bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Concern: Application of probability decision system and particle swarm optimization for improving soil moisture content
Authors: Zhu Panpan , Saadati Hossein , Khayatnezhad Majid 
Published: June 2021

Abstract
Drought is one of the natural disasters having the highest degrees in comparison to the other natural disasters in terms of rate, intensity, incident duration, region expansion, life losses, economic damages, and long-term effects. Hence, the prediction of drought as a meteorological phenomenon should be evaluated to determine the groundwater exploitation strategies in agriculture. The present study aims at investigating the impact of the drought duration and severity on soil moisture supplement for agricultural activities in Baghmalek plain, Khuzestan province, Iran. For this objective, a non-dimensional index of precipitation depth was defined for quantifying the drought characteristics. Furthermore, marginal distribution functions, correlation coefficients and joint functions were incorporated to a probabilistic decision-making framework to predict the variables in different return periods from 2-year to 100-year periods. Results showed that t copula was the best function for constructing the multivariate distribution in the study area based on the goodness-of-fit tests. Moreover, soil moisture content in the root zone achieved by the predetermined amounts of precipitation could be increased in the seasonal average.
Nitrate reduction by electrochemical processes using copper electrode: evaluating operational parameters aiming low nitrite formation
Authors: Beltrame T. F. , Zoppas F. M. , Ferreira J. Z. , Marchesini F. A. , Bernardes A. M. 
Published: June 2021

Abstract
This work aims to present different electroreduction and electrocatalytic processes configurations to treat nitrate contaminated water. The parameters tested were: current density, cell potential, electrode potential, pH values, cell type and catalyst use. It was found that the nitrite ion is present in all process variations used, being the resulting nitrite concentration higher in an alkaline pH. The increase in current density on galvanostatic operation mode provides a greater reduction of nitrate (64%, 1.4 mA cm−2) if compared to the potentiostatic (20%) and constant cell potential (37%) configurations. In a dual-chamber cell the nitrate reduction with current density of 1.4 mA cm−2 was tested and obtained as a NO3− reduction of 85%. The use of single chamber cell presented 32 ± 3% of nitrate reduction, indicating that in this cell type the nitrate reduction is smaller than in dual-chamber cell (64%). The presence of a Pd catalyst with 3.1% wt. decreased the nitrite (1.0 N-mg L−1) and increased the gaseous compounds (9.4 N-mg L−1) formation. The best configuration showed that, by fixing the current density, the highest nitrate reduction is obtained and the pH presents a significant influence during the tests. The use of the catalyst decreased the nitrite and enhanced the gaseous compounds formation.
Machine Learning, Molecular Modeling, and QSAR Studies on Natural Products Against Alzheimer’s Disease
Authors: de Moura Érika Paiva , Fernandes Natan Dias , Monteiro Alex France Messias , de Medeiros Herbert Igor Rodrigues , Scotti Marcus Tullius , Scotti Luciana 
Published: June 2021

Background:
Alzheimer's disease (AD) is a very common neurodegenerative
disorder in individuals over 65 years of age; however, younger individuals can also be affected
due to brain damage.

Introduction:
The general symptoms of this disease include progressive loss of memory,
changes in behavior, deterioration of thinking, and gradual loss of ability to perform daily
activities. According to the World Health Organization, dementia has affected more
than 50 million people worldwide, and it is estimated that there are 10 million new cases
per year, of which 70% are due to AD.

Methods:
This paper reported a review of scientific articles available on the internet
which discuss in silico analyzes such as molecular docking, molecular dynamics, and
quantitative structure-activity relationship (QSAR) of different classes of natural products
and their derivatives published from 2016 onwards. In addition, this work reports
the potential of fermented papaya preparation against oxidative stress in AD.

Results:
This research reviews the most recent studies on AD, computational analysis
methods used in proposing new bioactive compounds and their possible molecular targets,
and finally, the molecules or classes of natural products involved in each study.

