bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Demand for Red Blood Cells Using Artificial Intelligence Methods
Authors: GÖKLER Seda Hatice , BORAN Semra
Published: May 2022

Blood is a vital product with limited resources, available only from volunteers. For this reason, the blood components to be sent from the blood bank to the transfusion centers (hospitals) should be accurately predicted. There are many variables that affect the demand prediction. In this study, fifteen different qualitative and quantitative variables were determined. Artificial intelligence (AI) methods are used because the prediction has nonlinear, complex and uncertain relationships and thus it is also difficult to mathematically express on relationship in between input and output variables. AI methods have the feature of predicting the information that is not given or that may occur in the future by learning the past data. In the study, AI methods such as Decision Tree (DT), Support Vector Machine (SVM), Artificial Neural Network (ANN) and Deep Learning (DL) were applied to blood bank providing blood supply to public and private hospitals operating in four provinces. The data obtained from the prediction results of AI methods were compared with performance criteria (MAPE, MSE, MAE RMSE and R2) and values of overprediction, underprediction, minimum and maximum deviation. The weekly average over predictions are calculated as 9.69, 5.29, 8.45, and 15.65 and weekly average underpredictions as 17.57, 3.03, 3.94, and 14.69 for DT, SVM, ANN, and DL methods, respectively. SVM method was determined as giving the best prediction values. Therefore, it is envisaged that the blood component demand prediction can be calculated using the SVM method.
Evaluation of the least square support vector machines (LS-SVM) to predict longitudinal dispersion coefficient
Authors: Mohammadi Ghaleni Mehdi , Akbari Mahmood , Sharafi Saeed , Nahvinia Mohammad Javad
Published: May 2022

In this study, the least square support vector machines (LS-SVM) method was used to predict the longitudinal dispersion coefficient (DL) in natural streams in comparison with the empirical equations in various datasets. To do this, three datasets of field data including hydraulic and geometrical characteristics of different rivers, with various statistical characteristics, were applied to evaluate the performance of LS-SVM and 15 empirical equations. The LS-SVM was evaluated and compared with developed empirical equations using statistical indices of root mean square error (RMSE), standard error (SE), mean bias error (MBE), discrepancy ratio (DR), Nash-Sutcliffe efficiency (NSE) and coefficient of determination (R2). The results demonstrated that LS-SVM method has a high capability to predict the DL in different datasets with RMSE = 58–82 m2 s−1, SE = 24–39 m2 s−1, MBE = −1.95–2.6 m2 s−1, DR = 0.08–0.13, R2 = 0.76–0.88, and NSE = 0.75–0.87 as compared with previous empirical equations. It can be concluded that the proposed LS-SVM model can be successfully applied to predict the DL for a wide range of river characteristics.
Antibody Responses and CNS Pathophysiology of Mucormycosis in
Chronic SARS Cov-2 Infection: Current Therapies Against Mucormycosis
Authors: Beeraka Narasimha M. , Liu Junqi , Sukocheva Olga , Sinelnikov Mikhail Y. , Fan Ruitai
Published: May 2022

The incidence rate of opportunistic secondary infections through invasive fungi
has been observed to be 14.5% to 27% in the SARS CoV pandemic during the year
2003. However, the incidence of SARS CoV-2 is accompanied by a substantial rise in secondary
opportunistic infections like mucormycosis (black fungus), mainly in the immunocompromised
individuals and diabetic patients taking steroids. Substantial rates of
COVID-19 cases with mucormycosis were reported in India and other parts of the world.
Previous research reports delineated the ability of Mucorales to invade the various tissues
like lungs, brain, and sinus through the GRP78, and subsequently, this infection could invoke
crusting, edema, and necrosis of the brain parenchyma, ptosis, proptosis, and vision
loss due to intraorbital and intracranial complications. Similarities of these pathophysiological
complications with already existing diseases are causing clinicians to face several
challenges in order to diagnose and treat this disease effectively at the early stage. This
minireview depicts the mucormycosis-induced immune and pathophysiological alterations
in COVID-19 patients comorbid with diabetes and immunosuppression and also reported
the various clinical manifestations, the therapeutic modalities, and the failures of
anti-fungal vaccines. Therefore, the emerging mucormycosis in COVID-19 patients
needs rapid investigation and selective optimization of the effective therapeutic modalities,
including antifungal vaccines, to minimize the mortality rate.
Structure-Activity Relationship Insight of Naturally Occurring Bioactive
Molecules and Their Derivatives Against Non-Small Cell Lung
Cancer: A Comprehensive Review
Authors: Das Subham , Roy Shubham , Rahaman Seikh Batin , Akbar Saleem , Ahmed Bahar , Halder Debojyoti , Ramachandran Anu Kunnath , Joseph Alex
Published: May 2022

Background:

Non-small cell lung cancer (NSCLC) is a deadly disease that affects millions
globally and its treatment includes surgery, chemotherapy, and radiotherapy. Chemotherapy and
radiotherapy have many disadvantages, which include potential harmful side effects. Due to the widespread
use of drugs in lung cancer, drug treatment becomes challenging due to multidrug resistance
and adverse reactions. According to the recent findings, natural products (NPs) and their derivatives
are being used to inhibit and suppress cancer cells.

