bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in the Machine Learning-Based Drug-Target Interaction Prediction
Authors: Zhang Wen , Lin Weiran , Zhang Ding , Wang Siman , Shi Jingwen , Niu Yanqing
Published: August 2018

Background:

The identification of drug-target interactions is a crucial issue in drug discovery. In recent years, researchers have made great efforts on the drug-target interaction predictions, and developed databases, software and computational methods.

Results:

In the paper, we review the recent advances in machine learning-based drug-target interaction prediction. First, we briefly introduce the datasets and data, and summarize features for drugs and targets which can be extracted from different data. Since drug-drug similarity and target-target similarity are important for many machine learning prediction models, we introduce how to calculate similarities based on data or features. Different machine learningbased drug-target interaction prediction methods can be proposed by using different features or information. Thus, we summarize, analyze and compare different machine learning-based prediction methods.

Conclusion:

This study provides the guide to the development of computational methods for the drug-target interaction prediction.
Surgical Clips in Breast-conserving Surgery: Do they Represent the Tumour Bed Accurately?
Authors: Demircioglu Ozlem , Aribal Erkin , Uluer Meral , Ozgen Zerrin , Demircioglu Fatih
Published: August 2018

Introduction:

Radiotherapy after Breast-Conserving Surgery (BCS) is a standard treatment
for breast cancer. Currently, surgical clips are used to determine the tumour bed before radiotherapy
planning. This study aimed to evaluate the migration of these clips on mammograms.

Methods:

The study was conducted on 121 females who were treated with radiotherapy after BCS
at their first radiologic control examination 6 months after the end of treatment. MLO and CC
views of all cases were evaluated regarding the clips. The distance between the surgical scar centre
and the centre of the area covered by the clips was measured on both MLO and CC projections and
recorded separately. This distance was determined as the clip displacement. A displacement ≤10
mm was recorded as no displacement.

Results:

The clips were out of the images and were not evaluated in 45 cases (37.2%) on CC and in
9 cases (7.4%) on MLO projections. There were no clip displacements in 37 (30.6%) cases on CC
and in 43 (35.5%) cases on MLO views. The amount of displacement ranged from 11 to 56 mm
with a mean of 24.38 mm on CC views, while on MLO projections, displacement ranged from 11
to 66 mm with a mean of 24.42 mm.

Conclusion:

A clip displacement of greater than 10 mm was found in 64.5% of cases on MLO
views. Therefore, we believe that the reliability of these clips for accurate delineation of the tumour
bed in radiotherapy planning is controversial and other methods must be added.
Bioactivity and Functionality of Anthocyanins: A Review
Authors: Dini Cecilia , Zaro Maria J. , Viña Sonia Z.
Published: August 2018

:

Anthocyanins are flavonoid compounds imparting pink, red, blue, and purple colors to fruits, flowers, leaves, and some underground organs. These pigments play an important role in pollination and fruit and seed dispersal and they are related to the protection of plant tissues exposed to biotic and/or abiotic stress. Their consumption has been linked to diverse health benefits such as anti-inflammatory and anti-carcinogenic properties, diminution of cardiovascular disease incidence, obesity control, and diabetes mitigation effects. Also, in vitro studies have revealed certain potential cancer chemopreventive activities of anthocyanins. Reactive oxygen species scavenging as well as metal chelating and direct binding to proteins have been associated with anthocyanin health effects. Recent studies have indicated that these compounds can modulate decisive signaling pathways and gene regulation. Their action contributes to vascular homeostasis and to angiogenesis, inflammation, and platelet aggregation control. Likewise, anthocyanins have been associated with the prevention of a peroxynitrite-mediated disorder in endothelial cells. The potential use of anthocyanins as colorants in food has been extensively analyzed since they are the main hydrosoluble plant pigments. However, their instability and the influence of concentration, pH, temperature, and the presence of other compounds (phenolic acids, metals) on color properties can limit anthocyanin use as food ingredients and additives. Encapsulation has been proposed as an alternative to reduce food-processing damage and to deliver these compounds to their target site in the human body. Likewise, chemical lipophilization of anthocyanins has been assayed to obtain modified compounds with higher lipophilicity, more suitable for lipid-rich matrices.
The Antioxidant Potential of Black Cumin (Nigella sativa L.) Extracts Through Different Extraction Methods
Authors: Iqbal Muhammad J. , Butt Masood S. , Sohail Muhammad , Suleria Hafiz A.R.
Published: August 2018

Background:

Herbal foods possess significant amounts of essential bioactive nutrients and
offer clinical and therapeutic benefits. The aim of present research was to compare the antioxidant potential
of black cumin extracts obtained using different extraction modes.

Materials and Methods:

Three solvents (methanol, acetone and hexane) were employed at different
time intervals and ratios. However, Supercritical Fluid Extracts (SFE) were obtained at varying pressures
(5500, 6500 and 7500 psi).

Results:

Outcomes revealed that total phenolics were maximum in methanolic extract (790.79±31.67
mg GAE/100 g) at 50 min. Similarly, DPPH and FRAP activity of methanolic extract was also better
than other extracts as 80.99±4.02% and 27.44±0.88 mg TE/g, respectively. HPLC quantification exhibited
that highest recovery of major bioactive component (thymoquinone) was obtained via supercritical
extraction (12.38 mg/g) at 7500 psi.

