bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents
Authors: Misirlic-Dencic Sonja , Poljarevic Jelena , Isakovic Andjelka M. , Sabo Tibor , Markovic Ivanka , Trajkovic Vladimir 
Published: October 2018

Background::
The discovery of cisplatin and the subsequent research revealed the importance
of dinitrogen-containing moiety for the anticancer action of metal complexes. Moreover, certain
diamine ligands alone display cytotoxicity that contributes to the overall activity of corresponding
complexes.

Objective::
To summarize the current knowledge on the anticancer efficacy, selectivity, and the mechanisms
of action of metal complexes with various types of diamine ligands.

Method::
The contribution of aliphatic acyclic, aliphatic cyclic, and aromatic diamine ligands to the
anticancer activity and selectivity/toxicity of metal complexes with different metal ions were analyzed
by comparison with organic ligand alone and/or conventional platinum-based chemotherapeutics.

Results::
The aliphatic acyclic diamine ligands are present mostly in complexes with platinum. Aliphatic
cyclic diamines are part of Pt(II), Ru(II) and Au(III) complexes, while aromatic diamine ligands
are found in Pt(II), Ru(II), Pd(II) and Ir(III) complexes. The type and oxidation state of metal ions
greatly influences the cytotoxicity of metal complexes with aliphatic acyclic diamine ligands. Lipophilicity
of organic ligands, dependent on alkyl-side chain length and structure, determines their cellular
uptake, with edda and eddp/eddip ligands being most useful in this regard. Aliphatic cyclic diamine
ligands improved the activity/toxicity ratio of oxaliplatin-type complexes. The complexes with aromatic
diamine ligands remain unexplored regarding their anticancer mechanism. The investigated complexes
mainly caused apoptotic or necrotic cell death.

Conclusion::
Metal complexes with diamine ligands are promising candidates for efficient and more
selective alternatives to conventional platinum-based chemotherapeutics. Further research is required to
reveal the chemico-physical properties and molecular mechanisms underlying their biological activity.
Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods
Authors: Avram Speranta , Puia Alin , Udrea Ana Maria , Mihailescu Dan , Mernea Maria , Dinischiotu Anca , Oancea Florin , Stiens Johan 
Published: October 2018

Background::
Synthetic compounds with pharmaceutical applications in brain disorders
are daily designed and synthesized, with well first effects but also seldom severe side
effects. This imposes the search for alternative therapies based on the pharmaceutical potentials
of natural compounds. The natural compounds isolated from various plants and arthropods
venom are well known for their antimicrobial (antibacterial, antiviral) and antiinflammatory
activities, but more studies are needed for a better understanding of their structural
and pharmacological features with new therapeutic applications.

Objectives::
Here we present some structural and pharmaceutical features of natural compounds
isolated from plants and arthropods venom relevant for their efficiency and potency in
brain disorders. We present the polytherapeutic effects of natural compounds belonging to
terpenes (limonene), monoterpenoids (1,8-cineole) and stilbenes (resveratrol), as well as natural
peptides (apamin, mastoparan and melittin).

Methods::
Various experimental and in silico methods are presented with special attention on
bioinformatics (natural compounds database, artificial neural network) and cheminformatics
(QSAR, drug design, computational mutagenesis, molecular docking).

Results::
In the present paper we reviewed: (i) recent studies regarding the pharmacological
potential of natural compounds in the brain; (ii) the most useful databases containing molecular
and functional features of natural compounds; and (iii) the most important molecular descriptors
of natural compounds in comparison with a few synthetic compounds.

