bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics Analysis IdentifiesThrombospondin-1 and its related micro RNAs as biomarkers for Hepatocellular carcinoma
Authors: xuan Wei , Song Dandan , Ren Yunjia , Li Ming 
Published: July 2020

Abstract
Hepatocellular carcinoma (HCC) has a poor prognosis, while the diagnosis biomarkers or treatment targets for HCC are still lacking. Recently, mining strategies on public access databases has been successfully used to discover novel and sensitive biomarkers. In this study, bioinformatics analysis of the genomic and transcriptome data of HCC PBMC samples obtained from the Gene Expression Omnibus datasets. The analysis results showed that thrombospondin-1 (THBS-1) was dysregulated in HCC, and might be as biomarkers as it is a secretory protein and found to participate in liver dysfunction including HCC development. THBS-1 related micro RNAs are identified by bioinformatics analysis and tested as biomarkers as they are altered in many tumors and stable in circulation. The results showed that plasma THBS-1 and miR-194 were down-regulated in HCC patients and their correlations were positive. Whereas plasma level of miR-338-3p was significantly increased in the HCC patients and negatively correlated with THBS-1 and they showed a highly significant diagnostic value in discriminating HCC. In addition, THBS-1 and miR-338-3p combination displayed higher predictive power than them alone, and addition of miR-338-3p might enhance predictive power of AFP for HCC. Our data showed that THBS-1 and miR-338-3p displayed a highly significant diagnostic value in discriminating between HCC patients and control subjects. Addition of miR-338-3p might enhance the predictive potency of AFP for HCC.
Efficacy of Definite Concurrent Chemoradiotherapy for Patients with Limited-Disease Small-Cell Lung Cancer: A Retrospective, Nationwide, Population-Based Cohort Study
Authors: Ko Yoon Ho , Kim Seoree , Hong Ji Hyung , Sung Soo-Yoon , Kim Yeo Hyung , Chun Sang Hoon , Lee Hyun Woo , Lee Jung Soo 
Published: July 2020

Abstract
Background: Small-cell lung cancer (SCLC) is a highly proliferative, rapidly growing tumor with a poor prognosis, even in cases of limited disease (LD). Timely and accurate high-intensity therapy is necessary. For concurrent chemoradiotherapy (CCRT), etoposide/platinum (EP)-based regimens are recommended, although irinotecan/platinum (IP)-based regimens are also effective with radiotherapy. This large-scale, retrospective, nationwide cohort study aimed to analyze the efficacy of CCRT in patients with LD-SCLC.Methods: Population data registered between January 2008 and December 2018 were extracted from the Health Insurance Review and Assessment Service of Korea database. Survival outcomes of 4,446 LD-SCLC patients who received CCRT were analyzed.Results: Patients who received EP-CCRT (n = 4,187) showed better progression-free survival (PFS: 11.2 months) and overall survival (OS: 22.2 months) than did those who received IP-CCRT (n = 259; PFS: 9.6 months, P = 0.0477; OS: 16.4 months, P <0.0001). When CCRT failed, dual-agent chemotherapy (n = 925; OS: 9.1 months) provided a better survival benefit than did single-agent chemotherapy (n = 815; OS: 7.5 months). IP-based chemotherapy resulted in better OS (9.6 months) than did EP-based chemotherapy (7.1 months, P = 0.0170) in platinum-resistant relapsed patients; the opposite was observed for platinum-sensitive relapsed patients (OS: EP, 17.2 months; IP, 6.6 months; P <0.0001). Cox proportional hazards regression analysis demonstrated that age, EP-CCRT, and hypercholesterolemia retained significant associations with OS after adjustment for all variables.Conclusion: In the Korean population, the effects of EP-CCRT on OS and PFS are significantly more favorable than those of IP-CCRT.
Evaluation of Immunophenotypic Markers and Clinico-Hematological Profile in Chronic Lymphocytic Leukemia: Implications for Prognosis
Authors: Bagheri Marziye , Vosoughi Tina , Hosseinzadeh Mehran , Saki Najmaldin 
Published: July 2020

