bluuebunny/crossref_metadata_2025 huggingface dataset:
Body image and nonsuicidal self‐injury: Validation of the Body Investment Scale in participants with eating disorders
Authors: Marco J. H. , Cañabate M. , García‐Alandete J. , Llorca G. , Real‐López M. , Beltrán M. , Pérez S.
Published: September 2017

The Body Investment Scale (BIS) assesses body image feelings, body care, protection of the body, and comfort in touch, in order to identify and distinguish participants with self‐harming and self‐destructive tendencies. However, the psychometric properties of the BIS were not analysed in participants diagnosed with eating disorders. The main objective of the present study is to confirm the factor structure of the Spanish version of the BIS and analyse its psychometric properties in a sample composed of women diagnosed with eating disorders. Participants were 250 Spanish women between 12 and 60 years old (M = 26.05, SD = 11.97) diagnosed with eating disorders. A confirmatory factor analysis showed a poor fit of the original BIS. The final model showed an acceptable 4‐factor structure (Body Feelings, α = .88; Body Touch, α = .82; Body Protection, α = .77; Body Care, α = .68), with a good fit to the data (SBχ2(246) = 393.21, CFI = .906, IFI = .908, RMSEA = .049). The relationships between the BIS and both the Purpose‐In‐Life Test—10 Items and Beck Hopelessness Scale were analysed, as well as differences in the BIS score according to nonsuicidal self‐injuries and suicidal ideation in the past year. The BIS is an appropriate instrument to assess the body investment dimension of body image in women with eating disorders.
Modeling and performance analysis of a new secure address resolution protocol
Authors: Younes Osama S.
Published: September 2017

Address Resolution Protocol (ARP) is an essential protocol for the operation of local area networks. It is used for mapping the logical address to the physical address. However, ARP was designed without any security features. Therefore, ARP is vulnerable to many ARP spoofing attacks, such as the host impersonation, man‐in‐the‐middle (MITM), and denial of service (DoS) attacks. Many techniques were introduced in the literature for mitigating ARP spoofing attack. However, they could not provide protection against the host impersonation and DoS attacks. This work introduces a new technique to secure address resolution protocol called ARP Authentication (ARP‐A). The proposed technique provides authentication for ARP messages and entities. In addition, it converts ARP from a stateless to a stateful protocol. To evaluate the performance of ARP‐A, it was implemented on Linux. To investigate the scalability of ARP‐A, a new analytical model was designed for it using stochastic reward nets. The results show that, compared with other related schemes introduced in the literature, ARP‐A is more efficient in terms of security and performance.
Energy‐efficient power allocation for multi‐user MIMO systems with GZI precoding
Authors: Tian Feng , Yu Yue , Zhao Tingting , Li Dapeng , Zhang Xuejun , Yang Zhen
Published: September 2017

To achieve the energy efficiency (EE) for multi‐user multiple‐input multiple‐output (MU‐MIMO) systems with GZI precoding, based on an actual power consumption model, the paper investigates the power allocation (PA) optimization problem with guaranteeing the sum rate for all downlink users and the different rate requirements for different downlink users. For the case of guaranteeing the sum rate for all downlink users, the highly complex optimization problem is firstly reformulated into an equivalent pseudo‐convex form to be handled by the Lagrange Multiplier method. Then, it is simplified with reducing 2‐dimension PA parameter into 1 dimension. Finally, the closed‐form optimal solution is obtained through deriving of complex equations involving the log function. And for the case of guaranteeing the different rate requirements for different downlink users, the concrete numerical solution to the optimization problem is iteratively obtained through convex optimization toolbox in MATLAB. Simulation results validate the efficacy of the proposed optimization scheme. Furthermore, it is illustrated that the proposed optimization algorithm shows more optimal than average PA and antenna selection algorithms.
Temporal trends in quality of primary care for patients with type 2 diabetes mellitus: A population‐based retrospective cohort study after implementation of a quality improvement initiative
Authors: Wong Carlos K.H. , Fung Colman S.C. , Yu Esther Y.T. , Wan Eric Y.F. , Chan Anca K.C. , Lam Cindy L.K.
Published: September 2017

Background

This study examined whether temporal trends exist in treatment of patients with type 2 diabetes (T2D) and quality of diabetes care after implementation of quality improvement initiative in primary care setting.

Methods

We conducted a population‐based retrospective cohort study of 202,284 patients with T2D who were routinely managed in primary care clinics. We examined the change over time and the variability between clinics in quality of care from Hospital Authority administrative data over a 5‐year period (2009‐2013) and used multilevel logistic regression to adjust for patient and clinic characteristics. Observational period was partitioned in 5 calendar years. Ten quality‐of‐care criteria were selected: adherence to 7 process of care criteria (HbA1c test, renal function test, full lipid profile, urine protein analysis, retinal screening, lipid‐lowering agent prescriptions among patients with hypercholesterolaemia, and angiotensin converting enzyme inhibitor/angiotensin receptor blocker prescriptions among patients with microalbuminuria) and 3 outcome of care criteria (HbA1c ≤ 7%, BP ≤ 130/80 mmHg, and LDL‐C ≤ 2.6 mmol/L). Variability of standards between clinics was assessed by using intracluster correlation coefficients.

