bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigations on the fouling characteristic of humic acid and alginate sodium in capacitive deionization
Authors: Zhang Huizhong , Tian Jiayu , Hao Xiujuan , Liu Dongmei , Cui Fuyi 
Published: February 2021

Abstract
Capacitive deionization (CDI) has been investigated for brackish water desalination, selective removal of ions, and water softening. We used humic acid (HA) and alginate sodium (SA) to simulate different kinds of natural organic matter to investigate the fouling phenomena during CDI operation. Adsorption amount and energy efficiency were studied. Results showed that both SA and HA could decrease the removal of NaCl during CDI operation. There existed a slight decrease of energy consumption in SA solutions which was opposite to that in HA solutions. HA can compete with ions adsorbed by electrodes and attach to electrodes adhesively, resulting in co-ion repulsion. SA is not sensitive to electrical field and its fouling is not obvious. The amount of adsorbed Mg2+ would increase from 0.927 mg/g to 1.508 mg/g in ten cycles' operation and the increment of Ca2+ was from 1.885 mg/g to 2.878 mg/g in SA solutions. This increase of adsorption was due to the complexation between SA and cations. Simultaneously, energy consumption was decreased. In HA solutions, energy consumption of Mg2+ and Ca2+ adsorption increased. In ten cycles' operations, both HA and SA could reduce the efficiency of CDI operation. The types of organic substances are important factors in fouling of CDI electrodes.
GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma
Authors: Nanda Sitansu S. , Hossain Md I. , Ju Heongkyu , Papaefthymiou Georgia C. , Yi Dong K. 
Published: February 2021

Background:
Glycogen syntheis kinase (GSK-3) inhibitors are novel therapeutic agents
for treating various types of cancer, such as breast, lung, and gastric cancer. No pathological
changes have been found by the morphological examination of GSK-3.

Objectives:
This review describes recent procedures using GSK-3 inhibitors, primarily in treating
colon carcinoma. Furthermore, it also explains the mechanism of action of different GSK-3 inhibitors
in treating various types of cancers and proposes some additional mechanisms may be useful
for further research on GSK-3 inhibitors for cancers, including colon carcinoma.

Results:
The majority of the cancerous and pre-cancerous lesions are stimulated by the transformation
of membrane-bound arachidonic acid (AA) to eicosanoids, a transformation that promotes for
the viability, proliferation, and spread of cancer. GSK-3 inhibitors can reinstate hostility to tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) responsiveness in gastric adenocarcinoma
cells. GSK-3, the final enzyme in glycogen synthesis, is a serine/threonine kinase that phosphorylates
varied sequences that are more than a hundred in number, within proteins in an array of
heterogeneous pathways. It is an essential module of an exceptionally large number of cellular processes,
playing a fundamental role in many metabolic processes and diseases. Many patients diagnosed
with colon cancer achieve long-term remission with outstanding survival through the GSK-3
inhibitors.

Conclusion:
Prior to the extensive application of these proposed mechanisms of GSK-3 inhibitor,
further evaluation and clinical studies are needed. Only after the completion of appropriate clinical
studies and morphological examinations, would extensive application be apprpriate.
Expert Design and Optimization of Ethyl Cellulose-Poly (ε-Caprolactone) Blend Microparticles For Gastro-Retentive Floating Delivery of Metformin Hydrochloride
Authors: Salatin Sara , Jelvehgari Mitra 
Published: February 2021

Background:
Metformin Hydrochloride (MH) is an oral anti-hyperglycemic agent belonging
to the biguanide class of drugs.

Objective:
The present study involves the formulation and evaluation of gastro-retentive floating
microparticles containing MH as a model drug for the prolongation of absorption time.

Methods:
Three levels of a three-factor, Box-Behnken design were used to evaluate the critical formulation variables.
Microparticles were prepared using a water-in-oil-in-water double-emulsion solvent evaporation method and examined in
terms of production yield, particle size, entrapment efficiency, floating ability, morphology, FTIR (Fourier transform
infrared spectroscopy), and in vitro drug release.

Results:
The optimum conditions for preparing MH microparticles were predicted to be the content
of ethyl cellulose content (150 mg),poly (ε-caprolactone) (150 mg), and polyvinyl alcohol
(1%w/v).The optimized MH microparticles were found to be spherical with a mean size of 350.2
μm. Entrapment efficiency was 58.62% for microparticles. 63.94% of microparticles showed floating
properties. The FTIR analysis confirmed no chemical linkage between microparticle components.
in vitro release study showed a controlled release for up to 8h.

