bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast Cell's Role in Cytokine Release Syndrome and Related Manifestations of
COVID-19 Disease
Authors: Özdemir Öner , Göksu Erol Azize Yasemin , Dikici Ümmügülsüm 
Published: October 2022

Background-aim:
In this narrative review, firstly we describe the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of its infection in humans. Later, the importance of mast cells in SARS-CoV-2 infection and their role in Coronavirus Disease 2019 (COVID-19) will be discussed. SARS-CoV-2 is a transmissible agent frequently detected in some mammalian species and nowadays also in humans.

Methods:
Literature data published in PubMed that covered mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease was reviewed by the authors independently and collectively. Recommendations for the management of cytokine release syndrome and related manifestations were made by the authors.

Results:
Mast cells are concentrated in environments where they encounter viruses, bacteria, and toxins, especially in the skin, nasal mucosa, lungs, airways, gastrointestinal tract, and meninges, to prevent their entry into the human body. Once SARS-CoV-2 enters the host, it stimulates one of them, mast cells, together with pre-existing innate immune cells that form a defensive barrier in the submucosa of the respiratory tract and nasal cavities against pathogenic microorganisms. The roles of mast cells in SARS-CoV-2 -induced hyper inflammation and cytokine storms have recently been one of the hot topics mostly discussed in the literature.

Conclusion:
Physicians should keep in mind the mast cells' role in cytokine release syndrome and related manifestations of COVID-19 disease. Mast cell-targeting therapies (eg, H1 and H2 receptor antagonists) can reduce the severity and course of the disease when used after complications associated with COVID-19 are suspected or seen.
Residual Right-to-Left-Shunt Following Transcatheter Patent Foramen Ovale
Closure: The Role of Antithrombotic Treatment
Authors: Katsianos Efstratios , Oikonomou Evangelos , Kalogeras Konstantinos , Manousaki Alexandra , Kalantzis Charalambos , Pantelidis Panteleimon , Vavuranakis Michael-Andrew , Aggeli Konstantina , Siasos Gerasimos , Tsioufis Costas , Vavuranakis Manolis 
Published: October 2022

Background:
Transcatheter closure of patent foramen ovale (PFO) is a highly effective therapy for
patients with left circulation thromboembolism, not attributable to other conditions.

Objectives:
This retrospective cohort study investigates the impact of baseline foramen ovale anatomy on the
severity of the postclosure shunt.

Methods:
Patients with PFO, who underwent percutaneous closure, were followed up for at least 5 years postimplantation.
Patients were classified into two groups based on the presence of high-risk features of the baseline
PFO anatomy. At the follow-up follow-up, residual right-to-left shunt was assessed for the high and non-highrisk
anatomy groups, via transcranial Doppler at rest and after performing the Valsalva maneuver, with the injection
of agitated saline.

Results:
38 patients were examined after a mean follow-up period of 9 ± 3 years after implantation. After retrospective
evaluation of the baseline transthoracic and transesophageal echo studies, 14 patients with high-risk
PFO anatomy were identified. The degree of the residual right-to-left shunt, as assessed by the number of microbubbles
was higher in the high-risk PFO anatomy group compared to the non-high-risk group, both at rest
[1.50 (IQR: 0.00-3.25) vs. 0.00 (IQR: 0.00-0.00), p < 0.001] and post-Valsalva maneuver [7.50 (IQR: 1.50-
10.25) vs. 0.00 (IQR: 0.00-3.75), p = 0.003]. Furthermore, in the high-risk group, more microbubbles were detected
at rest (p = 0.008) and post-Valsalva (p = 0.002) in subjects without antiplatelet treatment compared to
subjects on prolonged antiplatelet therapy.

Conclusions:
Baseline PFO anatomy affects the severity of the residual right-to-left shunt. Prolonged antiplatelet
therapy may benefit patients with high-risk anatomical features.
Cabozantinib Carries the Risk of Drug-Drug Interactions via Inhibition of UDPglucuronosyltransferase
(UGT) 1A9
Authors: Wang Zhe , Jiang Lili , Wang Xiaoyu , Yin Hang , Wang Zhen , Lv Xin , Liu Yong 
Published: October 2022

Background:
Cabozantinib is a multiple receptor tyrosine kinases inhibitor (TKI) approved to treat progressive,
metastatic medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. Drugdrug
interactions (DDIs) for cabozantinib have been identified involving the role of cytochromes P450. Although the
previous study reported that cabozantinib showed a slight inhibition of UDP-glucuronosyltransferase (UGT) 1A1 at
the highest concentration tested, there are no reports on the potential for UGTs-mediated-DDIs. Hence, the current
study aims to address this knowledge gap.

