bluuebunny/crossref_metadata_2025_split huggingface dataset:
pH Sensitive Interpenetrating Network Bio Containers of Gum Ghatti for Sustained Release of Glipizide
Authors: Ray Somasree , Bera Mohua , Bhattacharyya Uttam Kumar , Das Samarpita , Seth Shalmoli , Pal Pallab Kumar , Aziz Abdul 
Published: October 2019

Objective:
A novel natural polymer, Gum Ghatti (GG) was explored to develop a new polymeric
system that will combine the biodegradable and biocompatible properties of GG and mechanical
properties of poly vinyl alcohol (PVA) for drug delivery application.

Methods:
Smart pH sensitive, porous, glutaraldehyde (GA) crosslinked interpenetrating network (IPN)
microspheres loaded with glipizide were developed by the emulsion crosslinking method. The drug
entrapment efficiency was 92.85±1.5%. FTIR confirmed the formation of IPN structure. Drug release
can be extended upto 7 hours by modulating the concentration of crosslinking agent. Swelling study and
diffusion co-efficient (D) of water transport were performed in order to understand the phenomenon of
water penetration through the microsphere. In vivo antidiabetic activity performed on alloxane induced
diabetic rats indicated that in case of pure glipizide sudden reduction of elevated blood glucose was
observed after 3 hours.

Results:
In case of rats treated with glipizide loaded IPN microparticles, the initial percentage reduction
of blood glucose level was slow within the first 3 hours of administration, as compared to pure glipizide
but after 6 hours 90% reduction was observed which confirmed sustained release nature of microspheres.

Conclusion:
Thus IPN microparticles were found suitable for sustained delivery of BCS class II drug
glipizide.
In Silico Identification and Molecular Characterization of Extracellular Cathepsin L Proteases from Giardia duodenalis
Authors: Durán-Pérez Sergio A. , Rendón-Maldonado José G. , de Jesús Hernandez-Diaz Lucio , Apodaca-Medina Annete I. , Jiménez-Edeza Maribel , Montes-Avila Julio 
Published: October 2019

Background:
The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal
parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic
cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption
syndrome. Little is currently known about the virulence of the parasite, but some cases of
chronic gastrointestinal alterations post-infection have been reported even when the infection was
asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage
at the level of the gastrointestinal mucosa.

Objective:
The aim of this study was the in silico identification and characterization of extracellular
cathepsin L proteases in the proteome of G. duodenalis.

Methods:
The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against
the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L
proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the
extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software
(MEGA X). The Robetta server was used for the construction of the three-dimensional models. The
search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas
performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool.

Results:
Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences
were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins
and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional
models were designed for both extracellular proteins and several inhibitory ligands with a
score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular
proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be
useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite.

Conclusion:
In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose
characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the
extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the
identification of inhibitory ligands with a high score. The results suggest that administration of those
compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases,
interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.
Phosphoproteomic Analysis of Spiroplasma eriocheiris and Crosstalk with Acetylome Reveals the Role of Post-Translational Modifications in Metabolism
Authors: Liu Peng , Hou Libo , Liu Min , Xu Xuechuan , Gao Qi , Deng Jiewen , Xiang Shasha , Cao Qian , Zhou Min , Yang Quanjie , Wang Wen , Gu Wei , Meng Qingguo 
Published: October 2019

Background:
Post-translational modifications (PTMs) such as phosphorylation are an essential regulatory mechanism of protein function and associated with a range of biological processes beyond genome and transcriptome. Spiroplasma eriocheiris, a wall-less helical bacterium, is one of the smallest known self-replicating bacteria and a novel pathogen of freshwater crustacean.

Methods:
To study the physiological characteristics and regulatory mechanism of S. eriocheiris, the protein phosphorylation in the bacterium were systematically investigated by iTRAQ analyzed by LC-MS/MS. Data are available via ProteomeXchange with identifier PXD015055.