Conclusion:
These results demonstrated that MH microparticles, as a drug delivery system, may
be useful to achieve a controlled drug release profile suitable for oral administration and may help
to reduce the dose of the drug and to improve patient compliance.
Montelukast Efficacy for Improvement of Adult Acute Phase Mild-Moderate Asthma Attack: A Clinical Trial Study
Authors: Motamed Hassan , Verki Mohammadreza Maleki , Barzegari Hassan , Shariat Siamak , Hesam Saeed 
Published: February 2021

Background:
Asthma, an inflammatory disease of the respiratory tract, is one of the
most frequent causes of referral to emergency departments. The aim of this study is to evaluate the
efficacy of montelukast as a member of LTRAs for the improvement of pulmonary function and
clinical symptoms of patients with asthma.

Methods:
The study was conducted on 80 patients with acute mild- moderate asthma, divided randomly
into two groups of 40 subjects. A double-blind clinical trial was conducted on asthmatic patients
who encounter an acute phase asthma attack. The experimental group received two montelukast
5 mg chewable tablets at arrival, accompanied by standard mild-moderate asthma treatment
consisting of oxygen and nebulization with albuterol 2.5 mg and ipratropium bromide 0.5 mg
in 3 doses for 60 minutes. The control group received standard mild-moderate asthma treatment
plus placebo chewable tablets at the beginning without any leukotriene inhibitors. Pulmonary function
tests, hemodynamic variables and Borg Dyspnea Scale were evaluated and analyzed at 0, 30,
60, 90 and 150 minutes in both case and control groups.

Results:
No significant differences were observed between the case and the control group in terms
of PEFR and FEV1 measurements during the study at different time points [P > 0.05]. There were
no significant differences in terms of hemodynamic variables [blood pressure, pulse and respiration
rate, pressure of oxygen in arterial blood] and Borg Dyspnea Scale in both groups as well.

Conclusion:
The study findings showed that the montelukast administration in mild-moderate
acute asthma attack setting had no significant impact on pulmonary function tests and clinical
symptoms of the studied patients rather than standard asthma treatment.
Phase 1 Clinical Trials of Small Molecules: Evolution and State of the Art
Authors: Sramek John J. , Murphy Michael F. , Adcock Sherilyn , Stark Jeffrey G. , Cutler Neal R. 
Published: February 2021

Background:Phase 1 studies comprise the first exposure of a promising new chemical entity in healthy volunteers or, when appropriate, in patients. To assure a solid foundation for subsequent drug development, this first step must carefully assess the safety and tolerance of a new compound and often provide some indication of potential effect, so that a safe dose or dose range can be confidently selected for the initial Phase 2 efficacy study in the target patient population.Methods:This review was based on a literature search using both Google Scholar and PubMed, dated back to 1970, using search terms including “healthy volunteers”, “Phase 1”, and “normal volunteers”, and also based on the authors’ own experience conducting Phase 1 clinical trials. This paper reviews the history of Phase 1 studies of small molecules and their rapid evolution, focusing on the critical single and multiple dose studies, their designs, methodology, use of pharmacokinetic and pharmacodynamic modeling, application of potentially helpful biomarkers, study stopping criteria, and novel study designs.Results:We advocate for determining the safe dose range of a new compound by conducting careful dose escalation in a well-staffed inpatient setting, defining the maximally tolerated dose (MTD) by reaching the minimally intolerated dose (MID). The dose immediately below the MID is then defined as the MTD. This is best accomplished by using appropriately screened patients for the target indication, as patients in many CNS indications often tolerate doses differently than healthy non-patients. Biomarkers for safety and pharmacodynamic measures can also assist in further defining a safe and potentially effective dose range for subsequent clinical trial phases.Conclusion:Phase 1 studies can yield critical insights into the pharmacology of a new compound in man and offer perhaps the only development period in which the dose range can be safely and thoroughly explored. Phase 1 studies often contain multiple endpoint objectives, the reconciliation of which can present a dilemma for drug developers and study investigators alike, but which can crucially determine whether a compound can survive to the next step in the drug development process.
Management of Leaks Following Laparoscopic Sleeve Gastrectomy Using Specifically Designed Large Covered Metal Stents
Authors: Luigiano Carmelo , Di Leo Milena , Eusebi Leonardo Henry , Barabino Matteo , De Nicola Enrico , Giovenzana Marco , Opocher Enrico , Iabichino Giuseppe , Palamara Maria Angela , Giacobbe Giuseppa , Tortora Andrea , Virgilio Clara , Abenavoli Ludovico , Pallio Socrate , Consolo Pierluigi 
Published: February 2021

Background:
Leaks are the major complication associated with laparoscopic sleeve gastrectomy.