Results

Characteristics of patients with T2D managed in primary care changed substantially during the observational period, with increasing age and usage of insulin and longer duration of diabetes but improved metabolic profiles (all P trend < .001). Performance rates of the 7 process and 3 clinical outcomes of care criteria increased remarkably over time (all P trend < .001). Variations in retinal screening delivery between clinics were considerable, albeit decreasing over time.

Conclusions

Coinciding with implementation of quality improvement initiative, quality of diabetes care improved significantly in the past 5 years, in part attributable to benefits of integrated multidisciplinary diabetes management.
Myelin development, plasticity, and pathology in the auditory system
Authors: Long Patrick , Wan Guoqiang , Roberts Michael T. , Corfas Gabriel
Published: September 2017

Myelin allows for the rapid and precise timing of action potential propagation along neuronal circuits and is essential for healthy auditory system function. In this article, we discuss what is currently known about myelin in the auditory system with a focus on the timing of myelination during auditory system development, the role of myelin in supporting peripheral and central auditory circuit function, and how various myelin pathologies compromise auditory information processing. Additionally, in keeping with the increasing recognition that myelin is dynamic and is influenced by experience throughout life, we review the growing evidence that auditory sensory deprivation alters myelin along specific segments of the brain's auditory circuit. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 80–92, 2018
Myelin plasticity, neural activity, and traumatic neural injury
Authors: Kondiles Bethany R. , Horner Philip J.
Published: September 2017

The possibility that adult organisms exhibit myelin plasticity has recently become a topic of great interest. Many researchers are exploring the role of myelin growth and adaptation in daily functions such as memory and motor learning. Here we consider evidence for three different potential categories of myelin plasticity: the myelination of previously bare axons, remodeling of existing sheaths, and the removal of a sheath with replacement by a new internode. We also review evidence that points to the importance of neural activity as a mechanism by which oligodendrocyte precursor cells (OPCs) are cued to differentiate into myelinating oligodendrocytes, which may potentially be an important component of myelin plasticity. Finally, we discuss demyelination in the context of traumatic neural injury and present an argument for altering neural activity as a potential therapeutic target for remyelination following injury. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 108–122, 2018.
Land use types influenced avian assemblage structure in a forest–agriculture landscape in Ghana
Authors: Deikumah Justus Precious , Kwafo Richard , Konadu Vida Asieduwaa
Published: September 2017

The conservation of biodiversity within tropical forest regions does not lie only in the maintenance of natural forest areas, but on conservation strategies directed toward agricultural land types within which they are embedded. This study investigated variations in bird assemblages of different functional groups of forest‐dependent birds in three agricultural land types, relative to distance from the interior of 34 tropical forest patches of varying sizes. Point counts were used to sample birds at each study site visited. Data from counts were used to estimate species richness, species evenness, and Simpson's diversity of birds. Mean species richness, evenness, and diversity were modeled as responses and as a function of agricultural land type, distance from the forest interior and three site‐scale vegetation covariates (density of large trees, fruiting trees, and patch size) using generalized linear mixed‐effect models. Mean observed species richness of birds varied significantly within habitat types. Mean observed species richness was highest in forest interior sites while sites located in farm centers recorded the lowest mean species richness. Species richness of forest specialists was strongly influenced by the type of agricultural land use. Fallow lands, density of large trees, and patch size strongly positively influenced forest specialists. Insectivorous and frugivorous birds were more species‐rich in fallow lands while monoculture plantations favored nectarivorous birds. Our results suggest that poor agricultural practices can lead to population declines of forest‐dependent birds particularly specialist species. Conservation actions should include proper land use management that ensures heterogeneity through retention of native tree species on farms in tropical forest‐agriculture landscapes.
A quadratic correlation between long‐term mean group size and group density in a cooperatively breeding passerine
Authors: Ke Dian‐Hua , Deng Yan‐Hui , Guo Wei‐Bin , Huang Zu‐Hao
Published: September 2017

