bluuebunny/crossref_metadata_2025 huggingface dataset:
Radikalisme Islam: Pergulatan Ideologi ke Aksi
Authors: Sefriyono Sefriyono , Mukhibat Mukhibat
Published: August 2018

Abstract: The violent actors in Islam known as terrorists ideologically always associated with kalam school which is called Khawarij. They are the fist ortodhox takfiri in Islam and their motto is who did not punish with His law, they were among those unbeliver. This paper with the critical history discusses the religious movement that often called activism with prevalently conflict, the radical movement in islam. Religous social movement can be interpreted with collective awarness who rise up their community for some value, a norm, and social practices in society during a certain period considered to be unfair and oppressive. The movement of the islamic activism in frame of social movement can be understood as fight with mobilization to support interest and the purpose of muslims. Based on the analysis of structure of islamic activism, the study on islamic activism is generally located on three large of domain, i.e. violence and contention, networks and alliance, and culture and framing.الملخص: إن القائمين بعملية العنف في الإسلام المسمّين بالإرهابيّين كانوا يرجعون عقائديّا إلى المذهب في علم الكلام )الخوارج(، الفرقة الأولى .» من لم يحكم بما أنزل الله فهو من الكافرين « للمذهب التكفيري بشعار حاولت هذه المقالة – بالمدخل النقدي التاريخي – دراسة الحركات الدينية أي حركات العنف في الإسلام. إن الحركات الدينية الإجتماعية يمكن أن يُفهم بوجود الوعي الجماعي الناشئ في نفوس المجتمع تجاه القيم و المعايير والعمليّات الإجتماعية الضالّة غير العادلة في مجتمع من المجتمعات في فترات معيّنة. وإن الحركات الإسلامية في ضوء الحركات الاجتماعية يمكن أن يكون له معنى تحريك روح العداوة لدعم فوائد وأهداف الأمة الإسلامية. واعتمادا على التحليل المؤسس على تنظيم الحركة الإسلامية، ة الحركات الإسلامية تقع في ثلات نقاط كبيرة: 1( العنف 􀋰􀋰 إن دراس والعداوة، 2( الشبكات والصلات، 3( الثقافة و الصياغة.Abstrak: Para pelaku kekerasan dalam Islam yang dikenal dengan teroris, secara ideolgis selalu dirujuk kepada aliran Kalam dalam Islam yang disebut dengan Khawarij sebagai kelompok takfiri ortodoks pertama dalam Islam dengan motto-nya siapa yang tidak berhukum dengan hukum Allah, mereka itu di golongkan kepada orang-orang kafir. Makalah ini dengan pendekatan kritis-historis mengkaji gerakan keagamaan yang sering disebut aktivisme Islam dalam kelaziman konfliktual yakni gerakan radikal dalam Islam. Gerakan sosial keagamaan dapat dimaknai dengan adanya kesadaran kolektif yang bangkit dalam diri masyarakat terhadap beberapa nilai, norma, dan praktek-praktek sosial di sebuah masyarakat pada periode tertentu yang dianggab tidak adil, menindas. Gerakan sosial/Aktivisme Islam dalam bingkai gerakan sosial bisa dimaknai dengan mobilisasi perseteruan untuk mendukung kepentingan dan tujuan kaum Muslimin. Berdasarkan analisis dengan struktur aktivisme Islam (Structur of Islamic Activisme), kajian terhadap aktivisme Islam umumnya berada pada tiga domain besar yakni, kekerasan dan perseteruan (violence and contention), jariangan dan aliansi (networks and alliances), dan kebudayaan dan pembingkaian (Culture and Framing).
Model Inovasi Produk Perbankan Syariah di Indonesia
Authors: Apriyanti Hani Werdi
Published: August 2018

Sharia banking faces various challenges in order to reach market share both sharia banking and the other one. The sharia banking industry in Indonesia must take competitive advantage through product innovation. This research suggests conceptual model product innovation for sharia banking industry using the opportunity of global sharia economic development and the international trust in Indonesia. Product innovation for sharia banking can achieved by strengthening Sharia Banking Working Group, sharia compliance, financial stability, product innovation activity. This model expected to encourage market expansion both domestically and abroad. It’s achieved by providing a variety of products that are closer and accepted by the community, with products that have a high social attachment (close to the society).Perbankan syariah saat ini dihadapkan pada persaingan yang ketat dalam meraih pangsa pasar, baik persaingan antara bank syariah dengan bank konvensional maupun antarsesama bank syariah. Oleh karena itu, perbankan syariah harus memiliki keunggulan kompetitif dengan melakukan inovasi produk. Penelitian ini mengusulkan model inovasi produk dengan memanfaatkan peluang pesatnya perkembangan ekonomi syariah global dan membaiknya kepercayaan dunia internasional terhadap ekonomi Indonesia dengan dukungan penguatan Working Group Perbankan Syariah (WGPS), pemenuhan ketentuan syariah (sharia compliance), pencapaian stabilitas keuangan, serta peningkatan dalam aktivitas inovasi produk. Model yang diusulkan diharapkan dapat mendorong perluasan pasar perbankan syariah baik di dalam negeri maupun luar negeri dengan menyediakan beragam produk yang lebih dekat dan diterima masyarakat. Perbankan syariah diharapkan melakukan inovasi produk yang memiliki kelekatan sosial tinggi (dekat, dapat diterima, serta sesuai dengan preferensi masyarakat).
Literature Study on Murābaḥah Financing in Islamic Banking in Indonesia
Authors: Maulidizen Ahmad
Published: August 2018

