bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound-assisted Synthesis of 6-substituted indolo[2,3-b]quinolines: their Evaluation as Potential Cytotoxic Agents
Authors: Marepu Nagaraju , Gosi Mahesh , Vedula Santhoshi Sumana , Yeturu Sunandamma , Pal Manojit 
Published: April 2019

<p>Background: The indolo[2,3-b]quinoline framework is often found in various natural products
displaying a range of pharmacological activities. This is an attractive template for the design and
discovery of potential drugs especially for the identification of new anticancer agents.

Methods:
The synthesis of 6-substituted indolo[2,3-b]quinolones was undertaken and carried out using
a ultrasound assisted method involving two sequential C-N bond forming reactions between 3-(2-
bromophenyl)-2-chloroquinoline and amines in a single pot in the presence of Pd(OAc)2 and a ligand
(S)-BINAP. All the synthesized compounds were tested in vitro against two cancer cell lines e.g.
MCF7 and HepG2 along with non-cancerous HEK293 cell lines.

Results:
Two of these compounds showed promising and selective growth inhibition of MCF7 cell
lines and one induced significant apoptosis in cancer (MCF7) cells.

Conclusion:
Compounds based on indolo[2,3-b]quinolone framework may be useful for the identification
of new cytotoxic agents thereby potential cure for breast cancer.</p>
Synthesis and Neuroprotective Biological Evaluation of Quinazolinone Derivatives via Scaffold Hopping
Authors: Yang Fan , He Wei-Ping , Yao Jia-Qi , Zou Dong , Chen Pu , Li Jie 
Published: April 2019

Objective:
To develop efficient method for the synthesis of quinazolinone derivatives bearing
different functional groups on ring A and ring B and evaluation as neuroprotective agents.

Methods:
Synthetic route to quinazolinone derivatives was furnished by condensation/cyclocondensation/
reduction sequence of the activated N-acylbenzotriazoles. The structures of the targets compounds
have been deduced upon their spectral data (1HNMR, 13CNMR and Mass spectroscopy). The
neuroprotective activities of the synthesized compounds are also evaluated.

Results:
Preliminary screening on a MPP+ induced SH-SY5Y cell injury model of the synthesized compounds
resulted in four compounds (6q, 6r, 6u, and 8e) showed promising neural cell protection activities. The action
mechanisms of these compounds on neuroprotection were then analyzed by docking and reverse docking
modeling.

Conclusion:
A series of quinazolinone derivatives, including different substitution types on rings A and B
were designed and synthesized via scaffold hopping. With the help of neuroprotective biological evaluation,
several efficient therapeutic neuroprotective agents were found for further evaluation as drug candidate against
neurodegenerative disorder.
Solvent-free Methods for Co-crystal Synthesis: A Review
Authors: Kumar Saroj , Prakash Om , Gupta Amresh , Singh Satyawan 
Published: April 2019

Background:
Pharmaceutical co-crystals are the homogeneous crystalline substances composed of
two or more substances bound together in the same crystal lattice via noncovalent interactions like hydrogenbonding,
electrostatic interaction and Vander Waals interactions. Currently, co-crystals provide excellent
opportunities to the formulation scientists in developing new pharmaceutical products by improving the
pharmaceutically significant properties like solubility, dissolution rate, bioavailability, stability, and some other
derived properties. Due to their ability to improve pharmacokinetic performance and their important
intellectual property status, co-crystals are likely to have a very significant role in future drug development.
Thus, formulation scientists have their focus on the development aspects of a co-crystallization process that
include a rational selection of co-former, the discovery of novel synthetic procedures and new characterization
techniques, and large scale production of these novel materials.

Objective:
The objective of this article is to present an extensive review of solvent-free methods for co-crystal
synthesis, mainly focusing on the principle mechanisms, advantages, and drawbacks of each method.