Objective:
The study aimed to assess the efficacy and safety of specifically designed large covered
metal stents for the management of post-laparoscopic sleeve gastrectomy leaks.

Methods:
Prospectively collected databases from three Italian Endoscopy Units were reviewed.
The primary outcome of the study was to evaluate the clinical success of stents placement, defined
as complete resolution of clinical and laboratory signs of sepsis with radiological evidence of leak
closure. Secondary outcomes were stent-related adverse events and mortality.

Results:
Twenty-one patients (67% females, mean age 45 years) were included in the study and a
total of 26 stents were placed. Technical success of stent placement was achieved in all cases
(100%). Clinical success was observed in 85.5% of patients. Stent-related adverse events occurred
in 9 patients (43%), with stent migration as the most frequent complication (33%). Adverse events
were more frequently observed in patients who had undergone bariatric surgery prior to laparoscopic
sleeve gastrectomy compared to patients without previous surgery (83% et al. 27%, p=0.018).

Conclusions:
The placement of specifically designed covered metal stents appears to be an effective
and safe therapeutic approach for post-laparoscopic sleeve gastrectomy leaks. Stent migration
can be a frequent complication.
Induced Fit Docking and Automated QSAR Studies Reveal the ER-α Inhibitory Activity of Cannabis sativa in Breast Cancer
Authors: Kikiowo Babatomiwa , Ogunleye Adewale J. , Iwaloye Opeyemi , Ijatuyi Taiwo T. , Adelakun Niyi S. , Alashe Wasiu O. 
Published: February 2021

Background:
Breast Cancer (BC), a common fatal disease and the deadliest cancer next
to lung cancer, is characterized by an abnormal growth of cells in the tissues of the breast. BC chemotherapy
is marked by targeting the activities of some receptors such as Estrogen Receptor alpha
(ER-α). At present, one of the most commonly used and approved marketed therapeutic drugs for
BC is tamoxifen. Despite the short-term success of tamoxifen usage, its long time treatment has
been associated with significant side effects. Therefore, there is a pressing need for the development
of novel anti-estrogens for the prevention and treatment of BC.

Objective:
In this study, we evaluate the inhibitory effect of Cannabis sativa phytoconstituents on
ER-α.

Methods:
Glide and induced fit docking followed by ADME, automated QSAR and binding free
energy (ΔGbind) studies were used to evaluate anti-breast cancer and ER-α inhibitory activity of
Cannabis sativa, which has been reported to be effective in inhibiting breast cancer cell proliferation.

Results:
Phyto-constituents of Cannabis sativa possess lower docking scores and good ΔGbind when
compared to that of tamoxifen. ADME and AutoQSAR studies revealed that our lead compounds
demonstrated the properties required to make them promising therapeutic agents.

Conclusion:
The results of this study suggest that naringenin, dihydroresveratrol, baicalein, apigenin
and cannabitriol could have relatively better inhibitory activity than tamoxifen and could be
a better and patent therapeutic candidate in the treatment of BC. Further research such as in vivo
and/or in vitro assays could be conducted to verify the ability of these compounds.
Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway
Authors: Chen Huiming , Zhao Junfeng , Jiang Ningning , Wang Zheng , Liu Chang 
Published: February 2021

Background:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a 5-
year survival rate of less than 10% because of the limited knowledge of tumor-promoting factors and their underlying
mechanism. Diabetes mellitus (DM) and hyperglycemia are risk factors for many cancers, including
PDAC, that modulate multiple downstream signaling pathways, such as the wingless/integrated (Wnt)/β--
catenin signaling pathway. However, whether hyperglycemia promotes PDAC initiation and progression by activating
the Wnt/β-catenin signaling pathway remains unclear.

