bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, In silico Screening, Synthesis, Characterisation and DFT-based Electronic Properties of Dihydropyridine-based Molecule as L-type Calcium Channel Blocker
Authors: Karmakar Sujoy , Basak Hriday Kumar , Paswan Uttam , Saha Soumen , Mandal Samir Kumar , Chatterjee Abhik 
Published: December 2023

Background:
People of all nationalities and social classes are now affected by the
growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A
range of therapeutic compounds, on the other hand, are often used to handle hypertension

Objective:
The objectives of this study are first to design potential antihypertensive drugs
based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate
their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise
the best ligand.

Materials and Methods:
Due to the lack of 3D structures for human Cav1.2, the protein structure
was modelled using a homology modelling approach. A protein-ligand complex's strength and
binding interaction were investigated using molecular docking and molecular dynamics techniques.
DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2-
TZVP level of theory. The SwissADME website was used to study the ADMET properties.

Results:
In this study, a series of DHP compounds (19 compounds) were properly designed to
act as calcium channel blockers. Among these compounds, compound 16 showed excellent
binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised.
To assess the structural features of the synthesised molecule quantum chemical calculations
were performed.

Conclusion:
Based on molecular docking, molecular dynamics simulations, and drug-likeness
properties of compound 16 can be used as a potential calcium channel blocker.
Therapeutic Potential and Prospects of L-arginine in Various Diseases and
its Clinical Intervention
Authors: Giri Sushil , Varshney Krishna Kumar , Srivastava Rajnish 
Published: December 2023

Abstract:
The goal of this review is to explored the therapeutic application of L-Arginine (L-ARG)
against various pathological illnesses, such as Alzheimer’s disease (AD), Parkinson’s disease (PD),
cardiovascular disorder, mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes
(MELAS), sickle cell anemia, tumour, epilepsy, erectile dysfunction therapy (ED), gestational
hypertension (GH), and menopause issues. L-ARG is an important semi-essential alpha-amino acid
that serves as a natural precursor for the synthesis of nitric oxide (NO). It is generally synthesized
from proteinogenic amino acid proline through glutamine and glutamate. The degradation of L-ARG
is a complex process due to the expression of multiple enzymes in the form of a substrate. The metabolism
of L-ARG takes place in various multiple pathways, such as nitric oxide synthase, Arginine
glycine amidinotransferase, and Arginine decarboxylase which results in the production of a diverse
range of biochemical compounds, such as nitric oxide, polyamines, proline, glutamate, creanine, agmatine
homoarginine, and urea. NO is a highly diffusible free radicle with a regulatory function in
the heart and acts as an important vasodilator in intact endothelium. NO serves as an important neurotransmitter
in the brain and a mediator of host defense in the immune system. L-ARG is also needed
for ammonia detoxification, which is a very toxic chemical to the central nervous system. This review
article focuses on the relevance of L-ARG in the prevention and treatment of a variety of illnesses.
Pyrazoles as Anti-inflammatory and Analgesic Agents: In-vivo and In-silico Studies
Authors: Chahal Geeta , Monga Jyoti , Rani Isha , Saini Shubham , Devgun Manish , Husain Asif , Lal Khokra Sukhbir 
Published: December 2023

Background::
Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moi-ety as celecoxib, and lonazolac as COX-II inhibitors.

Aims::
We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately.

Methods::
Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies.

Results::
The ADME profile of synthesized compounds was found to be satisfactory.

Conclusion::
The synthesized compounds can serve as lead for further drug designing.
Evaluation of Quercetin's Bioenhancing Effect on Oral Pharmacokinetics of Rosuvastatin in Wistar Rats Using RP-HPLC Method
Authors: Bhimanwar Rachana S. , Kothapalli Lata P. , Khawshi Akshay 
Published: December 2023

Background:
The absolute oral bioavailability of rosuvastatin (RST), a secondgeneration
statin, is low i.e. 20% and only 10% is recovered as metabolite N-desmethy l rosuvistatin.
Since it is a hydrophilic statin, RST relies on the organic anion transporting polypeptide-
1B1 (OATP-1B1), as the key mechanism for active transport into hepatocytes. Quercetin
(QUE) being a bio enhancer and inhibitor of OATP1B1 can augment the bioavailability and
pharmacokinetics of RST.