Islamic banking in Indonesia has experienced significant growth, including assets, financing provided and the number of customers. Islamic bank financing 70-80% is given to the community by using the contract of murābaḥah, in the form of consumptive and productive. Islamic bank operations must be guided by Fatwa of the National Sharia Council in order to carry out its optimal function economically and to run the Shari'a comprehensively. Therefore, this article will explain the concept of murābaḥah conceptually and application in Islamic banking in Indonesia. The purpose of writing this article so that the implementation of Murābaḥah contract in Islamic Bank in Indonesia can be in accordance with the principles of Shari'a that put forward the principle of justice and no party is harmed.Perbankan syariah di Indonesia telah mengalami pertumbuhan yang signifikan, termasuk aset, pembiayaan yang diberikan dan jumlah pelanggan. Pembiayaan bank syariah 70-80% diberikan kepada masyarakat dengan menggunakan kontrak murābaḥah, dalam bentuk konsumtif dan produktif. Kegiatan bank syariah harus dipandu oleh Fatwa Dewan Syariah Nasional untuk menjalankan fungsi optimalnya secara ekonomis dan menjalankan syariat secara komprehensif. Oleh karena itu, artikel ini akan menjelaskan tentang konsep murābaḥah secara konseptual dan aplikasinya pada Bank Islam di Indonesia. Tujuan penulisan artikel ini agar pelaksanaan kontrak Murābaḥah di Bank Syariah di Indonesia dapat sesuai dengan prinsip syariah yang mengedepankan asas keadilan dan tidak ada pihak yang dirugikan.
Wakaf sebagai Instrumen Ekonomi Pembangunan Islam
Authors: Fuadi Nasrul Fahmi Zaki
Published: August 2018

This study aimed to analyze the role of waqf as an economic instrument for Islamic development. This was motivated by unresolved poverty conditions. That poor people still experience difficulties in meeting their primary needs. On the other hand, endowments as Islamic economic instruments have excellent potential in developing the economy and providing benefits to the community. This study uses qualitative methods by reviewing kinds of literature in obtaining waqf models in several countries and their success. The results show that endowments have potential in economic development. Some countries show their success in managing waqf and providing benefits to the community. The results of this study also show that Indonesia has a very good waqf potential and is able to be a solution to the problem of poverty.Artikel ini mencoba untuk menganalisis bagaimana peran wakaf sebagai intrumen ekonomi pembangunan Islam. Hal tersebut dilatarbelakangi oleh kondisi kemiskinan yang belum terselesaikan. Bahwa penduduk miskin masih mengalami kesulitan dalam memenuhi kebutuhan primernya. Di sisi lain, wakaf sebagai intrumen ekonomi Islam memiliki potensi yang sangat baik dalam pengembangan perekonomian dan memberikan manfaat bagi masyarakat. Penelitian ini menggunakan metode kualitatif dengan mengkaji beberapa sumber dalam mendapatkan model wakaf di beberapa negara dan keberhasilannya. Hasil penelitian menunjukkan bahwa wakaf memiliki potensi dalam pembangunan ekonomi. Beberapa negara menunjukkan keberhasilannya dalam mengelola wakaf dan memberikan manfaat bagi masyarakat. Hasil dari penelitian ini juga menunjukkan bahwa Indonesia memiliki potensi wakaf yang sangat baik dan mampu menjadi solusi dari masalah kemiskinan.
The Development of Pharmacophore Modeling: Generation and Recent Applications in Drug Discovery
Authors: Lu Xin , Yang Hongyu , Chen Yao , Li Qi , He Si-yu , Jiang Xueyang , Feng Feng , Qu Wei , Sun Haopeng
Published: August 2018

Background:

The pharmacophore concept in modern drug research is of great importance and promotes
the development of drug industry as indicated by the number of publications available.

Methods:

: In this article, we reviewed and highlighted some successful examples of pharmacophore modeling,
which was applied either in virtual screening for efficient hit discovery or in the optimization of the lead compounds.
Meanwhile, the analysis of some important aspects of pharmacophore modeling such as a database, the
software was listed as well.

Results: Based on the analysis of these examples, we intended to provide an overview of pharmacophore-based
virtual screening, which we hope to help readers gain insight into this powerful technique.