Conclusions:

It is concluded that Pakistani variety of black cumin possess appreciable antioxidant activity
which directly depends upon the extraction conditions. Among conventional solvents, methanol
was evidenced to be more efficient. However, supercritical fluid extracts have proved a reliable mean
for the extraction of thymoquinone.
Ganoderma lucidum Polysaccharides as An Anti-cancer Agent
Authors: Sohretoglu Didem , Huang Shile
Published: August 2018

The mushroom Ganoderma lucidum (G. lucidum) has been used for centuries in Asian countries to
treat various diseases and to promote health and longevity. Clinical studies have shown beneficial effects of G.
lucidum as an alternative adjuvant therapy in cancer patients without obvious toxicity. G. lucidum polysaccharides
(GLP) is the main bioactive component in the water soluble extracts of this mushroom. Evidence from in
vitro and in vivo studies has demonstrated that GLP possesses potential anticancer activity through immunomodulatory,
anti-proliferative, pro-apoptotic, anti-metastatic and anti-angiogenic effects. Here, we briefly summarize
these anticancer effects of GLP and the underlying mechanisms.
Phosphonium Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines
Authors: D Dhanyalayam , G Palma , AR Cappello , A Mariconda , MS Sinicropi , F Giordano , V Del Vecchio , A Ramunno , C Arra , P Longo , C Saturnino
Published: August 2018

Due to an oversight one of the author’s name was published wrong in the article entitled “Phosphonium
Salt Displays Cytotoxic Effects Against Human Cancer Cell Lines” in “Anti-Cancer Agents in Medicinal
Chemistry, 2015, Vol. 17, No. 13. pp. 1796.”

The correct names of all authors are given below:

Dhanyalayam D, Palma G, Cappello AR, Mariconda A, Sinicropi MS, Giordano F, Del Vecchio V, Ramunno A, Arra C, Longo P, Saturnino C.
Extensive Phytochemistry, Comprehensive Traditional Uses, and Critical Pharmacological Profile of the Great Mullein: Verbascum thapsus L
Authors: Dar Mohd A. , Bhat Mohammad F. , Hassan Reyaz , Masoodi Mubashir H. , Mir Showkat R. , Mohiuddin Roohi
Published: August 2018

Background:

Great Mullein; Verbascum thapsus has been traditionally used as an analgesic, anti-inflammatory, antiseptic, spasmolytic, astringent, diuretic, emollient, expectorant piles, bruises and frostbites in Greece, Western United States, Rome, India, Turkey, Italy, and Pakistan.

Objective:

The aim of the present review is to summarize ethnopharmacology and past/recent studies on phytochemistry, plant profile, botany and pharmacological profile of V. thapsus. The review also updates related information regarding the potential therapeutic targets and new metabolites isolated from V. thapsus.

Methods:

All the information was supplied by the library database and electronic search (Google Scholar, ScienceDirect, PubMed, ResearchGate, etc.). In addition, all the synonyms of V. thapsus were searched in Non-English journals and English/Non-English- MS and PhD thesis databases (e.g., CKNI-China, JAIRO-Japan, Shodhganga-India, Myto-Malaysia, etc.). Thorough literature survey on V. thapsus revealed compounds like glycosides, flavonoids, saponins, and terpenoids that have previously been reported and new compounds under these chemical classes and other classes have also been reported.

Conclusion:

Based on the literature survey, many of these isolated compounds or different extracts of V. thapsus possess a wide range of biological activity including but not limited to, antioxidant, wound-healing, antimicrobial, antiviral, anticancer, cytotoxic, antihyperlipidemic, anti-germination, hepatoprotective and nephroprotective activity.
Al-Au Heterogeneous Dimer-trimer Nanostructure for SERS
Authors: Katyal Jyoti
Published: August 2018

Background:

Tunability in resonance wavelength and the enhancement of the electromagnetic field intensities
around the surface are two unique properties which make metal as a plasmonic material. A theoretical
investigation on the LSPR and field enhancement for heterogeneous dimer–trimer metallic nanostructure by
constituting Al and Au as two different plamsonic materials has been studied. Since electrons in Al exhibit
free behavior for LSPR of Au, therefore, they influence the electric field magnitude generated by Au LSPR.

Methods:

The electromagnetic simulations reported in this paper were performed using the FDTD Solutions
(version 7.5.1), a product of Lumerical Solutions Inc., Vancouver, Canada. We adopted a cubic Yee cell of 1
nm side and a time step Δt= 1.31•10-18 s, bounded by Courant condition.

Results:

The extinction spectrum shows LSPR peak over UV-visible region for isotropic nanostructure
which shifts to NIR region for anisotropic shape nanostructure. The spherical shape hetero dimer nanostructure
shows enhancement factor ~ 3.9 X 105 whereas it increases to ~ 6.2 X 106 for anisotropic shape at 610
nm. The field distribution corresponding to the trimer nanostructure reveals a large dipolar field distribution
on each of the three nanoparticles, oscillating approximately in-phase. The spherical shape Al-Au-Al shows
enhancement factor ~ 8.5 X 106 at 571 nm. The anisotropic shape increase the enhancement factor to ~ 2.4 X
107 at peak wavelength 700 nm i.e. tuning the plasmon wavelength towards NIR region.

