bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Novel 4-gene Diagnostic Model for Atrial Fibrillation
Risk Based on Integrated Analysis Across Independent Data Sets
Authors: Zhang Pei , Miao Qiang , Wang Xiao , Zhang Yong , Hou Yinglong 
Published: January 2021

Background:
Atrial fibrillation (AF) is the most common persistent arrhythmia and an important factor leading to cardiovascular morbidity and mortality. Several key genes and diagnostic markers have been discovered with the development of advanced modern molecular biology techniques, but the etiology and pathogenesis of AF remained unknown.

Methods:
In this study, three chip-seq data sets and a RNA-seq data set were integrated as a comprehensive network for pathway analysis of the biological functions of related genes in AF, hoping to provide a better understanding on the etiology and pathogenesis of AF.

Results:
Differential co-expression analysis identified 360 genes with specific expression in AF, and functional enrichment analysis further revealed that these genes were significantly correlated with focal expression (p <0.01), autophagy (p <0.01), and thyroid cancer. In addition, Af-specific protein-protein interaction (PPI) networks were constructed based on AF-specific expression genes. Network topology analysis identified PLEKHA7, YWHAQ, PPP1CB, WDR1, AKT1, IGF1R, CANX, MAPK1, SRPK2 and SRSF10 genes as hub genes of the networks, and they were considered as potential biomarkers of AF because they were found to participate in the development of AF through Oocyte meiosis and focal expression. Finally, a diagnostic model for AF established with support vector machine (SVM), demonstrated excellent predictive performance in internal and external data sets (AUC>0.9) and in different platform data sets (mean AUC>0.75).

Conclusion:
Finally, a diagnostic model for AF established, thus showing its potential in the early identification and prediction of AF.
Repositioning of RdRp Inhibitors Against HCV NS5B Polymerase
Utilizing Structure-Based Molecular Docking
Authors: Tarannum Heena , Nandi Sisir 
Published: January 2021

Objective:
Hepatitis C Virus (HCV) is very dreadful as it can attack an estimated 71 million people around the world. The World Health Organization (WHO) reported that every year about 399000 people die due to HCV caused by chronic cirrhosis and liver cancer globally. There are many drugs available for the treatment of HCV. But drug resistance and toxicity are major issues. The quest for potential drugs utilizing repositioning would be a very useful and economical method to combat the HCV.

Methods:
One of the most HCV targets is RNA dependent RNA polymerase (RdRp). The RdRp is common in HCV, Dengue virus (DENV), Zika virus (ZIKV), and Yellow fever virus (YFV) belonging to the same family of Flaviviridae. An attempt has been made in the present study to repositioning different DENV, ZIKV, and YFV RdRp inhibitors against HCV NS5B polymerase utilizing structure-based molecular docking which explores the affinity and mode of binding of these RdRp inhibitors.

Results:
Several 87 compounds having dengue, yellow fever and zika RdRp inhibitory activities have been taken into consideration for the screening of potential RdRp leads utilizing docking simulation which focuses the affinity and mode of binding of sofosbuvir diphosphate which is a standard HCV, RdRp inhibitor.

Conclusion:
It was found that the compounds 6 (N-sulfonylanthranilic acid derivative), 17 (R1479), 20 (DMB220), 23 (FD-83-KI26), 40 (CCG-7648), 50 (T-1106), 65 (mycophenolic acid), and 69 (DMB213) can produce docking score with the range of -7.602 to -8.971 Kcal/Mol having almost same mode of interaction as compared to the reference drug molecule. The drugs mentioned above can produce satisfactory affinity to bind the hepatitis C viral RdRp and thus may be used to treat the disease. Therefore, these predicted compounds may be potential leads for further testing of anti HCV activity and can be repurposed to combat HCV. The high throughput shotgun of drug repurposing utilizing structure-based docking simulation freeware would be a cost-effective way to screen the potential anti-HCV leads.
Post-Translational Modifications of BACE1 in Alzheimer's Disease
Authors: Wen Wen , Li Ping , Liu Panwang , Xu Shijun , Wang Fushun , Huang Jason H 
Published: January 2021