Objective:
The present study includes the development of a simple and validated bioanalytical
Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the estimation
of RST and to study the effect of co-administration of QUE as a bio enhancer on its bioavailability.

Methods:
An analytical column of Kromasil 100, C18 (250 mm × 4.6 mm, 5 μm), was used for
chromatographic separationand acetonitrile (ACN): acetic acid buffer pH 3.0 adjusted with glacial
acetic acid (55:45 Vol. %) as mobile phase with flow rate 1.0 ml/min monitored at 242 nm.
The ACN: methanol (50:50 Vol. %) was employed as the final solvent for extraction. The developed
method has been successfully applied in a study on the pharmacokinetics of the drug RST
in rats after co-administration of QUE, which was carried out using non-compartmental analysis
in order to estimate the blood concentration of the drug.

Results:
The pharmacokinetics of RST was found to be altered significantly (highest concentration
of RST in the blood (Cmax) = 67.3 ng/ml to 122.2 ng/ml) (p < 0.001), area under curve
(AUC)0-t (p < 0.0001) and AUC0-inf (p =0.0005) when co-administered with QUE at 120 min
(tmax).

Conclusion:
The results are in accordance with the fact that QUE increases plasma levels in rats
through herb-drug interactions.
Nordihydroguaiaretic Acid Affects Undifferentiated and Differentiated
Neuroblastoma Cells Differently through Mechanisms that Impact on Cell
Viability
Authors: Ferrera Patricia , De la Fuente-Muñoz César Espino , Arias Clorinda 
Published: December 2023

Aim:
We aimed to investigate the mechanisms involved in the neurotoxic effects of
NDGA on differentiated and undifferentiated human neuroblastoma cells (MSN), assessing cell viability,
changes in the actin cytoskeleton, cell migration and the expression of the 5-LOX enzyme
and the inhibitor of cell cycle progression p21WAF1/CIP1.

Background:
High expression and activity of the lipoxygenase enzyme (LOX) have been detected
in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential
therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has
been extensively tested as an antiproliferative drug against diverse types of cancer cells.

Objective:
In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that
did not affect cell survival when they differentiated to a neuron-like phenotype and the potential
mechanisms involved in the anticancer properties.

Methods:
We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before
and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell
viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor
p21WAF1/CIP1 and 5-LOX.

Result:
We found that differentiated human neuroblastoma cells are more resistant to NDGA than
undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration,
changes in actin cytoskeleton morphology, induction of p21WAF1/CIP1 and decreased levels of the
5-LOX enzyme.

Conclusion:
Conclusion: This study provides new evidence regarding the potential use of NDGA to induce cell
death in human neuroblastoma.
Evaluating the Balancing Ability of Older Adults with Diabetes Mellitus
Using the Multi-directional Reach Test
Authors: Amput Patchareeya , Wongphon Sirima , Phrompao Patcharin 
Published: December 2023

Background:
The incidence of elderly people experiencing falls is currently increasing,
which results in serious medical issues, such as fear of falling, limited physical activity, disability,
and bone fractures, especially hip fractures. This study aimed to investigate balancing
ability using a multi-directional reach test (MDRT) in older adults with and without diabetes
mellitus.

Methods:
72 older adults with and without diabetes mellitus were recruited, and divided into two
groups, including older adults without diabetes mellitus (n= 36) and older adults with diabetes
mellitus (n= 36). All subjects completed all directions of the MDRT.

Results:
There were no significant differences in MDRT scores in all directions between the two
groups (p>0.05). Both groups achieved the highest MDRT scores in the forward direction. In
contrast, the two groups had the lowest scores of MDRT in a backward direction. Furthermore,
older adults with diabetes mellitus had lower MDRT scores in all directions than older adults
without diabetes mellitus.