Objective:

Our objective is to highlight the importance of phytochemicals for treating NSCLC by focusing
on the structural features essential for the desired activity with fewer side effects compared to
synthetic molecules.

Method:

This review incorporated data from the most recent literature, including in vitro, in vivo,
nanoformulation-based recent advancements, and clinical trials, as well as the structure-activity relationship
(SAR), described for a variety of possible natural bioactive molecules in the treatment of NSCLC.

Results:

The analysis of data from recent in vitro, in vivo studies and ongoing clinical trials are highlighted.
The SAR studies of potential NPs signify the presence of several common structural features
that can be used to guide future drug design and development.

Conclusion:

The role of NPs in the battle against NSCLC can be effective, as evidenced by their
structural diversity and affinity toward various molecular targets. The main purpose of the review is
to gather information about NPs used in the treatment of NSCLC.
Role of Chemokines in the Pathogenesis of Visceral Leishmaniasis
Authors: Kumar Ramesh , Bhatia Madhav , Pai Kalpana
Published: May 2022

Visceral leishmaniasis (VL; also known as kala-azar), caused by the protozoan
parasite Leishmania donovani, is characterized by the inability of the host to generate an
effective immune response. The manifestations of the disease depend on the involvement
of various immune components such as activation of macrophages, cell mediated immunity,
secretion of cytokines and chemokines, etc. Macrophages are the final host cells for
Leishmania parasites to multiply, and they are the key to a controlled or aggravated response
that leads to clinical symptoms. The two most common macrophage phenotypes
are M1 and M2. The pro-inflammatory microenvironment (mainly by IL-1β, IL-6, IL-12,
IL-23, and TNF-α cytokines) and tissue injury driven by classically activated
macrophages (M1-like) and wound healing driven by alternatively activated
macrophages (M2-like) in an anti-inflammatory environment (mainly by IL-10, TGF-β,
chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). Moreover, on polarized
Th cells, chemokine receptors are expressed differently. Typically, CXCR3 and CCR5
are preferentially expressed on polarized Th1 cells, whereas CCR3, CCR4, and CCR8
have been associated with the Th2 phenotype. Further, the ability of the host to produce a
cell-mediated immune response capable of regulating and/or eliminating the parasite is
critical in the fight against the disease. Here, we review the interactions between parasites
and chemokines and chemokine receptors in the pathogenesis of VL.
(-)-Epigallocatechin Gallate Attenuates Spinal Motoneuron Death Induced by Brachial Plexus Root Avulsion in Rats
Authors: Lu Fatai , Zhang Guodong , Zhu Yingkang , Liu Zunpeng
Published: May 2022

Background:

Recent studies have indicated that epigallocatechin gallate
(EGCG) benefits a variety of neurological insults. This study was performed to investigate
the neuroprotective effect of EGCG after brachial plexus root avulsion in SD rats.

Methods:

One hundred twenty SD rats were randomized into the following three groups:
an EGCG group, an Avulsion group, and a Sham group. There were 40 rats in each
group. EGCG (100 mg/kg, i.p.) or normal saline was administered to rats immediately
following the injuries. The treatment was continued from day 1 to day 7, and the animals
were sacrificed on days 3, 7, 14, and 28 post-surgery for the harvesting of spinal cord
samples for Nissl staining, immunohistochemistry (caspase-3, p-JNK, p-c-Jun), and western
blot analysis (p-JNK, JNK, p-c-Jun, c-Jun).

Results:

EGCG treatment caused significant increases in the percentage of surviving motoneurons
on days 14 and 28 (p<0.05) compared to the control animals. On days 3 and 7
after avulsion, the numbers of caspase-3-positive motoneurons in the EGCG-treated animals
were significantly fewer than in the control animals (p<0.05). The numbers of p-
JNK-positive motoneurons and the ratio of p-JNK/JNK were no significant differences
between the Avulsion group and the EGCG-treated group after injury at any time point.
The numbers of p-c-Jun-positive motoneurons and the ratio of p-c-Jun/c-Jun were significantly
lower in the EGCG-treated group compared with the Avulsion group at 3d and 7d
after injury (p<0.05).

Conclusions:

Our results indicated that motoneurons were protected by EGCG against the
cell death induced by brachial plexus root avulsion, and this effect was correlated with inhibiting
c-Jun phosphorylation.
Long Non-coding RNA SNHG16 Facilitates Esophageal Cancer Cell
Proliferation and Self-renewal through the microRNA-802/PTCH1
Axis
Authors: Zhang Luquan , Liang Hao , Zhang Jinfeng , Yang Yingnan , Ling Xiaodong , Jiang Hao
Published: May 2022

Objective:

This research sought to explore the effect and mechanism of long
non-coding RNA SNHG16 on esophageal cancer (EC) cell proliferation and self-renewal.

Methods:

SNHG16 expression was measured in EC9706 and KYSE150 cells. EC9706
and KYSE150 cells were transfected with Lenti-SNHG16, sh-SNHG16, Lenti-protein
patched homolog 1 (PTCH1), miR-802 mimic, or miR-802 inhibitor. Flow cytometry
was used to sort cancer stem cells (CSCs) in EC9706 and KYSE150 cells. Cell proliferation
in EC cells was measured, in addition to colony and tumorsphere numbers. The possible
interactions among SNHG16, PTCH1, and miR-802 were identified by dual luciferase
reporter and RNA pull-down assays. The expression of the genes in the Hedgehog
pathway was detected. Nude mice were injected with SNHG16-silenced EC9706
cells to observe the tumorigenicity of EC9706 cells.