Objective:
This study aimed to investigate the inhibitory effect of cabozantinib on human UGTs and to quantitatively
evaluate the DDI potential via UGT inhibition.

Methods:
The inhibitory effects of cabozantinib on UGTs were determined by measuring the formation rates for 4-
methylumbelliferone (4-MU) glucuronide and trifluoperazine N-glucuronide using recombinant human UGT
isoforms in the absence or presence of cabozantinib. Inhibition kinetic studies were conducted to determine the type
of inhibition of cabozantinib on UGTs and the corresponding inhibition constant (Ki) value. In vitro-in vivo extrapolation
(IVIVE) was further employed to predict the potential risk of DDI in vivo.

Results:
Cabozantinib displayed potent inhibition of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, and
2B15. Cabozantinib exhibited noncompetitive inhibition towards UGT1A1 and 1A3 and inhibition towards UGT1A7
and 1A9. The Ki,u values (mean ± standard deviation) were calculated to be 2.15±0.11 μM, 0.83±0.05 μM, 0.75±0.04
μM and 0.18 ± 0.10 μM for UGT1A1, 1A3, 1A7 and 1A9, respectively. Co-administration of cabozantinib at the
clinically approved dose of 60 mg/day or 140 mg/day may result in approximately a 26% to 60% increase in the
systemic exposure of drugs predominantly cleared by UGT1A9, implying a high risk of DDIs.

Conclusion:
Cabozantinib has the potential to cause DDIs via the inhibition of UGT1A9; therefore, additional attention
should be paid to the safety of the combined use of cabozantinib and drugs metabolized by UGT1A9.
Inverted U-shaped Relationship Between Mean Platelet Volume/Platelet
Count Ratio and Post-thrombolytic Early Neurological Deterioration in
Patients with Mild and Moderate Stroke
Authors: Wang Zhen , Liu Xinfeng , Xu Wei , Guo Hongquan , Li Huiping , Song Kangping , Li Fangyi 
Published: October 2022

Objective:
The objective of this study is to investigate the relationship between mean
platelet volume (MPV)/platelet count (PC) ratio and post-thrombolytic early neurological deterioration
(END) in patients with mild and moderate stroke.

Methods:
Mild and moderate stroke patients treated with intravenous thrombolysis (IVT) at the
Affiliated Changsha Central Hospital of the University of South China between January 2016 and
March 2022 were prospectively and consecutively enrolled. END was defined as an increase in the
total National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or an increase in the
motor items of ≥1 point within 24 hours after IVT treatment. Logistic regression and restricted cubic
spline models were used to estimate the relationship between the MPV/PC ratio and postthrombolytic
END.

Results:
Among the 406 patients recruited, 64 (15.8%) patients developed END. Patients in the first
quintile of MPV/PC ratio (adjusted OR = 0.27, 95% CI = 0.11-0.66, p = 0.004) and the fifth quintile
(adjusted OR = 0.26, 95% CI = 0.10-0.69, p = 0.007) had a significantly lower risk of END compared
with those in the third quintile. Restricted cubic spline analysis revealed an inverted U-shaped
relationship between the MPV/PC ratio and END (p for nonlinearity = 0.016). MPV/PC ratio cut-off
value associated with the highest END risk was 51.0. An MPV/PC ratio ≤ 51.0 was shown to be
positively associated with END (adjusted OR = 1.07, 95% CI = 1.02-1.14, p = 0.012), while an
MPV/PC ratio >51.0 was negatively associated with END (adjusted OR = 0.94, 95% CI = 0.88-1.00,
p = 0.040). A significant interaction existed between the MPV/PC ratio and age in the low MPV/PC
ratio group (p = 0.012). MPV/PC ratio was positively associated with END only in patients ≥ 60
years, whereas this association was insignificant in patients < 60 years.

Conclusion:
An inverted U-shaped relationship between the MPV/PC ratio on admission and postthrombolytic
END was identified in patients with mild and moderate stroke, with a threshold
MPV/PC ratio of 51.0. The MPV/PC ratio closer to the threshold was associated with a higher risk
of post-thrombolytic END.
Screening for Genetic Mutations Associated with Early-Onset Alzheimer’s
Disease in Han Chinese
Authors: Liu Cuicui , Cong Lin , Zhu Min , Wang Yongxiang , Tang Shi , Han Xiaojuan , Zhang Qinghua , Tian Na , Liu Keke , Liang Xiaoyan , Fa Wenxin , Wang Nan , Hou Tingting , Du Yifeng 
Published: October 2022

Background:
Early-onset Alzheimer’s disease (EOAD) is highly influenced by genetic factors.
Numerous mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN1 and
PSEN2) have been identified for EOAD, but they can only account for a small proportion of EOAD
cases.