Conclusion::
Our paper indicates that natural compounds are a real alternative for nervous
system therapy and represents a helpful tool for the future papers focused on the study of the
natural compounds.
Placebo Effect in Obsessive-Compulsive Disorder (OCD). Placebo Response and Placebo Responders in OCD: The Trend Over Time
Authors: Kotzalidis Georgios D. , Del Casale Antonio , Simmaco Maurizio , Pancheri Lucia , Brugnoli Roberto , Paolini Marco , Gualtieri Ida , Ferracuti Stefano , Savoja Valeria , Cuomo Ilaria , De Chiara Lavinia , Mosca Alessio , Sani Gabriele , Girardi Paolo , Pompili Maurizio , Rapinesi Chiara 
Published: October 2018

Background:
Placebo response appears to be increasing in antidepressant, antipsychotic
and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999.
Placebo response is generally considered as the extent to which placebo treatment is associated with
core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend
of both placebo response and placebo responder rates according to the year of publication with no
time restriction in OCD drug trials.

Methods:
We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase,
CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR
OCD). We included studies through investigator consensus. We then performed on data of included
studies log-linear joinpoint segmented regression models using a p<0.05 cutoff.

Results:
We included 113 studies from 112 published papers. Placebo mean annual response rates
in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of
0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017,
with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased
from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show
statistically significant APC changes between 1984 and 2017.

Conclusion:
We observed a tendency for placebo to increase both measures of response in OCD
clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes
in the type of study (moving from classical head to head comparisons to add-on studies in treatmentresistant
populations) and countries involved in experimentation may partially account for some
portion of these results. It appears that placebo effects are becoming more elusive and out of control.
The Relationship Between Vitamin D Deficiency and Insulin Resistance in Pregnant Women with Gestational Diabetes
Authors: Khorasani Zahra Mazloum , Bonakdaran Shokoufeh , Rafieie Hasan Pour 
Published: November 2018

Background:
Diabetes Mellitus is one of the most common medical disorders in pregnancy.
The possibility of vitamin D deficiency as a pathogenesis for impaired glucose tolerance tests show a
probable role of vitamin D in insulin secretion and reduction of insulin resistance. This study was assigned
to evaluate relation between serum vitamin D level and insulin resistance in Gestational Diabetes
Mellitus (GDM).

Methods:
This cross sectional study was done throughout one year between 2015-2016 in GDM patients
(age, 20-40 years). After history taking and physical examination, the laboratory tests including :
Fasting Blood Sugar (FBS), Glucose Tolerance Test (GTT), calcium, phosphorous, parathormone,
25(OH) vitamin D, insulin, HbA1C, TG, LDL, HDL were performed for all patients. Insulin resistance
was calculated according to HOMA-IR formula. Vitamin D level was compared between patients with
and without insulin resistance.

Results:
This research was performed in 93 GDM patients with average age (30.3 ± 5.6). Thirty eight
patients with insulin resistance and 55 patients without insulin resistance were detected. The prevalence
of vitamin D deficiency was 91.4% in all patients. There was no significant difference in vitamin D
levels between insulin resistant and non insulin resistant group (P-value=0.51).

:
In all variable parameters, only FBS and triglyceride level in insulin resistant group were more than non
insulin resistant group (P-value<0.05).

:
Obtained results showed not significant relationship between vitamin D deficiency and
insulin resistance in GDM patients.
Novel Small Molecule Inhibitors of Programmed Cell Death (PD)-1, and its Ligand, PD-L1 in Cancer Immunotherapy: A Review Update of Patent Literature
Authors: Kopalli Spandana R. , Kang Tae-Bong , Lee Kwang-Ho , Koppula Sushruta 
Published: October 2018