Methods:
In this study, we used bioinformatics analysis and clinical specimen analysis to evaluate the activation
states of the Wnt/β-catenin signaling pathway. In addition, colony formation assays, Transwell assays and
wound-healing assays were used to evaluate the malignant biological behaviors of pancreatic cancer cells (PCs)
under hyperglycemic conditions. To describe the effects of hyperglycemia and the Wnt/β-catenin signaling pathway
on the initiation of PDAC, we used pancreatitis-driven pancreatic cancer initiation models in vivo and pancreatic
acinar cell 3-dimensional culture in vitro.

Results:
Wnt/β-catenin signaling pathway-related molecules were overexpressed in PDAC tissues/cells and correlated
with poor prognosis in PDAC patients. In addition, hyperglycemia exacerbated the abnormal activation
of β-catenin in PDAC and enhanced the malignant biological behaviors of PCs in a Wnt/β-catenin signaling
pathway-dependent manner. Indeed, hyperglycemia accelerated the formation of precancerous pancreatic lesions
by activating the Wnt/β-catenin signaling pathway in vivo and in vitro.

Conclusion:
Hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β-
catenin signaling pathway.
Identification of New Hsp90 Inhibitors: Structure Based Virtual Screening, Molecular Dynamic Simulation, Synthesis and Biological Evaluation
Authors: Abbasi Maryam , Amanlou Massoud , Aghaei Mahmoud , Hassanzadeh Farshid , Sadeghi-Aliabadi Hojjat 
Published: February 2021

Background:
Heat shock protein90 (Hsp90) is overexpressed in tumor cells, thus the inhibition of the Hsp90 ATPase activity would be a meaningfully an effective strategy in cancer therapy.

Objective:
The present work was aimed at four steps: designing new Hsp90 inhibitors as anti-cancer by a virtual screening study; synthesize designed compounds; biological evaluation of them and finally molecular dynamic (MD) simulations of best compounds.

Methods:
A virtual screening study was performed on a library (100 compounds) of the ZINC database with
benzimidazole scaffold; then an extracted compound and two derivatives were synthesized. The anti-proliferative
and ATPase inhibitory activities of these compounds were evaluated by MTT and ATPase inhibition assays,
respectively. The western blot analysis was performed to the evaluation of the expression level of Hsp70 and
Her2 proteins. Finally, 200 ns molecular dynamic simulation was carried out to confirm the stability of the
strongest synthesized compound in Hsp90 active site.

Results:
ZINC00173501 compound with an aminobenzimidazole scaffold was chosen by the virtual screening
study. ZINC00173501 compound and two of its derivatives were synthesized. ATPase inhibitory activity of
three synthesized compounds shown that ZINC00173501 compound was the most potent inhibitor (IC50= 8.6
μM) with the anti-proliferative activity 14.41 μM, 19.07 μM and more than 100 μM against MCF-7, HeLa and
HUVEC cell lines, respectively. The high level of Hsp70 expression and low level of Her2 expression confirmed
ZINC00173501 as an Hsp90 inhibitor. Finally, molecular dynamics simulation showed that ZINC00173501 was
stable in Hsp90 active site during 200 ns simulation.

Conclusion:
The biological evaluation results show that 2-aminobenzimidazole scaffold could be suggested as a lead for inhibition of Hsp90.
Statistical Review of the Suicide Attempts Rates Committed on Polish Railway Tracks between the Years 2013-2016
Authors: Makara-Studzinska Marta , Czabański Adam , Gronowska Katarzyna , Leszek Jerzy , Mikhaylenko Elizaveta V. , Avila-Rodriguez Marco F. , Muresanu Cristian , Somasundaram Siva G. , Kirkland Cecil E. , Aliev Gjumrakch 
Published: February 2021

Suicides on railway tracks are one of the most drastic ones. No research concerning this
phenomenon has been conducted to this date in Poland. This article focuses on the connection between
suicidal behaviors on Polish railway tracks and sociodemographic traits and presents risk factors.

Background:
The Incidence of suicide is spread across many European countries. Of these, Poland
ranks 22nd in terms of suicide attempts. This study aims to highlight the suicide attempts rates
on Polish railways lines and their main risk factors. Limited available of statistical data before
2013.