Conclusion:

Owing to its’ convenience and efficiency, pharmacophore presents an essential method for drug
discovery.
Understanding the Binding Mechanism of Amyloid-β Inhibitors from Molecular Simulations
Authors: Tran Linh
Published: August 2018

In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development
has been carefully assessed to treat Alzheimer’s disease. Aβ peptides can transform structurally from random coil
monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the identification
of binding targets has been challenging due to the heterogeneity and metastable nature. A better understanding
of Aβ species’ assembly details and structural properties has been more characterized recently. Numerous
potential inhibitors have been identified that they can effectively bind to different Aβ species such as monomer,
oligomer or protofibril during the inhibition of Aβ aggregation process. This review highlights the diversity of
structural ensembles of Aβ species, from monomer to protofibril forms and the specific binding targets by their
potential inhibitors. Comprehending the binding mechanism of Aβ inhibitors is indispensable for searching novel
drug candidates against early-stage Alzheimer’s disease.
Redox Sensitive Polysaccharide Based Nanoparticles for Improved Cancer Treatment: A Comprehensive Review
Authors: Ghassami Erfaneh , Varshosaz Jaleh , Taymouri Somayeh
Published: August 2018

Background:

Among the numerous bio-responsive polymeric drug delivery systems developed recently,
redox-triggered release of molecular payloads have gained great deal of attention, especially in the field of
anticancer drug delivery. In most cases, these systems rely on disulfide bonds located either in the matrix crosslinks,
or in auxiliary chains to achieve stimuli-responsive drug release. These bonds keep their stability in extracellular
environments, yet, rapidly break by thiol–disulfide exchange reactions in the cytosol, due to the presence
of greater levels of glutathione. Polysaccharides are macromolecules with low cost, natural abundance,
biocompatibility, biodegradability, appropriate physical and chemical properties, and presence of numerous functional
groups which facilitate chemical or physical cross-linking.

Methods:

With regards to the remarkable advantages of polysaccharides, in the current study, various
polysaccharide-based redox-responsive drug delivery systems are reviewed. In most cases the in vitro/in vivo
effects of the developed system were also evaluated.

Results:

Considering the hypoxic and reducing nature of the tumor microenvironment, with several folds higher
glutathione levels than the systemic tissues, redox-sensitive polymeric systems could be implemented for tumorspecific
drug delivery and the results of the previous researches in this field indicated satisfactory achievements.

Conclusion:

According to the reviewed papers, the efficiency of diverse redox-responsive polysaccharide-based
nanoparticles with therapeutic payloads in cancer chemotherapy could be concluded. Nevertheless, more comprehensive
studies are required to understand the exact intracellular and systemic fate of these nano-carriers, as well
as their clinical efficacy for cancer treatment.
Cordycepin Modulates Body Weight by Reducing Prolactin Via an Adenosine A1 Receptor
Authors: Li Yuan , Li Yan , Wang Xueyan , Xu Hongyue , Wang Chao , An Yanan , Luan Wenjing , Wang Xuefei , Li Shulin , Ma Fangxue , Ni Lihui , Liu Mingyuan , Tang Xudong , Yu Lu
Published: August 2018

Background:

Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological
function. In previous studies, cordycepin has demonstrated an excellent anti-obesity effect, but the mechanism
is unclear. It was also demonstrated that prolactin played an important role in body weight regulation and
hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular
mechanism of the anti-obesity effect of cordycepin.

Methods:

In Vivo, the obese rat model was induced by high fat diet for five weeks, and the serum and liver lipid
levels coupled with the serum prolactin levels were reduced following cordycepin treatment (P<0.01).

Results:

The results suggested that cordycepin is a potential drug that lowers blood and liver lipid levels and
reduces body weight related to prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes
from lipotoxicity-induced inflammation. In vitro, cordycepin inhibited prolactin secretion in GH3 cells via
upregulating the expression of adenosine A1 receptor, and the inhibition effect was blocked by an antagonist of
adenosine receptor A1 DPDPX, demonstrating that cordycepin may work as an adenosine agonist. Additionally,
cordycepin inhibited the ERK/AKT/PI3K pathway in GH3 cells. At the same time, cordycepin blocked prolactininduced
upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In an in vivo
study, cordycepin downregulated the expression of prolactin receptor (PRLR) but not the phosphorylation of
JAK2.

Conclusion:

Thus, it was proved that cordycepin modulates body weight by reducing prolactin release via an
adenosine A1 receptor.
A Simple and One-pot Synthesis of Tetrahydrobenzo[b]pyrans and Spirooxindoles Catalyzed by H-Fe3O4@DA-SO3H as an Efficient, Light and Reusable Nanocatalyst
Authors: Mirhosseyni Marzie Sadat , Nemati Firouzeh , Elhampour Ali
Published: August 2018

Aim and Objective:

One of the principles of green chemistry is using inexpensive
reagents and catalysts to design green route for synthesis of organic compounds. Recently magnetic
nanoparticles have provided a considerable merits. In this study, hollow Fe3O4@Dopamine-SO3H
has been successfully applied for the green synthesis of tetrahydrobenzo[b]pyrans and
spirooxindoles via one-pot multi-component reaction.