Conclusion:
The current study indicated that MDRT could be used to investigate the ability of
balance in individuals with diabetes mellitus.
Autophagy Behavior in Endothelial Cell Regeneration
Authors: Marzoog Basheer Abdullah 
Published: December 2023

Abstract:
Autophagy plays a crucial role in maintaining endothelial cell homeostasis through the
turnover of intracellular components during stress conditions in a lysosomal-dependent manner.
The regeneration strategy involves several aspects, including autophagy. Autophagy is a catabolic
degenerative lysosomal-dependent degradation of intracellular components. Autophagy modifies
cellular and subcellular endothelial cell functions, including mitochondria stress, lysosomal
stress, and endoplasmic reticulum unfolded protein response. Activation of common signaling
pathways of autophagy and regeneration and enhancement of intracellular endothelial cell metabolism
serve as the bases for the induction of endothelial regeneration. Endothelial progenitor
cells include induced pluripotent stem cells (iPSC), embryonic stem cells, and somatic cells, such
as fibroblasts. Future strategies of endothelial cell regeneration involve the induction of autophagy
to minimize the metabolic degeneration of the endothelial cells and optimize the regeneration
outcomes.
Nicotinamide Mononucleotide in the Context of Myocardiocyte Longevity
Authors: Marzoog Basheer Abdullah 
Published: December 2023

Abstract:
Cellular and subcellular metabolic activities are crucial processes involved in the regulation
of intracellular homeostasis, including cellular and subcellular signaling pathways.
Dysregulation of intracellular regulation mechanisms is catastrophic and cumulates into cell
death. To overcome the issue of dysregulation of intracellular regulation mechanisms, the
preservation of subcellular and extracellular components is essential to maintain healthy cells
with increased longevity. Several physiopathological changes occur during cell ageing, one of
which is the dysregulation of intracellular physiology of the oxidative phosphorylation process.
Nicotinamide mononucleotide (NMN) remains in the debut of anti-aging therapeutic effect.
Aged myocardiocyte characterized by disrupted NMN and or its precursors or signaling pathways.
Simultaneously, several other pathophysiological occur that collectively impair intracellular
homeostasis. The NMN role in the antiaging effect remains unclear and several hypotheses
have been introduced into describing the mechanism and the potential outcomes from NMN exogenous
supply. Correction of the impaired intracellular homeostasis includes correction to the
NMN metabolism. Additionally, autophagy correction, which is the key element in the regulation
of intracellular intoxication, including oxidative stress, unfolding protein response, and other
degradation of intracellular metabolites. Several signaling pathways are involved in the regulation
mechanism of NMN effects on myocardiocyte health and further longevity. NMN protects
myocardiocytes from ischemic injury by reducing anabolism and, increasing catabolism and further
passing the myocardiocytes into dormant status. NMN applications include ischemic heart,
disease, and failed heart, as well as dilated cardiomyopathies. Cytosolic and mitochondrial
NADPH are independently functioning and regulating. Each of these plays a role in the determination
of the longevity of the myocardiocytes. NMN has a cornerstone in the functionality of
Sirtuins, which are an essential anti-senescent intrinsic molecule. The study aims to assess the
role of NMN in the longevity and antisenescent of myocardiocytes.
Residual Moisture Determination in Lyophilized Drug Product
Samples Using FT-NIR: A Comparison of Data Processing
Methods
Authors: Burtea R. , Upton T. , Jensen G.M. , Kim S. , Jalkanen K.J. 
Published: December 2023

Introduction:
Remdesivir for injection is a Gilead Sciences manufactured drug
product approved by the FDA to treat COVID-19. One of the critical attributes of this drug
product, which is lyophilized, is its water moisture content. The current method used to determine
the water content of remdesivir is the Karl Fischer titration method. The Karl
Fischer method is considered the gold standard for determining the residual water moisture
content of lyophilized drug products in the pharmaceutical industry. However, it is timeconsuming,
can at times be sensitive to difficult-to-control techniques, and most importantly
is destructive. The purpose of this study was to create a non-destructive residual water
moisture determination method using FT-NIR.