Background:In the last few decades, cancer immunotherapy has been extensively researched, and novel checkpoint signaling mechanisms involving Programmed Death (PD)-1 and PDLigand 1 (PD-L1) receptors have been targeted. The PD-1/PD-L1 binding and interaction play a critical role in the development of malignancies.Objective:The present review focuses on recent patents on the pharmacological and biological cancerregulating properties of PD-1/PD-L1 inhibitors involved in immunotherapeutic cancer drug development.Methods:Thorough patent literature search published during the last seven years, including the World Intellectual Property Organization (WIPO®), United States Patent Trademark Office (USPTO®), Espacenet®, and Google Patents, to identify PD-1/PD-L1-targeting small molecule immunomodulators.Results:Several small molecule PD-1/PD-L1 inhibitors were patented for regulation of tumor progression by academic and industry-associated investigators. Most of the claimed patents have been validated and confined to in vitro and in vivo mouse models limiting their entry into clinical settings. Majority of the patents are claimed by the researchers at Aurigene Ltd. (India) on novel peptidomimetic compounds. It is worth to be noted that macrocyclic compounds such as the peptides QP20, HD20, WQ20, SQ20, and CQ-22 from Bristol-Myers Squibb (BMS) Company, biaryl, and heterocyclic derivatives including 1,3-dihydroxy-phenyl compounds were efficient in regulating the PD-1/PD-L1 protein-protein binding and interaction compared to those of the approved monoclonal antibodies.Conclusion:PD-1/PD-L1 inhibitors show significant anti-cancer responses as stand-alone agents and in combination with other cancer therapies. More efficient experimental studies and clinical trials are necessary to evaluate the host-tumor cells’ interactions. Understanding the cancer microenvironment, and identifying specific biomarkers and X-ray crystalline structures of PD-1/PD-L1 complexes, including molecular and genomic signature studies are essential to determine the feasibility of PD-1/PD-L1 inhibitors for development into drug-like cancer immunotherapeutics.
Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro
Authors: Gao Ling , Dong Jianwei , Zhang Nanyang , Le Zhanxian , Ren Wenhao , Li Shaoming , Li Fan , Song Jianzhong , Wang Qibo , Dou Zhichao , Park Soo Y. , Zhi Keqian 
Published: October 2018

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.
Development of an Efficient Screening System for HDAC Inhibitor Based on TCF Response Element
Authors: Pang Chen , Dai Limeng , He Gang , Lu You , Zhang Bo 
Published: October 2018

Background:
Acetylation of core histones is governed by opposing actions of a variety of histone
acetyltransferases (HATs) and Histone Deacetylases (HDACs). Deregulation of histone acetylation has been
causally linked to cancer development and progression, and can be potentially reversed by drug treatments.
HDAC inhibitors (HDACis) have the anti-cancer effects such as induction of cell cycle arrest, promotion of cell
apoptosis, and inhibition of metastasis. Many of these HDACis are currently in clinical development.

Methods:
To screen for novel compound with HDACis activity, cell-based strategy has been developed in current
work. The interaction of HDACs and TCFs was determined by reporter assay, and Natural products library
(A10) was screened by our system in colon cancer cells.

Results:
Based on the interaction of HDACs and TCFs, compounds with HDACis activity could be easily
picked out from Natural products library (A10) by using this screening system. Finally, a compound Wsu-18
was preliminarily identified as a potential HDACis.

Conclusion:
These data suggest our screening system for HDACis was efficient and promising, and it is suitable
for screening other small molecular chemical libraries.
An Efficient Attribute Reduction and Fuzzy Logic Classifier for Heart Disease and Diabetes Prediction
Authors: Gadekallu Thippa R. , Gao Xiao-Z. 
Published: October 2018

Introduction:
Over the past decade Heart and diabetes disease prediction are major research
works in the past decade. For prediction of the Heart and Diabetes diseases, a model using an
approach based on rough sets for reducing the attributes and for classification, fuzzy logic system is
proposed in this paper.

Methods:
The overall process of prediction is split into two main steps, 1) Using rough set theory
and hybrid firefly and BAT algorithms, feature reduction is done 2) Fuzzy logic system classifies the
disease datasets. Reduction of attributes is carried out by rough sets and Hybrid BAT and Firefly optimization
algorithm.