Results:

Upregulated SNHG16 expression was found in CSCs, whose expression was decreased
during the differentiation of CSCs. SNHG16 or PTCH1 overexpression or
miR-802 inhibition promoted the proliferation, colony formation, and tumorsphere formation
of EC9706 and KYSE150 cells as well as SOX2, OCT4, Bmi-1, and PTCH1 expression.
Consistently, SNHG16 knockdown or miR-802 overexpression inhibited EC progression.
Moreover, SNHG16 and PTCH1 were competitively bound to miR-802, and
SNHG16 orchestrated the miR-802/PTCH1 axis to activate the Hedgehog pathway. SNHG16
silencing repressed the tumorigenicity of EC9706 in nude mice.

Conclusion:

Conclusively, SNHG16 acts as a sponge of miR-802 to upregulate PTCH1
and activate the Hedgehog pathway, thus promoting EC cell proliferation and self-renewal.
Designer Benzodiazepines’ Activity on Opioid Receptors: A Docking Study
Authors: Catalani Valeria , Botha Michelle , Corkery John Martin , Guirguis Amira , Vento Alessandro , Schifano Fabrizio
Published: May 2022

Background:

Previous studies have reported that benzodiazepines (BZDs) seem to enhance euphoric and reinforcing properties of opioids in opioid users so that a direct effect on opioid receptors has been postulated together with possible synergistic induction of severe side-effects due to their co-use. This is particularly worrisome given the appearance on the market of designer benzodiazepines (DBZDs), whose activity/toxicity profiles are scarcely known.

Objectives:

This study aimed to evaluate, through computational studies, the binding affinity (or lack thereof) of 101 DBZDs identified online on the kappa, mu, and delta opioid receptors (K, M, DOR); and to assess whether their mechanism of action could include activity on t of the latter

Methods:

MOE® was used for the computational studies. Pharmacophore mapping based on strong opioids agonist binder’s 3D chemical features was used to filter the DBZDs. Resultant DBZDs were docked into the crystallised 3D active conformation of KOR (PDB6B73), DOR (PDB6PT3) and MOR (PDB5C1M). Co-crystallised ligands and four strong agonists were used as reference compounds. A score (S, Kcal/mol) representative of the predicted binding affinity, and a description of ligand interactions were obtained from MOE® .

Results:

The docking results, filtered for S < -8.0 and interaction with the aspartic acid residue, identified five DBZDS as putative OR binders across the three ORs: ciclotizolam, fluloprazolam, JQ1, Ro 48-6791, Ro 48-8684.

Conclusion:

It may be inferred that at least some DBZDs may have the potential to activate opioid receptors. This could mediate/increase their anxiolytic, analgesic, and addiction potentials, as well as worsen the side-effects associated with opioid co-use.
A Critical Review on Recent Advances in Base-Assisted Smiles Rearrangement
Authors: Kumar K. Shiva , Gugulothu Kishan , Reddy Sabbasani R. , Venkateswarlu Katta
Published: May 2022

Rearrangement reactions of organic substrates is a versatile and sustainable tool in
the construction of complex and bioactive organics by virtue of their atom-economic, stepeconomic
and waste-, time- as well as energy-minimizing attributes. The X → C (or Y) aryl
rearrangement reaction through an intramolecular nucleophilic aromatic substitution is referred
to as Smiles rearrangement. The Smiles rearrangement enables access to complex natural products
and is a useful tool to obtain various types of compounds with diversified applications,
which have undergone a potent revival in recent years. In this review, we summarize the recent
reports on Smiles rearrangement and most of them require a base. A few examples of the reported
base-free Smiles rearrangements were also reviewed to provide comprehensive information
on the selected topic. The literature review covers the published work on Smiles rearrangement
reaction since 2017. The published work in these articles include simple Smiles, Truce-Smiles, radical
Smiles, Ugi-Smiles, light-assisted Smiles, Dohmori-Smiles, electrochemical Smiles and phospha-Smiles rearrangement
reactions for the construction of a variety of organic compounds including acyclic, heterocyclic, carbocyclic
and polycyclic compounds. The formation of organic compounds with unusual ring sizes has also been discussed in
the published work. Several domono/sequential reactions were also observed in these reports involving Smiles rearrangement
as a crucial step. The selected examples demonstrate the synthetic power of this approach and hence this
review may be highly useful to the synthetic chemists aimed to use Smiles rearrangement in their plan.
Dracaenone, a Novel Type of Homoisoflavone: Natural Source, Biological Activity
and Chemical Synthesis
Authors: Li Mei-Mei , Lu Jun , Deng Yun
Published: May 2022