Both mean group size (MGS) and mean group density (MGD) are critical indices to characterize a population of cooperatively breeding birds. When a population reaches its carrying capacity, both long‐term MGS and long‐term MGD will remain relatively stable. However, there has been little study of how these two variables relate. The Masked laughingthrush Garrulax perspicillatus is a cooperatively breeding bird living in fragmented habitats. During 2010 and 2012‐2016, we used song playback to observe and confirm the group sizes and territory ranges of the birds and the data of bird presence to determine habitat suitability. By grouping the nearest territories according to their geographical coordinates, we divided the whole study area into 12 subareas and the whole population into 12 subpopulations. Then, we calculated both MGS and MGD for different time durations for each subpopulation. Finally, using MGD as independent variable and MGS as the dependent variable, we explored the correlations between MGS and MGD by fitting quadratic functions and modeling quadratic regression. Both MGS and MGD were averaged for different time durations and were cross‐related. Our results show that the MGS for more than 2 years significantly correlated with MGD for more than 3 years in a reverse parabolic shape, differing from that of short‐term effects. Our findings suggest that long‐term MGD is a better predictor of long‐term habitat quality and that long‐term MGS is determined by long‐term habitat quality in Masked Laughingthrushes. Based on above findings, we can infer that: (1) Long‐term habitat quality determines the long‐term MGS, but it sets no prerequisite for the status and source of group members; (2) Long‐term MGS in certain populations is adapted to the corresponding level of long‐term habitat quality, it facilitates us to predict the helper effects on current or future survival or reproduction in different situations. These findings and inferences are both helpful for us to understand the evolution of cooperative breeding.
State–space mark–recapture estimates reveal a recent decline in abundance of North Atlantic right whales
Authors: Pace Richard M. , Corkeron Peter J. , Kraus Scott D.
Published: September 2017

North Atlantic right whales (Eubalaena glacialis Müller 1776) present an interesting problem for abundance and trend estimation in marine wildlife conservation. They are long lived, individually identifiable, highly mobile, and one of the rarest of cetaceans. Individuals are annually resighted at different rates, primarily due to varying stay durations among several principal habitats within a large geographic range. To date, characterizations of abundance have been produced that use simple accounting procedures with differing assumptions about mortality. To better characterize changing abundance of North Atlantic right whales between 1990 and 2015, we adapted a state–space formulation with Jolly‐Seber assumptions about population entry (birth and immigration) to individual resighting histories and fit it using empirical Bayes methodology. This hierarchical model included accommodation for the effect of the substantial individual capture heterogeneity. Estimates from this approach were only slightly higher than published accounting procedures, except for the most recent years (when recapture rates had declined substantially). North Atlantic right whales' abundance increased at about 2.8% per annum from median point estimates of 270 individuals in 1990 to 483 in 2010, and then declined to 2015, when the final estimate was 458 individuals (95% credible intervals 444–471). The probability that the population's trajectory post‐2010 was a decline was estimated at 99.99%. Of special concern was the finding that reduced survival rates of adult females relative to adult males have produced diverging abundance trends between sexes. Despite constraints in recent years, both biological (whales' distribution changing) and logistical (fewer resources available to collect individual photo‐identifications), it is still possible to detect this relatively recent, small change in the population's trajectory. This is thanks to the massive dataset of individual North Atlantic right whale identifications accrued over the past three decades. Photo‐identification data provide biological information that allows more informed inference on the status of this species.
The genetics of phenotypic plasticity. XV. Genetic assimilation, the Baldwin effect, and evolutionary rescue
Authors: Scheiner Samuel M. , Barfield Michael , Holt Robert D.
Published: September 2017

We used an individual‐based simulation model to examine the role of phenotypic plasticity on persistence and adaptation to two patterns of environmental variation, a single, abrupt step change and continual, linear change. Our model tested the assumptions and predictions of the theory of genetic assimilation, explored the evolutionary dynamics of the Baldwin effect, and provided expectations for the evolutionary response to climate change. We found that genetic assimilation as originally postulated is not likely to occur because the replacement of plasticity by fixed genetic effects takes much longer than the environment is likely to remain stable. On the other hand, trait plasticity as an enhancement to continual evolutionary change may be an important evolutionary mechanism as long as plasticity has little or no costs. Whether or not plasticity helps or hinders evolutionary rescue following a step change in the environment depends on whether plasticity is costly. For linear environmental change, noncostly plasticity always decreases extinction rates, while costly plasticity can create a fitness drag and increase the chance of extinction. Thus, with changing climates plasticity can enhance adaptation and prevent extinction under some conditions, but not others.
Prediction Interval Estimation of Demand Curve in Electric Power Distribution System
Authors: YAMAZAKI TOMOHIDE , WAKAO SHINJI , ITO HIROKAZU , SANO TSUNEYO
Published: September 2017

In a distribution line, power system control and power equipment investment are planned based on a measured power system current. However, recently the mass introduction of photovoltaic (PV) make it difficult for us to precisely measure the demand curve that is a current consumed by electrical equipment because the reversal power flow from PV systems is superposed. Therefore, the prediction of demand curves of distribution line is indispensable for power system management. In addition, it is also necessary to estimate the reliability of the predicted values as well as predicted current itself. In this paper, we propose the estimation method of the prediction interval that is the index of reliability based on the past demand curve database. The feature of the proposed method based on Just‐In‐Time (JIT) modeling make it possible for us to accurately estimate the prediction interval by the normalized database of demand curve. In this paper, some numerical examples are presented, which demonstrate the effectiveness of the proposed method.
Recent Advances in Prins Spirocyclization
Authors: Subba Reddy B. V. , Nair Preethi Narayanan , Antony Aneesh , Srivastava Nikhil
Published: September 2017