Results and Discussion:
Then the classification of datasets is carried out by the fuzzy system which is
based on the membership function and fuzzy rules. The experimentation is performed on several
heart disease datasets available in UCI Machine learning repository like datasets of Hungarian,
Cleveland, and Switzerland and diabetes dataset collected from a hospital in India. The experimentation
results show that the proposed prediction algorithm outperforms existing approaches by achieving
better accuracy, specificity, and sensitivity.
Electrically Triggered Transdermal Drug Delivery Utilizing Poly(Acrylamide)-graft-Guar Gum: Synthesis, Characterization and Formulation Development
Authors: Birajdar Ravindra P. , Patil Sudha S. , Alange Vijaykumar V. , Kulkarni Raghavendra V. 
Published: October 2018

Objective:
The study aimed to prepare electrically-triggered transdermal drug delivery
systems (ETDS) using electrically responsive polyacrylamide-graft-gaur gum (PAAm-g-GaG) copolymer.

Methods:
The PAAm-g-GaG copolymer was synthesized by adopting free radical polymerization
grafting method. This PAAm-g-GaG copolymer hydrogel acts as a drug reservoir and blend films of
Guar Gum (GaG) and Polyvinyl Alcohol (PVA) were included as Rate Controlling Membranes
(RCM) in the system. The PAAm-g-GaG copolymer was characterized by FTIR, neutralization
equivalent values, thermogravimetric analysis and elemental analysis.

Results:
On the basis of results obtained, it is implicit that the drug permeation decreased with an increase
in the concentration of glutaraldehyde and RCM thickness; while drug permeation rate was
increased with increasing applied electric current strength from 2 to 8 mA. A two fold increase in
flux values was observed with the application of DC electric current. An increase in drug permeation
was witnessed under on condition of electric stimulus and permeation was decreased when electric
stimulus was "off". The skin histopathology study confirmed the changes in skin structure when
electrical stimulus was applied.

Conclusion:
The electrically-sensitive PAAm-g-GaG copolymer is a useful biomaterial for transdermal
drug delivery application.
Alternative Beginnings
Authors: Aceves Sepulveda Gabriela , Azlisadeh Matilda 
Published: October 2018

In this paper, we discuss three alternative approaches to the dominant histories of techniques of illusion and interaction that emerged in the context of the panel “Alternative Beginnings: Towards an-Other history of immersive arts and technologies” sponsored by the New Media Caucus presented at the 2018 College Art Association Conference. Bringing together recent insights by media archaeologists (Huhtamo and Parikka 2011, Parikka 2012), decolonial thinkers (Mignolo 2011a, b), feminist and indigenous media scholars (Zylinska 2014, Todd 1996, Todd 2015) we invited papers that gave visibility to diverse genealogies of immersion, outside the dominant western art historical canon, to contextualize our current interest for embodied and multi-sensorial experiences. Focusing on the Latin American context – both geographically and epistemologically— the three critical approaches proposed include a discussion on the decolonizing potential of immersion as it moves away from a purely ocular regime towards an embodied one, an exploration of strategies that delink the development of immersive technologies from the military and for-profit game industry, and an emphasis on how localized sites can highlight the decolonizing potential of the local/global relationship in our possible rethinking of immersive technologies.
PENGARUH PEMEGANG SAHAM PENGENDALI TERHADAP KOMPENSASI DIREKSI DENGAN MEKANISME PEMEGANG SAHAM INSTITUSIONAL SEBAGAI VARIABEL PEMODERASI
Authors: Bustari Andre 
Published: October 2018