Results:
We identified 465 phosphorylation sites in 246 proteins involved in a broad spectrum of fundamental biological process ranging from regulation of metabolic pathways to protein synthesis. Notably, most proteins in glycolysis and all proteins in the arginine deiminase system were phosphorylated. Meanwhile, the cytoskeleton proteins (Fibril, Mrebs and ET-Tu) were all phosphorylated suggest that the phosphorylation also may play a crucial role in cell skeleton formation. We have got a lot of highly conserved proteins and phosphorylation sites by analysis, and those proteins or phosphorylation sites were mainly participated in glucose metabolism and protein synthesis. Crosstalk analysis with protein-protein interaction networks in relation to phosphorylated proteins and acetylated proteins found that the two PTMs are required for playing crucial roles in many physiological processes in S. eriocheiris. By comparing the relative positions of acetylation versus phosphorylation, we found that the two modifications often found close to proximity on the same protein.

Conclusions:
The results imply that there is previously unreported hidden role of phosphorylation that define the functional state of Spiroplasma.
Cationic Ruthenium-Catalyzed Bis-Homo-Diels-Alder Cycloaddition
Authors: Petko Dina , Stratton Matthew , Koh Samuel , Tam William 
Published: October 2019

Objective:
The ruthenium-catalyzed Bis-Homo-Diels-Alder cycloaddition between 1,5-
cyclooctadiene and alkynes was explored, and the use of commercially available cationic catalysts was
investigated. It was noted that [CpRu(CH3CN)3]PF6 was effective at catalyzing this cycloaddition and yields of
the desired tricyclo[4.2.2.02,5]dec-7-ene adduct ranging from 13 to 83% were achieved using this cationic
catalyst. Several cycloadducts that were previously unobtainable with the use of the neutral (Cp*RuCl(COD)
catalysts were also successfully made using [CpRu(CH3CN)3]PF6 albeit in low yields.

Methods:
Commercially available, and previously synthesized alkynes were combined with 1,5-cyclooctadiene
and treated with a ruthenium catalyst within a glovebox. The reaction mixture was stirred for 72h at temperatures
ranging from 25 to 70oC. The desired cycloadduct was then isolated using flash column chromatography
and analyzed and characterized using NMR, IR and MS.

Results:
Several previously unattainable adducts were synthesized using the cationic [CpRu(CH3CN)3]PF6.
When this catalyst was compared to the neutral Cp*RuCl(COD) greater yields were observed.

Conclusion:
The present study describes an improved method for the formation of the tricyclo[4.2.2.02,5]dec-7-
ene framework using a commercially available cationic ruthenium catalyst. It was noted that the use of
[CpRu(CH3CN)3]PF6 led to improved yields when compared to Cp*RuCl(COD).
Synthesis, Antioxidant Activity, and Determination of Binding Parameters of Meso-Tetra-4-Actophenyl-Porphyrin and its Palladium (II) Complex with Superoxide Anion Radicals
Authors: Boutarfaia Amira , Bechki Lazhar , Lanez Touhami , Lanez Elhafnaoui , Kadri Mohamed 
Published: October 2019

Background:
Meso-tetra-4-actophenyl-porphyrin (TAcPPH2) was synthesized by reacting 4-
acetyl-benzaldehyde with pyrrole in propionic acid, and used as a ligand for the synthesis of palladium
(II) complex (PdTAcPP). The structure of the ligand and the complex were characterized by NMR and
electronic spectroscopy.

Methods:
he antioxidant activity and the binding parameters of both the ligand and its complex with
superoxide anion radical .
(O2 -) were measured using cyclic voltammetry based assay. The assays were
based on the measurement of the anodic peak current density of .
O2− electrochemically generated by
reduction of molecular oxygen in DMF.

Results:
The complex PdTAcPP showed the highest antioxidant activity (0.73 ± 0.01 mg/mL) which is
four times higher than that of the standard antioxidant α-tocopherol (3.04 ± 0.03 mg/mL).

Discussion:
Binding parameters like binding constants, the ratio of binding constants and binding free
energies were also measured.

