bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors
Authors: Rivellese Felice , Lobasso Antonio , Barbieri Letizia , Liccardo Bianca , de Paulis Amato , Rossi Francesca Wanda 
Published: February 2018

:
Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial
inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several
systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the
main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis.

:
Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In
addition, the widespread adoption of treat to target and tight control strategies has led to a substantial
improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the
treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of
patients do not respond to current treatments, including biologics. Small-molecule therapies offer
an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5
years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed.
Since JAKs are essential for cell signaling in immune cells, in particular controlling the response
to many cytokines, their inhibitors quickly became a promising class of oral therapeutics
that proved effective in the treatment of RA.

:
ofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed
more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II
and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit
an overall acceptable safety profile similar to that of biologic agents, with infections being the
most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still
limited. Long-term follow-up and further research are needed to evaluate the general safety profile
and the global risk of malignancy of these small molecules, although no clear association with malignancy
has been reported to date.

:
Here, we will review the main characteristics of JAK inhibitors, including details on their
molecular targets and on the clinical evidences obtained so far in the treatment of RA.
Numeric, Agent-based or System Dynamics Model? Which Modeling Approach is the Best for Vast Population Simulation?
Authors: Cimler Richard , Tomaskova Hana , Kuhnova Jitka , Dolezal Ondrej , Pscheidl Pavel , Kuca Kamil 
Published: February 2018

Background:
Alzheimer’s disease is one of the most common mental illnesses. It is posited
that more than 25% of the population is affected by some mental disease during their lifetime. Treatment
of each patient draws resources from the economy concerned. Therefore, it is important to quantify
the potential economic impact.

Methods:
Agent-based, system dynamics and numerical approaches to dynamic modeling of the population
of the European Union and its patients with Alzheimer’s disease are presented in this article.
Simulations, their characteristics, and the results from different modeling tools are compared.

Results:
The results of these approaches are compared with EU population growth predictions from the
statistical office of the EU by Eurostat. The methodology of a creation of the models is described and
all three modeling approaches are compared. The suitability of each modeling approach for the population
modeling is discussed.

Conclusion:
In this case study, all three approaches gave us the results corresponding with the EU
population prediction. Moreover, we were able to predict the number of patients with AD and, based on
the modeling method, we were also able to monitor different characteristics of the population.
The Sesamum indicum Rhizosphere Associated Bacterium: A Source of Antifungal Compound
Authors: Chaudhary Renu , Balhara Meenakshi , Jangir Deepak , Dangi Mrridula , Dangi Mehak , Khatri Savita , Chhillar Anil K. 
Published: February 2018

Background:
The impact of fungal infections on human health has increased considerably
within a past few decades. Although drugs with antifungal properties are available, but they are less effective
and are associated with side effects.

Objective and Method:

To screen the bacterial isolates from Sesamum indicum and to investigate the
antifungal activity of the screened bacterial isolates against Aspergillus sp. Co-culture assay and agar
overlay were used to scrutinize the anti-Aspergillus activity. Furthermore, optimization of media and
growth conditions to enhance the production of anti-Aspergillus compound.

Results:
Several bacterial cultures were isolated from Sesamum indicum rhizosphere collected from
Mandi (H.P.) India. These bacterial cultures were assayed for antifungal activity against Aspergillus species
i.e. A. fumigatus and A. niger. Two most potent strains were chosen for more detailed analyses. The
biochemical characterization and 16S ribosomal RNA sequencing revealed that Burkholderia sp. strain
RC1 and Acinetobacter pittii strain RC2 exhibit strong similarity (100%) with Burkholderia sp. SR2-07
and Acinetobacter sp. strain 3-59. Additionally, it was also validated that RC1 and RC2 showed
significant difference in the production of anti-Aspergillusactivity under altered growth conditions.