The discovery and synthesis of natural products, especially those possessing novel
scaffolds, are crucial to the development of new drugs. Dracaenones are part of homoisoflavone
natural products, owning a complex spiro-bridged polycyclic structure bearing benzylic
quaternary carbon centers, and some of them reveal considerable biological activity. There
have been continuous studies on these compounds due to the rare structure and important biological
properties. However, a systematic summary and analysis for dracaenone is lacking.
This review aims to generally summarize the natural source, synthetic strategies and biological
activities of dracaenones, moreover, the limitations, challenges, and future prospects were
discussed, wishing to provide references for the follow-up study of compounds with similar
skeleton.
FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell
Carcinoma
Authors: Liu Jianguo , Guan Xiaoyan , Liao Chengcheng , Wang Qian , An Jiaxing , Wang Hui , Xiao Linlin , Long Qian , Zhao Hongbo
Published: May 2022

Background:

Although head and neck squamous cell carcinoma (HNSCC) is a common
malignancy, the molecular biology landscape underlying its occurrence and development remains
poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four
family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been
previously reported to be closely associated with various human malignancies.

Methods:

Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive
Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible
biological function and key pathways regulated by the FAM3 family in HNSCC were probed.

Results:

High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and
energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and
be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC
were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the
finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration,
inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway.
FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased
OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression
was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell
infiltration. FAM3C expression was also positively correlated with the expression of epithelial and
mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote
the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance
factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor
immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the
FAM3 gene family were correlated with the overall survival rate of HNSCC.

Conclusion:

The FAM3 family may be applied as a biomarker and potential therapeutic target for
HNSCC.
Cannabinoids as Potential Molecules for Addiction Disorders
Authors: Martín Giménez Virna Margarita , Mazzei Luciana , Sanz Raúl , Manucha Walter
Published: May 2022

Background:

Addictions are a group of chronic and recurrent diseases of the brain characterized
by a pathological search for reward or relief through the use of a substance or other action. This
situation implies an inability to control behavior, difficulty in permanent abstinence, a compelling desire
to consume, decreased recognition of significant problems caused by behavior and interpersonal
relationships, and a dysfunctional emotional response. The result is a decrease in the quality of life of
the affected person, generating problems in their work, academic activities, social relationships, or
family or partner relationships. Unfortunately, there are not enough pharmacotherapeutic solutions to
treat addictions due to the complexity of their physiopathology and signaling pathways. Therefore, it is
an imperative search for new pharmacological alternatives which may be used for this purpose.

Purpose of Review:

This review summarizes the main recent findings of the potential therapeutic effects
of different cannabinoids on treating several addictions, including alcohol, opioids, methamphetamine,
cocaine, and nicotine use disorders.

Highlights Standpoints:

It has been demonstrated that many phyto, synthetic, and endogenous cannabinoids
may act as therapeutic molecules in this psychiatric pathology through their action on multiple
cannabinoid receptors. To highlight, cannabinoid receptors, types 1 and 2 (CB1 and CB2) have a crucial
role in modulating the anti-addictive properties of these compounds.
Enhancing the Therapeutic Potential of Nanomedicines by Modifying Surface
Characteristics
Authors: Gulati Nisha , Dua Kamal , Dureja Harish
Published: May 2022

Nanomedicines have been used over time because of their significant impact on human health
care for the prevention, early detection, diagnosis, treatment, and follow-up of a wide range of illnesses.
Nanomedicines must be adequately characterized in order to develop well-defined nanomedicines with
therapeutic value. The surface charge of nanomedicines plays an important role to determine how they
interact with biological components where the zeta potential is a useful tool for describing the chemical
composition of particle surfaces, such as functional groups, adsorption/desorption, and so on. The main
goal of this review is to present an overview of the impact of nanomedicines' surface charges on absorption,
distribution, metabolism, and in vivo drug release, for example negatively charged nanoparticles
diffuse well through mucus for mucosal drug delivery, whereas positively charged nanoparticles are
preferred for transvascular transport, tumor penetration, and cellular absorption. In this review, we also
highlight how to improve nanomedicines' therapeutic potential by altering their surface characteristics
with the help of various polymers. Future research should be focused on enhancing the therapeutic efficiency
of nanomedicines by changing their surface properties, as well as conducting in-depth mechanistic
studies by changing the surface properties of nanomedicines for the efficient treatment of diseases
with low or no nanomedicine toxicity.
Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies,
and Pathogenic Microglial Activation in 5XFAD Mice
Authors: Di Meco Antonio , Kemal Shahrnaz , Popovic Jelena , Chandra Sidhanth , Sadleir Katherine , Vassar Robert
Published: May 2022

Background:

Alzheimer’s disease (AD) is initiated by aberrant accumulation of amyloid
beta (Aβ) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is
characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal
dysfunction, microtubule disruption, and impaired axonal transport. Aβ-induced plasma membrane
damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation.

Objective:

We tested whether promoting membrane integrity by brain administration of a safe FDA
approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo.

Methods:

Three-month-old 5XFAD male mice were administered several concentrations of P188 in the
brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid
pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation, and lysosomal
/ vesicular trafficking markers in the brain.

Results:

P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12,
and 120μM) were well tolerated. P188 increased brain Aβ burden, potentially through activation of the
γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated
by increased LAMP1 accumulation around Aβ deposits. Pathogenic microglial activation was increased
by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calciumdependent
vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration.