The classical Prins cyclization has been one of the most intensively studied reactions during the last two decades, and it has found many applications in key steps of natural product syntheses, especially for products containing tetrahydropyran motifs and related structures in their core skeletons. The application of this reaction to the synthesis of spirocylic networks has made substantial progress recently. Spiro motifs are found in many natural products with promising biorelevance and are increasingly being incorporated in drug candidates. Further, various spirocyclic chiral ligands have shown promising efficiency in asymmetric synthesis. Here a compilation of recent spiroannulation reactions by Prins cyclization is presented, focusing on the scope and versatility of this method.
Determination of Quercetin and Luteolin in Paprika Samples by Voltammetry and Partial Least Squares Calibration
Authors: Chamizo‐González Francisco , Monago‐Maraña Olga , Galeano‐Díaz Teresa
Published: September 2017

Quercetin and luteolin are flavonoids with beneficious properties, which are present in paprika. In this work, both have been determined in paprika by using electrochemistry combined with chemometrics. The electrochemical oxidation mechanisms of both analytes have been studied through sampled direct current (DC) voltammetry, differential pulse voltammetry (DPV) and Square Wave Voltammetry (SWV), making use of a glassy carbon electrode. The final technique selected for the quantification was DPV due to its high repeatability with respect SWV. The chemical variables and the instrumental parameters were optimized and the final conditions employed were ethanol: water (20 : 80), 0.75 mol dm−3 of HCl, and a pulse amplitude of 50 mV. Due to the facts that oxidation potential of both analytes were quite similar, their DPV peaks were overlapped, and also because the analytes interaction during the electrochemical process causes a non‐additivity of the signals, they could not be quantified separately by direct measurement of peak intensity. For this reason, a chemometric algorithm was applied (partial least squares (PLS) regression in its modality PLS‐2). In the case of validation samples, appropriate sets of calibration and validation were built and good results were obtained. This methodology was applied to real paprika samples and the results were similar to those obtained with a HPLC method previously reported.
Organic polymer‐based monolithic stationary phases with incorporated nanostructured materials for HPLC and CEC
Authors: Ganewatta Nisansala , El Rassi Ziad
Published: September 2017

This review article is concerned with the recent advances made in the field of organic polymer‐based monoliths with incorporated nanostructured materials (NSMs) for use in liquid chromatography and capillary electrochromatography. It covers the pertinent literature published over the last 7–8 years with a total of 56 references. The present article has two distinct parts: one major part encompassing “traditional” organic polymer‐based monoliths modified with NSMs and a minor part on cryogels modified with NSMs.
Pedagogical Principles of Evaluation: Interpreting Freire
Authors: Patton Michael Quinn
Published: September 2017

Pedagogy of evaluation entails examining how and what evaluation teaches. Embedded in different evaluation approaches are varying assumptions, values, premises, priorities, sense‐making processes, and principles. Elucidating and illuminating principles is fundamental to identifying and understanding a pedagogy of evaluation. Ten pedagogical principles from Paulo Freire's writings are identified and explained. Each principle is then examined for its relevance to a critical pedagogy of evaluation for evaluation theory and practice today and looking forward. Freire understood and taught us that all interactions between and among people are pedagogical, something is always being taught, conveyed, and proselytized. Extending this insight to evaluation, Freire's work reminds us that all evaluation approaches constitute a pedagogy of some kind. What any particular evaluation teaches and how it is taught varies, but evaluation is inherently and predominantly a pedagogical interaction. This leads to the concluding question: What is your pedagogy of evaluation?
The association between insulin resistance, metabolic variables, and depressive symptoms in Mexican‐American elderly: A population‐based study
Authors: Diniz Breno S. , Fisher‐Hoch Susan , McCormick Joseph
Published: September 2017

Objective

Depressive symptoms are common among older adults with obesity and diabetes. Nonetheless, the mechanisms for this association are not clear but may involve changes in the insulin cascade signaling. We aimed to investigate the association, and potential mediators, between obesity, insulin resistance, and depressive symptoms among older adults from a homogenous cohort of Mexican‐Americans.

Methods

We included a total of 500 Mexican‐American older adults assessed in the Cameron County Health Study. We evaluated depressive symptoms using the Center for Epidemiologic Survey Depression Scale (CES‐D). Central obesity was defined by waist circumference. Insulin resistance was evaluated by the HOMA‐IR index. We estimated the association between obesity, insulin resistance, and depressive symptoms by carrying out univariate and multivariate regression analyses.