Conclusion:
Thus, studies like this can orientate new research works on neurodegenerative
diseases, especially AD.
Suicide and Genetic Biomarkers: Toward Personalized Tailored-treatment with Lithium and Clozapine
Authors: De Berardis Domenico , Vellante Federica , Pettorruso Mauro , Lucidi Lorenza , Tambelli Antonio , Di Muzio Ilenia , Gianfelice Giulia , Ventriglio Antonio , Fornaro Michele , Serafini Gianluca , Pompili Maurizio , Perna Giampaolo , Fraticelli Silvia , Martinotti Giovanni , di Giannantonio Massimo 
Published: June 2021

Background:
Suicide is a major public health problem on a global scale, with about 800.000 deaths
every year. In particular, it represents one of the main causes of death among adolescents and young adults
aged between 15 and 29 years. The World Health Organization (WHO) describes suicide as “an act of deliberate
killing” and that is placed at the extreme end of the continuous spectrum of suicidal behaviors (SBs). These
include suicidal ideation, attempted suicide and suicide itself.

Objective:
The aim of the present review was to better clarify the suicide vulnerability genetic biomarkers and
genetic variants correlated with the response to lithium and clozapine and to evaluate some correspondences.

Methods:
We reviewed the current literature, focusing our attention on genetic molecular studies about neurobiological
systems involved in SBs and pharmacogenetic studies about antisuicidal drugs (lithium and clozapine).

Results:
The studies that we have reviewed have shown mixed results. Interestingly, rs1800532 polymorphism
of the SLC6A4 gene, encoding for the serotonin transporter, is potentially correlated with both suicide vulnerability
and a poor response to lithium and clozapine.

Conclusion:
Due to the impact of suicide on public health, more studies are needed to open a promising route
to prevent suicide in personalized and precise psychiatry.
Overcoming the Challenges in the Treatment of Glioblastoma via Nanocarrier- based Drug Delivery Approach
Authors: Mittal Saurabh , Ali Javed , Baboota Sanjula 
Published: June 2021

Background:
Glioblastoma multiforme is the most malignant form of high-grade astrocytoma. Clinically
it is characterized as 4th grade of astrocytoma having necrotic tissue and hyperplastic blood vessel. It is observed
to be the most frequent adult brain tumor representing an overall 15.4% of all brain tumors and about
60-75% of the entire astrocytoma. There are limited therapies available, and the most widely used therapy includes
surgical intrusion followed by radiotherapy plus chemotherapy (paclitaxel, temozolomide, docetaxel,
etc.), with an overall patient survival rate from 6-14 months. Various studies have proved that nanoformulations
offer considerable advantages like enhanced drug solubility, targeted activity, and attenuated side effects.

Objective:
The key objective of this review article is to exemplify numerous studies carried out using nanocarriers
for overcoming the challenges associated with the treatment of glioblastoma. It also describes the pathways
associated with the induction, initiation, and progression of glioblastoma.

Methods:
Research articles that focused on the use of nanocarrier-based drug delivery approach for the treatment of various glioblastoma were collected from different search engines, such as Google Scholar, Science Direct, and PubMed using keywords like glioblastoma, nanocarriers, Brain delivery, etc.

Results:
Nanocarriers have shown enormous potential in overcoming the challenges associated with the treatment of glioblastoma.

Conclusion:
Broad research is still needed so that these nanocarriers can be used clinically for the welfare of mankind, in the management of glioblastoma, in near future.
3 CpG Methylation Biomarkers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Blood Samples
Authors: Zeng Lei , Lu Ruling , Xie Linling , Jiang Xiaotao , Chen Yi , Huang Cihui , Chen Yanfen , Liu Guantong , Sun Wenxi 
Published: June 2021

