bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity
Authors: Hahn Roberta Zilles , Antunes Marina Venzon , Verza Simone Gasparin , Perassolo Magda Susana , Suyenaga Edna Sayuri , Schwartsmann Gilberto , Linden Rafael 
Published: June 2018

Background:
Irinotecan (IRI) is a widely used chemotherapeutic drug, mostly used
for first-line treatment of colorectal and pancreatic cancer. IRI doses are usually established
based on patient’s body surface area, an approach associated with large inter-individual variability
in drug exposure and high incidence of severe toxicity. Toxic and therapeutic effects of
IRI are also due to its active metabolite SN-38, reported to be up to 100 times more cytotoxic
than IRI. SN-38 is detoxified by the formation of SN-38 glucuronide, through UGT1A1. Genetic
polymorphisms in the UGT1A1 gene are associated to higher exposures to SN-38 and
severe toxicity. Pharmacokinetic models to describe IRI and SN-38 kinetic profiles are available,
with few studies exploring pharmacokinetic and pharmacogenetic-based dose individualization.
The aim of this manuscript is to review the available evidence supporting pharmacogenetic
and pharmacokinetic dose individualization of IRI in order to reduce the occurrence
of severe toxicity during cancer treatment.

Methods:
The PubMed database was searched, considering papers published in the period
from 1995-2017, using the keywords irinotecan, pharmacogenetics, metabolic genotyping,
dose individualization, therapeutic drug monitoring, pharmacokinetics and pharmacodynamics,
either alone or in combination, with original papers being selected based on the presence
of relevant data.

Conclusion:
The findings of this review confirm the importance of considering individual patient
characteristics to select IRI doses. Currently, the most straightforward approach for IRI
dose individualization is UGT1A1 genotyping. However, this strategy is sub-optimal due to
several other genetic and environmental contributions to the variable pharmacokinetics of IRI
and its active metabolite. The use of dried blood spot sampling could allow the clinical application
of limited sampling and population pharmacokinetic models for IRI doses individualization.
Rational Drug Design Approach of Receptor Tyrosine Kinase Type III Inhibitors
Authors: Kim Cheolhee , Kim Eunae 
Published: June 2018

:Rational drug design is accomplished through the complementary use of structural biology and computational biology of biological macromolecules involved in disease pathology. Most of the known theoretical approaches for drug design are based on knowledge of the biological targets to which the drug binds. This approach can be used to design drug molecules that restore the balance of the signaling pathway by inhibiting or stimulating biological targets by molecular modeling procedures as well as by molecular dynamics simulations. Type III receptor tyrosine kinase affects most of the fundamental cellular processes including cell cycle, cell migration, cell metabolism, and survival, as well as cell proliferation and differentiation. Many inhibitors of successful rational drug design show that some computational techniques can be combined to achieve synergistic effects.
Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol
Authors: César da Silva Rodrigo , Veiga Fabiano , Vilela Fabiana Cardoso , Pereira André Victor , Tavares da Silva Cunha Thayssa , Tesch Roberta , Viegas Claudio , Dias Danielle Ferreira , Giusti-Paiva Alexandre , Veloso Marcia Paranho , Fraga Carlos Alberto Manssour 
Published: June 2018

Background: :
A new series of O-benzyloximes derived from eugenol was synthesized
and was evaluated for its antinociceptive and anti-inflammatory properties.

Methods: :
The target compounds were obtained in good global 25-28% yields over 6 steps, which
led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4-
(methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4-
(methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes.

Results::
These compounds have significant analgesic and anti-inflammatory effects, as evidenced
by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin
test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities
and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory
effects, exceeding the standard drugs indomethacin and celecoxib.

Conclusion: :
Molecular docking studies have provided additional evidence that the pharmacological
profile of these compounds may be related to inhibition of COX enzymes, with slight preference for
COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive
prototypes, with a novel structural pattern capable of being explored in further studies aiming at
their optimization and development as drug candidates.
Anti-Microbial and Free Radical Scavenging Activities of Nigella Sativa Colloidal-Emulgel
Authors: Eid Ahmad M. , Jaradat Nidal A. , Elmarzugi Nagib A. , Alkowni Raed , Hussen Fatima , Ayyash Laila A. , Sawafta Maher , Danaa Hadeel 
Published: June 2018

Background:
Nigella sativa L. (N. sativa) has been reported to have biological activities
such as anti-bacterial, anti-inflammatory, anti-oxidant and anti-fungal activities.

Objective:
This study aims to develop N. Sativa colloidal-emulgel with the evaluation of its antibacterial,
anti-oxidant and in-vivo irritation and sensation testing.