Conclusion:
The value of the binding free energy ranging from -7.89 kJmol-1 for TAcPPH2 to -17.59
kJ.mol-1for PdTAcPP suggests an electrostatic interaction of .
O2− with TAcPPH2 and PdTAcPP which
has been found to be the dominant interaction mode. The kinetics of the interaction reaction of the
ligand and complex was quantified having second-order rate constant values equal to 0.2 and 1.3 M-1 s-1,
respectively.
First-in-Human Study of the Safety, Tolerability, Pharmacokinetics and - Preliminary Dynamics of Neuroprotectant 2-Iminobiotin in Healthy Subjects
Authors: van Hoogdalem Ewoud-Jan , Peeters-Scholte Cacha M.P.C.D. , Leufkens Paul W.T.J. , Hartstra Jan , van Lier Jan J. , de Leede Leo G.J. 
Published: October 2019

Background:
2-iminobiotin (2-IB) is an investigational neuroprotective agent in development
for the reduction of brain cell injury after cerebral hypoxia-ischemia.

Objective:
The present first-in-human study evaluated the safety, tolerability, pharmacokinetics
(PK) and -dynamics (PD) of 2-IB in healthy male subjects, intravenously infused with or without
Captisol® as a solubilizing agent.

Methods:
This randomized, double-blind, placebo-controlled, dose-escalation study was executed
in 2 groups of 9 healthy male subjects. A single dose of 2-IB 0.6 mg/kg or placebo was infused over
periods between 15 min and 4 h, and repeated doses escalating from 0.6 mg/kg to 12 mg/kg, or
placebo were infused every 4 h for 6 administrations in total.

Results:
Single and multiple doses of 2-IB up to 6 doses of 6 mg/kg with and without Captisol®
were safe and well-tolerated in healthy male subjects. 2-IB proved to be a high-clearance drug with
a volume of distribution slightly exceeding total body water volume, and with linear PK that appeared
not to be affected by the presence of Captisol®.

Conclusion:
Sulfobutyletherbeta-cyclodextrin (SBECD) in Captisol® had a low-clearance profile
with a small volume of distribution, with time-independent PK. Preliminary PD characterization of
repeated iv dosing of 2-IB in an acute peripheral hypoxic ischemia model in healthy subjects did
not reveal any notable effects of 2-IB, noting that this model was not selected to guide efficacy in
the currently pursued indication of cerebral hypoxia-ischemia.
The “Scourge of the Renaissance”. A Short Review AboutTreponema palliduminfection
Authors: Santacroce Luigi , Bottalico Lucrezia , Topi Skender , Castellaneta Francesca , Charitos Ioannis A. 
Published: October 2019

Background:There is not a time in the history when epidemics did not loom large: infectious diseases have always had civilisation and evolution-altering consequences. Throughout history, there have been a number of pandemics: cholera, bubonic plague, influenza, smallpox are some of the most brutal killers in human history. Historical accounts of pandemics clearly demonstrate that war, unhygienic conditions, social and health inequality create conditions for the transmission of infectious diseases, and existing health disparities can contribute to unequal morbidity and mortality. The Renaissance was a period of European cultural, artistic, political and economic “rebirth” following the Middle Ages, but it was also the time when new infectious disease appeared, such as Syphilis. The epidemic spread of Syphilis began between the late 15th century and early 16th century due to the increased migration of peoples across Europe. The rapid spread of venereal syphilis throughout Europe suggests the introduction of a disease into a population that had not previously been exposed. Syphilis is a type of treponematosis, which includes syphilis, bejel, yaws, and pinta, but, while syphilis is venereal disease, the others are nonvenereal. Syphilis was, at the beginning, a disease of great severity due to its novelty, as the population had no time to gain any immunity against this venereal disease.Methods:The purpose of this study is to investigate the origin of syphilis and the evolution of the treatments from the empiric means to the discovery of penicillin, but also to understand how this venereal disease has largely influenced human lifestyle and evolution.Conclusions:The first of the three hypotheses about its origins is the Columbian hypothesis, which states that Columbus's crew acquired syphilis from Native Americans and carried it back to Europe in 1493 A. D. On the contrary, the second hypothesis (pre-Columbian) asserts that syphilis was present in Europe long before Columbus's voyage and was transferred to the New World by Columbus's men. The Unitarian theory argues that syphilis, bejel, yaws, and pinta are not separate diseases but they represent syndromes caused by slightly different strains of one organism. Nowadays, Syphilis’ origin is still uncertain and remains controversial. However, the large impact on the social behavior and international public health is an important reason to investigate about its origins and how to prevent the transmission.
Evolution of World and Brazilian Markets for Enzymes Produced by Solid-state Fermentation: A Patent Analysis
Authors: Rodrigues Heb C.S.R. , Carvalho Andrea L. , Souza Carolina O. , Umsza-Guez Marcelo A. 
Published: October 2019