Background:Polycystic ovary syndrome (PCOS) is a common endocrine disease in women that seriously interferes with patient's metabolic and reproductive functions. The current diagnostic criteria for PCOS are expert-based and still disputed. Previous studies have identified changes in DNA methylation in peripheral blood of women with PCOS, but their diagnostic potential for PCOS remains to be studied.Objective:The present study aimed to identify potential methylation biomarkers for the diagnosis of PCOS in blood.Methods:Methylation profiling of peripheral blood was downloaded from a public database, Gene Expression Omnibus (GEO), including 30 PCOS patients (diagnosed with the revised 2003 Rotterdam consensus criteria) and 30 age-matched healthy women recruited from Centre of Reproductive Medicine, Linyi People’s Hospital, Shandong, China. Weighted gene co-expression network analysis (WGCNA) was utilized to identify PCOS-related co-methylation CpG sites (co- MPs). Functional enrichment analysis was performed on the localized genes of PCOS-related co- MPs. The least absolute shrinkage and selection operator (LASSO) regression was used to screen out CpG methylation signatures for PCOS diagnosis, and receiver operating characteristic (ROC) analysis was conducted to evaluate their diagnostic accuracy. To assess the accuracy of the combination of the investigated indicators, multivariate ROC analysis was performed on the predicted probability values obtained using binary logistic regression on the methylation levels of selected CpGs.Results:Seven co-methylation modules were obtained, among which the turquoise module is the most relevant to PCOS, containing 194 co-MPs. The genes that these co-MPs located in were mainly associated with the immune-related pathway. According to LASSO regression, three Co- MPs (cg23464743, cg06834912, cg00103771) were identified as potential diagnostic biomarkers of PCOS. ROC analysis showed an AUC (area under curve) of 0.7556 (sensitivity 60.0%, specificity 83.3%) for cg23464743, 0.7822 (sensitivity 70.0%, specificity 80.0%) for cg06834912, and 0.7611 (sensitivity 63.3%, specificity 83.3%) for cg00103771. The diagnostic accuracy of the combination of these 3 indicators presented to be higher than any single one of them, with the AUC of 0.8378 (sensitivity 73.3%, specificity 93.3%).Conclusion:The combination of 3 CpG methylation signatures in blood was identified with a good diagnostic accuracy for PCOS, which may bring new insight into the development of PCOS diagnostic markers in the future.
Preliminary Study of microRNAs Allele-specific Targeting in Allergic
Rhinitis Patients from Central China
Authors: Tao Ze-Zhang , Deng Yu-Qin , Li Song , Liang Zheng-Yan , Li Fen , Wen Si-Lu 
Published: June 2021

Background:
Abnormal expression of miRNA is a common feature in many diseases.
Some studies have also emphasized that miRNAs play an important role in asthma and allergic
rhinitis (AR). This study attempts to reveal the differences between miRNAs expression and normal
nasal mucosa in AR patients by microarray method so as to further understand the molecular
mechanism of AR development.

Method:
MiRNA microarrays were used for analyzing six samples of the nasal mucosa of AR and
six samples of nonallergic patients. Quantitative reverse transcriptase-polymerase chain reaction
(RT-PCR) of some differently expressed miRNAs was used to confirm the array results.
Furthermore, pathway analysis was carried out.

Results:
The microarray identified that 64 miRNAs showed altered expression in the nasal mucosa
of the AR group when compared with the control group. Moreover, the expression levels of ten
miRNAs were significantly altered in the AR group. To verify the results of microarray, three
differentially expressed miRNA were determined by RT-PCR, and the results also confirmed these
changes. Ten differentially expressed miRNAs were present in the nasal mucosa of AR patients
compared with the control group, and three differentially expressed miRNAs as miR-1244, miR-
4651, and miR-7641 were determined by RT-PCR. The results also confirmed the changes,
indicating that they play important roles in the process of AR.

Conclusion:
MiR-1244, miR-4651, and miR-7641 may play important roles in the process of AR.
Sequencing analysis indicated that three kinds of mutations existed in MAPK8 3’UTR, which may
play a role in binding with miR-7641, and then influence the AR process. Single miRNA or, more
probably, their sets hold the promise for their use as biomarkers of allergic rhinitis. They are also a
promising target of future therapies.
FABP1 Gene Variant is Associated with Risk of Metabolic Syndrome
Authors: Mozaffari Majid , Ghayour-Mobarhan Majid , Zare-Feyzabadi Reza , Valizadeh Mohsen 
Published: June 2021

Background:
Metabolic Syndrome (MetS) is defined by a clustering of metabolic
abnormalities associated with an increased risk of cardiovascular disease and type 2 diabetes
mellitus. There has been an increasing interest in the associations of genetic variant involved in
diabetes and obesity in the FABP1 pathway. The relationship between the rs2241883 polymorphism
of FABP1 and risk of MetS remains unclear.

Objective:
We aimed to examine the association between this genetic polymorphism and the
presence of MetS and its constituent factors.

Methods:
A total of 942 participants were recruited as part of the Mashhad Stroke and Heart
Atherosclerosis Disorders (MASHAD study) Cohort. Patients with MetS were identified using the
International Diabetes Federation (IDF) criteria (n=406) and those without MetS (n=536) were also
recruited. DNA was extracted from peripheral blood samples that was used for genotyping for the
FABP1 rs2241883T/C polymorphism using Tetra-Amplification Refractory Mutation System
Polymerase Chain Reaction (Tetra-ARMS PCR). Genetic analysis was confirmed by gel
electrophoresis and DNA sequencing.