Conclusion:

P188 brain delivery exacerbated amyloid pathology, dystrophic neurites, and pathogenic
microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation
of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against
AD pathogenesis.
mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment
of Absence Epilepsy: Preclinical and Human Genetics Data
Authors: Russo Emilio , Celli Roberta , Striano Pasquale , Citraro Rita , Di Menna Luisa , Cannella Milena , Imbriglio Tiziana , Koko Mahmoud , Euro Epinomics-Cogie Consortium  , De Sarro Giovambattista , Monn James A. , Battaglia Giuseppe , Luijtelaar Gilles Van , Nicoletti Ferdinando , Leo Antonio
Published: May 2022

Background:

Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for the treatment of absence epilepsy. However, no information is available on mGlu3 receptors.

Objective:

To examine whether (i) abnormalities changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy.

Methods:

Animals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; real-time PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior.
Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other IGE/GGE Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls.

Results:

mGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls.

Conclusions:

We suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment.
Structural Optimization for 4-hydroxyphenylpyruvate Dioxygenase Inhibitors
Based on 3D-QSAR, Molecular Docking, SBP Modeling and MOLCAD
Studies
Authors: He Jiaqin , Zhang Mei , Chen Keying , Wang Xiaomeng , Wang Juan , Lin Zhihua
Published: May 2022

Background:

The research based on natural product herbicides has been increasingly attractive
in the field of agriculture. 4-hydroxyphenylpyruvate dioxygenase (HPPD) is one of the most promising
compounds in the field of herbicide innovation.

Objective:

This paper aims to study the relationship between the activity and structure of quinazoline-
2,4-dione derivatives, and to design novel HPPD inhibitors.

Methods:

A set of quinazoline-2,4-dione derivatives underwent 3D-QSAR studies as well as molecular
docking. MOLCAD analysis and 8-point pharmacophore model provided an important reference for us to
understand the interaction mode of HPPD and antagonists.

Results:

The CoMFA (n = 5; q2 = 0.778; r2 = 0.985) and CoMSIA (n = 6; q2 = 0.776; r2 = 0.95) models
had remarkable stability and predictability. MOLCAD studies and pharmacophore modeling proved the
validity of the 3D-QSAR model. On the basis of the gained information, nine novel derivatives as potential
candidates of HPPD inhibitors with better predicted activities were designed, mainly binding to HPPD
via lipophilic interaction and hydrogen bonding. The key hydrophobic residues of HPPD, Phe381,
His308, Asn282, Phe392 and Leu368, were found to be antagonist binding sites that are important factors
for the stability of the antagonist binding site.

Conclusion:

The structural basis and activity of HPPD inhibitors were revealed, which might provide
clear and solid insights to guide the rational design of novel HPPD inhibitors.
Insights into Evolutionary and Conservancy Analytics on Human Insulin
Receptor Proteins
Authors: Dwivedi Manish , Dharshini Kottaisamy Chidhambara Priya , Raj Divya S.
Published: May 2022

Background:

The insulin receptor protein of humans is proposed to have substantial application
in the regulatory pathway of glucose levels in the blood. The cellular function of the insulin hormone
is initiated by its association with the insulin receptor (IR) protein, and this process is common to most
vertebrate species. Thus, phylogenetic analysis of IR protein among various associated species in vertebrates
can elucidate the importance of residues and structure, and the relationship with its function as the
conserved region of residues is associated with evolutionary conservation on insulin receptor proteins. In
the present study, we have used various in silico approaches and conducted the phylogenetic analysis.

Method:

The basic local alignment search tool (BLAST) was employed to screen the 250 vertebrates.
After evolutionary analysis, Pan troglodytes (Chimpanzees) have been observed as the closest relatives of
Homo sapiens concerning insulin receptor proteins.

Results:

Human insulin receptor protein was found to have hydrophobic nature by hydrophobicity profile
analysis, where most of the positions were above the mean hydrophobicity value from n-terminal to cterminal
residues, whereas carboxy-terminal residues were observed as hydrophilic. High entropy was
observed at the short stretch at N-terminal, C-terminal, and a linker region within the alignment, but the
overall positions which were aligned showed low entropic regions.

Conclusion:

The outcomes of this work have revealed some unexplored specific characteristics of the
conserved domains among different taxa of selected vertebrates and have also illustrated the hierarchical
assemblage-based inconsistent variation of the IR proteins, and further conservancy analysis discloses the
significance of each site for protein structure or function.
Trends of Receptor Tyrosine Kinase Researches Based on Bibliometric
Analysis
Authors: Rao Guo-Wu , Li Ying , Fang Hui , Wang Ju , Wan Yue-Hua
Published: May 2022

Malignant tumor is one of the diseases threatening human life and health. Traditional antitumor therapy has some limitations in clinical application, so the development of targeted antitumor drugs has become one of the important research directions of cancer medicine. Since the first tyrosine kinase inhibitor was approved in 2001, this research field has attracted global attention. In this survey, the Web of Science database was adopted to make a bibliometric analysis of the global scientific production of receptor tyrosine kinases in recent 20 years. A total of 14378 documents related to the subject were retrieved and analyzed according to six main aspects: area, journal, country, institution, authors, and keywords. The results show that the United States is currently in a leading position in this field and has established the largest cooperation network with other countries. Harvard University has made the greatest contribution to the field of receptor tyrosine kinases, including the number of publications, the average number of citations per paper, and the h-index. Besides, PLOS One ranked first among the top 15 academic journals in the number of publications related to receptor tyrosine kinases during the survey period. Our research comprehensively evaluates the research status and cooperation network of receptor tyrosine kinases, hoping help researchers to guide their projects or find potential collaborators.
The Importance of Fracture Liaison Services to the Healthcare System: A Review
Authors: Patel Shaan , Daniels Natasha Faye , Lim Jiang An , Zhou Andrew Kailin , Thahir Azeem , Krkovic Matija
Published: May 2022

