bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-to-neutrophil Ratio after Intravenous Thrombolysis Predicts Unfavorable Outcomes in Acute Ischemic Stroke
Authors: Wang Mei-Qi , Sun Ying-Ying , Wang Yan , Yan Xiu-Li , Jin Hang , Sun Xin , Zhang Peng , Zhu Hong-Jing , Guo Zhen-Ni , Yang Yi 
Published: May 2020

Background and Purpose:
Platelet-to-neutrophil ratio (PNR) was suggested to be an independent
protective predictor for 90-days outcomes in acute ischemic stroke (AIS) patients in previous
studies. This study aims to investigate the association between PNR and outcomes of AIS in
intravenous thrombolysis (IVT) group.

Methods:
Data on acute ischemic stroke patients who received intravenous thrombolysis from April
2015 to March 2019 were collected. We defined the PNR value at admission as pre-IVT PNR and
after IVT within 24 h was defined as post-IVT PNR. Clinical outcome indicators included early neurological
deterioration (END), hemorrhagic transformation (HT), delayed neurological deterioration
(DND), and poor 3-month outcome (3m-mRS >2).

Results:
A total of 581 patients were enrolled in the final analysis. The age was 61(53-69) years, and
423(72.8%) were males. Post-IVT PNR was independently associated with hemorrhagic transformation
(OR = 0.974; 95%CI = 0.956-0.992; P=0.006), early neurological deterioration (OR = 0.939;
95%CI = 0.913-0.966; P = 0.01), delayed neurological deterioration (OR = 0.949; 95%CI = 0.912-
0.988; P = 0.011), and poor outcome (OR = 0.962; 95%CI = 0.948-0.976; P<0.001). PNR level was
identified as high (at the cut-off value or above) or low (below the cut-off value) according to receiver
operating curve (ROC) analyses on each endpoint. Comparison of early neurological deterioration,
hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome
(3m-mRS >2) between patients at high and low levels for platelet-to-neutrophil ratio (PNR) showed
statistical differences (p<0.001).

Conclusions:
Post-IVT PNR was independently associated with early neurological deterioration,
hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome. Lower
PNR can predict a worse outcome.
Small Molecule CDK Inhibitors for the Therapeutic Management of Cancer
Authors: Goel Bharat , Tripathi Nancy , Bhardwaj Nivedita , Jain Shreyans K. 
Published: May 2020

:Cyclin-dependent kinases (CDKs) are a group of multifunctional enzymes consisting of catalytic and regulatory subunits. The regulatory subunit, cyclin, remains dissociated under normal circumstances, and complexation of cyclin with the catalytic subunit of CDK leads to its activation for phosphorylation of protein substrates. The primary role of CDKs is in the regulation of the cell cycle. Retinoblastoma protein (Rb) is one of the widely investigated tumor suppressor protein substrates of CDK, which prevents cells from entering into cell-cycle under normal conditions. Phosphorylation of Rb by CDKs causes its inactivation and ultimately allows cells to enter a new cell cycle. Many cancers are associated with hyperactivation of CDKs as a result of mutation of the CDK genes or CDK inhibitor genes. Therefore, CDK modulators are of great interest to explore as novel therapeutic agents against cancer and led to the discovery of several CDK inhibitors to clinics. This review focuses on the current progress and development of anti-cancer CDK inhibitors from preclinical to clinical and synthetic to natural small molecules.
Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors
Authors: Wadhwa Pankaj , Jain Priti , Jadhav Hemant R. 
Published: May 2020

:
Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which
has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and
GSK3β. However, GSK3β is highly expressed in different areas of the brain and has been implicated
in Alzheimer’s disease as it is involved in tau phosphorylation. Due to its high specificity concerning
substrate recognition, GSK3 has been considered as an important target. In the last decade, several
GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the
information published in the last decade about the role of GSK3 in Alzheimer’s disease and progress in
the development of its inhibitors. Using this collated information, medicinal chemists can strategize
and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer’s disease.
Computer-Aided Structure Prediction of Bluetongue Virus Coat Protein VP2 Assisted by Optimized Potential for Liquid Simulations (OPLS)
Authors: Prajapati Leena , Khandelwal Ravina , Yogalakshmi Kadapakkam Nandabalan , Munshi Anjana , Nayarisseri Anuraj 
Published: May 2020

Background:
The capsid coated protein of Bluetongue virus (BTV) VP2 is responsible for
BTV transmission by the Culicoides vector to vertebrate hosts. Besides, VP2 is responsible for BTV
entry into permissive cells and hence plays a major role in disease progression. However, its mechanism
of action is still unknown.

