bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclotron-Based Production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a Liquid Target
Authors: Rodnick Melissa E , Sollert Carina , Stark Daniela , Clark Mara , Katsifis Andrew , Hockley Brian G , Parr D. Christian , Frigell Jens , Henderson Bradford D , Abghari-Gerst Monica , Piert Morand R , Fulham Michael J , Eberl Stefan , Gagnon Katherine , Scott Peter J. H. 
Published: June 2020

Abstract
Purpose: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module.Methods: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2-0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50-75 min) and beam currents (27-40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use.Results: The decay corrected yield of 68Ga at EOB was typically >3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically >99.8% at EOB and met the requirements specified in the European Pharmacopoeia (<2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically >50% (~1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~1.67GBq, 45mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing , and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators.
Cell differentiation and aging is accompanied by depletion of the ACE2 protein
Authors: Bartova Eva , Legartova Sona , Krejci Jana , Arcidiacono Orazio A. 
Published: June 2020

Abstract
Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase involved in the renin-angiotensin system (RAS). It is well known that ACE and ACE2 are central regulators of blood pressure. Moreover, recently, it was observed that the ACE2 protein is the main target of the SARS-CoV-2 virus, so we have tried to reveal if there is a distinction in the levels of the ACE2 protein in distinct cell types (sensitive to virus infection), during cell differentiation and aging. We observed that depletion of the ACE2 protein appears in aorta-associated parts during the aging of adult mice, and the level of ACE2 was lowest in kidneys of old female animals in comparison to male mice. Differentiation into enterocytes and more pronouncedly into cardiomyocytes was accompanied by depletion of the ACE2 protein. The deficiency of histone deacetylase 1 (HDAC1) also caused a decrease in the level of both ACE2 and its interacting partner renin. However, experimental cardiomyogenesis was associated with renin up-regulation. In human lung adenocarcinoma cells, vitamin D2, but not chloroquine, slightly increased the level of ACE2. Together, the higher level of the ACE2 protein appears in non-differentiated cells and tissue of young mice, in comparisons to terminally differentiated cells and old animals; thus, a higher level of the ACE2 protein, also seen after vitamin D2 treatment, seems to be a barrier against SARS-CoV-2, because it is known that tissues of young individuals are less sensitive to viral infection.
Anthraquinone derivatives as an immune booster and their therapeutic option against COVID-19
Authors: Khanal Pukar , Patil BM , chand Jagdish , Naaz Yasmin 
Published: June 2020

Abstract
Multiple Anthraquinolines derivatives are reported for their immune-boosting, anti-inflammatory and anti-viral efficacy. Hence, the present study dealt to investigate the reported anthraquinone derivatives as an immune booster molecule in COVID-19 infection and evaluate their binding affinity with three reported targets of novel coronavirus i.e. 3CLpro, PLpro and spike proteins. The reported anthraquinone derivatives were retrieved from an open-source database and filtered based on a positive druglikeness score. Further, the probably modulated gene by compounds with positive druglikeness score was evaluated for the modulation of proteins using DIGEP-Pred and the interaction of proteins was evaluated using STRING; associated pathways were recorded concerning the KEGG pathway database. Finally, docking was carried using autodock4; pose scoring minimum binding energy was chosen to visualize the ligand-protein interaction. Among 101 compounds, 36 scored positive druglikeness scores; modulating multiple pathways for immune-boosting as well as pathways involved in infectious and non-infectious diseases. Similarly, docking study revealed torososide B to have the highest binding affinity with PLpro and 3clpro and 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone-3-O-(6'-O-acetyl)-β-D-xylopyranosyl-(1->2)-β-D-glucopyranoside with spike protein
Exploring the impact of cultural variability on COVID-19-related mortality: A meta-analytic approach
Authors: Erman Aysegul , Medeiros Mike 
Published: June 2020