Method:
Colloidal-emulgel formulations were prepared for N. sativa using different surfactants
(Sodium Lauryl Sulphate (S.L.S) and sucrose ester). N. sativa emulsion formulations were prepared
using heat inversion technique. After that, the optimum formulation was mixed with Carbopol to
produce the colloidal-emulgel. The droplet size, size distribution, and rheological behavior were
measured for emulgel formulations. Anti-bacterial and anti-oxidant activities were also reported in
the in vivo studies for sensitivity, irritancy and spreadability.

Results:
It was found that the sucrose ester was able to produce the optimum emulsion formulation
with droplets size of less than 1 μm. In the anti-bacterial test for Staphylococcus aureus, it was
found that emulgel has an inhibition zone of 2.5 cm in diameter, but the oil alone being 1.3 cm.
According to MRSA, the inhibition zone for emulgel was 1.1 cm, but for oil, it was 0.5 cm in diameter.
Emulgel does not show any irritation or sensitivity. Also it has a homogeneous appearance
with a smooth texture. In addition, it shows fair mechanical properties, and easy spreadability with
acceptable bio-adhesion.

Conclusion:
It is concluded that N. sativa emulgel has been prepared with dermatological and cosmeceutical
benefits.
A One-pot Multicomponent ‘Click’ Approach to the Synthesis of Novel Tamoxifen-triazole Conjugates using Nano Iron Oxide Catalyst and their Preliminary Antiproliferative Activity Studies
Authors: Katiki Mohana Rao , Kommula Dileep , Polepalli Sowjanya , Jain Nishant , Murty Madugula Sree Rama 
Published: June 2018

Background:
In an effort to establish new drug candidates with improved antiproliferative
activity, we report here a novel class of compounds designed rationally by the replacement of
an ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) and the introduction of 1,4-
substituted 1,2,3-triazoles in the basic side chain.

Methods:
Magnetically separable iron oxide nanoparticles have been found to effectively catalyze
the one-pot multicomponent click synthesis of 1,4-disubstituted 1,2,3-triazole conjugates in water.
IR, 1HNMR, 13CNMR and HRMS experiments have been implemented for the unmistakable determination
of the regiochemistry of the process. The novel compounds were evaluated for their antiproliferative
activity against four human tumor cell lines, namely, MCF-7, MDA-MB-231, HeLa,
and A549. Cell growth inhibition was assessed according to the standard Sulforhodamine B (SRB)
cell proliferation method.

Results:
The most active compounds 4h, 4n and 5a have been identified with superior GI50 values
in the range of 0.13–0.31 µM as compared with the reference drug, tamoxifen (0.25-0.72 µM).

Conclusion:
Additionally, taking the stereochemistry into consideration, E isomers seem slightly
more active towards the tested cancer cell lines with respect to Z isomers.
Hypotensive Effect of Hydroalcoholic Ziziphus jujuba Extract on Normotensive Rats
Authors: Mohebbati Reza , Rahimi Maryam , Bavarsad Kosar , Beheshti Farimah , KhajaviRad Abolfazl , Shafei Mohammad N. 
Published: June 2018

Objective:
Ziziphus jujuba (Z.J) is a medicinal plant with several properties such as antioxidant,
antibacterial, hypnotic and wound healing activity. It also has lowering blood pressure effect
and people use it to treat hypertension. In the present study, the effect of hydroalcoholic extract of Z.J
on cardiovascular parameters in the normotensive rats was investigated.

Methods:
Animal groups include: 1) Sham, only cannulation of artery 2) saline, received saline for
four weeks 3-5) Z.J groups (100, 200 and 400 mg/kg) that treated with Z.J via gavage for four weeks.
In the experiment day (28th Day) femoral artery of all rats cannulated and Systolic Blood Pressure
(SBP), Mean Atrial Pressure (MAP) and Heart Rate (HR) recorded by a power lab system. The weight
of animal in all groups also was recorded in the beginning and the last day of experiment.

Results:
There was no significant difference in HR, SBP and MAP parameters between sham and control
groups. The SBP and MAP in higher doses of Z.J (200 and 400 mg) significantly decreased compared
to control group. The HR only in dose 200 mg of Z.J significantly decreased than the control
group.