Abstract
Objective: Chronic lymphocytic leukemia (CLL) is an adult leukemia presented with clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. This is a study of the association between immunophenotypic markers expression with complete blood cell count (CBC) values and clinical parameters. Results: Peripheral blood samples were collected from 35 new CLL patients. The expression of immunophenotypic markers and CBC were evaluated. Platelet counts and hemoglobin concentration had a significant, negative association with Rai staging, modified Rai staging, Binet staging systems (all p< 0.001 in both parameters), and splenomegaly (p = 0.001 and 0.007, respectively). The platelet/lymphocyte ratio (PLR) had a significant, negative association with Rai staging (p = 0.014), modified Rai staging (p = 0.024), Binet staging systems (p = 0.027), and splenomegaly (p = 0.033). However, CD38, CD25, and double-positive CD56/CD117 expression, as group3 of innate lymphocyte cells (ILC3s), had no significant association with clinical parameters. In regression analysis, that ILC3s has a negative correlation with neutrophil/lymphocyte ratio (r = -0.340, p = 0.046). Given that there is a negative association between PLR and advanced clinical stages, it seems that PLR may have prognostic value in CLL.
CERTL Reduces C16 Ceramide, Amyloid-β Levels and Inflammation in a Model of Alzheimer's Disease
Authors: Crivelli Simone Mwenda , Luo Qian , Stevens Jo , Giovagnoni Caterina , Kruining Daan van , Bode Gerard , Hoedt Sandra den , Hobo Barbara , Scheithauer Anna-Lena , Walter Jochen , Mulder Monique T , Exley Christopher , Mielke Michelle M. , De Vries Helga E , Wouters Kristiaan , Hove Daniel L.A. van den , Berkes Dusan , Ledesma María Dolores , Verhaagen Joost , Losen Mario , Bieberich Erhard , Martinez-Martinez Pilar 
Published: July 2020

Abstract
Background: Deregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers, crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.Methods: The plasmid expressing CERTL, the long isoform of CERTs, was used to study the interaction of CERTL with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERTL protein was employed to study interaction of CERTL with amyloid-β (Aβ), Aβ aggregation process in presence of CERTL, and the resulting changes in Aβ toxicity in neuroblastoma cells. CERTL was overexpressed in neurons by adeno associated virus (AAV) in a familial mouse model of familial AD (5xFAD). Ten weeks after transduction animal were challenged with behavior tests for memory, anxiety and locomotion. At week twelve brains were investigated for sphingolipid levels by mass spectrometry, plaques and neuroinflammation by immunohistochemistry, gene expression and/or immunoassay.Results: Here, we report that CERTL, binds to APP, modifies Aβ aggregation and reduces Aβ neurotoxicity in vitro. Furthermore, we show that intracortical injection of AAV, mediating the expression of CERTL, decreases levels of ceramide d18:1/16:0 and increases sphingomyelin levels in the brain of male transgenic mice, modelling familial AD (5xFAD). CERTL in vivo over-expression has a mild effect on animal locomotion and decreases Aβ formation and modulates microglia by decreasing their pro-inflammatory phenotype.Conclusion: Our results demonstrate a crucial role of CERTL in regulating ceramide levels in the brain, in amyloid plaque formation and neuroinflammation, thereby opening research avenues for therapeutic targets of AD and other neurodegenerative diseases.
Understanding the Effects of Beetroot Juice Intake on CrossFit Performance by Assessing Hormonal, Metabolic and Mechanical Response: A Randomized, Double-Blind, Crossover Design
Authors: Garnacho-Castaño Manuel V. , Palau-Salvà Guillem , Serra-Payá Noemí , Ruiz-Hermosel Mario , Berbell Marina , Viñals Xavier , Bataller Manuel Gomis , Carbonell Teresa , Vilches-Saez Sergio , Cobo Eulogio Pleguezuelos , Molina-Raya Lorena 
Published: July 2020