Abstract
Deaths associated with COVID-19 shows a high degree of heterogeneity across different populations. An assessment of the global variability in COVID-19-attributable deaths is essential for predicting the health and economic impact of future outbreaks in different settings. Moreover, a comprehensive understanding of population-level predictors is also crucial for devising better-targeted and more appropriate emergency preparedness measures. While, demographic, economic and health-system capacity have featured prominently in recent work, cultural and behavioural characteristics have largely been overlooked. However, cultural differences likely shape both the public policy response and individuals’ behavioural responses to the crisis in ways that can impact infection dynamics and key health outcomes. To address this gap, we used meta-analytic methods to explore the global variability of COVID-19-attributed deaths during the first-wave of the pandemic and identified cultural/behavioural attributes (e.g., individualism, uncertainty avoidance) as independent predictors of COVID-19 fatalities after adjusting for important demographic, political, economic and health-system-related predictors.
Optimized coagulation of humic acid and mineral turbidity at alkaline pH using high basicity PACl
Authors: Saxena Kanika , Brighu Urmila 
Published: June 2020

Abstract
In this study, the simultaneous removal of inorganic turbidity and organics was investigated at alkaline pH to avert the need for pH adjustment and overdosing. The aim was to compare the doses for conventional and enhanced coagulation and, consequently, arrive at optimized coagulation where both had synergistic maximum removal. High basicity PACl was used to coagulate simulated waters prepared by humic acid (HA) and kaolin. The removal of turbidity, total organic carbon (TOC), dissolved organic carbon (DOC) and UV254 was evaluated. The impact of varying input concentrations of HA and turbidity on doses was studied. The enhanced coagulation doses were higher than conventional ones. However, with an increase in input TOC, the difference between enhanced and conventional doses narrowed. The doses for optimized coagulation ranged from 2 to 9 mg Al/L. At optimized coagulation, the removal of TOC, DOC and UV254 varied from 30–85%, 30–89% and 73–91% respectively. Fourier transform infrared (FTIR) spectroscopy revealed the presence of Si-O-C bond. The interactions of unsaturated bonds of hydrophobic organics to inorganic clay were possibly favoured over hydrophilics. HA agglomeration reduced coagulant consumption as the input TOC increased. It was concluded that instead of a stoichiometric approach, a modified dosing approach can be applied for limiting underdosing and overdosing while ensuring maximum removal of impurities.
Withdrawal Notice: Pharmacological analysis of Cannabis sativa L.: A potent herbal plant
Authors: Husnain Muhammad , Imran Muhammad , Ibrahim Muhammad , Assiri Mohammad Ali , Wattoo Naveed Zubair , Irfan Ahmad 
Published: June 2020

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Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

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Synthesis and Antimicrobial Evaluation of Some Novel Pyrimidine, Pyrazole, Chromene and Tetrahydrobenzo[b]thiophene Derivatives Bearing Pyrimidinthione Moiety
Authors: Reheim Mohamed Ahmed Mahmoud Abdel , Hafiz Ibrahim Saad Abdel , Elian Mohamed Ahmed 
Published: June 2020

Aim and Objective:
A novel collection of fused pyrimidine, pyridine, pyrazole, chromene and thiophene
derivatives 2-30 have been newly synthesized by using the 1a, b as starting material. Fused pyrane exhibits
a range of pharmacological activity such as cancer agents [1], antimicrobial [2-4], antioxidant [5], antiproliferative
[6], cytotoxic activity [7], anticipated antitumor [8], antiparkinsonian [9] and anti-inflammatory [10].
Moreover, pyrane derivatives are well known for bacterial biofilm disruptor [11], anticonvulsant [12] and inhibitors
of mycobacterium bovis [13].