Conclusion:

The tunability in plasmon wavelength and field enhancement factor has been evaluated for heterogeneous
nanostructure over wider spectrum range i.e. DUV-Visible-NIR using Au-Al dimer and trimer
nanostructure. The isotropic shape Au-Al hetero nanostructure shows larger enhancement in the UV-visible
region, whereas the anisotropic shape nanostructure contributes towards the NIR region.
Biosolids and Sludge Management
Authors: Brisolara Kari Fitzmorris , Qi Yinan , Kendrick Quanita , Davis Yasmin
Published: August 2018

The field of biosolids and sludge has progressed significantly over the past year. This review includes summations of the leading research published in journals and conference proceedings in 2017. The following sections are presented: biosolids regulations and management issues; biosolids characteristics, quality and measurement including microconstituents, pathogens, nanoparticles, and metals; sludge treatment technologies including pretreatment and sludge minimization, conditioning and dewatering, digestion, composting, and innovative technologies; disposal and reuse including combustion/incineration, agricultural uses, and innovative uses; odor and air emissions; and energy issues.
Modeling, Instrumentation, Automation, and Optimization of Water Resource Recovery Facilities
Authors: Sweeney Michael W. , Kabouris John C.
Published: August 2018

A review of the literature published in 2017 on topics relating to water resource recovery facilities (WRRF) in the areas of modeling, automation, measurement and sensors and optimization of wastewater treatment (or water resource recovery) is presented.
Pulp and Paper Mill Effluent Management
Authors: Elnakar Haitham , Buchanan Ian D.
Published: August 2018

This is a review of literature published in 2017 related to the prevention of water pollution by or recovery of beneficial materials from wastewater produced in the pulp and paper industry. This review includes the following main sections: cleaner production, biological treatment, and physico‐chemical treatment.
Effects of Pollution on Marine Organisms
Authors: Mearns Alan J. , Reish Donald J. , Bissell Matt , Morrison Ann Michelle , Rempel‐Hester Mary Ann , Arthur Courtney , Rutherford Nicolle , Pryor Rachel
Published: August 2018

This review covers selected 2017 articles on the biological effects of pollutants and human physical disturbances on marine and estuarine plants, animals, ecosystems and habitats. The review, based largely on journal articles, covers field and laboratory measurement activities (bioaccumulation of contaminants, field assessment surveys, toxicity testing and biomarkers) as well as pollution issues of current interest including endocrine disrupters, emerging contaminants, wastewater discharges, marine debris, dredging and disposal etc. Special emphasis is placed on effects of oil spills and marine debris due largely to the 2010 Deepwater Horizon oil blowout in the Gulf of Mexico and proliferation of data on the assimilation and effects of marine debris microparticulates. Several topical areas reviewed in the past (e.g.mass mortalities ocean acidification) were dropped this year. The focus of this review is on effects, not on pollutant sources, chemistry, fate or transport. There is considerable overlap across subject areas (e.g.some bioaccumulation data may be appear in other topical categories such as effects of wastewater discharges, or biomarker studies appearing in oil toxicity literature). Therefore, we strongly urge readers to use keyword searching of the text and references to locate related but distributed information. Although nearly 400 papers are cited, these now represent a fraction of the literature on these subjects. Use this review mainly as a starting point. And please consult the original papers before citing them.
Petrochemical Wastewater and Produced Water
Authors: Wei Xinchao , Zhang Shicheng , Sun Yongsheng , Brenner Sara A.
Published: August 2018

Petrochemical and oil & gas industries are crucial for global economy while great attention is needed for the related contamination and its impact on the environment. Papers reviewed herein represent the recent research and development on petrochemical wastewater and produced water from oil & gas industry, published in 2017 and beginning of 2018 globally. In the petrochemical wastewater, progresses were made in characterization, physicochemical treatment and biological treatment. In the oil & gas produced water, efforts were made on the characterization, the environmental impact and treatment options.
Ecological and Human Health Risk Assessment
Authors: Charabi Yassine , Choudri B.S. , Ahmed Mushtaque
Published: August 2018

The review of literature in this paper includes the assessment of risk process and addresses issues of both human as well as ecological receptors. The main objective of this review is to highlight an overview of the scientific research literature published in year 2017. The review is focused on assessment of risk on human and ecology published in the literature such as analysis, methodology, interpretation, management, uncertainty, policy and regulatory guidance. The review on ecological and human health risk assessment is divided into two main sections namely ecological and human health. The focus of the review is on the risk assessment process as it is applied to human health, ecoological systems, site investigation, aspects of remediation as well as natural resources.
Molecular biological methods in environmental engineering
Authors: Li Chunying , Pulin Zhou , Wei Li , Wei Dong , Jia Ouyang , Chang Chein‐Chi
Published: August 2018

Environmental bioremediation technologies are undoubtedly more economical and environmental friendly, and present a good application prospect. Microorganisms can be used to monitor environmental changes for their quickly respond to environmental changes. Microbiological molecular biology methods have attracted more and more attention from human beings, and their applications in the environment is also expanding. Genomics, transcriptomics, proteomics, and metabolomics are four major molecular biology techniques. This review summarizes application of molecular biological methods in environmental engineering in 2017. The summary includes methods for DNA, RNA, and protein extraction, the application of four major technologies in the environmental field, and commonly used methods for in situ monitoring in the environment, including fluorescence in situ hybridization, real‐time quantitative PCR, and amplicons sequencing technology.
Impact of initiating long-acting injectable antipsychotics on hospitalization in patients with bipolar I disorder
Authors: Yan Tingjian , Greene Mallik , Chang Eunice , Touya Maëlys , Broder Michael S
Published: August 2018