Results:
Using both univariate and multivariate analyses after adjusting for age, sex and physical
activity, carriers of C allele (CT/CC genotypes) in FABP1 variant was related to an increased risk of
MetS, compared to non-carriers (OR: 1.38, 95%CI: 1.04,1.82, p=0.026).

Conclusion:
The present study shows that C allele in FABP1 variant can be associated with an
increased risk of MetS. The evaluation of these factors in a larger population may help further
confirm these findings.
Association of Posture Instability with Dopamine Drop of Nigrostriatal System and Hypometabolism of Cerebral Cortex in Parkinson’s Disease
Authors: Wang Hongyan , Li Hong-Yu , Guo Xiuhai , Zhou Yongtao 
Published: June 2021

Background:
Posture Instability (PI) is known to be a severe complication in Parkinson’s
Disease (PD), and its mechanism remains poorly understood. Our study aims to explore the
changes of brain network in PI of PD, and further investigate the role of peripheral inflammation
on activities of different brain regions in PD with PI.

Methods:
167 individuals were recruited, including 36 PD cases with PI and 131 ones without PI.
We carefully assessed the status of motor and cognitive function, measured serum inflammatory
factors, and detected the dopaminergic pathways and the metabolism of different brain regions by
Positron Emission Tomography (PET). Data analysis was conducted by variance, univariate analysis,
chi-square analysis, logistic regression, and partial correlation.

Result:
No difference was found for age or onset age between the two groups (P>0.05). Female
patients were susceptible to posture impairment and had a 2.14-fold risk for PI compared with male
patients in PD (P<0.05). Patients with PI had more severe impairment of motor and cognitive function
for a longer duration than those without PI (P<0.05). The mean uptake ratios of presynaptic
vesicular monoamine transporter (VMAT2), which were detected in the caudate nucleus and putamen,
were lower in PI group than those without PI (P<0.05). There were lower activities of the midbrain,
caudate nucleus, and anterior medial temporal cortex in PI group than those in the non-PI
group (P<0.05). Although serum concentrations of immunoglobulins (IgG, IgM, and IgA) and complements
(C3, C4) were higher in the PI group than those in the non-PI group, only serum IgM concentration
had a significant difference between the two groups (P<0.05). We further explored significant
inverse correlations of IgG, IgM, IgA, and C4 with activities of some cerebral cortex in PI of
PD (P<0.05).

Conclusion:
Female patients were susceptible to posture instability and had a 2.14-fold risk for PI
of PD. Patients with PI had more severe impairments of motor and cognitive function for a longer
duration than those without PI. PI was associated with a dopamine drop of the nigrostriatal system
and lower activities of the limbic cortex in PD. Peripheral inflammation may be involved in degeneration
of the cerebral cortex in PD combined with PI.
CDK-associated Cullin 1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Human Glioblastoma
Authors: Zhang Xiaohua , Zhang Tianying , Han Xiaojuan , Qiu Zhongying , Cheng Jianghong , Gao Xingchun , Gou Xingchun 
Published: June 2021

Background:
Glioma is the most common intracranial primary tumour of adult humans,
and its pathological mechanism and molecular characteristics are still under investigation. CDK-associated
cullin 1 (CACUL1) has been shown to regulate colorectal carcinoma, lung cancer, and gastric
cancer development.

Objective:
This study aims to explore the role of CACUL1 in the pathogenesis of human glioma.

Methods:
CACUL1 levels in human glioma tissue microarrays were detected by immunohistochemistry
analysis. Two glioblastoma cell lines, namely, U87 and U251, were transfected with CACUL1
siRNA, and cell proliferation, cell cycle, cell apoptosis, and regulating molecules, including cyclinE1,
cyclinA2, CDK2, p21, Bcl2, and Bax were assessed by CCK8, flow cytometry, and Western
blot.

Results:
CACUL1 expression in glioma tissue was significantly higher than that in normal brain tissue.
CACUL1 knockdown impeded cell proliferation, induced cell apoptosis, and caused G1/S transition
arrest in glioblastoma cells. The cell cycle-related proteins CDK2, cyclinE1, and cyclinA2
were dramatically decreased in the CACUL1 siRNA group compared to the non-targeting siRNA
group in both U87 and U251 cells, while the CDK inhibitory protein p21 was increased in U87
cells. Additionally, the Bcl-2/Bax ratio was significantly decreased.