Materials and Methods:

Chemical reagents were purchased from Merck and Aldrich. Melting points
were determined using an Electrothermal 9100. Fourier transform infrared and NMR spectra were
recorded with a Shimadzu 8400 spectrometer and Bruker spectrometer, respectively.

Results:

The reaction between benzaldehyde, malononitrile and dimedone was selected as the model
for synthesis of tetrahydrobenzo[b]pyran. The obtained results showed that the best amount of
catalyst is 0.01 g and the reaction has occurred in solvent free condition at 70°C. The results showed
that both electron-withdrawing and electron-donating substituents have an acceptable yield in the
reaction. After that the scope of this method was evaluated in one-pot synthesis of spirooxindole
derivatives through three-component reaction of isatin derivatives, malononitrile or ethyl
cyanoacetate and 1,3-cycllic diketone. The optimum condition was 0.01 g catalyst using H2O under
reflux condition. Then other derivatives produced in excellent yields during short reaction times.

Conclusion:

Tetrahydrobenzo[b]pyran and spirooxindole derivatives in the presence of this catalyst
were synthesized. The ease of preparation and handling of the catalyst and operational simplicity are
some of the main advantages of this work. In addition, the catalyst could be recycled and reused at
least six times without notable reduction in its catalytic activity.
Probiotic Supplementation in Patients with Alzheimer’s Dementia - An Explorative Intervention Study
Authors: Leblhuber Friedrich , Steiner Kostja , Schuetz Burkhard , Fuchs Dietmar , Gostner Johanna M.
Published: August 2018

Background:

Dysbiosis of intestinal microbiota in the elderly can cause a leaky gut, which
may result in silent systemic inflammation and promote neuroinflammation - a relevant pathomechanism
in the early course of Alzheimer’s disease.

Objective:

The rebalancing of the microbiome could benefically impact on gut inflammation and immune
activation.

Methods:

In this study, routine laboratory tests in twenty outpatients (9 females, 11 males, aged 76.7 ±
9.6 years) with Alzheimer’s disease were investigated. The mean Mini Mental State Examination score
was 18.5 ± 7.7. Biomarkers of immune activation – serum neopterin and tryptophan breakdown - as
well as gut inflammation markers and microbiota composition in fecal specimens were analyzed in 18
patients before and after probiotic supplementation for 4 weeks.

Results:

After treatment a decline of fecal zonulin concentrations and an increase in Faecalibacterium
prausnitzii compared to baseline were observed. At the same time, serum kynurenine concentrations
increased (p <0.05). Delta values (before - after) of neopterin and the kynurenine to tryptophan ratios
(Kyn/Trp) correlated significantly (p <0.05).

Conclusion:

Results show that the supplementation of Alzheimer’s disease patients with a multispecies
probiotic influences gut bacteria composition as well as tryptophan metabolism in serum. The correlation
between Kyn/Trp and neopterin concentrations points to the activation of macrophages and/or dendritic
cells. Further studies are warranted to dissect the potential consequences of Probiotic supplementation
in the course of Alzheimer’s disease.
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors, Reality or Dream in Managing Patients with Cardiovascular Disease
Authors: Alkhalil Mohammad
Published: August 2018

Background:

Statins have been a major keystone in the management of patients with atherosclerotic cardiovascular
disease. The benefits of inhibiting HMG CoA reductase, via statins, were translated into reduction in
LDL-c with proportionate decrease in cardiovascular events in response to the magnitude of LDL-c reduction. Despite
major advances in pharmacological treatments, including the use of high-dose statins, there are urgent need to
further reduce future cardiovascular risk. This is in particularly important since 1 out of 5 high-risk atherosclerotic
patients who achieve low LDL-c return with a second cardiovascular event within five years. Although this residual
risk post-statin is largely heterogeneous, lowering LDL-c beyond ‘normal’ or guidelines-recommended level using
novel therapies has resulted in further reduction in cardiovascular events.

Objective: The current review will discuss the use of PCSK9 inhibitors in patients with atherosclerotic disease.
PCSK9 inhibitors are a new class of lipid-lowering drugs that are either fully human monoclonal antibodies (evolocumab
and alirocumab) or humanised monoclonal antibodies (bococizumab) that effectively reduce LDL-c to unprecedented
level. By blocking circulating PCSK9, these drugs would preserve LDL receptors and prevent them
from cellular degradation. This process promotes recycling of LDL receptors back to hepatocytes surface, leading
into further reduction of LDL-c. Combining PCSK9 inhibitors with statin have led into lower LDL-c, reduction in
plaque volume and more importantly reduction in future cardiovascular events.