Aim:
To compare risk of hospitalization in patients with bipolar I disorder (BD-I) initiating long-acting injectable antipsychotics (LAIs).
Materials & methods:
Using Truven Health Analytics MarketScan
®
(Medicaid, Commercial and Medicare Supplemental) databases (2012–2016), patients (≥18 years) with BD-I with a LAI (aripiprazole once monthly [AOM 400], fluphenazine-LAI, haloperidol-LAI, risperidone-LAI and paliperidone-4-week-LAI) were identified.
Results:
The adjusted odds of having hospitalization were significantly higher in haloperidol-LAI (Odds ratio [95% CI]: 1.39 [1.03–1.87] all-cause; p = 0.029; 1.41 [1.03–1.93] psychiatric-specific; p = 0.032) and risperidone-LAI (1.54 [1.12–2.13]; p = 0.009; 1.68 [1.20–2.37]; p = 0.003) users versus AOM 400 users. Risks of hospitalization did not differ comparing fluphenazine-LAI and paliperidone-LAI users with AOM 400 users.
Conclusion:
AOM 400 may be more beneficial at reducing hospitalization rates in BD-I versus haloperidol-LAI and risperidone-LAI.
Ética en la investigación en educación médica: consideraciones y retos actuales
Authors: Lara Gutiérrez Yazmín Alejandra , Pompa Mansilla Maura
Published: August 2018

La investigación se lleva a cabo con el fin de descubrir nueva información de carácter científico que colabore en ampliar el conocimiento en beneficio de la sociedad. De ahí que exista una preocupación importante con respecto a las consideraciones éticas en las investigaciones. En este caso nos enfocaremos primordialmente en la investigación en educación médica. La discusión sobre ética e investigación se inició en el ámbito de la investigación biomédica después de la Segunda Guerra Mundial como respuesta a una profunda crisis de legitimidad del quehacer científico. A su vez existieron diversos estudios que involucraron como sujetos a seres humanos que tuvieron como consecuencia la creación de declaraciones internacionales y regulaciones en diversos países para proteger a los sujetos participantes en dichas investigaciones. En este artículo abordaremos las consideraciones éticas que deben tenerse en cuenta al desarrollar una investigación vinculada a la educación médica, sus antecedentes y ejemplos de algunos estudios que ponen de relieve algunos de los retos que se enfrentan actualmente.
Crítica al programa de la signatura Metodología de la Investigación Política.
Authors: SÁNCHEZ NORIEGA ARMENGOL María de los Ángeles
Published: August 2018

Metodología de la investigación política, es una asignatura que aparece en el Plan de estudios de la Licenciatura en Ciencias Políticas y Administración Pública, la autora nos presenta un análisis sobre los aspectos y fundamentos bajo los que se rige la asignatura impartida en el tercer semestre de la carrera, asimismo ofrece una serie de propuestas que logran establecer un vínculo con las demás asignaturas y posteriores semestres, ya que el perfil profesional de un politólogo debe poseer una solida formación teórica, analítica, metodológica y técnica
El presente y el futuro de España como impulsores del acercamiento de la Unión Europea hacia América Latina.
Authors: DÁVILA ALDAS Francisco Rafael
Published: August 2018

El trabajo señala que los logros alcanzados por España son el resultado claro de su acelerada modernización gracias al esfuerzo tesonero de su pueblo y a la ayuda recibida por la CEE y la actual UE; lo que la ponen en un terreno privilegiado para impulsar acercamiento de América Latina a esa región. Sin embargo, es necesario que su gobierno ponga una especial dedicación a fomentarla, precisamente para ganar mayor peso, importancia y prestigio en el seno de la UE, justamente cuando esta última emprende un nuevo ensanchamiento y profundización de su construcción comunitaria.
Sobre la esperanza de estos tiempos.
Authors: FERNÁNDEZ CHRISTLIEB Paulina
Published: August 2018

Flores Olea, Víctor, "Tiempos de abandono y esperanza", 2004.
Reseña
Authors: GONZÁLEZ AYERDI Francisco
Published: August 2018

Georg Jellinek, Teoría General del Estado, México, FCE, 1 a reimpresión 2002, 687 pp. (Prólogo y traducción Fernando de los Ríos).
Ley General de Desarrollo Social: un nuevo papel para las organizaciones sociales en México.
Authors: VALVERDE VIESCA Karla , PALMA DELGADO Erika Andrea
Published: August 2018

La búsqueda de modelos gerenciales y participativos dentro de la creación de políticas públicas, es una tendencia contemporánea. En este sentido, la participación comunitaria en la preparación, diseño, gestión y evaluación de los proyectos, programas o políticas en sus comunidades se constituye en una forma para expandir la colaboración a todos los sectores de la sociedad. Frente a esta dinámica, la creación de marcos que definan funciones, objetivos y estrategias se vuelve sustantiva. Los avances al respecto, en el caso mexicano, son recientes. Este trabajo analiza la creación de la Ley General de Desarrollo Social, a fin de caracterizar las aportaciones que las organizaciones sociales hicieron a su diseño y el papel que éste marco normativo les otorga como impulsaras del desarrollo.
Elecciones del 2 de julio de 2006, datos y cifras.
Authors: SINGER SOCHET Martha
Published: August 2018

El material expuesto se compone de cifras y datos estadísticos para la comprensión de las elecciones del 2 de julio de 2006 en México, como: el Padrón Electoral y la Lista Nominal de electores, los distritos electorales de mayoría indígena, el financiamiento público de la elección, entre otros datos relevantes para su estudio en su dimensión cuantitativa.
Rejecting the death of passwords: Advice for the future
Authors: Bosnjak Leon , Brumen Bostjan
Published: August 2018