<p class="Default"><em>Penelitian ini bertujuan </em><em>untuk membuktikan</em><em> </em><em>pemegang saham pengendali terhadap kompensasi direksi dengan </em><em>mekanisme </em><em>pemegang saham </em><em>institusional sebagai variabel pemoderasi</em><em>. Sampel penelitian ini adalah </em><em>22 perusahaan</em><em> </em><em>yang menjadi emiten tetap terbesar termasuk kedalam Likuiditas 45 (LQ45) </em><em>dari </em><em>periode 2011 sampai dengan 2015</em><em>. Metode penelitian yang digunakan adalah metode kuantitatif. Uji statistik yang gunakan dalam penelitian ini adalah Regresi Linear Berganda. </em><em>Teori keagenan memperediksi bahwa pemegang saham pengendali berpengaruh positif terhadap kompensasi direksi. Hasil penelitian pertama tidak dapat membuktikan </em><em>pengaruh </em><em>pemegang saham </em><em>pengendali </em><em>terhadap kompensasi </em><em>direksi</em><em> dikarenakan fungsi pemegang saham pengendali dilaksanakan oleh Komite Independen sesuai yang diisyaratkan oleh peraturan-peraturan yang diterbitkan oleh Otorita Jasa Keuangan </em><em>sehingga </em><em>pemegang saham </em><em>pengendali tidak mempengaruhi pemberian kompensasi kepada direksi. Hasil penelitian kedua tidak membuktikan </em><em>pengaruh </em><em>pemegang saham </em><em>institusional dalam memperlemah pengaruh </em><em>pemegang saham </em><em>pengendali </em><em>terhadap kompensasi </em><em>direksi</em><em>.</em><em> Ini diduga </em><em>pemegang saham </em><em>institusional menilai pemberian kompensasi dan pengawasnya sudah dilaksanakan dengan adanya </em><em>komite </em><em>independen internal perusahaan.</em><em></em></p><p class="Default"> </p><p class="Default"><em>This study aims to prove the controlling shareholder to the compensation of the directors with the mechanism of institutional shareholders as a moderating variable. The sample of this research is 22 companies which become the biggest listed company including into Liquidity 45 (LQ45) from period 2011 to 2015. The research method used is quantitative method. The statistical test used in this study is Multiple Linear Regression. The agency theory predicts that the controlling shareholders positively influence the compensation of the board of directors. The results of the first study cannot prove the influence of the controlling shareholder on the compensation of the directors because the controlling shareholder function is carried out by the Independent Committee in accordance with the rules issued by the Financial Services Authority so that the controlling shareholder does not affect the compensation to the directors. The results of the second </em><em>study</em><em> do not prove the influence of institutional shareholders in weakening the influence of the controlling shareholder on the compensation of the directors. It is alleged that the institutional shareholders assess the compensation and the supervisor has been implemented with the company's internal independent committee.</em></p>
O grande carrossel urbano de Jacques Tati: a transição para uma modernidade urbana construída através dos filmes Mon Oncle e Playtime
Authors: Kuster Eliana 
Published: October 2018

O artigo atravessa dois filmes do mesmo diretor francês para, na transição entre eles, promover a compreensão da ideia de modernidadeurbana, não apenas em sua morfologia, mas, em especial, no sentidosociológico. Os filmes de Tati mostram a transição entre duas cidades: vemos revezarem-se na tela a Paris do século XIX, com suas vielas estreitas, suas construções em tons pastel e sua mistura de usos e ocupação do território e uma Paris que já pertence ao século XX, com novas formas, nova tecnologia e novos comportamentos. Trataremos, a partir desses filmes, o tema de como os sinais do moderno se impõem, trazendo mudanças nas formas de comportamento, na estética e nas maneiras de viver.
El cuerpo como posibilidad informativa, reflexiva y creativa
Authors: Rodríguez-Plaza Patricio 
Published: October 2018

¿Es el cuerpo efectivamente un envoltorio de algo más que sus propios límites carnales, que pueda sorprendernos todavía desde la perspectiva de las experiencias artísticas? ¿Existirá el alma como una dimensión necesariamente trascendente respecto de esto que en nuestras lenguas romances llamamos, siguiendo al latín, corpus? ¿Es el cuerpo la literal o la metafórica encarnación de los sentidos, que ubicados más allá de su materialidad, solo instrumentalizan temporalmente las expresiones creativas?