Objective:
This study aimed to screen genetic mutations and variants associated with EOAD among
Han Chinese adults.

Methods:
This study included 34 patients with EOAD and 26 controls from a population-based study
and neurological ward. We first sequenced mutations in APP/PSENs and then performed whole-exome
sequencing in the remaining patients with negative mutations in APP/PSENs to screen for additional
potential genetic variants. Among patients who were negative in genetic screening tests, we further
evaluated the risk burden of genes related to the Aβ metabolism-centered network to search for other
probable causes of EOAD.

Results:
We identified 7 functional variants in APP/PSENs in 8 patients, including 1 APP mutation (p.
Val715Met), 3 PSEN1 mutations (p. Phe177Ser; p. Arg377Met; p. Ile416Thr), and 3 PSEN2 mutations
(p. Glu24Lys; p. Gly34Ser; p. Met239Thr). Of the remaining 26 EOAD cases without mutations in
APP/PSENs, the proportion of carrying rare variants of genes involved in Aβ and APP metabolism was
significantly higher than that of controls (84.6% vs. 73.1%, P=0.042). Thirty-one risk genes with 47
variants were identified in 22 patients. However, in 26 normal subjects, only 20 risk genes with 29
variants were identified in 19 subjects.

Conclusions:
Our findings demonstrate the role of APP/PSENs mutations in EOAD, identifying a new
PSEN2 missense mutation, and further offer valuable insights into the potential genetic mechanisms of
EOAD without APP/PSENs mutations among Han Chinese.
Impact of GSTT1 and GSTM1 Polymorphisms in the Susceptibility to
Philadelphia Negative Chronic Myeloid Leukaemia
Authors: Elderdery Abozer Y. , Idris Hadeil M.E. , Tebien Entesar M. , Diab Nada Abdalfatah , Hamza Siddiqa M.A. , Suliman Bandar A. , Alhamidi Abdulaziz H. , Omer Nawal Eltayeb , Mills Jeremy 
Published: October 2022

Materials and Methods:
We report on a case-control study with 126 participants, divided into 26 patients
with Ph-ve CML (57.7% male, 42.3% female) and 100 healthy volunteers (51% male, 49% female)
with no medical history of cancer as a control population. All Ph-ve CML patients were diagnosed
according to standard hematologic and cytogenetic criteria based on CBC, confirmed by Reverse
Transcriptase Polymerase Chain Reaction (RT-PCR) to determine the presence or absence of the BCRABL
gene, followed by bone marrow (BM) examination.

Background:
Our research aimed to clarify the role of genetic polymorphisms in GST (T1
and M1) in the development of Ph-ve CML.

Results:
Of the 26 studied cases, 50% had the GSTT1 null genotype against 21% of the control group,
a statistically significant difference (CI= 1.519 - 9.317; p-value= 0.004). The GSTM1 null genotype
was detected in 23.1% of cases and 35% of controls, a difference not statistically significant (OR=
0.557; CI= 0.205-1.515; p-value= 0.252). The distribution of GSTT1 and GSTM1 polymorphisms was
also examined according to gender, age and ethnic grouping; these findings revealed no statistically
significant differences.

Conclusion:
Our study reveals a strong correlation between GSTT1 polymorphism and Ph-ve CML,
whereas the data for GSTM1 polymorphisms indicates no role in the initial development of the disease.
More studies are required to further clarify these and other genes' roles in disease development.
Recent Developments in Microfluidic Paper-based Analytical Devices for
Pharmaceutical Analysis
Authors: Khamcharoen Wisarut , Kaewjua Kantima , Yomthiangthae Phanumas , Anekrattanasap Ananyaporn , Chailapakul Orawon , Siangproh Weena 
Published: October 2022