Objective:
The present investigation aimed to predict the 3D structure of Viral Protein 2 of the bluetongue
virus assisted by Optimized Potential for Liquid Simulations (OPLS), structure validation, and an
active site prediction.

Methods:
The 3D structure of the VP2 protein was built using a Python-based Computational algorithm.
The templates were identified using Smith waterman’s Local alignment. The VP2 protein structure validated
using PROCHECK. Molecular Dynamics Simulation (MDS) studies were performed using an
academic software Desmond, Schrodinger dynamics, for determining the stability of a model protein.
The Ligand-Binding site was predicted by structure comparison using homology search and proteinprotein
network analysis to reveal their stability and inhibition mechanism, followed by the active site
identification.

Results:
The secondary structure of the VP2 reveals that the protein contains 220 alpha helix atoms,
40 310 helix, 151 beta sheets, 134 coils and 424 turns, whereas the 3D structure of Viral Protein 2 of
BTV has been found to have 15774 total atoms in the structure. However, 961 amino acids were found
in the final model. The dynamical cross-correlation matrix (DCCM) analysis tool identifies putative protein
domains and also confirms the stability of the predicted model and their dynamical behavior difference
with the correlative fluctuations in motion.

Conclusion:
The biological interpretation of the Viral Protein 2 was carried out. DCCM maps were calculated,
using a different coordinate reference frame, through which, protein domain boundaries and
protein domain residue constituents were identified. The obtained model shows good reliability. Moreover,
we anticipated that this research should play a promising role in the identification of novel candidates
with the target protein to inhibit their functional significance.
Relationship between Invasive and Non-Invasive Hemodynamic Measures in Experimental Pulmonary Hypertension
Authors: Benavides-Córdoba Vicente , Gómez Mauricio Palacios 
Published: May 2020

Introduction:
Animal models have been used to understand the pathophysiology of
pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active
ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal
model. In this model, invasive and non-invasive hemodynamic variables that resemble human
measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic
measures in the monocrotaline-induced pulmonary hypertension model.

Materials and Methods:
Twenty 6-week old male Wistar rats weighing between 250-300g from the
bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the
relationships between invasive and non-invasive variables are sustained in different conditions
(healthy, hypertrophy and treated). The animals were organized into three groups, a control group
who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension
induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary
hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection
fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured.
The functional relation between any two variables was evaluated by the Pearson correlation
coefficient.

Results:
It was found that all correlations were statistically significant (p <0.01). The strongest
correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index
also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between
the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right
ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other
three variables studied, although with relatively low correlation.

Conclusion:
The correlations obtained in this study indicate that the parameters evaluated in the
research related to experimental pulmonary hypertension correlate adequately and that the
measurements that are currently made are adequate and consistent with each other, that is, they have
good predictive capacity.
The Possible Role of Saponin in Type-II Diabetes- A Review
Authors: Choudhary Neeraj , Khatik Gopal Lal , Suttee Ashish 
Published: May 2020

Background:
The possible role of secondary metabolites in the management of diabetes is a
great concern and constant discussion. This characteristic seems relevant and should be the subject of
thorough discussion with respect to saponin.

Objective:
The current data mainly focus on the impact of saponin in the treatment of type-II diabetes.
The majority of studies emphasize on other secondary metabolites such as alkaloids and flavonoids, but
very few papers are there representing the possible role of saponin as these papers express the narrow
perspective of saponin phytoconstituents but lacking in providing the complete information on various
saponin plants. The aim of the study was to summarize all available data concerning the saponin containing
plant in the management of type-II diabetes.