:
Beta-Amyloid Cleaving Enzyme1 (BACE1) is a monospecific enzyme for the key rate-limiting step in the synthesis of beta-amyloid(Aβ) from cleavage of amyloid precursor protein (APP), to form senile plaques and causes cognitive dysfunction in Alzheimer's disease (AD). Post-translation modifications of BACE1, such as acetylation, glycosylation, palmitoylation, phosphorylation, play a crucial role in the trafficking and maturation process of BACE1. The study of BACE1 is of great importance not only for understanding the formation of toxic Aβ but also for the development of an effective therapeutic target for the treatment of AD. This paper review recent advances in the studies about BACE1, with focuses being paid to the relationship of Aβ, BACE1 with post-translational regulation of BACE1. In addition, we specially reviewed studies about the compounds that can be used to affect post-translational regulation of BACE1 or regulate BACE1 in the literature, which can be used for subsequent research on whether BACE1 is a post-translationally modified drug.
Effect of Type 2 Diabetes Mellitus and Diabetic Medication on Pulmonary Function
Authors: Hammad Alaa M. , Al-Qerem Walid , Alassi Ameen , Hyassat Dana 
Published: January 2021

Background:
Type 2 diabetes mellitus (T2DM) is a chronic condition with an impairing
effect on multiple organs. Numerous respiratory disorders have been observed in patients with
T2DM. However, the effect of T2DM on pulmonary function is inconclusive.

Aims:
In this study, we investigated the effect of T2DM on respiratory function and the correlation
of glycemic control, diabetes duration and insulin intake.

Methods:
1500 patients were recruited for this study; 560 having T2DM for at least a year were included
in the final data, in addition to 540 healthy volunteers. Forced expiratory volume in one second
(FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% (FEF 25-75%), as
well as FEV1/FVC ratio values were measured.

Results:
A two-sample t-test showed that z-scores produced by Al-Qerem et al.’s equations for
FEV1, FVC, and FEF 25-75% were significantly lower for the T2DM group than the control group
(p < 0.01). FEV1/FVC ratio in the T2DM group was significantly higher (p < 0.01). Multiple linear
regression analysis found that glycemic control represented by HbA1c as well as disease duration
were negatively associated with the pulmonary function (p < 0.01). However, insulin intake was
found to have no significant correlation with pulmonary function.

Conclusion:
T2DM was linked to reduced pulmonary function and was consistent with a restrictive
ventilation pattern. HbA1c, as well as disease duration, were found to be independent risk factors
for reduced pulmonary function.
Association of Low BMI with Aortic Stiffness in Young Healthy Individuals
Authors: Patil Satish G. , Arakeri Sneha , Khode Vitthal 
Published: January 2021

Background:
Increased arterial stiffness is an independent predictor of cardiovascular morbidity and mortality.
It is not known whether low-BMI has any detrimental effect on arterial wall early during young age.

Objectives:
The present study was aimed to determine if low-BMI can increase arterial stiffness in young healthy
individuals.

Methods:
A cross-sectional study was conducted on young healthy subjects (n=100) with low-BMI <18.5 (n=50) and
normal-BMI: 18.5-24.9 (n=50) with age ranging between 15-23 years. BMI, heart rate, blood pressure and arterial
stiffness indices such as regional pulse wave velocity (PWV) between brachial-ankle (baPWV), carotid-femoral (cfPWV),
heart-ankle (haPWV), heart-brachial (hbPWV) were measured.

Results:
A significantly increased pulse pressure (p=0.014), baPWV (1059.2 ± 140.26 cm/s vs
994.66 ± 129.23 cm/s; p=0.019) and cfPWV (641.03 ± 113.83 cm/s vs 583.96 ± 120.48 cm/s;
p=0.017) was found in individuals with low BMI than normal BMI group. There was a significant
negative correlation between BMI and central arterial PWV. Further multiple regression analysis
showed that BMI was robustly associated with cf-PWV (p=0.004) and baPWV (p=0.016) even after
multiple adjustments with potential confounders using several models.