Conclusion:
Results from this study recommend that plant rhizosphere remains a rich hotspot for delivering
a novel antifungal compounds.
Design, Synthesis and Biological Evaluation of Novel Urea and Thiourea Bearing thieno[3,2-d]-pyrimidines as PI3 Kinase Inhibitors
Authors: Bodige Srinu , Ravula Parameshwar , Gulipalli Kali Charan , Endoori Srinivas , Chandra J.N. Narendra Sharath , Cherukumalli Purna Koteswara Rao , Vanaja G.R , Seelam Nareshvarma 
Published: February 2018

Background:
Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly
involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore,
inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer.

Methods:
The present research work involves molecular docking studies performed to screen derivatives of urea
and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The
designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their
anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme.

Results:
Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2-
d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines
with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent
PI3Kα inhibitory activity with IC50 value of 1.26 µM.

Conclusion:
Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction
at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory
agents for cancer therapy.
Caffeine Effect on HIFs/VEGF Pathway in Human Glioblastoma Cells Exposed to Hypoxia
Authors: Maugeri Grazia , D'Amico Agata G. , Rasà Daniela M. , Saccone Salvatore , Federico Concetta , Magro Gaetano , Cavallaro Sebastiano , D'Agata Velia 
Published: February 2018

Background:
Caffeine represents the most used psychoactive drug in the world acting through different
mechanisms of action and on several molecular targets. It exerts an anti-cancer role in glioblastoma multiforme
(GBM). This neoplasia is characterized by extensive hypoxic foci triggering hypoxia-inducible factors
(HIFs) expression. Among these factors, HIF-1α performs a crucial role in the induction of vascular endothelium
growth factor (VEGF), a key player in angiogenesis and cell migration.

Methods:
In this work, we have investigated whether caffeine counteracts GBM progression by modulating
hypoxic event. Moreover, we analyzed the activation of phosphoinositide three kinase (PI3K)/Akt and mammalian
mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling cascades.

Results:
Our results have indicated that this psychostimulant drug significantly reduced HIF-1α and VEGF
expression in GBM cells exposed to hypoxia. This effect is mediated through inhibition of PI3K/Akt and
MAPK/ERK signaling pathways both implied in HIFs regulation.

Conclusion:
The present data give new insight into antitumor activity of caffeine during GBM progression.
Lysosomal Potassium Channels: Potential Roles in Lysosomal Function and Neurodegenerative Diseases
Authors: Feng Xinghua , Zhao Zhuangzhuang , Li Qian , Tan Zhiyong 
Published: February 2018

Background & Objective: The lysosome is a membrane-enclosed organelle widely found in
every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it
also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction.
Similar with the plasma membrane, the lysosome membrane is furnished with various proteins,
including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels
have been identified: large-conductance and Ca2+-activated potassium channel (BK) and
TMEM175. TMEM175 has been linked to several neurodegeneration diseases, such as the Alzheimer
and Parkinson disease. Recent studies showed that TMEM175 is a lysosomal potassium channel with
novel architecture and plays important roles in setting the lysosomal membrane potential and maintaining
pH stability. TMEM175 deficiency leads to compromised lysosomal function, which might be
responsible for the pathogenesis of related diseases. BK is a well-known potassium channel for its
function on the plasma membrane. Studies from two independent groups revealed that functional BK
channels are also expressed on the lysosomal plasma membrane. Dysfunction of BK causes impaired
lysosomal calcium signaling and abnormal lipid accumulation, a featured phenotype of most lysosomal
storage diseases (LSDs). Boosting BK activity could rescue the lipid accumulation in several LSD
cell models. Overall, the lysosomal potassium channels are essential for the lysosome physiological
function, including lysosomal calcium signaling and autophagy. The dysfunction of lysosomal potassium
channels is related to some neurodegeneration disorders.