Materials and Methods:
All melting points were measured using the Akofler Block instrument and are uncorrected.
IR spectra (KBr) were recorded on a FTIR 5300 spectrometer (υ, cm-1). The 1H-NMR spectra were recorded
on a Varian Gemini spectrometer. The 1H-NMR spectra were run at 300, 400 MHz and 13C-NMR spectra
were run at 100 MHz in DMSO-d6, CDCl3 as solvents. The chemical shifts are expressed in parts per million
(ppm) by using tetramethylsilane (TMS) as an internal reference, 1000 EX mass spectrometer at 70 eV. The purity
of synthesized compounds was checked by thin-layer chromatography (TLC) (aluminum sheets) using nhexane,
EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical Research
Center, Faculty of Science, and Microanalytical Unit, Faculty of Pharmacy, Cairo University, Egypt.

Results and Discussion:
A novel series of azoles and azines were designed and prepared via the reaction of 7-amino-
5-(4-chlorophenyl)-4-phenyl-2-thioxo-2,5-dihydro-1H-pyrano- [2,3-d]pyrimidine-6-carbonitrile 1a and 7-amino-4,5-
diphenyl-2-thioxo-2,5-dihydro-1H-pyrano[2,3-d]-pyrimidine-6-carbonitrile 1b with some electrophilic and nucleophilic
reagents. The structures of target compounds were confirmed by elemental analyses and spectral data. The
novel synthesized compounds showed good antimicrobial activity against the previously mentioned microorganisms.

Conclusion:
In conclusion, compounds 1a, 1b underwent ready cyclization to give fused heterocyclic compounds
through reaction with different reagents and under different conditions and subjected to antimicrobial screening.
Evaluating Phenyl Propanoids Isolated from Citrus medica as Potential Inhibitors for Mitotic kinesin Eg5
Authors: Makala Himesh , Ulaganathan Venkatasubramanian , Sivasubramanian Aravind , Rajendran Narendran , Subramanian Shankar 
Published: June 2020

Background:Human mitotic kinesins play an essential role in mitotic cell division. Targeting the spindle separation phase of mitosis has gained much attention in cancer chemotherapy. Spindle segregation is carried out mainly by the kinesin, Eg5. Many Eg5 inhibitors are in different phases of clinical trials as cancer drugs. This enzyme has two allosteric binding sites to which the inhibitors can bind. The first site is formed by loop L5, helix α2 and helix α3 and all the current drug candidates bind un-competitively to this site with ATP/ADP. The second site, formed by helix α4 and helix α6, which has gained attention recently, has not been explored well. Some inhibitors that bind to this site are competitive, while others are uncompetitive to ATP/ADP. Phenylpropanoids are pharmacologically active secondary metabolites.Methods:In this study, we have evaluated fourteen phenyl propanoids extracted from Citrus medica for inhibitory activity against human mitotic kinesin Eg5 in vitro steady-state ATPase assay. Ther interactions and stability using molecular docking and molecular dynamics simulations.Results and Discussions:Of the fourteen compounds tested, naringin and quercetin showed good activity with IC50 values in the micromolar range. Molecular docking studies of these complexes showed that both the molecules interact with the key residues of the active site predominantly thorough hydrophobic & aromatic π–π interactions consistent with the known inhibitors. Besides, these molecules also form hydrogen bonding interactions stabilizing the complexes. Molecular dynamics simulations of these complexes confirm the stability of these interactions.Conclusion:These results can be used as a strong basis for further modification of these compounds to design new inhibitors with higher potency using structure-based drug design.
A New Stability-indicating Chiral RP-HPLC Method for the Determination of Degradation Products in Meclizine Hydrochloride
Authors: Gowramma Bryan , Kumar Ramachandran Senthil , Lakshmanan Kaviarasan , Kalirajan Rajagopal , Meyyanathan Subramania Nainar 
Published: June 2020

Background:An enantiomeric separation of the stability-indicating high-performance liquid
chromatographic method was developed and validated for the analysis of Meclizine enantiomers. The
degradation behavior of Meclizine Hydrochloride was investigated under different stress conditions
recommended by the International Conference on Harmonization (ICH).