Conclusion:
The results of present study show that hydroalcoholic extract of Z.J has an inhibitory effect
on basal cardiovascular parameters and its best effects have been shown in dose 200 mg/kg.
Evaluation of Optic Nerve Head Biomechanical Properties in Pseudoexfoliation Glaucoma with Real-time Elastography
Authors: Unal Ozlem , Caglayan Mehtap , Kosekahya Pinar , Yulek Fatma , Taslipinar Guzin 
Published: June 2018

Purpose:
To investigate the biomechanical properties of the optic nerve head in patients
with Pseudoexfoliation (PEX) glaucoma using Real-time Elastography (RTE) and to compare these
results with those of Primary Open Angle Glaucoma (POAG) patients and healthy subjects.

Methods:
Twenty eyes of 20 PEX glaucoma patients (PEX group), 20 eyes of 20 POAG patients
(POAG group), and 20 eyes of 20 healthy subjects (control group) were enrolled in this prospective
study. The strain Ratios of Orbital Fat to Optic Nerve head (ROFON) and lateral rectus muscle to
optic nerve head (RLRON) were determined. Comparisons were performed using Chi-square,
Kruskal Wallis, Mann-Whitney U, and One-way ANOVA tests.

Results:
The strain ratios of orbital fat to optic nerve head were 2.34, 6.85 and 1.76 in PEX glaucoma, POAG, and control groups, respectively (p<0.001). The strain ratios of the lateral rectus muscle to the optic nerve head were 0.51, 0.82, and 0.55 in PEX glaucoma, POAG, and control groups, respectively (p=0.256).

Conclusion:
The strain ratios of orbital fat to optic nerve head were different in PEX glaucoma patients than in POAG and control groups. RTE can provide biomechanical assessment of the optic
nerve head in a non-invasive, quick, easily accessible, and user-friendly manner.
Detoxification of Aflatoxin B1 in Peanut Oil by Iodine Doped Supported TiO2 Thin Film Under Ultraviolet Light Irradiation
Authors: Xu Chengpeng , Ye Shengying , Cui Xiaolei , Zhang Quan , Liang Yan 
Published: June 2018

Background:
Improper storage and raw materials make peanut oil susceptible to Aflatoxin
B1 (AFB1). The semiconductor TiO2 photocatalysis technology is an effective technology
which is widely used in sewage treatment, environmental protection and so on. Moreover, the photocatalytic
efficiency can be improved by doping I.

Method:

The experiment is divided into two parts. In the first part, supported TiO2 thin film (STF)
was prepared on the quartz glass tube (QGT) by the sol-gel and calcination method and the supported
iodine doped supported TiO2 thin film (I-STF) was synthesized using potassium iodate solution. In
the second part, the photocatalytic degradation of AFB1 was performed in a self-made photocatalytic
reactor. The AFB1 was detected by ELISA kit.

Results:

The photocatalytic degradation of AFB1 has been proven to follow pseudo first-order reaction
kinetics well (R2 > 0.95). The maximum degradation rate of 81.96%, which was reached at the
optimum iodine concentration of 0.1mol/L, was 11.38% higher than that with undoped STF.

Conclusion:

The doping of iodine reduces the band-gap of TiO2, thereby increasing the photocatalytic
response range. The proportion of Ti4+ in I-STF has decreased, which means that Ti4+ are replaced
by I. The I-STF prepared at iodine concentration of 0.1mol/L has good photocatalytic properties.
IoT based Low Power Wearable ECG Monitoring System
Authors: Kulkarni A.S. , Suchetha M. , Kumaravel N. 
Published: June 2018

Background:
An electrocardiogram device monitors the cardiac status of a patient by
recording the heart’s electrical potential vs time. Such devices play a very important role to save
the life of patients who survive a heart attack or suffer from these patients. An early detection of
conditions that lead to the onset of cardiac arrest allows doctors to provide proper treatment on
time and prevents death or disability from cardiac arrest. Most developing countries have very
poor information about these health care issues.

Methods:
An actual deployment of the system was used to evaluate key aspects of the system
architecture, in particular, the possibility to monitor the ECG signal of single patients in a large
area and for a long time the possibility to access ECG data through the web interface. The test
deployment consisted of ECG sensor AD8232, wi-fi module and IoT server. The IoT server was
installed on a Linux/ windows machine. The wifi has been configured to connect to the server,
through an ADSL router.