Methods:
Statistical review of the available Central Police headquarters database and analyses of
the influence of the risk factors on people’s awareness during the suicide attempts and their geographical
distribution in Poland during the years 2013-2016. The prevalence of railway suicides in
individual voivodeships (provinces) in Poland has been indicated in a 3D map.

Results:
There were 834 cases of railway suicide fatalities across the entire country. Of the total
suicide statistics by any means, 3.75% are railway related. The average known age of those committing
railway suicides were: 37.9 years for men (n = 627) and 34.6 for women (n = 155). In most
cases, suicides were committed by bachelors (54.3%). The largest group of people who committed
suicide had a primary level of education (42.0%). Among the suicides, a significant group are unemployed
(45.2%). Alcohol intoxication was found established responsible for a person’s low
awareness of his actions in 70.9% of cases. Almost 63.3% of people had a higher propensity for
suicidal ideation and behavior, resulting in their being treated for mental health issues.

Conclusion:
Alcohol intoxication, illegal narcotics and psychotropic medication are responsible for a
person’s lower awareness of his or her actions, in most of the cases of suicide on Polish railway lines.
Ticagrelor Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by
the Inhibition of TGF-β1/Smad3 and PI3K/AKT/mTOR Pathways
Authors: Wanas Hanaa , El Shereef Zeinab , Rashed Laila , Aboulhoda Basma Emad 
Published: February 2021

Background:
Idiopathic pulmonary fibrosis (IPF) is a serious disease with high mortality rate. Activation of transforming growth factor (TGF)-β1 production and signalling is considered the corner stone in the epithelial-mesenchymal transition (EMT) process. EMT plays a central role in development of fibrosis in many organs including the lungs. Activated platelets are an important source of TGF-β1 and play a pivotal role in EMT and fibrosis process. The antiplatelet, ticagrelor was previously found to inhibit the EMT in different types of cancer cells, but its ability to serve as an anti-pulmonary fibrosis (PF) agent was not previously investigated.

Objective:
In this study, we aim to investigate the potential ability of ticagrelor to ameliorate bleomycin-induced fibrosis in rats.

Methods:
PF was induced in rats by intratracheal BLM at a dose of 3 mg/kg. The effect of daily daily 20 mg/kg oral ticagrelor on different histological and biochemical parameters of fibrosis was investigated.

Results:
Our results revealed that ticagrelor can alleviate lung fibrosis. We found that ticagrelor inhibited TGF-β1 production and suppressed Smad3 activation and signaling pathway with subsequent inhibition of Slug and Snail. In addition, ticagrelor antagonized PI3K/AKT/mTOR pathway signaling. Moreover, ticagrelor inhibited the EMT that revealed by its ability to up-regulate the epithelial markers as E-cadherin (E-cad) and to decrease the expression of the mesenchymal markers as vimentin (VIM) and alpha-smooth muscle actin (α-SMA).

Conclusion:
Our results suggest that the P2Y12 inhibitor, ticagrelor may have a therapeutic potential in reducing the progression of PF.
Application of Artificial Intelligence in Drug Repurposing: A mini-review
Authors: Selvaraj Gurudeeban , Kaliamurthi Satyavani , Peslherbe Gilles H. , Wei Dong-Qing 
Published: February 2021

Background and aim:
This study aims at the advancement of extra-ordinary biomedical
data (genomics, proteomics, metabolomics, drug libraries, and patient care data), evolution of supercomputers,
and continuous development of new algorithms that lead to a generous revolution in artificial
intelligence (AI). Currently, many biotech and pharmaceutical companies made reasonable
investments in and have co-operation with AI companies increasing the chance of better healthcare
tools development, includes biomarker and drug target identification, designing a new class of drugs
and drug repurposing. Thus, the study is intended to project the pros and cons of AI in the application
of drug repositioning.

Methods:
Using the search term “AI” and “drug repurposing” the relevant literature retrieved and
reviewed from different sources includes PubMed, Google Scholar, and Scopus.

Results:
Drug discovery is a lengthy process; however, leveraging the AI approaches in drug repurposing
via quick virtual screening may enhance and speed-up the identification of potential drug
candidates against communicable and non-communicable diseases. Therefore, in this mini-review,
we have discussed different algorithms, tools and techniques, advantages, limitations on predicting
the target in repurposing a drug.

Conclusions:
AI technology in drug repurposing with the association of pharmacology can efficiently
identify drug candidates against pandemic diseases.