Background:
The use of enzymes in various industrial processes has become increasingly frequent. When added to productive processes, it can accelerate reactions and generate a number of new products. The solid state fermentation (SSF), among other applications, has been employed also to obtain enzymes.

Objective:
The purpose of this prospection was to map registered patent documents about enzymes
production by this type of fermentation in the world, identify the most obtained enzymes with patent
documents and compilate information about the world and Brazilian enzyme markets.

Methods:
The experimental design was carried out by the keyword-driven scope through the advanced
search in the Espacenet database European Patent Office (EPO). The keywords selected
were solid-state fermentation and the International Patent Classification code, C12N9 (enzymes;
proenzymes), for prospecting of interest.

Results:
In 2012, there was the higher number of registered patents (12). China holds 84% of deposited
patents. Among the types of depositors, 54% of the selected patent documents were deposited
by universities and institutes, and 44% by companies. 76.5% of the evaluated patents used
fungi as enzyme producer. Analyzing the enzymes obtained in the registered patents, it is verified
that the majority belongs to the group of carbohydrases with 43%, followed by proteases (25%),
which are also the two classes of enzymes most commercialized in the market.

Conclusion:
China holds the majority of the registered patents but North America gets the largest
global enzyme market revenue followed by Europe and Pacific Asia. Carbohydrases were the
most commercialized enzymes and with the highest number of patents registered. Among the carbohydrases,
cellulases, xylanases and amylases are the most frequent in patent registration while
being fungi produced.
Potential of Radiolabeled PSMA PET/CT or PET/MRI Diagnostic Procedures in Gliomas/Glioblastomas
Authors: Bertagna Francesco , Albano Domenico , Cerudelli Elisabetta , Gazzilli Maria , Giubbini Raffaele , Treglia Giorgio 
Published: October 2019

Background:
Radiolabeled prostate-specific membrane antigen PSMA-based PET/CT or
PET/MRI is a whole-body imaging technique currently performed for the detection of prostate cancer
lesions. PSMA has been also demonstrated to be expressed by the neovasculature of many other solid
tumors.

Objective:
The aim of this review is to evaluate the possible diagnostic role of radiolabeled PSMA
PET/CT or PET/MRI in patients with gliomas and glioblastomas, by summarizing the available literature
data.

Methods:
A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane
library databases was conducted to find relevant published articles about the diagnostic performance
of radiolabeled PSMA binding agents in PET/CT or PET/MRI imaging of patients with suspected
gliomas or glioblastomas.

Results:
Seven case reports or case series and 3 studies enrolling more than 10 patients showed that
gliomas and glioblastoma are PSMA-avid tumors.

Conclusion:
Radiolabeled PSMA imaging seems to be useful in analyzing glioma/glioblastoma. Further
studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of
radiolabeled PSMA in this setting and its possible position in the diagnostic flow-chart.
Watershed fragility Assessment: a Methodological Approach of Siltation and Pollution Vulnerability on a Rural Watershed in Ibiúna (Southeastern Brazilian Region)
Authors: Da Veiga Denise Piccirillo Barbosa , Cruz Bruna Botti , Nardocci Adelaide Cassia , Manfré Luiz Augusto , Machado Cláudia Aparecida Soares , Quintanilha José Alberto 
Published: October 2019

Background:
The São Paulo State area has been facing a water crisis that caused
water shortage in many cities, and a series of socioeconomic problems as an outcome. Water
supply massive land-use alteration throughout São Paulo State river basins, coupled with
climate change effects might produce severe damage to the region if preventive actions are
not enforced in time.