Results

In unadjusted regression analysis, HOMA‐IR (unstandardized β = 0.31 ± 0.12, P = 0.007), waist circumference (unstandardized β = 0.066 ± 0.0.028, P = 0.017), and Hb1Ac levels (unstandardized β = 0.52 ± 0.24, P = 0.03) were significantly associated with CES‐D scores. The association of HOMA‐IR and CES‐D remained statistically significant after controlling for socio‐demographic and clinical variables in multivariate analysis (unstandardized β = 0.28 ± 0.11, P = 0.01).

Conclusion

Our results suggest that depressive symptoms are associated with insulin resistance in older Mexican‐American adults. In addition, poorer glucose control and obesity are important mediators of this relationship. Additional studies are needed to evaluate whether interventions that increase insulin sensitivity can also reduce depressive symptoms in this population.
Evidence‐based source modeling of nociceptive cortical responses: A direct comparison of scalp and intracranial activity in humans
Authors: Bradley Claire , Bastuji Hélène , Garcia‐Larrea Luis
Published: September 2017

Background

Source modeling of EEG traditionally relies on interplay between physiological hypotheses and mathematical estimates. We propose to optimize the process by using evidence gathered from brain imaging and intracortical recordings.

Methods

We recorded laser‐evoked potentials in 18 healthy participants, using high‐density EEG. Brain sources were modeled during the first second poststimulus, constraining their initial position to regions where nociceptive‐related activity has been ascertained by intracranial EEG. These comprised the two posterior operculo‐insular regions, primary sensorimotor, posterior parietal, anterior cingulate/supplementary motor (ACC/SMA), bilateral frontal/anterior insular, and posterior cingulate (PCC) cortices.

Results

The model yielded an average goodness of fit of 91% for individual and 95.8% for grand‐average data. When compared with intracranial recordings from 27 human subjects, no significant difference in peak latencies was observed between modeled and intracranial data for 5 of the 6 assessable regions. Morphological match was excellent for operculo‐insular, frontal, ACC/SMA and PCC regions (cross‐correlation > 0.7) and fair for sensori‐motor and posterior parietal cortex (c‐c ∼ 0.5).

Conclusions

Multiple overlapping activities evoked by nociceptive input can be disentangled from high‐density scalp EEG guided by intracranial data. Modeled sources accurately described the timing and morphology of most activities recorded with intracranial electrodes, including those coinciding with the emergence of stimulus awareness. Hum Brain Mapp 38:6083–6095, 2017. © 2017 Wiley Periodicals, Inc.
A CRISPR reimagining: New twists and turns of CRISPR beyond the genome‐engineering revolution
Authors: Plummer Robert J. , Guo Yi , Peng Ying
Published: September 2017

Despite its explosive applications in genome engineering, CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) has been developed into a versatile tool beyond its well‐known nuclease function. In this prospect article, we summarize a few exciting “off‐label” applications of CRISPR including manipulating DNA sequences, visualizing chromosomal loci in living cells, and modulating transcription and chromatin structures. These novel applications will likely elevate CRISPR tools into yet another level of sophistication and diversity, leading to many more exciting cell biological discoveries.
Efficacy of different chemotherapy regimens in treatment of advanced or metastatic pancreatic cancer: A network meta‐analysis
Authors: Zhang Shu‐Hua , Liu Gui‐Feng , Li Xue‐Feng , Liu Lin , Yu Shao‐Nan
Published: September 2017

We performed a network meta‐analysis (NMA) to compare the short‐ and long‐term efficacy of Gemcitabine, Gemcitabine + S‐1 (tegafur), Gemcitabine + nab‐paclitaxel, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, FOLFIRINOX (oxaliplatin + irinotecan + fluorouracil + leucovorin), Gemcitabine + oxaliplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, Gemcitabine + pemetrexed, Gemcitabine + 5‐FU, and S‐1 in treating advanced or metastatic pancreatic cancer (PC). The odds radios (OR) or weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) were evaluated by a combination of direct evidence and indirect evidence. In total twenty studies were included in this paper. For short‐term efficacy, the overall response rate (ORR) was lower for patients treated with Gemcitabine compared with Gemcitabine + S‐1, Gemcitabine + Cisplatin, Gemcitabine + irinotecan and S‐1. The ORR for FOLFIRINOX was higher compared with Gemcitabine, Gemcitabine + Capecitabine and Gemcitabine + Cisplatin. The disease control rate (DCR) for Gemcitabine was lower compared with Gemcitabine + S‐1, Gemcitabine + Cisplatin, and FOLFIRINOX. For long‐term efficacy, the 12‐month overall survival (OS) rate for FOLFIRINOX was higher compared with Gemcitabine, Gemcitabine + Capecitabine, Gemcitabine + Cisplatin, Gemcitabine + irinotecan, Gemcitabine + Exatecan, and Gemcitabine + pemetrexed. The SUCRA revealed that FOLFIRINOX was relatively better in both short‐ and long‐term efficacy, while Gemcitabine was relatively poorer. In both short‐ and long‐term efficacy, FOLFIRINOX had the best short‐ and long‐term efficacy among the 12 chemotherapy regimens while efficacy of Gemcitabine was relatively poorer in the treatment of advanced or metastatic PC.
Functional role of mesenchymal stem cells in the treatment of chronic neurodegenerative diseases
Authors: Lo Furno Debora , Mannino Giuliana , Giuffrida Rosario
Published: September 2017