Abstract
Background: Acute beetroot juice (BJ) intake has shown to enhance aerobic and anaerobic performance. However, no studies have evaluated the effects of BJ intake on CrossFit (CF) performance by linking hormonal, metabolic, and mechanical responses. The purpose of this study was to determine the causal physiological association between hormonal, metabolic and mechanical responses, and CF workouts performance after acute BJ intake. Methods: Twelve well-trained male practitioners undertook a CF workout ﻿after drinking 140 mL of BJ (~ 12.8 mmol NO3−) or placebo. The two experimental conditions (BJ or placebo) were administered using a randomized, double-blind, crossover design. The CF workout consisted of repeating the same exercise routine twice: Wall ball (WB) shots plus full back squat (FBS) with 3-min rest (1st routine) or without rest (2nd routine) between the two exercises. A 3-min rest was established between the two exercise routines. Results: An interaction effect was observed in the number of repetitions performed (p = 0.04). The Bonferroni test determined a higher number of repetitions after BJ than placebo intake when a 3-min rest between WB and FBS (1st routine) was established (p = 0.007). An interaction effect was detected in cortisol response (p = 0.04). Cortisol showed a higher increase after BJ compared to placebo intake (76% vs. 36%, respectively). No interaction effect was observed in the testosterone and testosterone/cortisol ratio (p > 0.05). A significant interaction effect was found in oxygen saturation (p = 0.01). A greater oxygen saturation drop was observed in BJ compared to placebo (p < 0.05). An interaction effect was verified in muscular fatigue (p = 0.03) with a higher muscular fatigue being observed with BJ than placebo (p = 0.02). Conclusions: BJ intake improved anaerobic performance only after the recovery time between exercises. This increase in performance in the first routine probably generated greater hypoxia in the muscle mass involved, possibly conditioning post-exercise performance. This was observed with a fall in oxygen saturation and in muscle fatigue measured at the end of the CF workout. The greatest perceived changes in cortisol levels after BJ intake could be attributed to the nitrate-nitrite-nitric oxide pathway
Multi-omic analysis reveals the anti-aging impact of sulforaphane on the microbiome and metabolome
Authors: Se-Ran Jun , Cheema Amrita , Bose Chhanda , Boerma Marjan , Palade Philip T , Awasthi Sanjay , Singh Sharda Prakash 
Published: July 2020

Abstract
Background Dietary factors may modulate many complex interactions between the microbiome, metabolome, and immune system and can have an impact on the functional status of older adults. Sulforaphane (SFN), a natural compound and Nrf2-related activator of cytoprotective genes, provides a wide range of biological effects from cancer prevention to reducing insulin resistance. We have shown that SFN increased survival and improved cardiac and skeletal muscle function in a mouse model of aging. This study aims to investigate the anti-aging effects of SFN on the gut microbiome and metabolome.Results Young (6-8 weeks of age) and old (21-22 months of age) male C57BL/6J mice were provided regular rodent chow or chow containing SFN for 2 months. Fecal samples were collected right before and at the completion of SFN administration. We profiled the gut microbiome and applied global metabolomic profiling to fecal samples. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the microbiome, and metabolome. Microbial diversity, composition and functional capacity varied substantially across different age groups. On a global level, in old mice we observed that the SFN diet restored the gut microbiome to mimic that in young mice. In old mice, the SFN diet enriched bacteria associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. In addition, the tricarboxylic acid cycle, central in cellular respiration, was decreased and amino acid metabolism-related pathways were increased. SFN diet induced metabolite biomarkers in old mice that are associated majorly with the genera, Oscillospira , Ruminococcus , and Allobaculum.Conclusion In old mice, SFN directed the metabolic potential to that of young animals. Integrated microbiome and metabolome analyses revealed metabolite biomarkers that could be modulated by bacteria and contribute to the anti-aging effects of SFN. Collectively, our results provide evidence in support of a novel hypothesis that SFN diet exerts anti-aging effects by influencing the gut microbiome and metabolome. Although further investigations are needed to identify precise mechanisms, modulating the gut microbiome by SFN may have the potential to promote healthier aging.
Fusing Multiple Biological Networks to Effectively Predict miRNA-disease Associations
Authors: Zhu Qingqi , Fan Yongxian , Pan Xiaoyong 
Published: July 2020

Background:
MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with
about 22 nucleotides, and they play a significant role in a variety of complex biological processes.
Many researches have shown that miRNAs are closely related to human diseases. Although the
biological experiments are reliable in identifying miRNA-disease associations, they are timeconsuming
and costly.