Conclusion:
We have proposed a wireless wearable ECG monitoring system enabled with an IoT
platform that integrates heterogeneous nodes of ECG sensor and applications, has a long battery
life and provides a high-quality ECG signal. The system allows monitoring single/multiple
patients on a relatively large indoor area (home, building, nursing home, etc). As observed, this
result is obtained through a careful set of choices at the level of components, circuit solutions, and
algorithms. We would like to stress the fact that a dedicated overall output is not enough to
achieve an advantage in terms of overall sensor performance. The latter depends on the
optimization of the whole sensor. Indeed, this proposed ECG sensor, based on a high-performance
ADC and an arm processor, provides much better performance, in terms of power consumption
and noise, than many proposed system based on a purposely designed front-end chip.
Tuberculosis and HIV Coinfection–the Challenge in the Prevention, Detection and Treatment of Tuberculosis
Authors: Wang Yiyi , Wu Qi , Zhang Wei , Zhang Ning 
Published: June 2018

Background:
Tuberculosis (TB) is still a major public health concern world-wide. The
increasing global burden of TB is linked to HIV infection. HIV-TB coinfection has also
conditioned clinical aspects of the TB. Since the HIV is beginning in the 1980s, the HIV infection
poses a significant challenge in global TB control.

Objective:
In this review we focused on the challenges of epidemiological and clinical feature of
tuberculosis presented by the HIV coinfection.

Method:
The article consists of a summary of the most important effects presented by the HIV
coinfection on epidemiological and clinical feature of tuberculosis. The article analyzes and
summary the causes for these challenges.

Results:
The major challenges to strategy of TB control and clinical feature of TB-HIV coinfection
are presented in this paper.

Conclusion:
HIV/TB co-infection is synergic, interactive and reciprocal with significant impact.
The infection of HIV and Mtb affect each other and the breakdown the immune function in
TB/HIV coinfected individual. HIV infection has changed the strategy of TB control, however
HIV increases global burden of TB, the reduction in the TB incidence rate is far from sufficient.
Atypically clinical manifestations in TB/HIV co-infected patients and increased MDR-TB and
XDR-TB contribute to the challenges in the diagnosis and treatment. Increased complexity of
managing patients requires expertise in the clinical m knowledge. The focused efforts to control
HIV-related TB are of great urgency. These findings will provide insight into the prevention,
detection and treatment of tuberculosis and will guide advances towards tuberculosis control.
Este é um chamado à ação contra a escravidão na América – abolicionismos e movimentos sociais na terra da liberdade.
Authors: Cardoso Neves Fernando Henrique , Braida Ricardo 
Published: June 2018

O tema deste trabalho é abolicionismo penal e movimentos sociais. Dentro desta perspectiva, voltamos nossa atenção para a greve prisional que teve início em 9 de setembro de 2016 nos Estados Unidos. Apesar de muitos movimentos sociais tomarem para si um discurso anti-prisional, o posicionamento examinado rompe com esta homogeneidade. O objetivo deste artigo é demonstrar os grupos e as estratégias que participam deste movimento. Tal exercício dar-se-á pela análise do material exposto na internet desde os chamados anteriores à greve. Os resultados demonstram tanto sua heterogeneidade como as implicações desta numa reflexão entre Direito e movimentos sociais.
Asset Impairment and Depreciation before the 15th Century
Authors: Kuter Mikhail , Gurskaya Marina , Andreenkova Angelina , Bagdasaryan Ripsime 
Published: June 2018

ABSTRACT
This paper investigates impairment and depreciation accounting in the 13th to 15th century. It finds that the first known instance of impairment accounting was in 1321, while for depreciation, it was 1399 not, as has previously been claimed, 1299. The study demonstrates the difference in approach at that time between the two forms of adjustment and shows that impairment was the original form of adjustment for reduction in asset values, a form that was applied in situations where physical assets had been lost, or deteriorated, or devalued over the reporting period. In contrast, depreciation was algorithmic, linked to a time-based straight-line depreciation charge equivalent to 10 percent per annum. These findings not only relocate recognition of the emergence of depreciation provisions to the end of the 14th century but, also, from France to Spain. However, in both cases, in Italian firms with Italian accountants.
Use of Big-Data Algorithms to Characterize Patients with T2D on Basal Insulin (BI) Who Add a Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) and Predict Their A1C Response
Authors: ZIMMERMANN ESTHER , LENART ADAM , DA ROCHA FERNANDES JOAO DIOGO , EGGERT SARAH , RANTHE MATTIS F. 
Published: June 2018