Mesenchymal stem cells (MSCs) can differentiate into not only cells of mesodermal lineages, but also into endodermal and ectodermal derived elements, including neurons and glial cells. For this reason, MSCs have been extensively investigated to develop cell‐based therapeutic strategies, especially in pathologies whose pharmacological treatments give poor results, if any. As in the case of irreversible neurological disorders characterized by progressive neuronal death, in which behavioral and cognitive functions of patients inexorably decline as the disease progresses. In this review, we focus on the possible functional role exerted by MSCs in the treatment of some disabling neurodegenerative disorders such as Alzheimer's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Parkinson's Disease. Investigations have been mainly performed in vitro and in animal models by using MSCs generally originated from umbilical cord, bone marrow, or adipose tissue. Positive results obtained have prompted several clinical trials, the number of which is progressively increasing worldwide. To date, many of them have been primarily addressed to verify the safety of the procedures but some improvements have already been reported, fortunately. Although the exact mechanisms of MSC‐induced beneficial activities are not entirely defined, they include neurogenesis and angiogenesis stimulation, antiapoptotic, immunomodulatory, and anti‐inflammatory actions. Most effects would be exerted through their paracrine expression of neurotrophic factors and cytokines, mainly delivered at damaged regions, given the innate propensity of MSCs to home to injured sites. Hopefully, in the near future more efficacious cell‐replacement therapies will be developed to substantially restore disease‐disrupted brain circuitry.
Regulating osteogenesis and adipogenesis in adipose‐derived stem cells by controlling underlying substrate stiffness
Authors: Zhang Tao , Lin Shiyu , Shao Xiaoru , Shi Sirong , Zhang Qi , Xue Changyue , Lin Yunfeng , Zhu Bofeng , Cai Xiaoxiao
Published: September 2017

Cells reside in a complex microenvironment (niche) in which the biochemical and biophysical properties of the extracellular matrix profoundly affect cell behavior. Extracellular stiffness, one important bio‐mechanical characteristic of the cell niche, is important in regulating cell proliferation, migration, and lineage specification. However, the mechanism by which mechanical signals guide osteogenic and adipogenic commitment of stem cells remains difficult to dissect. To explore this question, we generated a range of polydimethylsiloxane‐based matrices with differing degrees of stiffness that mimicked the stiffness seen in natural tissues and examined adipose stem cell morphology, spreading, vinculin expression, and differentiation along the osteogenic and adipogenic pathways. Rigid matrices allowed broader cell spreading, faster growth rate and stronger expression of vinculin in adipose‐derived stem cells. In the presence of inductive culture media, stiffness‐dependent osteogenesis and adipogenesis of the adipose stem cells indicated that there was a combinatorial effect of biophysical and biochemical cues; no such lineage specification was observed in normal media. Osteogenic differentiation behavior showed a correlation with matrix rigidity, as well as with elevated expression of RhoA, ROCK‐1/‐2, and related proteins in the Wnt/β‐catenin pathway. The result provides a comprehensive understanding of how stem cells respond to the surrounding microenvironment and points to the fact that matrix stiffness is a critical element in biomaterial design and this will be an important advance in stem cell‐based tissue engineering.
Role of viruses in gastrointestinal cancer
Authors: Mirzaei Habibollah , Goudarzi Hossein , Eslami Gita , Faghihloo Ebrahim
Published: September 2017

Gastrointestinal cancers are a global public health problem, which represent a vast majority of all cancer‐caused deaths in both men and women. On the other hand, viral pathogens have been long implicated as etiological factors in the onset of certain human cancers, including gastrointestinal tumors. In this regard, Human Papilloma Virus (HPV), Epstein‐Barr Virus (EBV), and John Cunningham Virus (JCV) have been more strongly suggested to be involved in gastrointestinal carcinogenesis; so that, the association of HPV with oropharyngeal and anal cancers and also the association of EBV with gastric cancer have been etiologically confirmed by epidemiological and experimental investigations. Although, the association of other viruses is less evident, but may rely on co‐factors for their oncogenic roles. Therefore, to improve the prevention and treatment of these classes of cancer, their association with viral agents as potential risk factors should be investigated with care. In this respect, the present review has focused on the existing literature on the subject of viral involvement in gastrointestinal tumorgenesis, by covering and discussing various gastrointestinal cancers, corresponding viral agents and their oncogenic aspects and then summarizing evidences either supporting or rejecting a causal role of these pathogens in gastrointestinal malignancies.
Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells
Authors: Phillips Jessica L. , Taberlay Phillippa C. , Woodworth Alexandra M. , Hardy Kristine , Brettingham‐Moore Kate H. , Dickinson Joanne L. , Holloway Adele F.
Published: September 2017