Objective:
Thus, computational methods are urgently needed to effectively predict miRNA-disease
associations.

Methods:
In this paper, we proposed a novel method, BIRWMDA, based on a bi-random walk
model to predict miRNA-disease associations. Specifically, in BIRWMDA, the similarity network
fusion algorithm is used to combine the multiple similarity matrices to obtain a miRNA-miRNA
similarity matrix and a disease-disease similarity matrix, then the miRNA-disease associations were
predicted by the bi-random walk model.

Results:
To evaluate the performance of BIRWMDA, we ran the leave-one-out cross-validation and
5-fold cross-validation, and their corresponding AUCs were 0.9303 and 0.9223 ± 0.00067,
respectively. To further demonstrate the effectiveness of the BIRWMDA, from the perspective of
exploring disease-related miRNAs, we conducted three case studies of breast neoplasms, prostate
neoplasms and gastric neoplasms, where 48, 50 and 50 out of the top 50 predicted miRNAs were
confirmed by literature, respectively. From the perspective of exploring miRNA-related diseases, we
conducted two case studies of hsa-mir-21 and hsa-mir-155, where 7 and 5 out of the top 10 predicted
diseases were confirmed by literatures, respectively.

Conclusion:
The fusion of multiple biological networks could effectively predict miRNA-diseases
associations. We expected BIRWMDA to serve as a biological tool for mining potential miRNAdisease
associations.
In Vitro Antifungal Activity of Green Synthesized Silver Nanoparticles in Comparison to Conventional Antifungal Drugs Against Trichophyton Interdigitale, Trichophyton Rubrum and Epidermophyton Floccosum
Authors: Mahmoudi Shahram , Vahidi Mahmoud , Malekabad Ebadollah Shiri , Izadi Alireza , Khatami Mehrdad , Dadashi Alireza 
Published: July 2020

Background:
Dermatophytosis is a globally distributed fungal infection. Treatment failure and relapse is common in this disease. Silver nanoparticle are known for their promising antimicrobial activity. The aim of this study was to determine the antifungal activity
of these nanoparticles against common dermatophyte species.

Methods:
A set of 30 molecularly identified dermatophytes including Trichophyton interdigitale (n=10), Trichophyton rubrum (n=10), and
Epidermophyton floccosum (n=10) were used in this study. Green synthesized silver nanoparticles using chicory (Cichorium intybus) were
tested for their antifungal activity in comparison to fluconazole, itraconazole and terbinafine. Interspecies differences in minimum inhibitory concentrations of antifungal drugs and silver nanoparticles were tested using Kruskal–Wallis test in SPSS software version 21.

Results:
The highest minimum inhibitory concentrations (MICs) among antifungal drugs were observed
for fluconazole [range: 4–64 μg/mL, geometric mean (GM) =17.959 μg/mL], followed by
itraconazole (range: 0.008–0.5, GM= 0.066) and terbinafine (range: 0.004–0.25 μg/mL, GM=0.027
μg/mL). Silver nanoparticles showed potent antifungal activity against all dermatophyte isolates
with MICs (range: 0.25–32 μg/mL, GM=4.812 μg/mL) higher than those of itraconazole and terbinafine,
but lower than fluconazole.

:
MIC values of silver nanoparticles demonstrated significant differences between species
(P=0.044), with E. floccosum having the highest MICs (GM=9.849 μg/mL) compared to T. interdigitale
(GM=3.732 μg/mL) and T. rubrum (GM=3.031 μg/mL).