Passwords have been a recurring subject of research ever since Morris and Thompson first pointed out their disadvantages in 1979. Several decades later, textual passwords remain to be the most used authentication method, despite the growing number of security breaches. In this article, we highlight technological advances that have the potential to ease brute-force attacks on longer passwords. We point out users? persistently bad password creation and management practices, arguing that the users will be unable to keep up with the increasingly demanding security requirements in the future. We examine a set of real, user-generated passwords, and compare them to the passwords collected by Morris and Thompson. The results show that today?s passwords remain as weak as they were nearly four decades ago. We provide insight on how the current password security could be improved by giving recommendations to users, administrators, and researchers. We dispute the reiterated claim that passwords should be replaced, by exposing the alternatives? weaknesses. Finally, we argue passwords will remain widespread until two conditions are met: First, a Pareto-improving authentication method is discovered, and second, the users are motivated to replace textual passwords.
Beyond Firm-Level Determinants: The Effect of M&A Features on the Extent of M&A Disclosure
Authors: Florio Cristina , Lionzo Andrea , Corbella Silvano
Published: August 2018

Although the accounting literature demonstrates country- and firm-related factors drive disclosure in financial statements, whether transaction-specific features also affect the extent of disclosure is still unclear. In this paper, we examine such issues by investigating the association between the disclosures offered in mergers and acquisitions (M&A) and multiple determinants incidental to the M&A itself. Referring to the unique Italian setting, which shows high discretion and potential sensitivity toward disclosure, we document that acquirers increase disclosure for larger M&A and reduce disclosure for increasing M&A materiality and extreme amounts of goodwill recognized on the transaction. By disentangling mandatory and voluntary disclosure, empirical evidence shows that the latter is sensitive to more M&A-specific features than the former. Additional analyses and robustness tests support our main findings. The study contributes to the accounting literature by highlighting the importance to include transaction-specific features when modeling for transaction-related disclosure, and has practical implications for investors, standard setters, and regulators.

JEL Classifications: M40; M41.
Auditor Rotation and Perceived Competence and Independence: The Effect of Fees and Industry Specialization
Authors: Kamath Roger , Huang Ting-Chiao , Moroney Robyn A.
Published: August 2018

Regulators and practitioners argue the relative merits of firm and partner rotation, while researchers report mixed results on the consequences of rotation. This study uses an experiment to examine the effect of an upcoming rotation on perceptions of auditor competence and independence and finds that participants appear to be indifferent to whether rotation is at the firm or partner level; they only react to concurrent changes in audit fees and the industry specialization status of the new auditor. Specifically, participants assess auditor competence and independence (specifically attention to detail, effort, and skeptical attitude) to be higher when fees increase rather than decrease significantly at the time of a rotation, and they assess auditor competence to be higher when rotation is to an industry specialist rather than a nonindustry specialist. These findings hold regardless of whether rotation is at the firm or partner level.

JEL Classifications: M42.

Data Availability: Data and the tasks used in this study are available on request.
Impaired Store-Operated Calcium Entry and STIM1 Loss Lead to Reduced Insulin Secretion and Increased Endoplasmic Reticulum Stress in the Diabetic β-Cell
Authors: Kono Tatsuyoshi , Tong Xin , Taleb Solaema , Bone Robert N. , Iida Hitoshi , Lee Chih-Chun , Sohn Paul , Gilon Patrick , Roe Michael W. , Evans-Molina Carmella
Published: August 2018

Store-operated Ca2+ entry (SOCE) is a dynamic process that leads to refilling of endoplasmic reticulum (ER) Ca2+ stores through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Pathogenic reductions in β-cell ER Ca2+ have been observed in diabetes. However, a role for impaired SOCE in this phenotype has not been tested. We measured the expression of SOCE molecular components in human and rodent models of diabetes and found a specific reduction in STIM1 mRNA and protein levels in human islets from donors with type 2 diabetes (T2D), islets from hyperglycemic streptozotocin-treated mice, and INS-1 cells (rat insulinoma cells) treated with proinflammatory cytokines and palmitate. Pharmacologic SOCE inhibitors led to impaired islet Ca2+ oscillations and insulin secretion, and these effects were phenocopied by β-cell STIM1 deletion. STIM1 deletion also led to reduced ER Ca2+ storage and increased ER stress, whereas STIM1 gain of function rescued β-cell survival under proinflammatory conditions and improved insulin secretion in human islets from donors with T2D. Taken together, these data suggest that the loss of STIM1 and impaired SOCE contribute to ER Ca2+ dyshomeostasis under diabetic conditions, whereas efforts to restore SOCE-mediated Ca2+ transients may have the potential to improve β-cell health and function.
Glucolipotoxicity-Inhibited miR-299-5p Regulates Pancreatic β-Cell Function and Survival
Authors: Huang Qiqing , You Weiyan , Li Yating , Sun Yi , Zhou Yuncai , Zhang Yan , Liu Dechen , Zhan Shanshan , Zhu Yunxia , Han Xiao
Published: August 2018