Conclusion:
From the review of the topic, it is clear that the solvent-free methods can offer numerous advantages
over solvent-based methods in the design and the production of co-crystals of pharmaceutical use and
these methodologies can also pave the path to advancing the field of co-crystal synthesis. Some of the advantages
accompanied with solvent-free methods are the use of no or very less amount of solvent(s), exceptional
purity and quality of produced co-crystal, large scale production and the short reaction times in few cases.
Environmental (Lifestyle) Risk Factors for LADA
Authors: Carlsson Sofia 
Published: April 2019

<P>Background: In order to prevent diabetes it is important to identify common, modifiable
risk factors in the population. Such knowledge is extensive for type 2 diabetes but limited for autoimmune
forms of diabetes.
</P><P>
Objective: This review aims at summarizing the limited literature on potential environmental (lifestyle)
risk factors for LADA.

Methods:
A PubMed search identified 15 papers estimating the risk of LADA in relation to lifestyle.
These were based on data from two population-based studies; one Swedish case-control study and one
Norwegian cohort study.

Results:
Studies published to date indicate that the risk of LADA is associated with factors promoting
insulin resistance and type 2 diabetes such as overweight, physical inactivity, smoking, low birth
weight, sweetened beverage intake and moderate alcohol consumption (protective). Findings also indicate
potential effects on autoimmunity exerted by intake of coffee (harmful) and fatty fish (protective).
This supports the concept of LADA as being a hybrid form of diabetes with an etiology including factors
associated with both insulin resistance and autoimmunity.

Conclusion:
LADA may in part be preventable through the same lifestyle modifications as type 2 diabetes
including weight loss, physical activity and smoking cessation. However, current knowledge is
hampered by the small number of studies and the fact that they exclusively are based on Scandinavian
populations. There is a great need for additional studies exploring the role of lifestyle factors in the development
of LADA.</P>
The Identification of Characteristic Macro- and Micronutrients and the Bioactive Components of Indonesian Local Brown Rice as a Functional Feed in Obesity Nutrition Therapy
Authors: Sulistyowati Etik , Rudijanto Achmad , Soeharto Setyawati , Handayani Dian 
Published: April 2019

Background:Public interest and awareness of the use of functional food as an obesity nutrition therapy are increasing.Objective:This study aims to analyze the content of energy, macronutrients, minerals (magnesium, manganese, and potassium), and bioactive components (fiber, β-glucan) in Indonesian varieties of brown rice compared to white rice, to provide precise information on the nutritional content of brown rice as a functional food in obesity nutrition therapy.Methods:This research took the form of a laboratory analysis to identify the content of energy, macronutrients, fiber, β-glucan, magnesium, manganese, and potassium in brown rice varieties Sinta Nur. The energy content of rice was analyzed using bomb calorimetry; macronutrients were analyzed by spectrophotometry, gravimetric extraction, and acid-base titration; dietary fiber, and β-glucan were analyzed by enzymatic methods; and mineral contents were analyzed by spectrophotometry and atomic absorption spectrophotometry.Results:The results demonstrated that the energy and macronutrient content of brown rice are higher than white rice. However, brown rice also has dietary fiber and β-glucan contents that are 5 times higher than white rice. For the macronutrient, in brief, magnesium content was 7.7 times higher, potassium was 5.7 times higher, and manganese was 1.59 times higher within the brown rice. Cooked rice is known for lower nutritional value, but the nutritional value of Indonesian brown rice is still higher than white rice.Conclusion:The results of this study indicate that brown rice has nutrient content and bioactive components that allegedly contribute to higher obesity intervention than white rice.
First Example of Antiparasitic Activity Influenced by Thermochromism: Leishmanicidal Evaluation of 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine Metal Complexes
Authors: Méndez-Arriaga José M. , Oyarzabal Itziar , Martín-Montes Álvaro , García-Rodríguez Judith , Quirós Miguel , Sánchez-Moreno Manuel 
Published: April 2019

Background:
The World Health Organization catalogues illnesses such as Leishmaniasis
as neglected diseases, due to low investment in new drugs to fight them. The search of novel
and non-side effects anti-parasitic compounds is one of the urgent needs for the Third World. The
use of triazolopyrimidines and their metallic complexes has demonstrated hopeful results in this
field.

Objective:
This work studies the antiparasitic efficacy of a series of 5,7-dimethyl-1,2,4-
triazolo[1,5-a]pyrimidine first row transition metal complexes against three leishmania spp.
strains.