Osteoporosis is an important public health concern, with secondary fragility fractures
carrying a poor prognosis. The role of a Fracture Liaison Service (FLS) is to identify fragility fracture
patients via investigation and risk assessment. This serves to address the osteoporosis treatment
care gap that exists where the majority of patients with a new fragility fracture over 50-years-old
fail to receive a bone mass density (BMD) scan and osteoporosis treatment, ultimately receiving inadequate
care. Osteoporosis medication is effective in reducing secondary fragility fractures. However,
treatment adherence poses a problem. The FLS serves to prevent more serious secondary fragility
fractures such as hip fractures. This minimises operative costs and the cost of postoperative
care and results in fewer secondary care and care home admissions, increasing healthcare savings.
Implementation of the FLS is effective in increasing investigation, treatment initiation, and adherence,
with a corresponding decrease in refracture rate and mortality. This paper aims to evaluate the
previous osteoporosis treatment care gap, the effectiveness of osteoporosis medications currently
available, and finally, the cost and clinical effectiveness of the FLS serving as a secondary prevention
tool.
The Spectrum of Airway Disease Associated with Rheumatoid Arthritis
Authors: Siddiqui Mohd Faizan , Sherbaevna Salieva Rana , Tashalievich Mamasaidov Abdumitalib , Momunovna Azhimamatova Rakhima , Alrefaee Salhah Hamed , Sovetbekovna Musaeva Begaiym , Mirzaevna Mamatova Sabirakhan
Published: May 2022

Airway involvement results from long-standing rheumatoid arthritis leading to severe pulmonary complications, correlated with increased mortality and socioeconomic costs. Different types of pulmonary lesions, including pulmonary rheumatoid nodule, pulmonary arteritis, diffuse interstitial fibrosis, and rheumatoid pneumoconiosis or Caplan's syndrome, are believed to be relat-ed to rheumatoid arthritis (R.A.). The above changes may indicate the increased susceptibility to the infection, toxins from a disease, or chronic immunity activation. The symptoms vary from asymp-tomatic to severe life-treating conditions, and the prognosis varies depending on the genre and se-verity of involvement. Our study aims to assess the prevalence and characteristics of airways asso-ciation in rheumatoid arthritis as these data provide a brief insight into early diagnosis and treat-ment, which could be applied to minimize complications of airways diseases in rheumatoid arthritis.
Evaluation of Left Ventricular Function in Patients with Coronary Slow Flow by the Dobutamine Stress Echocardiography
Authors: Huang Rongchong , Yang Yanzong , Wu Jian , Meng Shuang , Wang Hui
Published: May 2022

Background:

The study aims to assess the changes to left ventricular (LV) function of patients
with the coronary slow flow (CSF) in response to stress induced by low dose dobutamine.

Methods:

Based on coronary angiography (CAG) results, a total of 186 patients undergoing CAG for
chest pain and suspected coronary heart disease were assigned to the CSF group (n = 142) and control
group (n = 44). Patients in the CSF group underwent two-dimensional speckle-tracking echocardiography
(STE) during the dobutamine stress test to evaluate LV systolic and diastolic functions.

Results:

At rest, there were no statistically significant differences in LV peak systolic longitudinal
strain (LS), LV peak systolic longitudinal strain rate (LSRs), LV peak early diastolic longitudinal
strain rate (LSRed), LV circumferential strain (CS), or LV circumferential strain rate (CSRed) between
the CSF and control groups. In the CSF group, LS and LSRs first increased as the infusion rate was
increased to 10 μg/kg/min (all, p < 0.05), before decreasing at infusion rates of 15 and 20 μg/kg/min
(all, p < 0.05). CS and CSRed increased in the CSF group at infusion rates of 5, 10, and 15 μg/kg/min,
(all, p < 0.05), but decreased significantly at 20 μg/kg/min (all, p < 0.05).

Conclusions:

At rest, LV systolic and diastolic functions were comparable between the CSF and control
groups. However, when blood flow to the heart muscles was insufficient, LSRed decreased first, followed
by LS. In terms of sensitivity to myocardial ischemia, LS is a better strain parameter than CS.
Dynamic Volume Computed Tomography for Characterizing Pulsatile
Tinnitus Caused by Sigmoid Sinus Diverticulum with Bone Defects: Clinical
Implications
Authors: Pan Yu-Ning , Li Ai-Jing , Zhang Jie , Mao Quan-Liang , Shen Fang-Jie
Published: May 2022

Objective:

The objective of this study is to investigate the diagnosis of dynamic volume
computed tomography (CT) for pulsatile tinnitus caused by sigmoid sinus diverticulum (SSD) and
bone defects.