Methods:
All relevant papers on saponin were selected. This review summarizes the saponin isolation
method, mechanism of action, clinical significance, medicinal plants and phytoconstituents responsible
for producing a therapeutic effect in the management of diabetes.

Results:
The saponin is of high potential with structural diversity and inhibits diabetic complications
along with reducing the hyperglycemia through different mechanisms thereby providing scope for improving
the existing therapy and developing the novel medicinal agents for curing diabetes.

Conclusion:
Saponins having potential therapeutic benefits and are theorized as an alternative medication
in decreasing serum blood glucose levels in the patient suffering from diabetes.
High Prevalence of Vitamin D Deficiency and Correlation with Cystatin-C and Other Cardiovascular and Renal Risk Biomarkers in Patients with Type 2 Diabetes Mellitus Complicated with Hypertension
Authors: Alkhatatbeh Mohammad J. , Smadi Sajedah A. , Abdul-Razzak Khalid K. , Saadeh Nesreen A. 
Published: May 2020

Background:
Vitamin D is increasingly investigated as having a role in Type 2 Diabetes
Mellitus (T2DM) and its cardiovascular and renal complications.

Objective:
This study aimed to investigate the association between 25-hydroxyvitamin D (25-OHD) and
biomarkers of cardiovascular and renal complications, including cystatin-C.

Methods:
This cross-sectional study involved 117 participants with T2DM that was not complicated
with cardiovascular or renal diseases except hypertension. 25-OHD was measured by electrochemiluminescence
immunoassay, while cystatin-C was measured by enzyme-linked-immunosorbent-assay. Other
biomarkers, including lipids, creatinine, urea and glycemic measures, were determined by the routine
biochemistry assays.

Results:
The prevalence of vitamin D deficiency was 74.36%. There was no significant difference in
cardiovascular and renal biomarkers, including glucose, HbA1c, lipids, urea, creatinine and cystatin-C
between participants with adequate and deficient vitamin D (p-values>0.05). Participants with adequate
vitamin D were older in age, more obese and having lower eGFR (p-values<0.05). 25-OHD was weakly
correlated with age, duration of DM, urea, creatinine and inversely correlated with eGFR (rvalues<
0.32, p-values<0.05). Although creatinine and cystatin-C were directly correlated (r=0.42, pvalue<
0.001), cystatin-C and 25-OHD were not correlated (p-value>0.05). Hypertensive participants
were more obese, having a longer duration of DM and higher urea and cystatin-C compared to nonhypertensive
participants (p-values<0.05). Binary logistic regression analysis revealed that hypertension
could be predicted from increased BMI.

Conclusion:
25-OHD was not found to be correlated with cardiovascular risk biomarkers, but it was
correlated with renal biomarkers, including urea, creatinine and eGFR. Cystatin-C and 25-OHD were
not observed to be correlated to each other, but both were correlated to renal function. Obesity was a
significant predictor of hypertension.
Multiparametric MRI Evaluation of Developmental Venous Anomalies in the Brain: Association with Signal Changes on FLAIR in Patients with Multiple Sclerosis
Authors: Sagtas Ergin , Guneyli Serkan , Akyilmaz Dincer Aydin , Yavas Huseyin Gokhan , Cakmak Pinar , Ufuk Furkan 
Published: May 2020

Background:
Developmental venous anomalies (DVAs) can be determined on magnetic
resonance imaging (MRI), and they may be associated with multiple sclerosis (MS) lesions.

Purpose:
The objective was to evaluate the MRI findings of DVAs in the brain, to compare the prevalence
of them between MS patients and control subjects, and to investigate the correlation of
DVA-associated fluid-attenuated inversion recovery (FLAIR) hyperintensities and MRI-derived parameters
between MS patients and control subjects having DVA.

