bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a method of multi-criteria evaluation under uncertainty
Authors: Sova Oleg , Shyshatskyi Andrii , Nalapko Oleksii , Marchenko Halyna , Trotsko Oleksandr , Symonenko Oleksandr , Merkotan Dmytro , Lyashenko Anna , Havryliuk Oksana , Velychko Vira 
Published: March 2022

The object of research is decision-making support systems. Local wars and armed conflicts of recent decades are characterized by high dynamics of operations (combat operations) and a significant amount of diverse information circulating in information systems. These features determine the search for new approaches to increase the efficiency of decision-making support systems, given their reliability. This article solves the problem of developing a method of multicriteria evaluation in conditions of uncertainty.
In the course of the research, the authors used the main provisions of the theory of artificial intelligence, automation theory, theory of complex technical systems and general scientific methods of cognition, namely analysis and synthesis. The proposed methodology was developed taking into account the practical experience of the authors of this work during the military conflicts of the last decade. The method of multicriteria evaluation is universal and can be used to assess the state of the objects of analysis of any architecture. The results of the research will be useful in:
– development of new control algorithms in decision-making support systems;
– substantiation of recommendations for improving the efficiency of operational management;
– analysis of analysis (monitoring) objects in the course of hostilities (operations);
– creation of perspective technologies to increase the efficiency of operational management;
– assessment of the adequacy, reliability, sensitivity of the scientific and methodological apparatus of operational management in decision-making support systems;
– development of new and improvement of existing management models.
Areas of further research will be aimed at developing a methodology for intelligent management in special-purpose decision-making support systems.
Photogallery. Erythema
Authors: Teplyuk Natalia P. , Lepekhova Anfisa A. 
Published: March 2022

Erythema is a disease characterized by the appearance of erythematous lesions on the skin caused by various factors. There is no generally accepted classification of erythema. Depending on the cause, there are erythema arising from exposure to exogenous factors (mechanical, biological, radiation and temperature), infections (viruses and bacteria), inflammation. Erythema can be part of a symptom complex or represent a separate nosology.
We publish a photo gallery dedicated to this issue.
Acute ischemic stroke thrombolysis- experience from a rural hospital in Kerala, India
Authors: Sanjeev V K , Thomas Ancil George 
Published: March 2022

Outcome assessment of thrombolysis with intravenous rt-PA in acute ischemic stroke.All patients with acute ischemic stroke patients who underwent IV thrombolysis with rt-PA from January 2019 to December 2021 were studied retrospectively. Clinical efficacy outcome was the favourable outcome on modified Rankin scale at 90 days defined as a score of ≤2. During our study period, a total of 50 patients with ischemic stroke thrombolysis underwent intravenous recombinant tissue plasminogen activator (rt‑PA). The study consisted of 33 males and 17 females with a mean age of 64.82 ( 12.21 standard deviation) years. The median time from onset of symptoms to IV rt-PA administration was 120 minutes (interquartile range 90 - 160). The mean door to needle time was 50.1 ( 21.32 SD) minutes. Favourable outcome (mRS score ≤2) was observed in 38 patients (76%) at three months’ follow-up. Poor outcome (mRS score &#62;2) was seen in the remaining 12 patients (24%).Large artery atherosclerosis had the most favourable outcome followed by small vessel occlusive stroke. Factors predicting favourable outcome in our study were age &#60;60 years (p = 0.03), female gender (p &#60; 0.001) and large vessel occlusion (p &#60; 0.001). Factors predicting poor outcome were hypertension (p &#60; 0.001), dyslipidemia (p = 0.01), prior stroke (p &#60; 0.001) and symptomatic haemorrhage (p = 0.02). Ischemic stroke patients can be thrombolysed in a safe and effective even in rural settings if proper institutional protocol is formulated and its implementation is ensured.
Perbandingan Efektivitas Sacubitril/Valsartan dengan Enalapril pada Pasien Gagal Jantung: Literature Review
Authors: Mumpun Jitayu Sekarininta , Maharani Laksmi , Endriastuti Nialiana Endah 
Published: March 2022