Methods:
The in vitro antiproliferation of promastigote forms of different strains of leishmania
spp. (L. infantum, L. braziliensis and L donovani) and the cytotoxicity in macrophage host cells are
reported here. The antiparasitic assays have been complemented with enzymatic tests to elucidate
the mechanisms of action. New crystal structure description, thermal analysis, magnetic susceptibility
and magnetization experiments have also been carried out in order to present a whole characterization
of the studied compounds and interesting physical properties besides the biological tests.

Results:
The results of antiproliferation screening and cytotoxicity show great antiparasitic efficacy
in the studied complexes. The superoxide dismutase enzymatic assays exhibit a different
behaviour according to the thermochromic triazolopyrimidine form tested.

Conclusion:
Antiproliferative assays and enzymatic tests corroborate the synergetic leishmanicidal
effect present in coordination triazolopyrimidine complexes. The changes in coordination sphere
derived from thermochromism affect the physical properties as well as the biological efficacy.
Development and Validation of a Microbiological Agar Assay for Determination of Thiamphenicol in Soft Capsules
Authors: Martins Yugo Araújo , dos Santos Sousa Reginaldo , de Oliveira Cristiani Lopes Capistrano Gonçalves 
Published: April 2019

Background:
Thiamphenicol belongs to the amphenicol class of antibiotic and possesses a
broad-spectrum antimicrobial activity. An alternative microbiological assay for quantification of thiamphenicol
in pharmaceutical formulations has not yet been reported in the literature.

Objective:
This study aimed to develop and validate an agar diffusion method for quantification of thiamphenicol
in soft capsules.

Methods:
The assay was based on the inhibitory effect of thiamphenicol on the following: a strain of
Kocuria rhizophila ATCC 9341, used as the test microorganism, Antibiotic 1culture medium, phosphate
buffer pH 6, 0, inoculum at a concentration of 1%, as well as standard and sample solutions at the concentrations
of 20.0, 40.0 and 80.0 μg mL-1.

Results:
The method validation yielded good results for the parameters of linearity, precision, accuracy,
robustness and selectivity. The experimental statistic results were analyzed using analysis of variance
(ANOVA). The method was found to be linear (r2 = 0.9992) in the range of 20-80 μg mL-1, precise
(inter-assay R.S.D = 0.09%), accurate (R.S.D. = 4.65%), specific, and robust.

Conclusion:
The results demonstrated the validity of the proposed bioassay, which allows for reliable
quantification of thiamphenicol in a pharmaceutical sample. An alternative methodology for thiamphenicol
determination in routine quality control has been reported herein.
Crystal Transition and Drug-excipient Compatibility of Clarithromycin in Sustained Release Tablets
Authors: Li Yu , Kong Xiangwen , Hu Fan 
Published: April 2019

Background:
Clarithromycin is widely used for infections of helicobacter pylori. Clarithromycin
belongs to polymorphic drug. Crystalline state changes of clarithromycin in sustained release
tablets were found.

Objective:
The aim of this study was to find the influential factor of the crystal transition of clarithromycin
in preparation process of sustained-release tablets and to investigate the possible interactions
between the clarithromycin and pharmaceutical excipients.

Methods and Results:
The crystal transition of active pharmaceuticals ingredients from form II to form
I in portion in clarithromycin sustained release tablets were confirmed by x-ray powder diffraction.
The techniques including differential scanning calorimetry and infrared spectroscopy, x-ray powder
diffraction were used for assessing the compatibility between clarithromycin and several excipients as
magnesium stearate, lactose, sodium carboxymethyl cellulose, polyvinyl-pyrrolidone K-30 and microcrystalline
cellulose. All of these methods showed compatibilities between clarithromycin and the selected
excipients. Alcohol prescription simulation was also done, which showed incompatibility between
clarithromycin and concentration alcohol.

Conclusion:
It was confirmed that the reason for the incompatibility of clarithromycin with high concentration
of alcohol was crystal transition.
Higher Levels of Serum TLR2 and TLR4 in Patients with Hashimoto's Thyroiditis
Authors: Aktaş Tugba , Celik Sevim K. , Genc Gunes C. , Arpaci Dilek , Can Murat , Dursun Ahmet 
Published: April 2019

Objective:
Hashimoto’s thyroiditis (HT) is an autoimmune disorder caused by the interaction
between genes and environmental triggers. HT is the most common endocrine disorder, as well as
the most common cause of hypothyroidism. Autoimmunity plays a crucial role in the pathogenesis of
HT and recent studies suggest that Toll-like receptor (TLR) signals lead to increased inflammatory
response. The aim of our study is to investigate whether TLR-2 and TLR-4 levels and gene polymorphisms
contribute to the damaged immune response leading to HT.