Inhibition of microRNAs (miRNAs) essential for pancreatic β-cell biology (e.g., miR-375) results in β-cell failure and diabetes in rodent models. Whether the downregulation of miRNAs in pancreatic islets is involved in the development of human type 2 diabetes remains unclear. Here, with the use of an miRNA microarray, we identified a set of miRNAs that were differentially expressed in healthy human islets under glucolipotoxic conditions. A downregulated miRNA, miR-299-5p, was preferentially studied because its inhibition causes dramatic β-cell dysfunction and apoptosis. Proteomic profiling and bioinformatics methods identified four target genes, including a Trp53 effector, Perp, that were further confirmed by luciferase reporter assays. We narrowed down the effector of miR-299-5p downregulation to PERP owing to its upregulation in islets from diabetic rodents. Indeed, Perp inhibition prevented the β-cell impairment caused by either miR-299-5p reduction or glucolipotoxicity. Additional investigations confirmed the modulatory effect of PERP on insulin secretion. Collectively, miR-299-5p appears to be an essential regulator of β-cell biology, and its downregulation links PERP enhancement to β-cell dysfunction and apoptosis in glucolipotoxic settings. Our work demonstrates a novel mechanism of glucolipotoxicity-induced β-cell failure mediated through miR-299-5p downregulation.
Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans
Authors: Mezza Teresa , Ferraro Pietro M. , Sun Vinsin A. , Moffa Simona , Cefalo Chiara M.A. , Quero Giuseppe , Cinti Francesca , Sorice Gian Pio , Pontecorvi Alfredo , Folli Franco , Mari Andrea , Alfieri Sergio , Giaccari Andrea
Published: August 2018

Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, primitive defect in proinsulin processing or be secondary to increased demand on β-cells (hyperinsulinemia secondary to insulin resistance). An alternative way to investigate the relation between relative hyperproinsulinemia and increased secretory demand is to study the dynamic changes in the proinsulin-to-insulin ratio after partial pancreatectomy, a model of acute increased β-cell workload on the remaining pancreas. To pursue this aim, patients without diabetes, scheduled for partial pancreatectomy, underwent 4-h mixed-meal tests and hyperinsulinemic-euglycemic clamps before and after surgery. After acute β-cell mass reduction, no changes were observed in the fasting proinsulin-to-insulin ratio, whereas the fold change in the proinsulin-to-insulin ratio significantly increased over time after the meal. Further, our data demonstrate that whole-body insulin resistance is associated with underlying defects in proinsulin secretion, which become detectable only in the presence of increased insulin secretion demand.
The Dysfunctional MDM2–p53 Axis in Adipocytes Contributes to Aging-Related Metabolic Complications by Induction of Lipodystrophy
Authors: Liu Zhuohao , Jin Leigang , Yang Jin-Kui , Wang Baile , Wu Kelvin K.L. , Hallenborg Philip , Xu Aimin , Cheng Kenneth K.Y.
Published: August 2018

Profound loss and senescence of adipose tissues are hallmarks of advanced age, but the underlying cause and their metabolic consequences remain obscure. Proper function of the murine double minute 2 (MDM2)–p53 axis is known to prevent tumorigenesis and several metabolic diseases, yet its role in regulation of adipose tissue aging is still poorly understood. In this study, we show that the proximal p53 inhibitor MDM2 is markedly downregulated in subcutaneous white and brown adipose tissues of mice during aging. Genetic disruption of MDM2 in adipocytes triggers canonical p53-mediated apoptotic and senescent programs, leading to age-dependent lipodystrophy and its associated metabolic disorders, including type 2 diabetes, nonalcoholic fatty liver disease, hyperlipidemia, and energy imbalance. Surprisingly, this lipodystrophy mouse model also displays premature loss of physiological integrity, including impaired exercise capacity, multiple organ senescence, and shorter life span. Transplantation of subcutaneous fat rejuvenates the metabolic health of this aging-like lipodystrophy mouse model. Furthermore, senescence-associated secretory factors from MDM2-null adipocytes impede adipocyte progenitor differentiation via a non–cell-autonomous manner. Our findings suggest that tight regulation of the MDM2–p53 axis in adipocytes is required for adipose tissue dynamics and metabolic health during the aging process.
Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes
Authors: Desai Urvi , Kirson Noam Y. , Kim Jennifer , Khunti Kamlesh , King Sarah , Trieschman Erich , Hellstern Michael , Hunt Phillip R. , Mukherjee Jayanti
Published: August 2018

OBJECTIVE

The goal of this study was to evaluate the association between the timing of treatment intensification and subsequent glycemic control among patients with type 2 diabetes in whom monotherapy fails.

RESEARCH DESIGN AND METHODS

This retrospective analysis of the U.K. Clinical Practice Research Datalink database focused on patients with type 2 diabetes and one or more HbA1c measurements ≥7% (≥53 mmol/mol) after ≥3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date). Baseline (6 months before the index date) characteristics were stratified by time from the index date to intensification (early: <12 months; intermediate: 12 to <24 months; late: 24 to <36 months). Intensification was defined as initiating after the index date one or more noninsulin antidiabetes medication in addition to metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA1c <7% [<53 mmol/mol] after intensification) was evaluated using Kaplan-Meier analyses and Cox proportional hazard models that accounted for baseline differences.

RESULTS

Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male; 80% taking metformin), 23,761 (25%) intensified <12 months after the index date; 11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after 24 to <36 months. Patients who intensified treatment ≥36 months after the index date (n = 9,638 [10%]) and those with no evidence of treatment intensification during the observable follow-up period (n = 41,062 [44%]) were not included in further analyses. The median times from intensification to control were 20.0, 24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining glycemic control was 22% and 28% lower for patients in the intermediate and late intensification groups, respectively, compared with those intensifying early (P < 0.0001).