Conclusion:

These drugs are very promising, nonetheless, the unselective approach of applying these monoclonal
antibodies may not prove to be cost-effective and potentially exposing some patients to unnecessary side effects.
Survey of Machine Learning Techniques in Drug Discovery
Authors: Stephenson Natalie , Shane Emily , Chase Jessica , Rowland Jason , Ries David , Justice Nicola , Zhang Jie , Chan Leong , Cao Renzhi
Published: August 2018

Background:

Drug discovery, which is the process of discovering new candidate medications, is very important for pharmaceutical industries. At its current stage, discovering new drugs is still a very expensive and time-consuming process, requiring Phases I, II and III for clinical trials. Recently, machine learning techniques in Artificial Intelligence (AI), especially the deep learning techniques which allow a computational model to generate multiple layers, have been widely applied and achieved state-of-the-art performance in different fields, such as speech recognition, image classification, bioinformatics, etc. One very important application of these AI techniques is in the field of drug discovery.

Methods:

We did a large-scale literature search on existing scientific websites (e.g, ScienceDirect, Arxiv) and startup companies to understand current status of machine learning techniques in drug discovery.

Results:

Our experiments demonstrated that there are different patterns in machine learning fields and drug discovery fields. For example, keywords like prediction, brain, discovery, and treatment are usually in drug discovery fields. Also, the total number of papers published in drug discovery fields with machine learning techniques is increasing every year.

Conclusion:

The main focus of this survey is to understand the current status of machine learning techniques in the drug discovery field within both academic and industrial settings, and discuss its potential future applications. Several interesting patterns for machine learning techniques in drug discovery fields are discussed in this survey.
Managing Clopidogrel Hypersensitivity without Interrupting Therapy: The Toronto Approach
Authors: Cheema Asim N.
Published: August 2018

Clopidogrel remains a widely used antiplatelet agent for patients with established or high risk
of atherothrombotic disease, particularly those treated with coronary, carotid or peripheral endovascular
stenting. Clopidogrel hypersensitivity is an uncommon but well established adverse drug reaction presenting
a challenge for patient management. The clinical presentation ranges from focal or diffuse cutaneous
manifestations in most patients to angioedema in some and a systemic immune response in rare
cases. The treatment options include drug discontinuation with or without desensitization therapy,
switching to alternate ADP receptor antagonists or administration of oral steroids while continuing
clopidogrel in patients at high risk of adverse events with clopidogrel discontinuation. In this review the
author describes the phenomenon of clopidogrel hypersensitivity, various treatment strategies.
Nitrite-stimulated Gastric Formation of S-nitrosothiols As An Antihypertensive Therapeutic Strategy
Authors: Oliveira-Paula Gustavo H. , Tanus-Santos Jose E.
Published: August 2018

Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. While enzymes with nitrite-reductase activity capable of generating NO from nitrite may contribute to antihypertensive effects of nitrite, another mechanism involving the generation of NO-related species in the stomach from nitrite has been validated. Under the acidic conditions of the stomach, nitrite generates NO-related species that form S-nitrosothiols. Conversely, drugs that increase gastric pH may impair the gastric formation of S-nitrosothiols, which may mediate antihypertensive effects of oral nitrite or nitrate. Therefore, it is now becoming clear that promoting gastric formation of S-nitrosothiols may result in effective antihypertensive responses, and this mechanism opens a window of opportunity in the therapy of hypertension. In this review, we discuss the recent studies supporting the gastric generation of S-nitrosothiols as a potential antihypertensive mechanism of oral nitrite. We also highlight some drugs that increase S-nitrosothiols bioavailability, which may also improve the responses to nitrite/nitrate therapy. This new approach may result in increased nitrosation of critical pharmacological receptors and enzymes involved in the pathogenesis of hypertension, which tend to respond less to their activators resulting in lower blood pressure.
Oral and Written Naming in Alzheimer’s Disease: A Longitudinal Study
Authors: Gonzalez-Nosti Maria , Cuetos Fernando , Martinez Carmen
Published: August 2018

Background:

The expressive difficulties in patients with Alzheimer’s dementia have been
extensively studied, mainly in oral language. However, the deterioration of their writing processes has
received much less attention.

Objective:

The present study aims to examine the decline of the performance of patients with Alzheimer’s
disease in both oral and written picture-naming tasks.

Method:

Sixty-four participants (half with Alzheimer’s disease and half healthy elderly) were compared
in the oral and written versions of a picture-naming task. Follow-up lasted two and a half years and patients
were evaluated every six months.

Results:

Cross-sectional data indicate that the controls performed better than the patients, and both
groups showed a different pattern of errors. In terms of longitudinal data, the results show a similar pattern
of deterioration in both tasks. In terms of errors, lexical-semantics were the most numerous at the
beginning and their number remained constant throughout all evaluations. In the case of non-responses,
there was a significant increase in the last session, both in oral and written naming.

Conclusion:

These results replicate those found in previous studies and highlight the utility of the naming
task to detect minimal changes in the evolution of patients with Alzheimer’s disease.
Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild Cognitive Impairment and Alzheimer’s Disease
Authors: Jiang Zihan , Yang Huilin , Tang Xiaoying
Published: August 2018

Objective: In this study, we investigated the influence that the pathology of Alzheimer’s disease
(AD) exerts upon the corpus callosum (CC) using a total of 325 mild cognitive impairment (MCI)
subjects, 155 AD subjects, and 185 healthy control (HC) subjects.