ARNI adalah terapi baru untuk pasien gagal jantung yang diakui pada 2016, yang merupakan kombinasi antara sacubitril (Neprilisin Inhibitor) dengan valsartan (ARB). Penelitian ini bertujuan untuk mengetahui perbandingan efektivitas pengunaaan sacubitril/valsartan dengan enalapril pada pasien gagal jantung melalui metode literature review. Pencarian artikel dilakukan pada database Cochrane dan PubMed. Kata kunci yang digunakan disusun berdasarkan PICO (heart failure, sacubitril/valsartan atau LCZ696, enalapril, dan efficacy or effectiveness). Kriteria inklusi pada penelitian yaitu artikel dalam bahasa inggris, full text dan bebas akses, publikasi 2010-2020, dan penelitian RCT. Kriteria eksklusi yaitu artikel review. Pencarian dilakukan pada 10 Juli hingga 23 Juli 2020 dan 20 Desember 2020. Didapatkan hasil pencarian 160 artikel, setelah dilakukan seleksi dan eligibilitas diperoleh 16 artikel sesuai kriteria inklusi sebagai arikel primer, dan 2 artikel ditambahkan sebagai artikel sekunder. Penelitian membuktikan bahwa sacubitril/valsartan menurunkan kejadian readmisi dan memiliki skor kualitas hidup lebih baik dibandingkan enalapril, serta dapat menurunkan resiko kematian. Berdasarkan penelitian primer PARADIGM-HF dan 15 artikel analisis lanjutan, diketahui bahwa sacubitril/valsartan lebih bermanfaat dibandingkan enalapril pada pasien gagal jantung.
Kata kunci: sacubitril/valsartan, enalapril, gagal jantung, literature review
In vitro and In silico Studies on Leonotis nepetifolia (L.) R. Br. Root Extract against Cancer Cells
Authors: Merecz-Sadowska Anna , Sitarek Przemysław , Śliwiński Tomasz , Zajdel Karolina , Malinowska Katarzyna , Zielińska-Bliźniewska Hanna , Kucharska Ewa , Zajdel Radosław 
Published: March 2022

Background:Leonotis nepetifolia (L.) R. Br. (Lamiaceae) is a shrub traditionally used to alleviate inflammatory conditions.Objective:The present study aimed at investigating the biological activity of methanolic nontrans-formed and transformed Rhizobium rhizogenes root extracts from L. nepetifolia against human melanoma cells.Methods:Cytotoxicity and genotoxicity properties, the impact on topoisomerase I activity, and proapoptotic activity were evaluated by the MTT test, comet assay, topoisomerase I assay, and fluorescence-activated cell sorting analysis. Moreover, the expressions of p53 were examined by qPCR and Western blot analysis. Docking studies were conducted to assess the potential interac-tions of the identified phytochemicals with the p53 binding protein Mdm-2, and computational analyses exhibited their antioxidant potential.Results:Both extracts showed cytotoxic potential against human melanoma cells, but generally the activity was more potent for transformed roots than untransformed (IC50 760 μg/mL and 980 μg/mL, respectively). A similar effect was revealed during the evaluation of genotoxic and proapoptotic properties. Moreover, the expression of p53 was also found to be increased after ex-tract treatment. The most dominant identified compounds in both extracts were as follows: (+)-catechin, p-coumaric acid, m-coumaric acid, and (+)-rosmarinic acid. Docking studies and compu-tational analysis showed that (+)-rosmarinic acid possesses the highest binding affinity to the p53 binding protein, Mdm-2, and exhibits the best antioxidant property from the most commonly iden-tified phytochemicals.Conclusion:Our findings revealed the potential of L. nepetifolia transformed root extract as a source of bioactive compounds with cytotoxic, genotoxic, and proapoptotic activity against human melanoma cells as well as antioxidant properties.
Nicotinamide Adenine Dinucleotide in the Development and Treatment of Cardiac Remodeling and Aging
Authors: Wang Fang , Pei Zuowei , Wang Kanglin , Wang Lei 
Published: March 2022

Background:
Recently, the beneficial effects of nicotinamide adenine dinucleotide (NAD+) as an antiaging and antioxidant molecule have become a focus of research. However, the mechanisms by which NAD+ supplementation affects the associated metabolites under physiological conditions remain unclear. Specifically, although NAD+ is involved in several processes that are dysregulated in cardiovascular diseases, some effects of NAD+ precursors and NAD+ on cardiac diseases have started to gain recognition only recently.

Objective:
To discuss the influence of NAD+ supplementation on adverse cardiac remodeling and aging.

Results:
Supplementation with NAD+ precursors or nicotinamide riboside, which enhances or supplements the NAD+ metabolome, might have a protective effect on the heart. NAD+ can alleviate chronic heart failure via a mitochondrial oxidation–reduction (redox) state mechanism. Furthermore, NAD+ replenishment can improve the life span of mice.