CONCLUSIONS

Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.
Executive Function Predicting Longitudinal Change in Type 1 Diabetes Management During the Transition to Emerging Adulthood
Authors: Berg Cynthia A. , Wiebe Deborah J. , Suchy Yana , Turner Sara L. , Butner Jonathan , Munion Ascher , Lansing Amy Hughes , White Perrin C. , Murray Mary
Published: August 2018

OBJECTIVE

The objective of this study was to examine 1) whether teens’ glycemic control and adherence to type 1 diabetes treatment regimen worsen during the transition from late adolescence to emerging adulthood, and 2) whether teens’ executive function (EF), as measured by performance and self-reported problems with EF, is predictive of these changes (after controlling for general intelligence).

RESEARCH DESIGN AND METHODS

High school seniors with type 1 diabetes (N = 236; mean age 17.74 years) were assessed at three yearly time points. At baseline, during the senior year of high school, participants completed a self-report measure of problems with EF and performance-based measures of EF and general intelligence (IQ). Glycemic control was determined on the basis of results collected from HbA1c assay kits, and teens reported their adherence at all three time points.

RESULTS

HbA1c increased significantly across the three time points and adherence declined. EF performance was not associated with adherence or HbA1c at baseline, nor with changes in adherence over time. However, better EF performance predicted slower increases in HbA1c over time (i.e., slope) while controlling for IQ. Teens’ self-reported problems with EF were associated with worse glycemic control and poorer adherence at baseline (i.e., intercept), but they did not predict changes in either HbA1c or adherence over time (i.e., slope).

CONCLUSIONS

Abilities involved in performance on EF tests may be one resource for maintaining better glycemic control during the transition to emerging adulthood. Assessment of such EF abilities may allow for the identification of individuals who are most at risk for deterioration of glycemic control during this transition.
Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988–2015
Authors: Cheng Yiling J. , Imperatore Giuseppina , Geiss Linda S. , Saydah Sharon H. , Albright Ann L. , Ali Mohammed K. , Gregg Edward W.
Published: August 2018

OBJECTIVE

Cardiovascular disease (CVD) mortality has declined substantially in the U.S. The aims of this study were to examine trends and demographic disparities in mortality due to CVD and CVD subtypes among adults with and without self-reported diabetes.

RESEARCH DESIGN AND METHODS

We used the National Health Interview Survey (NHIS) (1985–2014) with mortality follow-up data through the end of 2015 to estimate nationally representative trends and disparities in major CVD, ischemic heart disease (IHD), stroke, heart failure, and arrhythmia mortality among adults ≥20 years of age by diabetes status.

RESULTS

Over a mean follow-up period of 11.8 years from 1988 to 2015 of 677,051 adults, there were significant decreases in major CVD death (all P values <0.05) in adults with and without diabetes except adults 20–54 years of age. Among adults with diabetes, 10-year relative changes in mortality were significant for major CVD (−32.7% [95% CI −37.2, −27.9]), IHD (−40.3% [−44.7, −35.6]), and stroke (−29.2% [−40.0, −16.5]), but not heart failure (−0.5% [−20.7, 24.7]), and arrhythmia (−12.0% [−29.4, 77.5]); the absolute decrease of major CVD among adults with diabetes was higher than among adults without diabetes (P < 0.001). Men with diabetes had larger decreases in CVD death than women with diabetes (P < 0.001).

CONCLUSIONS

Major CVD mortality in adults with diabetes has declined, especially in men. Large reductions were observed for IHD and stroke mortality, although heart failure and arrhythmia deaths did not change. All race and education groups benefitted to a similar degree, but significant gaps remained across groups.
From Arctic Science to International Law: The Road towards the Minamata Convention and the Role of the Arctic Council
Authors: Platjouw Froukje Maria , Hovland Steindal Eirik , Borch Trude
Published: August 2018

The Minamata Convention, which entered into force on 16 August 2017, is a global, legally binding instrument on mercury. The initiative on the Minamata Convention was mainly driven by research showing negative effects on human health and the environment in the Arctic. The Arctic Council, an intergovernmental forum promoting cooperation on Arctic issues, and its Working Group, AMAP, played an important role in the process leading up to international negotiations on the Minamata Convention. This paper elucidates the evolutionary process in which scientific knowledge, herded by an intergovernmental, regional forum, is involved and forms the basis for a legally binding agreement. The paper provides new insight on multilevel governance of the mercury issue and unravels the role that AMAP has played in this dynamic process.
Students’ Creativity in Geometry Course : How a Mystery Box Game Plays Important Role
Authors: Yanuarto Wanda Nugroho
Published: August 2018

The purpose of this study are encouraging students’ creativity by mystery box games and become more aware of their mathematical thinking. The situational problem as the starting point helps students to relate what they learn to problems in daily life, and construct and interpret geometry that are related to real situations, and this helps to correct their alternative conceptions in geometry courseto encourage students’ creativity in Geometry Course. There are three abilities to encouraging students’creativity, they are synthetic ability, analytic ability, and practical ability. The subjects of this research is the students of the 1st semester of 2014 academic year class A of mathematical education of Muhammadiyah University of Purwokerto, Central Java, Indonesia. The data of this research is through observation sheet, recording videos, portofolios, and questionnaires. Those data was analyzed through data reduction, data presentation, and conclusion. This study shows that to encouraging students’ creativity can analyzed by mystery box in Geometry Course.
Penerapan Teknik 5R untuk Meningkatkan Keterampilan Menyimak Mahasiswa Prodi PGSD FKIP UST
Authors: Praheto Biya Ebi , Sayekti Octavian Muning
Published: August 2018