Conclusion:
Silver nanoparticles demonstrated promising anti-dermatophyte activity against the
studied dermatophytes. Due to their wide-spectrum activity against other fungal and bacterial pathogens,
they could be a potential choice, at least in the case of cutaneous and superficial infections.
Effect of Substrate-induced Strains on Ferroelectric and Dielectric Properties of Lead Zirconate Titanate Films Prepared by the Sol-gel Technique
Authors: Gatea Hamed A. 
Published: July 2020

Background:
Lead Zirconate Titanate (PZT) films were synthesized by sol gel technique.
The growth of films on ITO, Si\SiO2\Ti\Au, Si\Au and Si\SiO2\Ti\Al substrates discussed.
In this study, Zirconium nitrate, lead acetate, and Ti (IV) isoproxide used as raw materials. Besides,
acetic acid used as a solvent and 2-methoxy ethanol used as a stabilizer for Ti structure.
Along with this, PZT films have perovskite structure, thin-film perovskite structure with high dielectric
properties and hysteresis loop have been investigated.

Methods:
The effects of the type’s substrate on dielectric properties the ferroelectric properties
were investigated and compared PZT film which deposited in different substrates. The films annealed
at 600°C to complete crystalline films. XRD shows tetragonal PZT films have a strong perovskite
structure with [100] prefer plane orientation. SEM and cross-section technique used to
study for PZT surface films.

Results:
The dielectric constant at room temperature was different values depending on the types
of substrate. The dielectric properties of the PZT films measured at 1 kHz were 120-400 dielectric
constant and dielectric loss 0.02-0.08 at room temperature and 1 kHz.

Conclusion:
The largest remnant polarization (Pr) and coercive field (Ec) are obtained for PZT
film deposited on Si\SiO2\Ti\Au substrate, equal to 26.6 mC/cm2 and 38.3 kV/cm, as compared to
16.3 mC/cm2 and 32.2 kV/cm2 for PZT film deposited on ITO substrate.
The Impact of Varying Sinks on Load Distribution in IoT Routing Under
Static and Mobile Scenarios
Authors: Al-Qassas Raad S. 
Published: July 2020

:
The majority of routing algorithms proposed for IoT can be categorized under modifications
in routing protocols designated for IoT such as RPL objective functions enhancements, while
others are enhancements in routing algorithms derived from those which were designed for ad hoc
networks. We have thoroughly investigated the literature on these modifications or enhancements.
However, there is a lack of an in-depth study to examine the impact of mobility and the varying
number of sinks on routing algorithms based on MRHOF and OF0. In this study, we examine their
ability in distributing the load with the impact of the varying number of sink nodes under static and
mobile scenarios. This study has been conducted using various metrics including regular metrics
such as throughput and power consumption, and newly derived metrics including packets load deviation
and power deviation which are derived for the purpose of measuring load distribution.
KEBIJAKAN KRIMINAL DALAM PENANGGULANGAN PERKAWINAN DI BAWAH UMUR
Authors: Eli Dani Isma Mohd. Din Mujibussalim 
Published: July 2020

Reproductive health married at a young age at risk of causing twice as likely to die in childbirth as compared to those aged 20-25 years, while under-15-year-olds may die five times. Young women who are pregnant, based on research will experience several things, such as will experience bleeding, miscarriage, and difficulty in the process of childbirth. Therefore, early marriage has many negative impacts that are very important to be known by both teenagers and parents. Underage marriage phenomenon is not new in Indonesia as in the case of Syech praise and Lutfiana ulfa that caused controversy in the year 2009 ago, there are hundreds of cases underage marriages that do not stick to the surface and expose the media. In rural areas, there are many cases of underage marriages, such as in the Takengon area, Aceh Tengah District, Aceh Province, there are many cases of underage marriage, how is criminal policy in prevention of marriage of minors? A pakah effort undertaken in countermeasures of marriage of minors in Takengon Regency Central Aceh? Although countermeasures have been undertaken but underage marriages are still rife due to the absence of specific and firm legal arrangements concerning marriage of minors. Minors under Law No. 1 of 1974 on Marriage are children aged 19 years for men and 16 years for women. Although it has been affirmed that the minimum age limit is allowed to marry by law, on the other hand it is given an exception for marriage.
Keywords: Criminal, Marriage, Underage