Methods:
Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
method, single-nucleotide polymorphisms (SNPs) of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del
and TLR4 gene Asp299Gly, Thr399Ile were studied in 100 patients with HT and 100 healthy controls.
Also, we investigated serum levels of TLR-2 and TLR-4 in the immunopathogenesis of HT. TLR-2
and TLR-4 serum levels were found to be significantly higher in HT patients than the control group.
However, no statistical significance was found between patient and control groups in terms of genotype
frequencies and allele frequency distribution of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del
and TLR4 gene Asp299Gly, Thr399Ile polymorphisms.

Result:
TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphism
do not appear to have a role in the development of HT disease. However, in our study, serum
levels of TLR-2 and TLR-4 were found to be higher in HT patients than control groups

Conclusion:
These findings suggest that TLR-2 and TLR-4 play an important role in the immunopathologic
mechanism of disease by causing an increase in proinflammatory response.
GPU Accelerated Bilateral Filter for MR Image Denoising
Authors: Oza Shraddha D. , Joshi Kalyani R. 
Published: April 2019

Background:
Magnetic resonance (MR) imaging plays a significant role in the computer-
aided diagnostic systems for remote healthcare. In such systems, the soft textures and tissues
within the denoised MR image are classified by the segmentation stage using machine learning algorithms
like Hidden Markov Model. Thus, the quality of the MR image is of extreme importance
and is decisive in the accuracy of the process of classification and diagnosis.

Objective:
To provide real-time medical diagnostics in the remote healthcare intelligent setups, the
research work proposes CUDA GPU based accelerated bilateral filter for fast denoising of 2D
high- resolution knee MR images.

Methods:
To achieve optimized GPU performance with better speed-up, the work implements an
improvised technique that uses on-chip shared memory in combination with a constant cache.

Results:
The speed-up of 382x is achieved with the new proposed optimization technique which is
2.7x as that obtained with the shared memory only approach. The superior speed-up is along with
90.6%occupancy index indicating effective parallelization. The work here also aims at justifying
the appropriateness of bilateral filter over other filters for denoising magnetic resonance images.
All the patents related to GPU based image denoising are revised and uniqueness of the proposed
technique is confirmed.

Conclusion:
The results indicate that even for a 64Mpixel image, the execution time of the proposed
implementation is 334.91 msec only, making the performance almost real time. This will
surely contribute to the real-time computer-aided data diagnostics requirement under remote critical
conditions.
Chronic Urticaria: An Overview of Treatment and Recent Patents
Authors: Hon Kam L. , Leung Alexander K.C. , Ng Wing G.G. , Loo Steven K. 
Published: April 2019

Background:
Up to 1% of the general population in the USA and Europe suffer from
chronic urticaria (CU) at some point in their lifetime. CU has an adverse effect on the quality of life.

Objectives:
This study aims to provide an update on the epidemiology, pathogenesis, clinical manifestations,
diagnosis, aggravating factors, complications, treatment and prognosis of CU.

Methods:
The search strategy included meta-analyses, randomized controlled trials, clinical trials,
reviews and pertinent references. Patents were searched using the key term "chronic urticaria" at the
following links: www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com.