Conclusion:
NAD+ exerts considerable antiaging and antioxidant effects with promising therapeutic effects. However, its effect in humans and use as a dietary supplement need to be studied further.
Novel Compound, ND-17, Regulates the JAK/STAT, PI3K/AKT, and MAPK Pathways and Restrains Human T-lymphoid Leukemia Development
Authors: Ma Weina , Liu Yanhong , Lei Panpan , Zhu Man , Pan Xiaoyan 
Published: March 2022

Background:
T cell acute lymphoblastic leukemia (T-ALL) is an invasive hematological
malignant disorder of T cell progenitors. The Janus kinase-signal transducer and activator of transcription
(JAK-STAT) signaling pathway plays an important role in the development of T-ALL and in the
inhibition of the key molecule, JAK2, and could suppress T-ALL cell proliferation.

Objective:
The objective of this study was to investigate the in vitro anti-tumor effects of a novel nilotinib
derivative, ND-17, on cancer cell lines via its interactions with JAK2.

Methods:
The effects of ND-17 on cell proliferation and on cell cycle and apoptosis were evaluated
using the tetrazolium assay and flow cytometry, respectively. In addition, the ND-17/JAK2 binding
interactions were evaluated using surface plasmon resonance and western blot analyses.

Results:
ND-17 exerted the greatest inhibitory effects on T-ALL cells amongst all hematological cancer
cell lines tested. Flow cytometric analysis indicated that ND-17 blocked the cell cycle at the S
phase in T-ALL cells. Nilotinib did not significantly inhibit T-ALL cell growth or regulate the cell
cycle. Preliminary investigations revealed that the regulation of cyclin-dependent kinases/cyclins was
attributed to ND-17-induced cell cycle arrest. Furthermore, ND-17 could bind to JAK2 with strong
affinity, and more importantly, ND-17 bound to the ATP pocket of JAK2 in a manner similar to the
potent inhibitor. Thus, ND-17 treatment exhibited a prominent effect in inhibiting the phosphorylation
of JAK2 in T-ALL cells. An increase in the phosphorylation of JAK2 was observed in interleukin-6-
stimulated Jurkat cells, which was reversed by ND-17 treatment. Meanwhile, the combination of TG-
101348 and ND-17 led to further improvement in inhibiting the phosphorylation of JAK2. Moreover,
the transfection and knockdown of JAK2 altered the inhibitory effect of ND-17 on Jurkat cell viability.
In addition, ND-17 treatment suppressed the JAK/STAT, phosphatidylinositol-3-kinase/protein kinase
B/mechanistic target of rapamycin, and mitogen-activated protein kinase/extracellular signal-regulated
protein kinases 1 and 2 signaling pathways.

Conclusion:
These findings suggest that ND-17 could be a promising JAK2 inhibitor for the treatment
of T-ALL.
Electrochemical Cell-based Biosensors for Biomedical Applications
Authors: Özsoylu Dua , Wagner Torsten , Schöning Michael Josef 
Published: March 2022

Abstract:
Electrochemical cell-based biosensors have attracted increasing interest within the last 15 years, with a large number of reports generally dealing with the sensors’ sensitivity, selectivity, sta-bility, signal-to-noise ratio, spatiotemporal resolution, etc. However, only a few of them are now available as commercial products. In this review, technological advances, current challenges, and opportunities of electrochemical cell-based biosensors are presented. The article encompasses emerging studies on cell-based biological field-effect devices, cell-based impedimetric sensors, and cell-based microelectrode arrays, mainly focusing on the last five years (from 2016 to mid-2021). In addition, special attention lies in recent progress at the single-cellular level, including intracellular monitoring with high spatiotemporal resolution as well as integration into microfluidics for lab-on-a-chip applications. Moreover, a comprehensive discussion on challenges and future perspectives will address the future potential of electrochemical cell-based biosensors.
Rapid Analytical Method Development and Validation for the Simultaneous
Estimation of 5-Fluorouracil and Cannabidiol in Plasma and Lipid-based
Nanoformulations
Authors: Hasan Nazeer , Imran Mohammad , Jain Dhara , Shamim Athar , Beg Sarwar , Kesharwani Prashant , Jain Gaurav , Ahmad Farhan J. 
Published: March 2022

Background:
5-Fluorouracil (5-FU) is a well-established anticancer drug. Several studies have also demonstrated the anticancer potential of Cannabidiol (CBD) against various malignancies, including skin cancer. Reported synergistic effects of this combination fascinate researchers to consider this for the management of skin cancer.

Methods:
A simple and robust HPLC method for simultaneous estimation of 5-FU and CBD at its single wavelength (237 nm) was developed and validated. The separation of these compounds was performed on Waters® HPLC system with Hypersil™ C18 RP-column using methanol and water in gradient flow as mobile phase. The method could effectively quantify the nanogram levels of both analytes simultaneously in plasma spiked samples and various nanoformulations. The analytical performance of the proposed method was validated in terms of various parameters, such as linearity, ruggedness, specificity, and few others.