Methods:

Data obtained by dynamic volume CT from 35 patients with SSD were retrospectively collected.
Then the ear morphological parameters, including bone defect, transverse sinus stenosis, position
of the jugular bulb, jugular bulb diverticulum, defect of the jugular bulb wall, gross venous sinus
thrombosis and SSD, and blood perfusion parameters, including cerebral blood flow (CBF), cerebral
blood volume (CBV), and mean transit time (MTT), were evaluated and compared between the tinnitus
side and the asymptomatic side of the ear.

Results:

The maximum diameters of the bone defects on the tinnitus side were greater than those on
the asymptomatic side (Horizontal 6.36±2.35mm vs. 1.12±0.78mm; Longitudinal 4.87±1.25 vs.
0.88±0.06mm). Dynamic volume CT visually displayed the SSD herniated into the adjacent mastoid
via the bone defect. Transverse sinus stenosis, high position of the jugular bulb, jugular bulb diverticulum,
defect of the jugular bulb wall, and gross venous sinus thrombosis were present more frequently
on the tinnitus side than on the asymptomatic side (P < 0.05). Moreover, CBF, CBV, and MTT were
significantly greater on the tinnitus side than on the asymptomatic side (P < 0.05).

Conclusion:

Dynamic volume CT examination is an effective method for the diagnosis of pulsatile
tinnitus caused by SSD with bone defects.
The Relationship among Splenomegaly, Lung Involvement Patterns, and Severity Score in COVID-19 Pneumonia
Authors: Aksu Yusuf , Uslu Ali Ugur , Tarhan Gulten , Karagülle Mustafa , Tiryaki Şaban
Published: May 2022

Introduction:

The disease caused by the novel coronavirus (COVID -19) is a vital public
health problem that has now affected approximately 68,037,473 people and caused 1,552,802 deaths
around the world. We aimed to correlate the frequency of the lung involvement patterns, the segmental
distribution of lung infiltration, and TLSS in COVID-19 pneumonia patients with and without splenomegaly.

Material and Methods:

This retrospective study included patients admitted to Yunus Emre State Hospital
Emergency, Internal Medicine and Infectious Disease Departments between March 11, 2020, and
June 10, 2020, and diagnosed with COVID-19 by PCR test with a throat and nasal swab. The thoracic
and upper abdomen CTs and the clinical and demographic features of the patients were analyzed at the
time of initial diagnosis.

Results:

Consolidation (group 1 - 18 (47%), group 2 - 69 (28.2%); P = 0017), crazy pavement pattern
(15 (39.5%), 42 (17.1%); p = 0.001), pleural band formations (24 (63.2%), 87 (35.5%); p = 0.001), interlobular
septal thickening (23 (60.5%), 79 (32.2%); p = 0.001), and sequelae of secondary tuberculosis
(4 (10.5%), 8 (3.3%); p = 0.039) were more frequent in the patient with splemomegaly. The total lung
severity score was high in the group with splenomegaly (7.32 ± 6.15, 3.69 ± 5.16; p = 0.001).

Conclusion:

Consolidation, interlobular septal thickening, tuberculosis sequela, pleural band, and crazy
pavement patterns were frequent in the COVID-19 pneumonia patients with splenomegaly. The most
frequently affected segment was the superior segment of the right lower lobe. TLSS was higher in the
COVID-19 pneumonia patients with splenomegaly.
A Reverse Structure-based Design of HPV E7 Inhibitor
Authors: Othman Shatrah , Tan Wan Chein , Lim See Khai , Rashid Nurshamimi Nor , Heh Choon Han
Published: May 2022

Background:

Human papillomavirus (HPV) is a small, non-enveloped double-stranded circular
DNA virus. The high-risk types of HPV are claimed to be responsible for over 99% of cervical
cancers. One of the essential HPV oncoproteins, E7, is responsible for escaping from G1/S cell cycle
arrest in HPV-infected cells by binding to the retinoblastoma protein (pRb) through its LXCXE binding
site.

Objectives:

To design a peptide inhibitor targeting HPV E7 through an in silico approach.

Methods:

In this study, the LXCXE binding domain of pRb is used as a target to design peptide inhibitors
using a reverse structure-based approach. The designed amino acid sequence from the B pocket of
pRb, named peptide Y, was further investigated in vitro analysis. The cytotoxicity of the peptide was
analysed in two cell lines, namely, CaSki, containing an integrated HPV16 genome, and HaCaT, an
immortalized keratinocyte cell. Cell cycle analysis was also carried out in both cell lines treated with
peptides.

Results:

In the in silico approach, a 9-amino acids peptide sequence formed 4 conventional hydrogen
bonds with LXCXE motif was selected for in vitro assay. Based on the cytotoxicity analysis, the peptide
showed low toxicity in both cell lines, where the cell viability remained over 74% when treated
with peptide Y. The peptide also caused an accumulation of cells in G0/G1 (+5.4%) and S phase
(+10.2%) and a reduction of cells in the G2/M phase (-14.9%) in the CaSki cells with no significant effect
on normal cells, indicating it is a potential HPV inhibitor.