Conclusion:
Therefore, lysosomal potassium channels are suggested as potential targets for the intervention
of lysosomal disorders.
EFEKTIFKAH KEYWORD MNEMONIC DALAM MEMPELAJARI KOSAKATA?
Authors: Sudirman Nur Andini , Ridha Andi Ahmad 
Published: February 2018

Kosakata adalah hal yang penting untuk diingat oleh individu, namun terkadang individu merasa sulit untuk mengingat kosakata. Individu memerlukan sebuah metode yang dapat membantu untuk mengingat dengan mudah kosakata beserta artinya atau tidak mudah lupa dengan kosakata yang telah dipelajari sebelumnya. Keyword mnemonic merupakan salah satu cara untuk membantu individu dalam mengingat kosakata. Penelitian ini bertujuan untuk mengetahui efektifitas keyword mnemonic dalam meningkatkan kemampuan mengingat arti kosakata bahasa inggris. Subjek penelitian ini melibatkan 56 siswa SMP Negeri 13 Makassar yang belum menghafal kosakata bahasa Inggris beserta artinya. Desain eksperimen yang digunakan pada penelitian ini adalah control group posttest-only design. Hasil penelitian menunjukkan bahwa Terdapat perbedaan yang signifikan antara kelompok yang menggunakan keyword mnemonic dan kelompok kontrol. Kelompok yang menggunakan keyword mnemonic (mean=1.14) memperoleh hasil lebih tinggi dari kelompok kontrol (mean=-5.14) (p=0.000<0.05). Penelitian ini bermanfaat bagi individu yang ingin mengingat dengan mudah dan dapat digunakan dalam waktu jangka panjang. Kata kunci: Keyword mnemonic, mengingat, kosakata Vocabulary is an important thing to be remembered by the people, but sometimes people find it difficult to remember the vocabulary. Individuals need a method that can help to remember vocabulary and their meanings easily or not easily forget the vocabulary that have been studied previously. Keyword mnemonic is one of the method to assist individuals in remembering vocabulary. The purposed of this study was to determine the effectiveness keyword mnemonic to improve the ability to remember the meaning of the english vocabulary. Subjects of this study involving 56 students of senior high school of thirteen Makassar who have not memorized the English vocabulary and their meanings yet. Experimental design used in this study is the posttest-only control group design. The results showed that there are significant differences between the groups using the keyword mnemonic and control groups. The groups that use the keyword mnemonic (mean=1.14) obtain higher yields than the control group (mean=-5.14) (p=0.000<0.05). This study is beneficial for individuals who would like to recall with ease and can be used in the long term.Keyword: Keyword mnemonic, remember, vocabulary
Perempuan Salafi Memaknai Jilbab: Antara Alternatif dan Oposisional
Authors: Mahanani Prima Ayu Rizki 
Published: February 2018

AbstrakJilbab cadar merupakan benda yang menjadi penanda perempuan dari manhaj Salafi. Kajian dan analisis kritis ini menggali lebih dalam terhadap si pemakai jilbab yaitu perempuan Salafi yang memaknai jilbab cadar sebagai alternatif ataukah oposisional. Perempuan Salafi adalah subkultur yang mengonstruksi identitasnya melalui atribut yang menunjukkan ekspresi kulturalnya yaitu: muka ditutup dengan cadar, kerudung lebar yang menjuntai sebatas selutut, gamis yang tidak ketat, tidak tipis, tidak tembus pandang, tidak bermotif, warna kain cenderung gelap, tidak memakai harum-haruman, tidak mengenakan hiasan-hiasan, tidak menyerupai pakaian laki-laki, dan tidak menyerupai pakaian wanita kafir atau fasik Berdasarkan jawaban ketujuh informan, ditemukan makna oposisional yaitu adanya hasrat atau keinginan untuk menggantikan jilbab atau mengubah jilbab populer yang ditandai dengan misi berdakwah melalui lisan dan maupun tulisan secara bertahap. Makna oposisionalnya adalah tuntutan lingkungan yang banyak fitnah dan kerusakan seperti sekarang ini dirasa tidak lagi kondusif untuk menundukkan pandangan selain dengan jilbab cadar yang dianggap lebih utama.Kata Kunci: alternatif, jilbab, makna, oposisional, salafi AbstractHijab veil is a material which is a marker of the methodology Salafi women. Research and analysis is critical to dig deep against the wearer's head scarf that women who interpret the Salafi hijab veil as an alternative or oppositional. Women Salafi is a subculture that constructs its identity through attribute expression cultural namely: face covered with a veil, the veil width dangling limited to knee, the robe is not strict, not thin, opaque, not patterned, fabric colors tend to be dark, not wearing fragrance -haruman, no decorations, do not resemble men's clothing, women's clothing and did not resemble the infidels or wicked. Based on the answers to seven informants, oppositional meanings found that their intention or desire to replace the popular hijab headscarf or change marked by the mission and preaching through oral and written gradually. Oposisionalnya meaning is that many environmental claims defamation and damage, as now it is no longer conducive to lower his gaze beyond the veil that veils were considered more important.Keywords: alternative, hijab, meaning, oppositional, salafi
The Victory of Pluralism: The Role of International Law in The South China Sea Dispute
Authors: Siahaan Verdinand Robertua 
Published: February 2018