Methods:
Three FT-NIR methods were proposed as a non-destructive alternative to Karl
Fischer method: partial least squares regression, Beer’s law and area under the curve, and
Beer’s law and peak height. Results were statistically validated using RMSEC, RMSEP,
and R2, and the percent differences of predicted and accepted residual moisture values
were compared with external validation vials.

Results:
Results showed that the partial least squares regression method produced a 0.999
correlation coefficient and a 95% performance index score, highlighting the accuracy between
the actual Karl Fischer moisture values and the predicted FT-NIR moisture values.
The Beer’s law methods produced acceptable correlation coefficients of 0.996 and 0.982
for the peak area and height, respectively, but comparisons between the actual and predicted
values were not as closely matched as the partial least squares method.

Conclusion:
Our results support the use of a non-destructive partial least squares FT-NIRbased
moisture contest method, which is a useful alternative to the destructive Karl Fischer
method for determining residual water moisture of lyophilized drug products. Only an FTNIR
instrument and chemometric statistical software along with the appropriately
trained/educated analysts, and routine Karl Fischer instrumentation to measure/determine
moisture content values of either water spiked or lyo-thieved and normal lyophilized samples
are required.
Computer Modeling of the Thoracic Spine in Children: Assessment of the
Contribution of Rectified Kyphosis in the Possible Development of Adolescent
Idiopathic Scoliosis
Authors: Brandão Tainan Medeiros , Greco Marcelo , Aroeira Rozilene Maria Cota 
Published: December 2023

Introduction::
Adolescent Idiopathic Scoliosis is a spinal deformity. Its development
can be linked to hypokyphosis in the thoracic region.

Objective::
The present study proposed to investigate, through the finite element method, the biomechanics
of the immature thoracic spine segment T5-T10 in normal and rectified kyphosis under
axial load, flexion and extension.

Materials and Methods:
Intervertebral discs were modeled as hyperelastic material and vertebral
bone as elastic linear material. The bone was divided into trabecular and cortical regions. Furthermore,
discs were divided into nucleus pulposus and annulus fibrous.

Results::
Results indicate greater instability of rectified segments with larger strain and displacements,
mainly under extension.

Conclusion::
It was concluded that the rectified model is predisposed to the development of scoliosis
since higher deformations and displacements in this condition were observed, going in favor
of the assumption that this factor would be one of the causes of Adolescent Idiopathic Scoliosis.
A Recent Review on Nanocrystal Manufacturing Techniques with
Pharmaceutical Application
Authors: Rathod Prachiti S. , Narkhede Minal R. , Dongare Suraj L. 
Published: December 2023

Abstract:
This review article constitutes an introductory report on nanotechnology focusing on the various manufacturing approaches of nanocrystals. Nanocrystals are a solid form to tackle the issue identified with poor fluid solvency. Hence, it is a useful technique in improving the bioa-vailability of various poorly soluble drugs. On a broader way, nanocrystal technology is mainly classified as top-down technology, bottom-up technology and a combination of top-down and bottom-up technology. Top-down technology is based on the principle of breaking down a com-plex into small crystals. This process is executed by using high-pressure homogenization, laser ablation, media mills, ultrasound technology, vacuum dissolution, gas condensation and mechani-cal attrition. Bottom-up technology is based on the principle of preparation by gathering at-oms/molecules together. It is achieved by using precipitation, supercritical fluid, gel-gel technol-ogy, spray drying, hydrolysis, and condensation. Due to the diverse characteristics and properties of drugs, a combination of top-down and bottom-up techniques is best for manufacturing nano-crystals. Some of the promising technique includes nano-edge technology and smart-crystal tech-nology. These techniques are discussed in this review.
Structural Behavior of Steel Structure Retrofitted with Bracing Systems and Nonlinear Viscous Dampers
Authors: Amine Abid Mohamed , Afras Abderrachid , Abdelouafi El Ghoulbzouri 
Published: December 2023

Introduction:
A steel frame system becomes structurally less efficient
when subjected to large lateral loads such as a strong wind or a severe earthquake.
Several techniques could enhance the structural performance against these lateral
loads, including single diagonal and X-bracing systems, moment-resisting frames,
and viscous dampers.