Method:

Regionally-specific morphological CC abnormalities, as induced by AD, were quantified using
a large deformation diffeomorphic metric curve mapping based statistical shape analysis pipeline.
We also quantified the association between the CC shape phenotype and two cognitive measures; the
Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive
Behavior Section (ADAS-cog). To identify AD-relevant areas, CC was sub-divided into three subregions;
the genu, body, and splenium (gCC, bCC, and sCC).

Results:

We observed significant shape compressions in AD relative to that in HC, mainly concentrated
on the superior part of CC, across all three sub-regions. The HC-vs-MCI shape abnormalities were also
concentrated on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs-AD
shape differences, however, were only detected in part of sCC. In the shape-cognition association, significant
negative correlations to ADAS-cog were detected for shape deformations at regions belonging
to gCC and sCC and significant positive correlations to MMSE at regions mainly belonging to sCC.

Conclusion:

Our results suggest that the callosal shape deformation patterns, especially those of sCC,
linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring
the progression of AD.
Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse Model and Alzheimer’s Disease
Authors: Vega Irving E. , Umstead Andrew , Wygant Cassandra M. , Beck John S. , Counts Scott E.
Published: August 2018

Background:

The lack of diagnostic tools and disease-modifying treatments against Alzheimer’s
disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic
burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome
changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular
stress responses associated with tauopathy. These studies, however, need to be conducted taking
into consideration brain region specificity and stage of neurodegeneration in order to provide insights
about the pathological role of the identified proteins.

Methods:

We used a tauopathy mouse model (JNPL3) that expresses human tau bearing a P301L mutation
and develops motor impairment, the severity of which correlates with the increased accumulation of
pathological tau. Tissue was dissected from asymptomatic and severely motor impaired JNPL3 mice as
well as non-transgenic littermate controls and subjected to two-dimensional gel electrophoresis. Differentially
abundant protein spots were identified by tandem mass spectrometry. Postmortem mild cognitive
impairment (MCI), AD and normal aging controls were used to validate the pathological significance
of the identified protein.

Results:

Ezrin was identified as a protein that is upregulated in tau-mediated neurodegeneration. We
demonstrate that Ezrin protein abundance increased in JNPL3 mice preceded motor impairment and was
sustained in severely motor impaired mice. Ezrin expression was also increased in the temporal cortex of
MCI and AD patients.

Conclusion:

The results demonstrate that increased Ezrin protein abundance changes are associated with
the early stages of neurodegeneration in tauopathy models and human disease. Understanding the role of
Ezrin in tauopathies such as AD may provide new insights for targeting tau-mediated neurodegeneration.
The Evaluation of Animal Models in the Development of Anticancer Agents: From Preclinical to Clinical Tests
Authors: Wang Jie , Dong Haiyan , Liu Jian , Zheng Ning , Xie Xiaodong , Jia Lee
Published: August 2018

Background:

One of the main reasons for most of the anticancer drugs to fail in the late
preclinical testing and early clinical trials is the differences in drug effects observed from animals
and patients, and the challenge has been to find a balance to reduce the inherent differences from
species.

Objective:

Predicting safe starting doses and dosing schedules for human clinical trials is the main
purpose of toxicological studies of anticancer drugs.

Methods:

Relevant information and data were assimilated from manuscripts, congress publications,
and online sources.

Results:

We systematically overview the cons and pros of animal models and briefed the ways to
determine human clinical starting doses derived from animal toxicological studies for anticancer
drugs.

Conclusion:

This information helps smart select the suitable predictive model for anti-cancer drugs
with the different mechanisms and emphasized the pharmaceutical challenges behind and ahead.
Structure-Based Drug Design Strategies and Challenges
Authors: Wang Xin , Song Ke , Li Li , Chen Lijiang
Published: August 2018

Over the past ten years, the number of three-dimensional protein structures identified by advanced
science and technology increases, and the gene information becomes more available than ever
before as well. The development of computing science becomes another driving force which makes it
possible to use computational methods effectively in various phases of the drug design and research.
Now Structure-Based Drug Design (SBDD) tools are widely used to help researchers to predict the position
of small molecules within a three-dimensional representation of the protein structure and estimate
the affinity of ligands to target protein with considerable accuracy and efficiency. They also accelerate
discovery speed of potent drug and reduce the cost and times for drug research. Here we present an
overview of SBDD used in drug discovery and highlight its recent successes and major challenges to
current SBDD methodologies.
Overview of Free Software Developed for Designing Drugs Based on Protein-Small Molecules Interaction
Authors: Agrawal Piyush , Raghav Pawan Kumar , Bhalla Sherry , Sharma Neelam , Raghava Gajendra P.S.
Published: August 2018