Methods:Enantiomeric resolution of the drug and complete separation from its degradation products
were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 μm particle
size) column, using UV detector at a wavelength of 230 nm, with a mobile phase consisting of acetonitrile,
20mM ammonium bicarbonate at the ratio of 75:25 (v/v), and a flow rate of 1 mL/min. The
drug was subjected to alkaline, acidic, neutral, oxidative and photolytic conditions in order to mimic
stress conditions.

Result:The degradation products were well resolved from main peak and proving the stability-indicating power of the
method. The developed method provided linear responses within the concentration range 1-5 µg/mL, and regression
analysis showed a correlation coefficient value (r2) of 0.999. The HPLC method was validated as per ICH guidelines with
respect to specificity, precision, linearity and robustness. Limit of detection (LOD) and limit of quantification (LOQ) were
found to be 0.25 µg/mL and 1.00 µg/mL respectively.

Conclusion: The method provides good sensitivity and excellent precision and reproducibility. The method was highly
selective, where degradation products and co formulated compounds did not interfere. The proposed method was
successfully applied in pharmaceutical preparations.
Potential Cytokine Biomarkers in Intellectual Disability
Authors: Benmakhlouf Yousra , Zian Zeineb , Nourouti Naima G. , Barakat Amina , Mechita Mohcine B. 
Published: June 2020

:
Intellectual disability (ID), previously called mental retardation, is the most common neurodevelopmental
disorder characterized by life-long intellectual and adaptive functioning impairments
that have an impact on individuals, families, and society. Its prevalence is estimated to 3% of the general
population and its etiology is still insufficiently understood. Besides the involvement of genetic
and environmental factors, immunological dysfunctions have been also suggested to contribute to the
pathophysiology of ID. Over the years, immune biomarkers related to ID have gained significant attention
and researchers have begun to look at possible cytokine profiles in individuals suffered from this
disorder. In fact, in addition to playing crucial physiological roles in the majority of normal neurodevelopmental
processes, cytokines exert an important role in neuroinflammation under pathological
conditions, and interactions between the immune system and central nervous system have long been
under investigation. Cytokine levels imbalance has been reported associated with some behavioral
characteristics and the onset of some syndromic forms of ID.

:
In this review, we will focus on immunological biomarkers, especially the cytokine profiles that have
been identified in people with ID. Thus, data reported and discussed in the present paper may provide
additional information to start further studies and to plan strategies for early identification and managing
of ID.
Ruta Montana Evokes Antihypertensive Activity Through an Increase of Prostaglandins Release in L-NAME-Induced Hypertensive Rats
Authors: El-Ouady Fadwa , Eddouks Mohamed 
Published: June 2020

Aims:
The aim of the study was to experimentally investigate the antihypertensive effect of
Ruta Montana.

Background:
Ruta montana L. is traditionally used in Moroccan herbal medicine to treat hypertension.
This study aimed to experimentally evaluate the hypotensive and vasoactive properties of this plant.

Objective:
The objective of the study was to evaluate the effect of the aqueous extract of Ruta Montana
on blood pressure parameters in LNAME-induced hypertensive rats and to determine the vasorelaxant
activity of this aqueous extract.

Methods:
The antihypertensive effect of the aqueous extract obtained from Ruta montana aerial parts
(RMAPAE) (200 mg/kg) was evaluated in normal and anesthetized hypertensive rats. Blood pressure
parameters (systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure
(DBP)) and heart rate were measured using a tail-cuff and a computer-assisted monitoring device. The
acute and chronic effect of RMAPAE was recorded for 6 hours for the acute experiment and for 7 days
for the sub-chronic test. In the other set, the vasorelaxant effect of RMAPAE on the contractile response
was observed in the isolated thoracic aorta.

Results:
The results indicated that the RMAPAE extract significantly decreased SBP, MBP, DBP and
heart rate in L-NAME-induced hypertensive rats. Furthermore, RMAPAE was demonstrated to induce
a dose-dependent relaxation in the aorta precontracted with Epinephrine or KCl. More interestingly,
this vasorelaxant activity of RMAPAE seems to be probably mediated through the prostaglandins
pathway.