Conclusions:
These findings show a significant increased aortic stiffness and pulse pressure in low
BMI subjects compared to those with normal BMI. Low BMI was inversely and independently associated
with central arterial or aortic stiffness. These findings suggest that low BMI may be a risk
factor for aortic stiffness in young, healthy individuals.
Endothelial Dysfunction Induced by Cadmium and Mercury and its Relationship to Hypertension
Authors: Martins Airton C. , Santos Alessanda A.D. , Lopes Ana C.B.A. , Skalny Anatoly V. , Aschner Michael , Tinkov Alexey A. , Paoliello Monica M.B. 
Published: January 2021

:
Hypertension is an important public health concern that affects millions globally, leading
to a large number of morbidities and fatalities. The etiology of hypertension is complex and
multifactorial, and it involves environmental factors, including heavy metals. Cadmium and mercury
are toxic elements commonly found in the environment, contributing to hypertension. We
aimed to assess the role of cadmium and mercury-induced endothelial dysfunction in the development
of hypertension. A narrative review was carried out through database searches. In this review,
we discussed the critical roles of cadmium and mercury in the etiology of hypertension and provided
new insights into potential mechanisms of their effect, focusing primarily on endothelial dysfunction.
Although the mechanisms by which cadmium and mercury induce hypertension have yet
to be completely elucidated, evidence for both implicates impaired nitric oxide signaling in their hypertensive
etiology.
Validation of RP-HPLC Method for Determination of Omeprazole in Dissolution Media and Application to Study in-vitro Release from Solid- SNEDDS
Authors: Al-Nimry Suhair S. , Alkhamis Khouloud A. , Altaani Bashar M. 
Published: January 2021

Background:
Omeprazole has poor water solubility, is unstable in acidic solutions, and undergoes first pass metabolism which results in lowering its bioavailability. A solid Self-Nano Emulsifying Drug Delivery System (SNEDDS) was previously prepared to enhance its dissolution.

Objective:
Development and validation of a RP-HPLC method with UV detection for the determination of omeprazole in 0.1N HCl and in 0.01 M phosphate buffer (pH 7.4).

Methods:
Validation was according to the ICH Q2 (R1) guidelines in terms of linearity, accuracy and precision, lower limit of quantification, sensitivity, specificity, and robustness. The developed and validated method was used to study the in-vitro dissolution of the drug from the solid-SNEDDS, commercial products and of the unprocessed drug. The dissolution was studied in 500 ml of 0.1N HCl during the first 2 hours, and 900 mL of 0.01 M phosphate buffer (pH 7.4) during the last hour (37 ± 0.5 oC and 100 rpm).

Results:
The method was linear in the range 1-50 μg/ml, accurate and precise as indicated by the
ANOVA test. It was specific to the drug and the pharmaceutical excipients did not affect the determination
of its concentration. The method was robust to small changes in pH, composition, and
flow rate of the mobile phase. The dissolution rate of omeprazole from the Solid-SNEDDS was
faster than that from two commercial dosage forms and than the dissolution rate of the unprocessed
drug.

Conclusion:
The method met the acceptance criteria and was applied successfully in studying the rate of dissolution of the drug.
Comprehensive Study on the Chemical Profile and Anti-Tumor Activity of Secondary Metabolites Produced by Aspergillus niger
Authors: Chen Yung-Husan , Zhang Weiyun , Chen Pinghong , Yang Ching-Hsu , Wu Xiuna , Luo Lianzhong 
Published: January 2021

Objective:
Chemical investigation of the extract of sponge-derived fungus, Aspergillus niger,
was performed by liquid chromatography coupled with QExactive mass spectrometry for the first time.

Methods:
A total number of 444 constituents were detected, 288 of which were identified positively
or tentatively by the comprehensive utilization of accurate molecular weight and fragmentation
information acquired from quadrupole orbitrap mass spectrometry. The identified compounds
were divided into several types, namely, organic acid, alkaloid, saccharide, amino acid and cyclopeptide,
terpenoid, polyketone, phenylpropanoid and other types of compounds. Systematic diagnostic
ions and featured fragment patterns were summarized for each type, based on which 8 novel
compounds belonging to the same type were characterized.

Results:
This work provided a rapid approach for the research of micro constituents in a complex
analyte. Furthermore, the anti-tumor activity of the extract was evaluated on two different cell
lines-Bel-7402 and Hela-S3 in vitro. The tumor-inhibitory effect of the Aspergillus niger extract
was confirmed and may be mainly derived from its pro-apoptotic action. Moreover, the extract
exerted more significant cytotoxicity in Bel-7402 cells than Hela-S3 cells, indicative of its selectivity
on specific tumor cells.