Results:
CU is a clinical diagnosis, based on the episodic appearance of characteristic urticarial lesions
that wax and wane rapidly, with or without angioedema, on most days of the week, for a period of six
weeks or longer. Triggers such as medications, physical stimuli, and stress can be identified in 10 to
20% of cases. C-reactive protein/erythrocyte sedimentation rate, and complete blood cell count with
differential are the screening tests that may be used to rule out an underlying disorder. The mainstay of
therapy is reassurance, patient education, avoidance of known triggers, and pharmacotherapy. Secondgeneration
H1 antihistamines are the drugs of choice for initial therapy because of their safety and efficacy
profile. If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms
are intolerable, the dose of second-generation H1 antihistamines can be increased up to fourfold the
manufacturer’s recommended dose (all be it off license). If satisfactory improvement does not occur
after 2 to 4 weeks or earlier if the symptoms are intolerable after the fourfold increase in the dosage of
second-generation H1 antihistamines, omalizumab should be added. If satisfactory improvement does
not occur after 6 months or earlier if the symptoms are intolerable after omalizumab has been added,
treatment with cyclosporine and second-generation H1 antihistamines is recommended. Short-term use
of systemic corticosteroids may be considered for acute exacerbation of CU and in refractory cases.
Recent patents for the management of chronic urticaria are also discussed. Complications of CU may
include skin excoriations, adverse effect on quality of life, anxiety, depression, and considerable humanistic
and economic impacts. On average, the duration of CU is around two to five years. Disease
severity has an association with disease duration.

Conclusion:
CU is idiopathic in the majority of cases. On average, the duration of CU is around two to
five years. Treatment is primarily symptomatic with second generation antihistamines being the first
line. Omalizumab has been a remarkable advancement in the management of CU and improves the
quality of life beyond symptom control.
Pre-feasibility Study for Establishing Radioisotope and Radiopharmaceutical Production Facilities in Developing Countries
Authors: Perini Efrain Araujo , Skopchenko Mikhail , Hong Tran Thu , Harianto Rahmat , Maître Alexis , Rodríguez Maidelys Rosa Rodríguez , de Oliveira Santos Nathalia , Guo Yinglei , Qin Xiangyu , Zeituni Carlos A. , Starovoitova Valeriia N. 
Published: April 2019

Background:A significant number of developing countries have no facilities to produce medical radioisotopes and radiopharmaceuticals.Objective:In this paper we show that access to life-saving radioisotopes and radiopharmaceuticals and the geographical distribution of corresponding infrastructure is highly unbalanced worldwide.Methods:We discuss the main issues which need to be addressed in order to establish the production of radioisotopes and radiopharmaceuticals, which are especially important for developing countries as newcomers in the field. The data was gathered from several sources, including databases maintained by the International Atomic Energy Agency (IAEA), World Health Organization (WHO), and other international organizations; personal interactions with representatives in the nuclear medicine field from different regions of the world; and relevant literature.Results:Developing radioisotope and radiopharmaceutical production program and installing corresponding infrastructure requires significant investments, both man-power and financial. Support already exists to help developing countries establish their medical radioisotope production installations from several organizations, such as IAEA.Conclusion:This work clearly shows that access to life-saving radioisotopes and the geographical distribution of corresponding infrastructure is highly unbalanced. Technology transfer is important as it not only immediately benefits patients, but also provides employment, economic activity and general prosperity in the region to where the technology transfer is implemented.
Contaminación por ruido y el tráfico vehicular en la frontera de México
Authors: Zamorano-González Benito , Peña-Cárdenas Fabiola , Velázquez-Narváez Yolanda , Vargas-Martínez José Ignacio , Parra-Sierra Víctor 
Published: April 2019

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p><span><strong>Objetivo - </strong></span><span>determinar la relación entre el nivel de ruido de las principales intersecciones viales y el número de vehículos que transitan sobre ellas.</span></p><p><span><strong>Método - </strong></span><span>se utilizó un aforador vehicular electrónico no invasivo en periodos de una semana; evaluación del nivel de ruido en intervalos diarios durante la semana completa, utilizando sonómetros integradores tipo I. </span></p><p><strong>Resultados - </strong><span>se identificó el tráfico promedio diario anual de 2739 unidades; estimación del nivel de ruido de 77.6 dB para periodos de 12 horas; niveles máximos de 98.5 dB y 58.3 dB como nivel mínimo de ruido.</span></p><p><strong>Limitaciones - </strong><span>el desarrollo del trabajo de campo en un periodo menor a un año.</span></p><p><strong>Principales hallazgos - </strong><span>el nivel de ruido en la ciudad supera el referente de 65 decibeles, mencionado por la Organización Mundial de la Salud, lo que permite concluir que la ciudad presenta contaminación a causa del ruido derivado del tráfico vehicular. </span></p></div></div></div>