Conclusion:
CACUL1 can promote cell proliferation and suppress apoptosis of glioma cells and
might serve as a potential oncogene for gliomas.
In Silico and In Vitro Analysis of a Multiepitope L1-E7 Fusion Construct for Vaccine Development Against Human Papillomaviruses
Authors: Abbasifarid Elnaz , Bolhassani Azam , Irani Shiva , Sotoodehnejadnematalahi Fattah 
Published: June 2021

Background:
Human papillomavirus (HPV) infection is the major risk factor for cervical
cancer. Current prophylactic HPV vaccines provide immunity against most genital and carcinogenic
HPV types. However, these vaccines failed to produce immune responses against already established
HPV infections.

Methods:
To design a therapeutic vaccine candidate, we utilized immunoinformatics tools to design
a potential multiepitope fusion construct based on L1 and E7 genes from different high- and low-risk
HPV types. After determination of CD4+ and CD8+ T cell epitopes, the allergenicity, toxicity, immunogenicity,
conservancy, and population coverage were analyzed for epitopes selection. Then, hemolytic
probability of the selected epitopes, and molecular docking between major histocompatibility
complex (MHC) and the chosen epitopes were performed by different web servers. Next, a multiepitope
peptide construct consisting of 12 epitopes linked by AAY proteasomal sequence was designed.
After that, physicochemical properties, solubility, secondary and tertiary structures of this construct
were evaluated by bioinformatics tools. Finally, after amino acid reverse translation of the multiepitope
peptide construct, expression of the L1-E7 DNA construct (pEGFP-L1-E7) was investigated in
HEK-293T cells using fluorescent microscopy, flow cytometry, and western blotting.

Results:
Considering various parameters, the immunodominant peptides such as L1(MHC-I)-
DLDQFPLGRKFLLQ, L1(MHC-II)-NQLFVTVVDTTRSTN, E7-HPV16(MHC-I)-AEPDRAHYNI
VTF, E7-HPV18(MHC-I)-HGPKATVQDIVLHL, E7-HPV31(MHC-I)-KPDTSNYNIVTF, E7-HPV33
(MHC-I)-RPDGQAQPATADYYI, E7-HPV45(MHC-I)- RTLQQLFLSFV, E7-HPV16(MHC -II)-TLH
EYMLDLQPETTD, E7-HPV18(MHC-II)-LRAFQQLFLNTLSFV, E7-HPV31(MHC-II)-PTLQDYVL
DLQPEAT, E7-HPV33(MHC-II)-LKEYVLDLYPEPTDL and E7-HPV45(MHC-II)-LQQLFLSTLSF
VCPW were determined to design the vaccine construct. The results indicated efficient expression of
the L1-E7 DNA construct (74 ± 2.19%) in vitro. Moreover, the polyepitope peptide generated in the
cells was detected as a clear band of ~ 50 kDa in western blotting.

Conclusion:
Regarding the favorable transfection efficiency of the designed L1-E7 multi-epitope
construct, in vivo validation study on its therapeutic potential is underway.
Catheter-directed Thrombolysis versus Systemic Anticoagulation for Submassive
Pulmonary Embolism: A Meta-Analysis
Authors: Siordia Juan Arturo , Kaur Amanpreet 
Published: June 2021

Background:
The optimal therapy for submassive pulmonary embolism remains in question.
The following meta-analysis compiles the current evidence comparing Catheter-Directed
Thrombolysis (CDT) versus Systemic Anticoagulation (SA).

Methods:
An electronic search through PubMed and Google scholar revealed studies comparing
CDT versus SA in terms of mortality and major bleeding events. Thirty-day, 90-day, and one-year
mortality results were analyzed.

Results:
Six studies were included in the meta-analysis. Thirty-day and one-year mortality were
less with CDT compared to SA (OR 0.27 [CI 0.11-0.67]; and OR 0.50 [CI 0.28-0.89]). Ninety-day
mortality was similar between the two methods (OR 0.57 [CI 0.17-1.92]). Compilation of all
studies reporting at least greater than 30-day mortality revealed less mortality with CDT (OR 0.51
[0.30-0.86]). Major bleeding was similar between the two treatments (OR 1.63 [CI 0.63-4.20]).

Conclusion:
CDT has less 30-day and 1-year mortality with equivalent rates of major bleeding
compared to SA for treatment of submassive pulmonary embolism.