Objective:
This study aims to apply an adapted methodology of fragility analysis to a tributary
of the Itupararanga reservoir (Brazil) using a hydrological modeling tool. Based on the
determination of the flow and drainage system direction and object-based image analysis, a
final map of the fragility will be constructed.

Methods:
This paper presents a fragility assessment methodology on a local scale using a
rural watershed of the study area. This approach uses object-based classification of topography
data from Shuttle Radar Topography Mission to extract the most fragile territorial units
of the watershed area, in terms of pollution and siltation contribution risk, combined with
land cover classification.

Results:
The study area exhibits very high and medium fragility areas related to water contamination
and siltation risk that can be seen as priority areas for land cover management
and monitoring, although most of the basin area was classified as very low fragility.

Conclusion:
The methodology applications have great potential uses in territorial planning,
protected areas and restoration priorities delimitation, ecological-economic zoning, hazard
evaluation and mitigation, erosional processes and water protection and management at
both local and regional scale studies.
Study Design Guidelines
Authors: Sereda A. P. , Andrianova M. A. 
Published: October 2019

Complying with certain requirements or, more precisely, following the guidelines for the design of a scientific publication helps to make it not only more comprehensible for reviewers and readers, but actually enhances the quality of work. For example, even if some aspects in design logic were fulfilled but not described, other researchers doing meta-analysis may wrongly but for a good reason downgrade such publication and exclude it from the analysis. Understanding of the guidelines for study design ensures not only the proper description of the results but the initial planning of work. The CA RE guidelines were established for reporting of clinical cases, STROBE — for reporting observational studies (cohort and case-control studies), CO NSORT — for reporting randomized studies (these guidelines are often used also for other comparative and case series studies), STARD — for reporting diagnostic studies, and PRISMA — for reporting of systematic reviews and meta-analyses. The present paper describes the key aspects of those guidelines and provides templates for graphic display of study design in form of flow charts. Evidently, we should not forget that each study is unique and there is always a place for a reasonable compromise between “requirements” and the real logic of the research in place.
Long-Term Results of Total Hip Arthroplasty with RM Classic Cups
Authors: Danilyak V. V. , Klyuchevsky V. V. , Molodov M. A. , Goryunov E. V. , Marchenkova K. V. 
Published: October 2019

Relevance. The RM Classic monoblock titanium-coated polyethylene cup is widely used in the total hip arthroplasty. However, so far in Russia there has been no analysis of follow-up over 10 years for a limited number of patients in a single hospital. The aim of the study was to evaluate the long-term outcomes of total hip replacement with RM Classic acetabular component. Materials and Methods. The outcomes of 328 total hip arthroplasties (289 patients operated in the period from 1997 to 2007) with RM Classic cups were evaluated in a monocentral retrospective clinical study. The average follow-up period was 14.4 years. Revision procedure due to aseptic loosening, polyethylene wear or osteolysis was considered as the end point of the study. Results. 9 revisions during the short and medium follow-up periods (up to 10 years) were associated with malpositioning of RM Classic components and errors in surgical technique. The indications for later revision THA (19 cases) were polyethylene wear and aseptic loosening. Only in one case they were combined with pelvic bone osteolysis with the formation of III a defect according to W.G. Paprosky classification. Within 15 years the Kaplan-Meier survivorship of RM Classic cup was 92.5%. There was a statistically significant difference of the survival curves in the ceramic-on-poly against metal-on-poly bearings: 94.9% and 79.4%, respectively. The average Harris Hip Score was 88.6. Conclusion. RM Classic uncemented monoblock cup has proven its high efficiency and survival in 15 years follow-up period and over.