor gene.

Conclusion:
PES treatment inhibited MCF-7 cell proliferation and changed several HSPs- and cancer-related
gene expressions along with their interactions through a unique mechanism although it causes an interesting
increase at HSP70i gene and protein expressions. RB1 gene expression may play an important role in this effect
as revealed by the interaction network analysis.
Majra Honey Abrogated the Normal and Cancer Cells Proliferation Inhibition by Juniperus procera Extract and Extract/Honey Generated AgNPs
Authors: Ghramh Hamed A. , Ibrahim Essam H. , Kilnay Mona 
Published: February 2020

Background:
Juniperus procera and Majra honey are well-known as a folk medicine in many countries.

Objectives:
This work aimed to study the immunomodulatory effects after mixing Majra honey, J. procera
water leaves extract and silver Nanoparticles (AgNPs) on immune or cancer cells.

Methods:
Juniperus procera water leaves extract and 20% Majra honey were prepared. Both the extract and
honey were used separately to synthesize AgNPs. AgNPs were characterized using UV/Vis spectrophotometry
and electron microscopy. Bioactive molecules in honey and the extract were explored using Fourier Transform
Infrared (FT-IR) spectroscopy. Protein profile of honey was explored using Sodium Dodecyl Sulfate-
Polyacrylamide Gel Electrophoresis (SDS-PAGE) and honey sugar content was determined using High-
Performance Liquid Chromatography (HPLC). Biological activities of honey and the extract were tested.

Results:
The results demonstrated the ability of the extract/honey to produce AgNPs in a spherical shape. The
extract/honey contained many functional groups. SDS-PAGE of Majra honey showed many protein bands.
HPLC revealed honey is of good quality and no external additives are added to it. The extract and extract+
AgNPs inhibited the growth of normal rat splenic cells while honey stimulated it. The extract+honey
turned stimulatory to the splenic cells’ growth and significantly diminished the inhibitory potential of the extract
containing AgNPs. Both the extract and honey have antimicrobial activities, this potential increased in the presence
of AgNPs. Honey and Honey+AgNPs inhibited HepG2 cancer cell proliferation while Hela cell growth
inhibited only with honey+AgNPs.

Conclusion:
Both honey and the extract have antibacterial and immunomodulatory potentials as well as the
power to produce AgNPs. Majra honey alone showed anticancer activity against HepGe2 cells, but not against
Hela cells, and when contained AgNPs had anticancer activity on both cell lines. Mixing of Majra honey with J.
procera extract showed characterized immunomodulatory potentials that can be described as immunostimulant.