One of the fundamental challenges in designing drug molecule against a disease target or protein
is to predict binding affinity between target and drug or small molecule. In this review, our focus
will be on advancement in the field of protein-small molecule interaction. This review has been divided
into four major sections. In the first section, we will cover software developed for protein structure prediction.
This will include prediction of binding pockets and post-translation modifications in proteins. In
the second section, we will discuss software packages developed for predicting small-molecule interacting
residues in a protein. Advances in the field of docking particularly advancement in the knowledgebased
force fields will be discussed in the third part of the review. This section will also cover the
method developed for predicting affinity between protein and drug molecules. The fourth section of the
review will describe miscellaneous techniques used for designing drug molecules, like pharmacophore
modelling. Our major emphasis in this review will be on computational tools that are available free for
academic use.
Role of Biomacromolecules in Biomedical Engineering
Authors: Ruso Juan M. , Hassan Natalia
Published: August 2018

Biomacromolecules structures and their interaction between different systems have been
extensively studied in the last years. Nevertheless, in the medicinal context, it has not been studied
deeply. For this reason, the interest to investigate the behavior of different biomacromolecules such us
proteins, organelles, phospholipids, etc. with soft materials has opened new research lines. Computational
and experimental methodologies have tried to answer different questions that have been difficult
to solve, due to the complexity of the phenomenon, as an example, competition between biomacromolecules
and soft materials for a specific organ. In this review, we would like to demonstrate how soft
materials influence the biomacromolecules structures and how to change their response, biodistribution
and also biocompatibility for future applications.
Novel Classes of Antibacterial Drugs in Clinical Development, a Hope in a Post-antibiotic Era
Authors: Campanini-Salinas J. , Andrades-Lagos J. , Mella-Raipan J. , Vasquez-Velasquez D.
Published: August 2018

Bacterial resistance is a growing problem worldwide and is estimated that deaths by infectious
diseases associated with resistant pathogens will generate 10 million deaths per year in 2050. This
problem becomes more serious due to the low level of research and development of new drugs, which
has fallen drastically in the last 40 years. For example, in the last decade of a total of 293 new drugs
approved by the FDA, only 9 corresponded to antimicrobial drugs and none constituted a new structural
class. The majority of the molecules in the clinical phase II or III, coming from modifications of drugs
in clinical use, this strategy makes easier the bacterial susceptibility to generate resistance through the
mechanisms expressed for their drug predecessors.

Under this scenario, it is urgent to generate the most novel strategies for the development of antibacterial
compounds with new targets or mechanism of action, without a structural relationship with the antibiotic
drugs predecessors. Under this look, the present review addresses the development of the latest
antibacterial drugs in clinical phases II and III, analyzing the design strategies by which these new molecules
were obtained and the structure-activity relationship of these new families of antibiotics, in order
to define the state of the vanguard antibacterial drugs in the post-antibiotic era.
The Pleiotropic Effects of Statins – From Coronary Artery Disease and Stroke to Atrial Fibrillation and Ventricular Tachyarrhythmia
Authors: Oesterle Adam , Liao James K.
Published: August 2018

Statins, 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, have been used for decades
for the prevention of coronary artery disease and stroke. They act primarily by lowering serum
cholesterol through the inhibition of cholesterol synthesis in the liver, which results in the upregulation
of low-density lipoprotein receptors in the liver. This results in the removal of low-density lipoproteincholesterol.
Studies have suggested that statins may demonstrate additional effects that are independent
of their effects on low-density lipoprotein-cholesterol. These have been termed “pleiotropic” effects.
Pleiotropic effects may be due to the inhibition of isoprenoid intermediates by statins. Isoprenoid inhibition
has effects on the small guanosine triphosphate binding proteins Rac and Rho which in turn effects
nicotinamide adenine dinucleotide phosphate oxidases. Therefore, there are changes in endothelial nitric
oxide synthase expression, atherosclerotic plaque stability, pro-inflammatory cytokines and reactive
oxygen species production, platelet reactivity, and cardiac fibrosis and hypetrophy development. Recently,
statins have been compared to the ezetimibe and the recently published outcomes data on the
proprotein convertase subtilisin kexin type 9 inhibitors has allowed for a reexamination of statin pleiotropy.
As a result of these diverse effects, it has been suggested that statins also have anti-arrhythmic
effects. This review focuses on the mechanisms of statin pleiotropy and discusses evidence from the
statin clinical trials as well as examining the possible anti-arrhythmic effects atrial fibrillation and ventricular
tachyarrhythmias.
Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle
Authors: D`Urbano Vanessa , De Crignis Elisa , Re Maria Carla
Published: August 2018

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.
Hydrops Fetalis and THE Parvovirus B-19
Authors: Kontomanolis Emmanuel N. , Fasoulakis Z.
Published: August 2018

Definition:

Hydrops Fetalis (HF) or fetal hydrops is identified as an abnormal interstitial
collection of fluid in at least 2 or more compartments of the fetal torso (peritoneal cavity, pleura,
and pericardium). An alternative definition discusses about liquor accumulation in two fetal anatomical
areas or an effusion in one site and anasarca.

Background:

Parvovirus B-19 is a common childhood illness; the virus can cause fetal anemia,
non-immune fetal hydrops, and spontaneous abortion and might lead to fetal demise.