Integrins are transmembrane adhesion receptors that play an important role in hematopoiesis by facilitating interactions between hematopoietic cells and extracellular matrix components of the bone marrow and hematopoietic tissues. These interactions are important in regulating the function, proliferation, and differentiation of hematopoietic cells, as well as their homing and mobilization in the bone marrow. Not surprisingly altered expression and function of integrins plays a key role in the development and progression of cancer including leukemias. However, the regulation of integrin gene expression is not well characterized and the mechanisms by which integrin genes are disrupted in cancer remain unclear. Here we demonstrate for the first time that a key regulator of hematopoiesis, RUNX1, binds to and regulates the promoters of both the ITGA6 and ITGB4 genes in myeloid cells. The ITGA6 and ITGB4 integrin genes form the α6β4 integrin receptor. However, our data indicate that RUNX1 functions differently at these two promoters. RUNX1 regulates ITGA6 through a consensus RUNX1 binding motif in its promoter. In contrast, although the ITGB4 promoter is also activated by RUNX1, it does so in the absence of a recognized consensus RUNX1 binding motif. Furthermore, our data suggest that regulation of ITGB4 may involve interactions between the promoter and upstream regulatory elements.
Oroxyloside inhibits angiogenesis through suppressing internalization of VEGFR2/Flk‐1 in endothelial cells
Authors: Zhao Kai , Li Xiaorui , Lin Binyan , Yang Dawei , Zhou Yuxin , Li Zhiyu , Guo Qinglong , Lu Na
Published: September 2017

Increasing flavonoids have been reported to possess anti‐angiogenic effects. Inhibition of angiogenesis plays a critical role in the treatment of cancer, especially in advanced metastatic cancer. In this study, we assessed the effect of Oroxylin A‐7‐glucuronide (Oroxyloside), a main metabolite of Oroxylin A, on angiogenesis in human endothelial cell‐like EA.hy926 cells. Oroxyloside suppressed the migration and tube formation of EA.hy926 cells. Meanwhile, microvessels sprouting from aortic rings and new blood vessels on the chicken chorioallantoic membrane (CAM) were also inhibited. Mechanism studies showed that Oroxyloside reduced the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2/Flk‐1) while it up‐regulated the expression of R‐Ras and VE‐cadherin. In consequence, Oroxyloside inhibited the downstream Akt/MAPK/NF‐κB pathways and then decreased the nuclear translocation and DNA binding ability of NF‐κB. Furthermore, in vivo study showed that Oroxyloside exhibited a potential anti‐angiogenic effect in Matrigel plug assay and inhibited growth of xenografted tumors with low systemic toxicity, which could be ascribed to the inhibition of VEGFR2 internalization. Taken together, these results suggested that Oroxyloside could inhibit angiogenesis in vitro and in vivo via suppressing the internalization of VEGFR2 and might serve as a potential antitumor agent.
Fenofibrate reverses changes induced by high‐fat diet on metabolism in mice muscle and visceral adipocytes
Authors: Frias Flávia de T. , Rocha Karina C.e. , de Mendonça Mariana , Murata Gilson M. , Araujo Hygor N. , de Sousa Luís G.O. , de Sousa Érica , Hirabara Sandro M. , Leite Nayara de C. , Carneiro Everardo M. , Curi Rui , Silveira Leonardo R. , Rodrigues Alice C.
Published: September 2017