AbstractThis research discussed the role of Permanent Court of Arbitration’s decision on the dynamic of South China Sea dispute. Court’s decision in July 2016 to regulate South China Sea based on UNCLOS’s regulation has provoked China’s objection. This research question is on how to understand the role of international law in the South China Sea dispute using English School Theory. To answer the research question, this research is using English School Theory with its two pillars namely pluralism and solidarism. This research shows two findings. First, the PCA decision has been used by the Philippines to be momentum for transformation from solidarist mode of foreign policy to pluralist mode. Secondly, the pluralism pillar of English School is more relevant in analyzing the role of international law on South China Sea Dispute.Key words: English School, international law, Permanent Court of Arbitration, pluralism, solidarism, South China Sea AbstrakPenelitian ini membahas peran Permanent Court of Arbitration (PCA) di dalam resolusi konflik Laut Tiongkok Selatan (LTS). Keputusan PCA yang menggunakan UNCLOS sebagai tata kelola LTS memprovokasi kemarahan Tiongkok. Pertanyaan penelitian ini adalah bagaimana memahami peran hukum internasional dalam konflik Laut Tiongkok Selatan menggunakan teori English School. English School dengan kedua pilarnya pluralisme dan solidarisme menjadi pisau analisis utama untuk menjawab pertanyaan penelitian. Penelitian ini menghasilkan dua kesimpulan. Pertama, keputusan PCA digunakan sebagai Filipina sebagai momentum transformasi kebijakan luar negeri Filipina dari solidarisme menjadi pluralisme. Kedua, pilar pluralisme lebih relevan menjelaskan peran hukum internasional dalam sengketa Laut Tiongkok Selatan.Kata kunci: English School, hukum internasional, Laut Tiongkok Selatan, Permanent Court of Arbitration, pluralisme, solidarisme
Nuevo orden espacial de la globalización: encrucijadas y horizontes
Authors: Silveira María Laura 
Published: February 2018

<p>Para debatir las encrucijadas y horizontes del espacio geográfico en el período de la globalización este trabajo se estructurará en cinco puntos. El primero es una introducción sobre el peíodo de la glbalización, sus variables determinantes y los elementos que componen el respectivo orden espacial. El segundo punto aborda un elemento constitucional fundamental de ese orden espacial: la técnica, enfatizando su relación intrínseca con la ciencia. El tercer punto tratará del espacio geográficco nacional como un conjunto plural de divisiones territoriales del trabajo, con la hegemonía de la división del trabajo constituída por las variables determinantes. El cuarto punto analizará las complejas relaciones de cooperación y conflicto entre los oligopolios que conducen esa división territorial del trabajo moderno y el Estado. Finalmente, presentamos una discusión sobre las posibilidades de elaboración de otros pactos territoriales en el futuro.</p><p><strong>PALABRAS CLAVE: </strong>Espacio Geográfico, Período, Técnicas, División Territorial del Trabajo, Oligopolios</p>
La matriz MATAN, una propuesta de análisis paisajístico, mediante el uso de fotografías documentales, históricas y/o patrimoniales de los Andes Patagónicos Chilenos de principios del siglo XX
Authors: Paulsen Bilbao Abraham 
Published: February 2018