Methods:
Total 160 patients with a mean age of 45 ± 16 years who underwent multiparametric
MRI including susceptibility-weighted imaging (SWI), diffusion-weighted imaging, 3D FLAIR,
and contrast-enhanced imaging were included in this retrospective study. First, the presence of
DVA was compared between the MS and control groups using the Chi-square test. Then, among
the subjects having DVA, age, gender, and MRI-derived parameters such as the signal increase of
DVA on FLAIR, location, and drainage of DVA were compared between the MS and control
groups using Chi-square test.

Results:
The presence of DVA did not differ between the MS and control groups (P = 0.828). Signal
increase around DVA on FLAIR (P = 0.03) and the age of less than 45 years demonstrated a
significant correlation with MS group (P = 0.022).

Conclusion:
In our study, DVAs were effectively detected using SWI and 3D contrast-enhanced
T1-weighted imaging on MRI. The signal increase of DVA was better revealed on 3D FLAIR on
MRI, and it was the only significant MRI-derived parameter in patients with MS.
Synthesis of Thiazolyl-N-phenylmorpholine Derivatives and their Biological Activities
Authors: Al-Soliemy Amerah M. , Farghaly Thoraya A. , Abbas Eman M.H. , Shaaban Mohamed R. , Zayed Mohie E.M. , El-Naggar Tarek B.A. 
Published: May 2020

Background:
Morpholine and thiazole rings are two heterocycles which are wellknown
with a wide spectrum of different biological activities, especially antitumor activity.

Objective:
The aim of the work is to design and synthesize hybrid heterocyclic compounds of
morpholine and thiazole moieties via the reaction of morpholino-thiosemicarbazone derivatives
with various α-halocarbonyl compounds and screening their antitumor activity against three tumor
cell lines namely, TK-10, MCF-7 and UACC-62.

Methods:
An efficient synthesis of a series of N-phenylmorpholine derivatives linked with thiazole
moiety was accomplished. The reaction of N-subistituted-2-(N-phenylmorpholine)ethylidene) hydrazine-
1-carbothioamide (thiosemicarbazone derivative) with acetyl and ester-hydrazonoyl chlorides,
α-chloroketones, or α-bromoesters afforded the corresponding thiazole derivatives pendent
to N-phenylmorpholine moiety in good to excellent yields.

Result:
Mass, 1H NMR, 13C NMR, and elemental analysis were used to confirm the structure of
all the new derivatives. The antitumor activities of synthesized N-phenylmorpholine-thiazole derivatives
were investigated against three tumor cells namely, TK-10, MCF-7 and UACC-62. The
results of such investigation indicated that some derivatives showed good potential to inhibit the
growth of the two cells of the tested tumor cells. One of the tested compounds, N-ethyl thiosemicarbazone
derivative 7 revealed potent growth inhibition of all the three tumor cells.

Conclusion:
We have succeeded to synthesize a series of N-phenylmorpholine derivatives pendant
to thiazole moiety as antitumor agents.
A Validated LC-MS/MS Method for the Determination of Mezlocillin in Plasma: An Adapted Method for Therapeutic Drug Monitoring in Children
Authors: Tang Bo-Hao , Kan Min , Yang Xin-Mei , Wang Rong-Hua , Shi Hai-Yan , Zheng Yi , Hao Guo-Xiang , Song Lin-Lin , Zhao Wei 
Published: May 2020

Background:
Mezlocillin is off-label used for the treatment of respiratory infections in children.
Therapeutic Drug Monitoring (TDM) data are also limited in children. A sensitive Liquid chromatography-
tandem mass spectrometry (LC–MS/MS) method adapted to children was developed and
validated for the determination of mezlocillin plasma concentration in the present study.

Methods:
Mezlocillin, extracted from a volume of 50 μL plasma using acetonitrile, was analyzed on an
online LC-MS/MS system with an Agilent 1290 Infinity UHPLC (Agilent Technologies, CA, USA)
coupled to an AB SCIEX QTRAP 6500PLUS MS/MS (AB Sciex, Framingham, MA, USA) with ceftiofur
as an internal standard. HPLC separation was performed on a C18 column with ultra-pure water
and acetonitrile as gradient elution at a flow rate of 0.4 mL/min at 30°C. Analyst TM Version 1.5.2
(Applied Biosystems) was used for data acquisition. The total chromatographic run time was 1.6 min.