Conclusion:

A peptide inhibitor, peptide Y, that was designed from the LXCXE binding motif in pRb
can inhibit HPV E7 by causing a cell accumulation effect in G0/G1, and S phases of the cell cycle in
the HPV transformed cell lines. These findings could contribute to HPV E7 peptide inhibitor in the future.
A Review of Molecular Imprinting Polymer for Separation of Bisphenol-A
and its Analogues: Synthesis and Application
Authors: Shah Syed Asim Hussain , Mohamad Sharifah , Md Saleh Noorashikin , Yih Beh Shiuan , Rahim Nurul Yani , Miskam Mazidatulakmam , Asman Saliza
Published: May 2022

Background:

BPA and its analogues are poisonous and hazardous and found in water, food
and environmental samples. These are a dangerous class of endocrine-disrupting chemicals (EDCs) that
drastically affect the environment and human health. BPA and its analogues, such as BPS, BPF, BPE,
BPB, BPAF, and BPAP, are a serious threat to human beings.

Method:

Numerous methods are available for separating bisphenols (BPs) from water, food and environmental
samples. Molecularly imprinted polymers (MIPs) are a superior and eco-friendly technique that
eliminates BPs due to cavities in the shape, size, and functionality complementary to the template molecule.
MIPs are widely used to remove BPA and its analogues. The inexpensive MIPs are a more attractive
choice for separating various BPs due to their unique properties and offer a satisfactory pathway to adsorb
any BPs from water, food and environmental samples to overcome their hazardous effects on human
health.

Results:

This review aims to analyze and assess the recent advancements of MIPs for the separation of
bisphenols. Following a concise introduction for newcomers entering the field, a comprehensive critical
review of developments of MIPs and their applications for BPA and its analogues has been presented. In
this review, we have discussed the MIPs with the method and constituents of synthesis. Secondly, the
development of the different types of MIPs (particle, monolithic, membrane) has been presented for the
BPs. Finally, the use of MIP as a stationary phase in chromatography with an emphasis on BPs is described.
This section is subdivided into high-performance liquid chromatography (HPLC), capillary liquid
chromatography (CLC), and capillary electrochromatography (CEC).

Conclusion:

Molecular Imprinting technology (MIT) technology provides an attractive pathway for further
research and improvement in more efficient MIPs, with higher adsorption capacity. The significance
of applications allowed to separate the BPs and discharged from various samples, thus reducing health
risks. Therefore, MIPs may contribute to future prospective water, food and environmental samples
treatment processes.
Studies on the Anti-HBV Mechanism of Syringopicroside Based on Serum
Metabolomics
Authors: Dou Jinjin , Zhang Xiwu , Li Yang , Zhu Jian , Li Yongji , Liu Zhenqiang , Lu Zhenhua
Published: May 2022

Aims:

Syringopicroside (SYR) is an iridoid monomer compound isolated from the
leaves of clove. HBV is a hepatotropic virus that can cause severe liver diseases, including acute
and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Syringopicroside has a significant
effect on anti-HBV, but its mechanism of action is still unclear.

Methods:

A metabolomics approach based on UPLC-G2-Si-HDMS was performed to analyze the
serum biomarkers from HBV transgenic mice to find the biomarkers affected by syringopicroside.
Through the analysis of metabolic pathways, the key pathways of syringopicroside involved
in a therapeutic action were explored to study its potential mechanism. Using network pharmacology,
the "component-target-pathway" network of syringopicroside in the treatment of hepatitis
B was constructed and combined with the results of metabolomics. Furthermore, the mechanism
of action of syringopicroside against HBV was also discussed.

Results:

Serum metabolomics identified a total of 42 HBV-related biomarkers, of which 8 returned
to normal levels after syringopicroside treatment, involving a total of 6 metabolic pathways.
Five biomarkers returned to normal levels after lamivudine treatment, involving 2 metabolic
pathways. Network pharmacology analysis showed that syringopicroside in the treatment of
hepatitis B mainly acts on 26 targets, including MMP9, MAPK1, and SLC29A1, involving 4
pathways.

Conclusion:

This study elucidates the multi-target and multi-channel integration mechanism of
syringopicroside against HBV, lays a foundation for an in-depth study of the anti-HBV mechanism
of syringopicroside, and also provides support for the development of innovative traditional
Chinese medicines for the treatment of hepatitis B.
Insight into the Synthesis and Photocatalytic Applications of Bismuth
Vanadate-based Nanocomposites
Authors: Hooda Amit , Rawat Pooja , Vaya Dipti
Published: May 2022

To cope with environmental issues, scientists strive to develop innovative materials and
methods. Bismuth vanadate (BiVO4) has attracted attention because of its significant characteristics
like low toxicity, corrosion resistance, photo-stability, narrow band-gap, and ability to provide better
efficiency invisible light. However, fast recombination of charge carriers limits its photocatalytic
activity. Many researchers have improved BiVO4 properties by metal doping and coupling with other
semiconductors to improve charge separation and photocatalytic activity. This review addressed the
recent improvement in BiVO4 structural modification by doping and composite formation using
metal and non-metals and compared the efficiency with pure one. In addition, BiVO4 synthesis and
application are also extensively discussed, such as dye degradation, water splitting, and water purification.
This review can be beneficial for researchers and those interested in exploring and evolving
BiVO4-based material as an efficient photocatalyst.