Results:
5-FU as well as CBD were successfully detected at 237 nm with retention time 1.4 and 1.84 minutes respectively. Calibration curves were found to be linear with R2 values of 0.985 and 0.984 for 5-FU and CBD respectively. The method was linear, precise, specific and robust. Additionally, prepared method successfully employed in determining concentration of both drugs in combitorial nanoformulations.

Conclusion:
The findings show that the developed method was simple, reliable, sensitive and economical. It could be employed for the simultaneous estimation of 5-FU and CBD in various in vitro and in vivo studies.
The Potential Role of the Serotonin Transporter as a Drug Target
against Parasitic Infections: A Scoping Review of the Literature
Authors: Montazeri Mahbobeh , Fakhar Mahdi , Keighobadi Masoud 
Published: March 2022

Background:
Several in vitro and in vivo biological activities of serotonin, 5-
hydroxytryptamine (5-HT), as a bioactive molecule, and its transporter (5-HT-Tr) were
evaluated in parasitic infections.

Objective:
Herein, the roles of 5-HT and 5-HTR in helminths and protozoan infections with
medical and veterinary importance are reviewed.

Methods:
We searched information in 4 main databases and reviewed published literature
about the serotonin transporter's role as a promising therapeutic target against pathogenic
parasitic infections between 2000 and 2021.

Results:
Based on recent investigations, 5-HT and 5-HT-Tr play various roles in parasite
infections, including biological function, metabolic activity, organism motility, parasite survival,
and immune response modulation. Moreover, some of the 5-HT-TR in Schistosoma
mansoni showed an excess of favorite substrates for biogenic amine 5-HT compared to their
mammalian hosts. Furthermore, the main neuronal protein related to the G protein-coupled
receptor (GPCR) was identified in S. mansoni and Echinococcus granulosus, playing main
roles in these parasites. In addition, 5-HT increased in toxoplasmosis, giardiasis, and Chagas
disease. On the other hand, in Plasmodium spp., different forms of targeted 5-HTR
stimulate Ca2+ release, intracellular inositol triphosphate (ITP), cAMP, and protein kinase A
(PKA) activity.

Conclusion:
This review summarized the several functional roles of the 5-HT and the importance
of the 5-HT-TR as a drug target with minimal harm to the host to fight against
helminths and protozoan infections. Hopefully, this review will shed light on research regarding
serotonin transporter-based therapies as a potential drug target soon.
A Novel Method for Predicting Essential Proteins by Integrating Multidimensional
Biological Attribute Information and Topological Properties
Authors: Lu Hanyu , Shang Chen , Zou Sai , Cheng Lihong , Yang Shikong , Wang Lei 
Published: March 2022

Background:
Essential proteins are indispensable to the maintenance of life activities and
play essential roles in the areas of synthetic biology. Identification of essential proteins by computational
methods has become a hot topic in recent years because of its efficiency.

Objective:
Identification of essential proteins is of important significance and practical use in the areas
of synthetic biology, drug targets, and human disease genes.

Method:
In this paper, a method called EOP (Edge clustering coefficient -Orthologous-Protein) is proposed
to infer potential essential proteins by combining Multidimensional Biological Attribute Information
of proteins with Topological Properties of the protein-protein interaction network.

Results:
The simulation results on the yeast protein interaction network show that the number of essential
proteins identified by this method is more than the number identified by the other 12 methods (DC,
IC, EC, SC, BC, CC, NC, LAC, PEC, CoEWC, POEM, DWE). Especially compared with DC (Degree
Centrality), the SN (sensitivity) is 9% higher, when the candidate protein is 1%, the recognition rate is
34% higher, when the candidate protein is 5%, 10%, 15%, 20%, 25% the recognition rate is 36%, 22%,
15%, 11%, 8% higher, respectively.

Conclusion:
Experimental results show that our method can achieve satisfactory prediction results,
which may provide references for future research.
Synthesis and Biological Evaluation of Coumarin Carboxamides as Selective and
Potent Inhibitors of Carbonic Anhydrases IX and XII
Authors: Thacker Pavitra S. , Mohammed Arifuddin , Supuran Claudiu T. , Tiwari Prerna L. , Goud Nerella S. , Srikanth Danaboina , Angeli Andrea 
Published: March 2022

Background:
Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the reversible hydration of carbon dioxide to
bicarbonate and proton. Inhibition of isoforms IX and XII could aid in the amelioration of cancer.