Conclusion:
The present study illustrates the beneficial action of Ruta montana on hypertension and
supports its use as an antihypertensive agent.
Dapsone-Loaded Microsponge Gel for Acne Management: Preparation, Characterization and Anti-Microbial Activity
Authors: Rao Rekha , Jakhar Seema , Kadian Varsha 
Published: June 2020

Background:
Acne vulgaris is a chronic inflammatory disorder involving Propionibacterium
acnes and activation of lymphocytes and neutrophils. Dapsone (sulfone drug) possesses potent
anti-microbial activities and hence, it is used to cure multiple inflamed acne lesions. Howbeit, its therapeutic
utility is hampered, owing to its poor solubility and side effects like mild irritation and dryness.
These problems, along with orange-brown discoloration on skin, restrict the topical application
of this drug.

Objective:
The objective of the present investigation was to address the above-mentioned limitations
like irritation, dryness, and skin discoloration of dapsone via formulating microsponge based gel of
this moiety.

Methods:
Dapsone microsponges were fabricated and embedded into a carbopol gel for topical application.
The drug loaded ethylcellulose microsponges were crafted employing a quasi emulsion solvent
diffusion technique. Besides routine characterization, these microformulations were assessed for entrapment,
particle size analysis, and drug release. Furthermore, anti-acne potential was also evaluated
against Propionibacterium acnes and Staphylococcus aureus to check their therapeutic efficiency. The
prepared dapsone microsponge gel was assessed for its viscosity, spreadability, texture, and drug release.

Results:
Results revealed that dapsone loaded microsponges were successfully fabricated and found to
possess good encapsulation efficiency (84.68 ± 5.73%), which is in micro-size range (88.06 ± 2.97 μm
to 315.87 ± 1.99 μm) and showed cumulative drug release of 52.52 ± 0.2%. Field emission scanning
electron microscopy illustrated spherical, uniform, and spongy microparticles. The developed micro
formulation showed promising activity against the chosen acne bacterias and improved stability.

Conclusion:
The obtained results corroborate the premise that dapsone loaded microsponge gel can be
an effective strategy for acne management.
Design of Cellulose Derivative and Alginate Based Smart Polymers to
Develop Stomach Specific Floating Drug Delivery System
Authors: Sharma Vikrant , Devi Jogindera 
Published: June 2020

Background:
Polysaccharide based gastro-retentive drug delivery systems (GRDDSs) can retain in the gastric
fluid of stomach for longer time and release entrapped drug in controlled and localized manner, which can ensure optimal
drug concentration at the site of action with improved bioavailability and reduced side effects of acid suppressive drugs
like ranitidine.

Objective:
The objective of present study was to design smart polymers for gastro-retentive drug delivery of ranitidine
through ionic-gelation of carboxymethyl cellulose (CMC) and sodium alginate (ALG).

Methods:
The optimal reaction conditions for synthesis of beads were evaluated by varying reaction parameters during
synthesis and were obtained as [CMC] = 1.5% (w/v), [ALG] = 0.5% (w/v) and [CaCl2] = 0.1 M with maximum
equilibrium swelling ratio (2922.50±0.90)%. The drug loading was carried out by simultaneous and swelling equilibrium
methods. Beads were characterized by SEM, PXRD, FTIR, TGA, bead size and swelling studies.

Results:
Increase in Ca2+ ions and ALG concentration resulted in decrease in swelling capacity and increase in bead size.
Beads got collapsed in phosphate buffer solution and swelling had been occurred through non-Fickian diffusion
mechanism. Floating beads with (51.05±0.25)% entrapment efficiency for simultaneous drug loading method exhibited
Fickian diffusion mechanism and best fitted in Higuchi model. The diffusion coefficient and initial rate of drug release in
simulated gastric fluid demonstrated swelling controlled gastro-retentive release of ranitidine.

Conclusion:
These smart polymeric beads have potential to use as a promising candidate for the design of GRDDSs
meant for the treatment of gastric ulceration and gastro-oesophageal reflux disease.