Machine learning allows extensive analysis of big complex data. This study had two aims: 1) characterize patients on BI who add a GLP-1RA and 2) identify predictors of ≥1% decline in A1C. Patients with T2D who were prescribed BI for ≥90 days but not GLP-1RA for 180 days beforehand (in the U.S. IBM Explorys database between 2010 and 2016) were included (N=80,019). For the A1C analysis, A1C readings ≤180 days before, and 180-360 days after initiating GLP-1RA were required (N=8731). Logistic regression with 23 pre-specified variables, and subsequent hypothesis-free machine learning models, with 155000 additional variables covering clinical, claims and billing data addressed both aims. GLP-1RA initiators were characterized by a BI duration of &gt;180 days (vs. ≤180 days) estimated odds ratio (OR) 5.87 (95% CI: 5.49-6.27), receiving oral antidiabetic drugs(s) OR 1.70 (1.64-1.77) and co-medication(s) (both vs. none) OR 3.22 (2.96-3.50), a BMI &gt;30 kg/m2 (vs. &lt;30 kg/m2) OR 1.93 (1.84-2.03), age &lt;75 years (vs. ≥75 years) OR 3.63 (3.37-3.92) and private insurance (vs. non-private) OR 2.2 (2.10-2.31). Variable selection via machine learning confirmed the importance of these variables. Baseline A1C was the only strong predictor of ≥1% decline in A1C, ORs (95% CI) compared with A1C &lt;7% were 4.99 (3.29-7.57), 7.04 (4.77-10.39), 14.56 (9.98-21.24), 23.21 (15.92-33.85), 36.28 (25.05-52.54), 73.14 (50.32-106.32) for categories 7-&lt;7.5, 7.5-&lt;8, 8-&lt;8.5, 8.5-&lt;9, 9-&lt;10, ≥10%, respectively. Machine learning, applying 155000 variables, confirmed the importance of baseline A1C. On average, patients who improved lowered A1C from 10.0% (interquartile range [IQR]: 8.6-11.0) to 7.7% (IQR 6.7-8.4). Patients with T2D on BI who added a GLP-1RA were likely to be &lt;75 years old and had characteristics of progressed disease. Baseline A1C determined a ≥1% decline in A1C, suggesting patients on BI with high A1C would benefit from combination treatment with GLP-1RA.

Disclosure
E. Zimmermann: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. A. Lenart: Employee; Self; Novo Nordisk A/S. J. da Rocha Fernandes: Employee; Self; Novo Nordisk A/S, International Diabetes Federation. S. Eggert: Employee; Self; Novo Nordisk A/S. M.F. Ranthe: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S.
Effect of the Combination Therapy of Liraglutide, a GLP-1 Receptor Analog, and IDegAsp in Patients with Type 2 Diabetes
Authors: HARADA MARINA , SHINODA MINORI , SAKAMOTO RIKA , SUZUKI JUN , TAKAHASHI KENICHIRO , YAMAKAWA TADASHI 
Published: June 2018

Background: Diabetes care management aims to not only achieve good glycemic control but also maintain the quality of life (QoL). Basal insulin-treated patients frequently receive bolus insulin as a strengthening therapy; however, concerns exist about QoL due to the increasing number of injections. We examined the glycemic effect and QoL in patients treated with liraglutide (Lira) and insulin degludec/insulin aspart (IDegAsp).
Methods: Patients with type 2 diabetes treated with basal-supported oral therapy (BOT) and DPP-4 inhibitor were enrolled in this observational study. Basal insulin was switched to IDegAsp at the same dose and DPP-4 inhibitor to Lira simultaneously; no titration protocol was used. We estimated the clinical and laboratory parameters and assessed the change in QoL within 12 weeks using the diabetes therapy-related QoL (DTR-QoL) questionnaire. The timing of dose up in regard to IDegAsp and Lira was also determined.
Results: Fourteen patients were enrolled (male/female: 9/5, age (years): 63.6). The IDegAsp dose ranged from 9.1 to 13.7 U; all patients received 0.9 mg/day of Lira. The combination therapy significantly decreased HbA1c levels (8.7% vs. 7.1%, P=0.02), pre-breakfast glucose level (138.2 mg/dL vs. 108.9 mg/dL, P=0.044), bodyweight (62.9 kg vs. 60.3 kg, P=0.003), and BMI (24.6 vs. 23.5, P=0.004). The total DTR-QoL score at baseline was 61.6 and significantly improved to 73.2 (P=0.004). Significant improvement was also seen in D3 score (hypoglycemia; 63.6 vs. 81.4, P=0.036). D4 score (satisfaction with treatment) showed an increasing trend (59.0 vs. 78.2) and was negatively correlated with HbA1c levels (P=0.049).
Conclusion: The change from BOT to the combination therapy of Lira and IDegAsp significantly improved glycemic control and reduced the bodyweight without deteriorating QoL in type 2 diabetes, although the treatment modality changed from one-injection to two-injection therapy.

Disclosure
M. Harada: None. M. Shinoda: None. R. Sakamoto: None. J. Suzuki: None. K. Takahashi: None. T. Yamakawa: None.