Results:
LC/MS/MS method used for TDM of mezlocillin in children was developed and validated.
This assay has a lower limit of quantification of 0.025 μg/mL for mezlocillin with 50 μL plasma. Good
linearity was achieved for mezlocillin over the range from 0.025 to 20 μg /mL. The acceptance criteria
were met in all cases. Among 36 patients aged between 0.16-1.63 years old, only one patient had detectable
trough concentration higher than 1 μg/mL.

Conclusion:
LC-MS/MS method with 50 μL plasma developed in this study was successfully applied
to TDM of mezlocillin in children. The high variability of trough concentration highlighted that TDM
is important to optimize mezlocillin therapy in children.
Linezolid Induced Skin Reactions in a Multi Drug Resistant Infective Endocarditis Patient: A Rare Case
Authors: Rajan Asha K. , Kashyap Ananth , Chhabra Manik , Rashid Muhammed 
Published: May 2020

Rationale:
Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have
rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs
among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here,
we present a rare case report of LNZ induced CARs in a MDR IE patient.

Case report:
A 24-year-old female patient was admitted to the hospital with chief complaints of
fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days.
She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed
LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient
experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all
over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering
from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient
was prescribed corticosteroids along with other supportive care. Her reactions completely subsided
and infection got controlled following 1 month of therapy.

Conclusion:
Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients
on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover,
strengthened spontaneous reporting is required for better quantification.
Benzophenone Sulfonamide Derivatives as Interacting Partners and Inhibitors of Human P-glycoprotein
Authors: Farman Saira , Javed Aneela , Arshia  , Khan Khalid M. , Nasir Abdul , Khan Asif Ullah , Lodhi Muhammad A. , Gul Humaira , Khan Faisal , Asad Muhammad , Parveen Zahida 
Published: May 2020

Background:
Human P-glycoprotein (P-gp) is a transmembrane protein that belongs to the ATPBinding
Cassette (ABC) transporters family. Physiologically, it exports toxins out of the cell, however, its overexpression
leads to the phenomena of Multidrug-Resistance (MDR) by exporting a diverse range of compounds,
which are structurally and chemically different from each other, thus creating a hurdle in the treatment of various
diseases including cancer. The current study was designed to screen benzophenone sulfonamide derivatives
as a class of inhibitors and potential anticancer agents for P-gp.

Methods:
A total number of 15 compounds were evaluated. These compounds were screened in daunorubicin
efflux inhibition assays using CCRF-CEM Vcr1000 cell line that overexpressed human P-gp. Cytotoxicity assay
was also performed for active compounds 11, 14, and 13. These scaffolds were then docked in the homology
model of human P-gp using mouse P-gp as a template (PDB ID: 4MIM) and the recently published Cryo Electron
Microscopy (CEM) structure of human mouse chimeric P-gp to find their interactions with specified residues
in the binding pocket. Analysis was performed using Labview VI and Graph pad prism version 5.0.

Results:
Results revealed the potency of all these compounds in low nanomolar range whereas, compound 14
was found to be most active with IC50 value of 18.35nM±4.90 followed by 11 and 13 having IC50 values of
30.66nM±5.49 and 46.12nM±3.06, respectively. Moreover, IC50 values calculated for 14, 11 and 13 in cytotoxicity
assay were found to be 22.97μM±0.026, 583.1μM±0.027 and 117.8μM±0.062, respectively. Docking
results showed the interaction of these scaffolds in transmembrane helices (TM) where Tyr307, Tyr310, Tyr953,
Met986 and Gln946 were found to be the major interaction partners, thus they might play a significant role in
the transport of these scaffolds.

Conclusion:
Benzophenone sulfonamide derivatives showed IC50 values in low nanomolar range comparable to
the standard inhibitor Verapamil, therefore they can be good inhibitors of P-gp and can serve as anticancer
agents. Also, they have shown interactions in the transmembrane region sharing the same binding region of
verapamil and zosuquidar.