Conclusion:
The evidence suggested that the Aspergillus niger extract may potentially serve as a
remedy for the prevention and therapy of hepatic and breast carcinoma.
Nanocrystal for Dermatological Application: A Comprehensive Review
Authors: Singh Bhawana , Upadhyay Prabhat Kumar , Kumar Manish 
Published: January 2021

Background:
Dermatological problemsimposethe biggest challenges to formulation scientists because
oftheinnate structure of skin that offers an excellent barrier to the topical delivery of drugs. Conventional topical delivery
systems are associated with low encapsulation efficiency, stability issue and skin irritation,and reduction in therapeutic
efficacy. In recent years nanocrystal has emerged as an attractive option for topical delivery due toanenhanced saturation
solubility, increased surface area, adhesiveness, absence of excipients, and small particle size.

Objective:
The present review providesacomprehensive account of topical delivery for management of various
dermatological problemsthrough nanocrystal technology. The review highlighted the aptness of drug nanocrystals for skin
delivery.The various methods used for fabrication of nanocrystalsand,the mechanism of skin penetration have been
included and dealt with in this review. The main emphasis has given break worth achieved in management of
dermatological problem through nanocrystal so far a plethora of literature and patent filled based on nanocrystal
technology for topical deliveryhave been included in this review.

Conclusion:
Nanocrystal based topical delivery system can bea promising approach for drugs with poor skin penetration
as these system possesstremendous potential to overcome skin barrier and deliver drugs at relevant concentrations atthe
local tissue level and avoid skin irritations.
Interactions between Ketamine and Magnesium for the Treatment of Pain: Current State of the Art
Authors: Vujović Katarina S. , Vučković Sonja , Stojanović Radan , Divac Nevena , Medić Branislava , Vujović Aleksandar , Srebro Dragana , Prostran Milica 
Published: January 2021

Background:
Over the past three decades, NMDA-receptor antagonists have been
shown to be efficient drugs for treating pain, particularly pain resistant to conventional analgesics.
Emphasis will be on the old-new drugs, ketamine and magnesium, and their combination as a novel
approach for treating chronic pain.

Methods:
The MEDLINE database was searched via PubMed for articles that were published up to
March 1, 2020, with the keywords ‘ketamine’, ‘magnesium’, and ‘pain’ (in the title/abstract).

Results:
Studies in animals, as well as humans, have shown that interactions of ketamine and magnesium
can be additive, antagonistic, and synergistic. These discrepancies might be due to differences
in magnesium and ketamine dosage, administration times, and the chronological order of
drug administration. Different kinds of pain can also be the source of divergent results.

Conclusion:
This review explains why studies performed with a combination of ketamine and magnesium
have given inconsistent results. Because of the lack of efficacy of drugs available for pain,
ketamine and magnesium in combination provide a novel therapeutic approach that needs to be
standardized with a suitable dosing regimen, including the chronological order of drug administration.
Bacteriophages as Therapeutic Agents: Alternatives to Antibiotics
Authors: Samir Safia 
Published: January 2021

:
Bacteriophages are bacterio-specific viruses that constitute the main
portion of the environment. Bacteriophages inject their genome into the targeted
bacterial cells and some of them can disrupt the metabolism of bacteria and
cause bacterial cell disintegration. The application of bacteriophages to kill bacteria
is known as bacteriophage therapy. Since bacteriophages target bacteria and
are strain-specific, every bacteriophage/bacterial host pair is unique. They are believed
to cause no harm to humans. An additional advantage of the strain-specific
nature of bacteriophages is that they do not disrupt the beneficial natural flora
in the body. Bacteriophage therapy in the West is not a recognized medicine at
this time, and no products are registered. Some clinicians are turning to bacteriophage
therapy for the treatment of antibiotic-resistant infections. Lack of adverse
effects makes bacteriophage therapy ideal for use. Funding research, media attention,
and the increased publication of articles helped in a widespread understanding
of its therapeutic potential. The first prerequisite for the use of bacteriophage
therapy is simply the availability of bacteriophages for treatment, which is often
complicated at this stage of bacteriophage production. This includes providing access
to all biologically active bacteriophages against the bacterial isolate of the
patient and meeting regulatory criteria of purity, traceability, and characterization.
A monophage preparation, which is a single bacteriophage, or a phage cocktail,
which consists of a number of combined bacteriophages against one or more
bacterial species may be used. Accordingly, the antibiotic resistance crisis
brought back bacteriophage therapy as a potential complementary or alternative
treatment. Bacteriophages are promising cheap antibacterials.
Naringenin Ameliorates Palmitic Acid-induced Fatty Acid Stress in Hepatocytes
Authors: Maity Subhajit , Chakrabarti Partha , Chakraborti Abhay Sankar 
Published: January 2021