Abstract:
In the last decade, due to the global increase in diseases, drugs for biomedical applications have increased dramatically. Therefore, there is an urgent need for analytical tools to monitor, treat, investigate, and control drug compounds in diverse matrices. The new and challenging task has been looking for simple, low-cost, rapid, and portable analytical platforms. The development of microfluidic paper-based analytical devices (µPADs) has garnered immense attention in many analytical applications due to the benefit of cellulose structure. It can be functionalized and serves as an ideal channel and scaffold for the transportation and immobilization of various substances. Microfluidic technology has been considered an effective tool in pharmaceutical analysis that facilitates the quantitative measurement of several parameters on cells or other biological systems. The µPADs represent unique advantages over conventional microfluidics, such as the self-pumping capability. They have low material costs, are easy to fabricate, and do not require external power sources. This review gives an overview of the current designs in this decade for µPADs and their respective application in pharmaceutical analysis. These include device designs, choice of paper material, and fabrication techniques with their advantages and drawbacks. In addition, the strategies for improving analytical performance in terms of simplicity, high sensitivity, and selectivity are highlighted, followed by the application of µPADs design for the detection of drug compounds for various purposes. Moreover, we present recent advances involving µPAD technologies in the field of pharmaceutical applications. Finally, we discussed the challenges and potential of µPADs for the transition from laboratory to commercialization.
Lipoprotein-associated Phospholipase A2 in Coronary Artery Disease
Authors: Dimitroglou Yannis , Sakalidis Athanasios , Mavroudis Andreas , Kalantzis Charalambos , Valatsou Angeliki , Andrikou Ioannis , Christofi Angela , Mantzouranis Emmanouil , Kachrimanidis Ioannis , Bei Evellina , Lazarou Emilia , Tsioufis Costas , Tousoulis Dimitris , Lazaros George 
Published: October 2022

Abstract:Coronary artery disease (CAD) is the leading cause of morbidity and mortality in western societies. Therefore the identification of novel biomarkers to be used as diagnostic or therapeutic targets is of significant scientific interest. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is one such protein shown to be involved in endothelial dysfunction, vascular inflammation and ather-ogenesis. Several epidemiological studies have associated high Lp-PLA2 activity with an increased risk for CAD even when other CAD risk factors or inflammation markers were included in the mul-tivariate analysis. These findings were strengthened by the results of relevant meta-analyses. How-ever, randomized trials failed to establish Lp-PLA2 as a therapeutic target. Specifically, pharmaceu-tical inhibition of Lp-PLA2 when compared to the placebo failed to demonstrate a significant asso-ciation with improved prognosis of patients with stable CAD or after an acute coronary syndrome (ACS). This review focuses on the available data that have investigated the potential role of Lp-PLA2 as a biomarker for CAD.
Anticancer Tetrahydrocarbazoles: A Wide Journey from 2000 Till Date
Authors: Kumar Nitin , Gupta Pankaj 
Published: October 2022

Abstract:
Tetrahydrocarbazoles (THCz) are widespread in numerous indole alkaloids and have been
reported since time for exhibiting profound pharmacological potential. Many pharmaceuticals drugs have
tetrahydrocarbazole nucleus in their structure e.g. vinca alkaloids (Vincristine, Vinblastine, Vinorelbine),
Frovatriptan, (R)-Ramatroban, Ondansetron, etc. that are used in various multifactorial diseases. In this
review article, the anticancer potential of tetrahydrocarbazole based derivatives has been covered, enumerating
their vast journey from the year 2000 to 2021. Since the last twenty-one years, tetrahydrocarbazoles
have been a matter of focus among researchers worldwide, whereby several novel tetrahydrocarbazole
derivatives have been synthesized and reported for their anticancer potential against various cancer
cell lines. Tetrahydrocarabzole and its derivatives have exhibited profound anticancer potential mediated
via various cancer pathways like apoptosis, cell cycle arrest, microtubule inhibition, Nrf2 Modulators,
DNA intercalators, pERK and pRb phosphorylation, VEGF (Vascular Endothelial Growth Factor) and
TNF-α inhibition, TPSO (translocator protein), Histone Deacetylase (HDAC) Inhibitors also discussed.
The present review entails the synthesis, SAR studies, and anticancer mechanism of tetrahydrocarbazoles
derivatives reported in review literature till date, and would provide a strong database to the medicinal
chemist world over in discovering newer potential anticancer agent against various types of cancer diseases.
Rational Drug Design and In vitro Cell Line Studies of Some N-(4-(1Hbenzo[
d]imidazol-2-yl)phenyl)arylamine Derivatives as Aromatase Inhibitors
for the Treatment of Cancer
Authors: Sabale Prafulla M. , Sayyad Nusrat B. 
Published: October 2022

Background:
Aromatase is a catalytic enzyme involved in the biosynthesis of estrogen from androgen. It catalyzes the last rate-limiting/crucial critical step in estrogen biosynthesis. Following the success of the aromatase inhibitor, researchers are working on developing a small physiologically active molecule with fewer side effects and improved tolerance.

Objectives:
Inhibition of the aromatase enzyme, which plays a major role in the rate-limiting phase, is one strategy to prevent estrogen synthesis. After knowing the importance of nitrogen atom containing moieties in the treatment of breast cancer, we have designed some N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)arylamine derivatives through in silico screening such as ADMET analysis and molecular docking studies. From the present investigation we aimed for the synthesis and biological evaluation of the most potent derivatives obtained in this study.