Penelitian ini bertujuan untuk mengetahui peningkatan keterampilan menyimak melalui penerapan teknik 5R pada mahasiswa Program Studi Pendidikan Guru Sekolah Dasar Universitas Sarjanawiyata Tamansiswa. Penelitian ini merupakan penelitian tindakan kelas (PTK) yang terdiri atas empat tahap yaitu: perencanaan, tindakan, pengamatan, dan refleksi.Penelitian ini dilakukan di Prodi PGSD FKIP UST Yogyakarta. Subjek penelitian tindakan ini adalah mahasiswa semester 2 yang menempuh mata kuliah KBIL di Prodi PGSD FKIP UST tahun ajaran 2017/2018. Teknik pengumpulan data terdiri dari observasi, angket, wawancara atau diskusi, kajian dokumen, dan tes. Selanjutnya, untuk pemeriksaan validitas data digunakan triangulasi dan review informasi kunci. Teknik analisis data yang digunakan dalam penelitian ini adalah teknik deskripsi komparatif untuk membandingkan hasil antar siklus. Hasil dari penelitian ini yaitu menunjukkan mahasiswa yang tidak tuntas pada prasiklus sebanyak 30 mahasiswa atau sebesar 65,22%, siklus I 41,31% atau 19 mahasiswa dan pada siklus II 10,87% atau 5 mahasiswa. Di sisi lain, terjadi peningkatan ketuntasan belajar yaitu pada prasiklus 34,78% atau 16 mahasiswa, meningkat menjadi 58,69% atau 27 mahasiswa pada siklus I dan 89,13% atau 41 mahasiswa pada siklus II. Sedangkan nilai rata-rata pada prasiklus hanya mencapai rata-rata 64,13 dan mengalami peningkatan menjadi 73,67 pada siklus I serta menjadi 83 pada siklus II.
Patterns of Metacognitive Awareness Among Primary School Teachers
Authors: Palantis N.John , Mohamed Johan, A. , Ibrahim A.S. Mohd , Ismail S.H. , Anuar N.K. , Ma’rof A.M. , Buang N.
Published: August 2018

The purpose of this study is to identify level and patterns of metacognitive awareness among teachers in primary schools. This study focuses on aspects of declarative knowledge, procedural knowledge, conditional knowledge, planning, monitoring and evaluation of teachers. The study was descriptive in nature. A sample of 100 primary school teachers in Puchong, Selangor answered the Metacognitive Awareness Inventory for Teacher by Cem Balcikanli (2011). The data analysis was carried out using IBM Statistics version 24 to obtain descriptive measures. The results show that levels of metacognitive awareness among teachers are high at ninety three percent (93%). The results also show that there are no significant differences by gender, age, teaching experience, academic qualification and subject of teaching among primary school teachers. The metacognitive framework shows that metacognition knowledge and regulatory expertise were used by individuals to control their cognition. Teachers who have a higher level of metacognitive awareness can produce students with good academic achievement.
Types of maps used as a stimuli in cartographical empirical research
Authors: Słomska Katarzyna
Published: August 2018

Revisions of achievements of empirical studies in cartography focused on describing main research themes and diagnosing challenges to be approached. Intriguingly, there is no analysis of maps used as a stimuli in these experiments. In order to fill existing scarcity, this paper presents the analysis of the content of four journals affiliated by the International Cartographic Association. Four features (map medium, reactiveness, method of cartographic presentation, users familiarity with the depicted data) are described based on 103 papers presenting empirical studies. Types of maps were identified in scope of every feature. Most frequently used ones are displayed on the screen, non-interactive, depicting qualitative data and area unfamiliar for the participant of the study.
Aphrodisiac Activity of Ethanol Extract of Cratoxylum sumatranum (JACK) Blume Stems on Isolated Rat Corpus cavernosum
Authors: Ismail Sjarif , Aminyoto Meiliati
Published: August 2018

Cratoxylum sumatranum (Jack) Blume of the Hypericaceae family is known as â€œBentalengâ€ by Dayak Benuaq. In ethnobotany, Cratoxylum sumatranum stems (CSS) is used as energy drink or aphrodisiac, but its effect has not been scientifically proven. Research objective to study the aphrodisiac activity of CSS extract by screening the aphrodisiac activity in vitro. Method: CSS was collected from Kutai Kertanegara Regency, East Kalimantan Province. Extraction was by maceration with ethanol solvent for three days. Re-maceration was done twice. In vitro screening of aphrodisiac activity used isolated rat corpus cavernosum. The organ was placed into a 10 mL chamber containing Krebs-Henselheit solution at pH 7.4, 37Â°C and aerated with carbogen gas. After acclimation, a contraction test was performed with phenylephrine solution and after reaching the peak of contraction at plateau the Control (solvent extract) or CSS ethanol extract was administerd at cumulatively increased concentration. Vasodilation activity was known if the contraction response was decreased after the extractâ€™s administration and expressed in percent contraction with negative value. Results: CSS ethanol extract induce vasodilatory response on rat Corpus cavernosum blood vessels. Vasodilation activity is increasing with increasing concentration of extract given compared to Control. Conclusion the aphrodisiac activity of CSS ethanol extracts is directly through the vasodilation action mechanism on blood vessels in the rat corpus cavernosum.