Abstract:
Type 2 diabetes is strongly associated with the development of insulin resistance in
metabolically active tissues. Non-alcoholic fatty liver disease (NAFLD) is considered to be a manifestation
of hepatic insulin resistance. Saturated fatty acids such as palmitic acid (PA) induce insulin
resistance, which may be studied for therapeutic prevention by herbal agents. In the present
study, the role of naringenin, a bioflavonoid, is examined in PA-induced cytotoxicity in human hepatocellular
carcinoma (HepG2) cells. PA causes significant inflammation and apoptosis in these
cells primarily by inhibiting phosphorylation of Akt at serine 473 residue. Apoptosis assay, mitochondrial
transmembrane potential measurement and immunoblotting for protein expressions have
been used for demonstrating PA-induced abnormalities. Naringenin treatment effectively inhibits
the fatty acid-induced inflammation and cytotoxicity, along with improvement of insulin signalling.
Naringenin has a potential to prevent the fatty acid-induced stresses in hepatocytes, and
may be beneficial for improving hepatic insulin sensitivity and mitigating lipotoxicity.
Nigella sativa, as Preventive Strategy in COVID-19
Authors: Mathur Vaishali , Sharma Mahak 
Published: January 2021

:
The recent times have been difficult with the whole world fighting against the
COVID-19 pandemic. A herbal home-based spice can help people improve their immunity and
fight against this infection. Nigella sativa has been named as a prophetic spice as it has many therapeutic
effects. It is found to control diabetes, reduce high cholesterol levels, and serve as an anti-
oxidant, anti-cancer, anti-informatory, and immune booster. The compound thymoquinone can
be responsible for enhancing the immune system as it acts as an anti-oxidant and has an anti-inflammatory
property. Research has shown that to protect yourself from coronavirus, it is important to
avoid human contact and strengthen the immune system. This paper is a review of various studies
that prove that Nigella sativa can be beneficial in enhancing the immune system and thus fight
COVID-19.
Frequency and Inertia Response Effects, Capabilities, and Possibilities in
Renewable Energy Sources
Authors: Gomez Jishu Mary , Shanmugam Prabhakar Karthikeyan 
Published: January 2021

Background & Objectives:
The global power system is in a state of continuous evolution, incorporating more and more renewable energy systems. The converter-based systems are void of inherent inertia control behavior and are unable to curb minor frequency deviations. The traditional power system, on the other hand, is made up majorly of synchronous generators that have their inertia and governor response for frequency control. For improved inertial and primary frequency response, the existing frequency control methods need to be modified and an additional power reserve is to be maintained mandatorily for this purpose. Energy self-sufficient renewable distributed generator systems can be made possible through optimum active power control techniques. Also, when major global blackouts were analyzed for causes, solutions, and precautions, load shedding techniques were found to be a useful tool to prevent frequency collapse due to power imbalances. The pre-existing load shedding techniques were designed for traditional power systems and were tuned to eliminate low inertia generators as the first step to system stability restoration. To incorporate emerging energy possibilities, the changes in the mixed power system must be addressed and new frequency control capabilities of these systems must be researched.

Discussion:
In this paper, the power reserve control schemes that enable frequency regulation in the widely incorporated solar photovoltaic and wind turbine generating systems are discussed. Techniques for Under Frequency Load Shedding (UFLS) that can be effectively implemented in renewable energy enabled micro-grid environment for frequency regulation are also briefly discussed. The paper intends to study frequency control schemes and technologies that promote the development of self- sustaining micro-grids.

Conclusion:
The area of renewable energy research is fast emerging with immense scope for future developments. The comprehensive literature study confirms the possibilities of frequency and inertia response enhancement through optimum energy conservation and control of distributed energy systems.