Methods:
The selected derivatives were synthesized and confirmed by spectral analysis (FTIR, 1H NMR, and Mass). Cytotoxic activity of the compounds was evaluated by colorimetric MTT assay on MDA-MB-231 (breast adenocarcinoma), MCF-7(breast adenocarcinoma), A549 (lung adenocarcinoma) NCI-H23 (Lung carcinoma) and A-498 (Renal carcinoma) cell line using Doxorubicin hydrochloride as positive control.

Results:
From present investigation, we have concluded that compound 10 [N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-5-amine) is most potent and exhibited -9.5 kcal/mol binding affinity. It has formed conventional hydrogen bonds with ALA306 and THR310. It displayed most promising activity with GI50 value 0.796±0.06 µM, 0.695±0.05 µM, 1.14±0.06 µM, 2.15±0.04 µM, and 0.987±0.07 µM against MDAMB-231, MCF-7, A-549, NCI-H23, and A-498, respectively when compared with Doxorubicin (0.306±0.04 µM, 0.270±0.02 µM, 0.297±0.04 µM, 0.305±0.04 µM, and 0.345±0.09 µM).

Conclusion:
From present investigation it is concluded that the designed molecules had potential to be developed as broad spectrum anticancer agents.
Gefitinib: An Updated Review of its Role in the Cancer Management, its
Nanotechnological Interventions, Recent Patents and Clinical Trials
Authors: Kumar Pankaj , Mangla Bharti , Javed Shamama , Ahsan Waquar , Musyuni Pankaj , Ahsan Aarif , Aggarwal Geeta 
Published: October 2022

Background:
Gefitinib, a tyrosine kinase inhibitor, is effectively used in the targeted
treatment of malignant conditions. It suppresses the signal transduction cascades leading to cell
proliferation in the tumors and is now currently approved in several countries globally as secondline and third-line treatment for non-small cell lung cancer (NSCLC).

Objective:
This review is aimed to summarize the journey of gefitinib as an established anticancer
drug for the management of various cancers. Moreover, this review will focus on the mechanism
of action, established anticancer activities, combination therapy, nanoformulations, as well as recent clinical trials and patents on gefitinib

Methods:
The data for this review was collected from scientific databases such as PubMed, Science Direct, Google Scholar, etc. Recent patents on gefitinib granted in the last two years were
collected from databases Patentscope, USPTO, Espacenet, InPASS and Google Patents. Data for
the recent clinical trials were obtained from the U.S. National Library of Medicine database.

Results:
Recent pre-clinical and clinical studies during the period 2015-2021 demonstrating the
efficacy of gefitinib were selected and summarized. Total 31 patents were granted in the year
2020-2021 concerning gefitinib. The efficacy of gefitinib against lung cancer, as well as other
cancer types, including breast, prostate, colon, cervix etc., was reviewed.

Conclusion:
Gefitinib showed significant advantages in being more effective, safer and more stable, and the associated biopharmaceutical problems are addressed by the application of nanotechnology. The combination therapy using gefitinib and various anticancer molecules of natural and
synthetic origin has shown an improved anticancer profile.
Potential Action of Lactobacillus Probiotics Against Fungi of the
Genus Candida: A Bibliographic Review
Authors: Pimentel Milton Marcus Neves Sousa Carneiro , de Carvalho Alves Janaína , Pinheiro Lúcio Henrique Sousa , Roselino Mariana Nougalli 
Published: October 2022

Background:
The use of Lactobacillus probiotics may confer beneficial effects
on an individual’s health, such as the ability to act against fungi of the genus Candida.
There are about 200 species of those yeasts, and they can develop candidiasis infections,
which affect about 75% of adult women.

Objective:
This study aimed to raise articles that investigated the potential action of several
Lactobacillus strains in front of Candida species.

Method:
For this review, 15 articles published between 2015 and 2020 were studied.

Results:
The results showed the Lactobacillus species L. paracasei, L. acidophilus, L. helveticus,
L. rhamnosus, L. reuteri, and L. gasseri have the potential action to inhibit the
growth and quantity of colony-forming units of Candida species in vitro studies. Further,
they can reduce the rate of candidiasis recurrence and increase the cure rate, mainly when
associated with traditional pharmacotherapy, as observed in vivo studies.

Conclusion:
The time of use and the strain of Lactobacillus probiotics can also be determining
factors for the efficiency in the treatment against Candida species, suggesting that a
long time of use of Lactobacillus probiotics is directly associated with a better result.