Methods:
This study aimed to compare these techniques' ability to reduce the structure's
dynamic and static behavior when it faces lateral loads. The structure dynamic
behavior was discussed through its lateral displacement response computed from the
nonlinear dynamic analyses using different seismic and harmonic excitations. The
structure static behavior was investigated based on the demand capacity curves and
the plastic hinges response computed from the nonlinear static analyses (Pushover)
following FEMA P-1050-1 guidelines. In this paper, the viscous dampers were assumed
to have a nonlinear behavior (0<α<1) and the impact of the velocity exponent
α on their performance against the dynamic excitations was evaluated.

Results:
The results show that the X-braced frame performs better in reducing the
structure displacement response and plastic hinges performance levels formed in the
structural members than a single diagonal braced frame, followed by a momentresisting
frame. The results also indicate that the X-braced frame has a larger base
shear resistance capacity and a smaller deformation capacity than other structural
configurations.

Conclusion:
It was also concluded that, for the same damping coefficient, the performance
of nonlinear viscous dampers increased as the velocity exponent decreased.
Research on Internet of Medical Things: Systematic Review, Research
Trends and Challenges
Authors: Anand Dinesh , Kaur Avinash , Singh Manpreet 
Published: December 2023

Introduction:
Remote data exchange operations in healthcare are observed, consulted, monitored and treated by the Internet of Medical Things (IoMT). It is an extension of the
Internet of Things (IoT).

Method:
At the growing stage of IoT, IoMT is speedily drawing researchers’ interest due to its extensive use in healthcare systems. Smaller and lower-priced
wireless devices with various communication protocols have led to the formation of IoMT.
Healthcare data is exchanged through wireless communication with IoMT. The margining of
IoMT and healthcare can yield multiple benefits in terms of: better quality of life, care services
and developing solution/s at low cost. In this article, a systematic literature review has been
conducted on IoMT.

Results:
Authors have thoroughly investigated the different versions of
healthcare 1.0, 2.0, 3.0 and 4.0 as proposed by the healthcare industry. Furthermore, the taxonomy of IoMT has been designed and compared with existing surveys.

Conclusion:
This survey
is unique and stands different from the point of view of existing surveys. It supports the future
of IoMT researchers to bring new insight to their researches.
Schema Extraction in NoSQL Databases: A Systematic Literature Review
Authors: Belefqih Saad , Zellou Ahmed , Berquedich Mouna 
Published: December 2023

Introduction:
Nowadays, NoSQL databases have taken on an increasingly important
role in the storage of massive data within companies. Due to a common property called
schema-less, NoSQL databases offer great flexibility, particularly for the storage of data in different
formats. However, despite their success in data storage, schema-less databases are a major
obstacle in areas requiring precise knowledge of this schema, especially in the field of data
integration.

Method:
This study presents a Systematic Literature Review (SLR) to explore, evaluate, and
discuss relevant existing research and endeavors using novel schema extraction approaches.
Furthermore, we conducted this study using a well-defined methodology to examine and study
the problem of schema extraction from NoSQL databases.

Results:
Our research results highlight and emphasize the scheme extraction approaches and
provide knowledge to researchers and practitioners by proposing schema extraction approaches
and their limitations, which contributes to inventing new, more efficient approaches.

Conclusion:
In our future work, inspired by the recent advances in quantum computing and the
emergence of post-quantum cryptography (PQC), we aim to propose a schema extraction approach
that blends cutting-edge technologies with a strong focus on database security.