Objective:
A series of coumarin carboxamides (6a-j) were synthesized and were assayed against hCA isoforms I, II,
IX, and XII.

Methods:
Thin Layer Chromatography (TLC) analysis was done by utilizing Merck silica gel 60 F254 aluminum
plates. Stuart Digital Melting Point Apparatus (SMP 30) was used in determining the melting points of the compounds,
which are uncorrected. High Resolution Mass Spectra (HRMS) were determined by Agilent QTOF mass spectrometer
6540 series instrument and were performed using ESI techniques at 70eV.

Result:
All the compounds selectively inhibited isoforms IX and XII as against hCAs I and II. Compounds 6a-e exhibited
the best inhibitory profiles against hCA IX (Ki < 25 nM). The isoform hCA XII was effectively inhibited by all
compounds showing the Ki values less than 65 nM. The Compounds 6a, 6b, 6g, 6h, and 6j exhibited Ki values less
than 10 nM. The binding interactions of the most potent compounds, 6a and 6b, were investigated through docking
studies with hCAs IX and XII.

Conclusion:
These compounds may be utilized as useful starting points for the design and development of selective
and potent hCA IX and XII inhibitors.
Clinical Correlations of Lipid Profiles with the Age and Gender in the Coronary
Artery Disease Patients: A Study of 3878 CAD Patients from India
Authors: Mir Rashid , Elfaki Imadeldin , Frah Ehab A.M. , Alzahrani Khalid J. , Mir Mohammad Muzaffar , Banu Shaheena 
Published: March 2022

Background:
Cardiovascular diseases (CVDs) are crucial cause of death and
hospitalization all over the world including India. The CVDs including the coronary artery disease
(CAD) are developed by the interaction of genetic and environmental factors. Hyperlipidemia is a
traditional risk factor for CVD.The aim of this study was to study the clinical corrections of Lipid Profiles with the Age and Gender
in the Coronary Artery Disease Patients:

Methods:
In this study, we have investigated the effect of age and sex on in lipid profile in 3878
(1171 females and 2707 males) CAD patients from India.

Results:
The plasma TG was higher in males than in females regardless of the age. Results showed
that CAD female patients had significantly increased HDL-C than their aged matched males.
Moreover, the plasma TC and LDL-C were significantly higher in males than females until age 40
years. Then after the age of 40 years, TC and LDL-C become significantly higher in females than
in males. In addition, we found that more than 85% of CAD cases were <55 years old, and about
30% of CAD cases had normal lipid profile.

Conclusion:
We conclude that elderly females are at a greater risk for CAD than males. Moreover,
there were no significant differences in CVDs causes between nonelderly and elderly females. In
addition, a higher percentage of cases were premature CAD, and 30% of CAD may be caused by
loci that are not related to lipid metabolism.
Serum Cytokine Levels of Systemic Lupus Erythematosus Patients in the
Presence of Concomitant Cardiovascular Diseases
Authors: Melamud Mark M. , Ermakov Evgeny A. , Boiko Anastasiia S. , Parshukova Daria A. , Sizikov Alexey E. , Ivanova Svetlana A. , Nevinsky Georgy A. , Buneva Valentina N. 
Published: March 2022

Background:
Systemic lupus erythematosus (SLE) is known to be associated with an increased risk of cardiovascular diseases (CVD). SLE patients suffer from CVD 3.5 times more often than healthy people. Cytokine-mediated inflammation is actively involved in the development of cardiovascular pathology.

Objective:
Here, we analyzed serum levels of nine cytokines of steroids-treated SLE patients depending on the presence of concomitant CVD.

Methods:
The levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, IL-21, tumor necrosis factor α (TNFα), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were analyzed using multiplex immunoassay.

Results:
In the total group of SLE patients (n=29), the concentrations of IL-6 and IL-10 were higher, and the APRIL level decreased compared to healthy donors (n=39, p<0.05). The same changes were observed in the group of patients without CVD (n=15); the levels of IL-6 and IL-10 were found to be increased, and the level of APRIL was lower than in healthy individuals (p<0.05). In the group of SLE patients with CVD (n=14), the concentrations of IL-4, IL-6, IL-10, and TNFα were found to be increased (p<0.05). Interestingly, the levels of TNFα and BAFF in SLE patients with CVD were higher than in patients without cardiovascular pathology. Thus, TNFα and BAFF levels were significantly altered in SLE with concomitant CVD compared to SLE without CVD.

Conclusion:
These findings suggest that cytokine profiles in SLE with concomitant CVD and SLE without CVD are different, which should be considered in further research with large samples.