HF is the pathological distribution of body fluids between the interstitial and the intravascular areas
of the fetus. Normally, in the fetal organism there is a continuous circular movement of the lymph
from the interstitial space into the vascular system and vice versa. The detection of a solely effusion
represents the initial stage of a systemic disorder that will lead to a fully developed hydrops or remain
just a local disorder.

Objective:

The connection between parvovirus B-19 and fetal hydrops.

Conclusion:

The view is unbeatable, severely swollen babies; immune hydrops is surfaced because
of the maternal antibodies targeted against red blood cells with Rh positive antibody of the fetus,
while the non-immune is due to a variety of pathological conditions in pregnancy.
Post Chikungunya Chronic Arthritis: Systemic Inflammatory Status Triggering Acute Coronary Syndrome
Authors: Patel Dhruvkumar M. , Patel Mukundkumar V. , Sharma Kamal H. , Patel Greshaben R. , Patel Manish B. , Shah Vipul V.
Published: August 2018

Background:

Atherosclerosis, inflammation and coronary plaque destabilization are
linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome
(ACS) by systemic inflammation cascade.

Methods:

We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA)
among 400 consecutive ACS patients (Case group) and compared with control group subjected to
elective surgery by the prospective case-control observational study. Cases were excluded if standard
criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial
Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum
IgM anti-CCP positive patients were also excluded from the case as well as a control group.

Results:

The case and control groups were similar except, less number of heart failure (O.R.7.3,
95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective
surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control
group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often
women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted
analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4-
6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8).

Conclusion:

PCCA is common among patients with ACS and post-infective systemic inflammation
of PCCA may trigger plaque destabilization.
Potential Utility of Self-Report Measures of Affect to Optimise Exercise Adherence in People with Type 2 Diabetes
Authors: Cox Emily R. , Keating Shelley Elizabeth , Coombes Jeff S. , Burton Nicola W.
Published: August 2018

:

Exercise is essential for managing type 2 diabetes, however approximately only 40% of people
with the condition meet guidelines. The aim of this review is to examine the evidence regarding the
use self-report measures of affect to understand and predict exercise adherence. Self-reported affect has
been successfully used to regulate exercise intensity, monitor training load, prevent injury, and predict
future physical activity participation in otherwise healthy and some clinical populations.

:

Specific recommendations are provided for research to explore the utility of self-report measures of affect
to promote exercise adherence in people with type 2 diabetes.
Hypertension, Diabetes and Neurodegenerative Diseases: Is there a Clinical Link through the Ca2+/cAMP Signalling Interaction?
Authors: Bergantin Leandro Bueno
Published: August 2018

Background:

Hypertension, diabetes and neurodegenerative diseases are among the most prevalent medical problems around the world, costing millions of dollars to the medical health systems. Indeed, hypertension has been associated with higher risk for decline of cognition, as evidenced in patients with Alzheimer´s disease (AD). Furthermore, there is a clear relationship between hypertension and diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+) channel blockers (CCBs) have been classically prescribed for treating hypertension because of their mechanism of action due to reducing the influx of Ca2+ into the smooth muscles cells. In addition, many clinical and experimental studies have been demonstrating pleiotropic effects for CCBs. For instance, in hypertensive patients treated with CCBs, it can be observed lower incidence of neurodegenerative diseases such as AD. The virtual mechanism of action could be attributed to a restoration and maintenance of Ca2+ homeostasis, which is dysregulated in the neurodegenerative diseases, including also a reduction of neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in hypertensive patients treated with CCBs, it can be observed an improvement of diabetes status such as glycemic control. A possible mechanism of action under debate could be attributed to a restoration of insulin secretion, then achieving glycemic control, and reduction of pancreatic β-cell apoptosis.

Conclusion:

Considering the discovery of our group entitled “calcium paradox” due to Ca2+/cAMP signalling interaction, in this review I discussed the virtual involvement of this interaction in the pleiotropic effects of CCBs, including the possible role of the Ca2+/cAMP signalling interaction in the association between hypertension and higher risk for the decline of cognition, and diabetes.
Mesenchymal Stem Cells, Immune Cells and Tumor Cells Crosstalk: A Sinister Triangle in the Tumor Microenvironment
Authors: Razmkhah Mahboobeh , Abtahi Shabnam , Ghaderi Abbas
Published: August 2018

Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency. Many studies have demonstrated the immunomodulatory effects of MSCs on the innate and adaptive immune cells. As a result of interactions with tumor cells, microenvironment and immune-stimulating milieu, MSCs contribute to tumor progression by several mechanisms, including sustained proliferative signal in cancer stem cells [CSCs], inhibition of tumor cell apoptosis, transition to tumor-associated fibroblasts [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal transition [EMT], suppression of immune responses, and consequential promotion of tumor metastasis. Here, we present an overview of the latest findings on Janusfaced roles that MSCs play in the tumor microenvironment [TME], with a concise focus on innate and adaptive immune responses.