<p>Se asiste en la actualidad a un verdadero <em>revival</em> de los estudios geográficos del paisaje, basta revisar los contenidos de publicaciones como <em>Progress in Human Geography</em> y los <em>Annals of Profesional Geographers</em>, por ejemplo, desde la última década en adelante para constatar cómo este tema se ha “popularizado” entre geógrafos, arquitectos, urbanistas y planificadores, entre otros cientistas sociales e investigadores en humanidades. Tim Ingold, desde la antropología del paisaje, nos entrega algunas pistas de los aspectos que explican la resignificación adquirida por estudios enfocados en este concepto clave de la geografía, destacando, el impacto de nuevas concepciones acerca de las relaciones entre el observador y lo observado, que se distancian del cartesianismo tradicional (Ingold, 2011) y la influencia de la física teórica en las ideas referidas a tiempo y espacio (Ingold, 2000).</p><p>Sostenemos que, estas nuevas comprensiones permiten superar algunas contradicciones modernas, que incidían profundamente en el análisis: la primera, referida a las determinaciones sujeto – objeto aplicadas al problema de la percepción y del conocimiento del medio; la segunda, asociada a la consideración de que tiempo y espacio son dimensiones cuasi – irreconciliables y autónomas una con respecto a la otra; y, la tercera, la necesidad metodológica de considerar estáticas las dimensiones ya señaladas con el fin de realizar estudios mediante vías indirectas, como las fotografías, de paisajes ignotos o pretéritos. Hemos desarrollado una matriz analítica, la matriz MATAN, para analizar, desde la geografía, paisajes utilizando como recursos las fotografías, la cual aplicaremos a la colección fotográfica del sacerdote salesiano Alberto De Agostini referida a los Andes Patagónicos chilenos. Sostenemos que la aplicación de MATAN nos permitirá identificar los mensajes implícitos en la imagen, así como también otros aspectos referidos al paisaje como fenosistema, a las técnicas, motivaciones e intenciones del autor, así como también el mensaje religioso que contienen las fotografías, emanado directamente desde la visión de mundo y de realidad que convivían en la mente del sacerdote y científico italiano ya aludido.</p><p><strong>Palabras claves:</strong> Andes patagónicos, Alberto De Agostini, fotografía, paisaje, metalenguaje, matriz MATAN. </p>
Penetración neoliberal en Chile: posibilidades y restricciones para la participación ciudadana
Authors: Zunino Hugo Marcelo 
Published: February 2018

<p>Desde la revolución capitalista instaurada por el régimen militar chileno las decisiones en torno al uso del territorio han quedado sujetas a procedimientos técnico-racionales. Tal marco social e institucional ejerce su poder a través de reglas impidiendo o facilitando la expresión ciudadana en cuanto a la construcción social y política del territorio. En este contexto se busca reflexionar sobre las posibilidades y restricciones que enfrenta la participación ciudadana en un sistema de corte neoliberal. Para estudiar las formas de participación ciudadana frente a proyectos urbanos impuestos desde una institución central, se examinó la resistencia territorial que enfrentó el Proyecto Ribera Norte en la ciudad de Concepción durante los años 2001 y 2003. Metodológicamente se utilizó la identificación de actores estratégicos, entrevistas semiestructuradas y un análisis de reglas del proyecto en sus niveles de coordinación y operacionalización. Además se propone un marco teórico/conceptual útil para desarrollar investigaciones sobre movimientos ciudadanos insertos en contextos macro-sociológicos iguales o diferentes.</p><p><strong>PALABRAS CLAVE: </strong>sistema neoliberal, reglas, participación ciudadana, resistencia territorial, poder</p>