The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet‐induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high‐fat diet for 8 weeks. Fenofibrate (50 mg/Kg BW, daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin‐stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR‐103‐3p in adipose tissue, and miR‐1a, miR‐133a/b, miR‐206, let7b‐5p, miR‐23b‐3p, miR‐29‐3p, miR‐143‐3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho‐AMPKα2, Pgc1α, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated. In DIO mice, fenofibrate prevented weight gain induced by HFD feeding by increasing energy expenditure; improved whole body glucose homeostasis, and in skeletal muscle, increased insulin dependent glucose uptake, miR‐1a levels, reduced intramuscular lipid accumulation, and phospho‐AMPKα2 levels. In visceral adipose tissue of obese mice, fenofibrate decreased basal lipolysis rate and visceral adipocytes hypertrophy, and induced the expression of Glut‐4, Irs1, and Cav‐1 mRNA and miR‐103‐3p suggesting a higher insulin sensitivity of the adipocytes. The evidence is presented herein that beneficial effects of fenofibrate on body weight, glucose homeostasis, and muscle metabolism might be related to its action in adipose tissue. Moreover, fenofibrate regulates miR‐1a‐3p in soleus and miR‐103‐3p in adipose tissue, suggesting these microRNAs might contribute to fenofibrate beneficial effects on metabolism.
Radiomics signature: A potential biomarker for the prediction of MGMT promoter methylation in glioblastoma
Authors: Xi Yi‐bin , Guo Fan , Xu Zi‐liang , Li Chen , Wei Wei , Tian Ping , Liu Ting‐ting , Liu Lin , Chen Gang , Ye Jing , Cheng Guang , Cui Long‐biao , Zhang Hong‐juan , Qin Wei , Yin Hong
Published: September 2017

Background

In glioblastoma (GBM), promoter methylation of the DNA repair gene O‐methylguanine‐DNA methyltransferase (MGMT) is associated with beneficial chemotherapy.

Purpose/Hypothesis

To analyze radiomics features for utilizing the full potential of medical imaging as biomarkers of MGMT promoter methylation.

Study Type

Retrospective.

Population/Subjects

In all, 98 GBM patients with known MGMT (48 methylated and 50 unmethylated tumors).

Field Strength/Sequence

3.0T magnetic resonance (MR) images, containing T1‐weighted image (T1WI), T2‐weighted image (T2WI), and enhanced T1WI.

Assessment

A region of interest (ROI) of the tumor was delineated. A total of 1665 radiomics features were extracted and quantized, and were reduced using least absolute shrinkage and selection operator (LASSO) regularization.

Statistical Testing

After the support vector machine construction, accuracy, sensitivity, and specificity were computed for different sequences. An independent validation cohort containing 20 GBM patients was utilized to further evaluate the radiomics model performance.

Results

Radiomics features of T1WI reached an accuracy of 67.54%. Enhanced T1WI features reached an accuracy of 82.01%, while T2WI reached an accuracy of 69.25%. The best classification system for predicting MGMT promoter methylation status originated from the combination of 36 T1WI, T2WI, and enhanced T1WI images features, with an accuracy of 86.59%. Further validation on the independent cohort of 20 patients produced similar results, with an accuracy of 80%.

Data Conclusion

Our results provide further evidence that radiomics MR features could predict MGMT methylation status in preoperative GBM. Multiple imaging modalities together can yield putative noninvasive biomarkers for the identification of MGMT.

Level of Evidence: 4

Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1380–1387.
Ionic liquids: solvents and sorbents in sample preparation
Authors: Clark Kevin D. , Emaus Miranda N. , Varona Marcelino , Bowers Ashley N. , Anderson Jared L.
Published: September 2017

The applications of ionic liquids (ILs) and IL‐derived sorbents are rapidly expanding. By careful selection of the cation and anion components, the physicochemical properties of ILs can be altered to meet the requirements of specific applications. Reports of IL solvents possessing high selectivity for specific analytes are numerous and continue to motivate the development of new IL‐based sample preparation methods that are faster, more selective, and environmentally benign compared to conventional organic solvents. The advantages of ILs have also been exploited in solid/polymer formats in which ordinarily nonspecific sorbents are functionalized with IL moieties in order to impart selectivity for an analyte or analyte class. Furthermore, new ILs that incorporate a paramagnetic component into the IL structure, known as magnetic ionic liquids (MILs), have emerged as useful solvents for bioanalytical applications. In this rapidly changing field, this Review focuses on the applications of ILs and IL‐based sorbents in sample preparation with a special emphasis on liquid phase extraction techniques using ILs and MILs, IL‐based solid‐phase extraction, ILs in mass spectrometry, and biological applications.
Excellent outcomes in combined liver‐kidney transplantation: Impact of kidney donor profile index and delayed kidney transplantation
Authors: Ekser Burcin , Mangus Richard S. , Kubal Chandrashekhar A. , Powelson John A. , Fridell Jonathan A. , Goggins William C.
Published: September 2017

The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver‐kidney transplantation (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on kidney donor profile index [KDPI]) or the delayed approach KT contributes to improved patient survival. In total, 130 CLKTs were performed between 2002 and 2015, 69 with simultaneous KT (group S) and 61 with delayed KT (group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50 ± 15 hours). All patients were categorized according to the KDPI score: 1%‐33%, 34%‐66%, and 67%‐99%. Recipient and donor characteristics were comparable within groups S and D. Transplant outcomes were comparable within groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. The combination of delayed KT and KDPI 1%‐33% resulted in 100% patient survival at 3 years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3 years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more extended criteria donor and donation after circulatory death kidneys. Liver Transplantation 24 222–232 2018 AASLD.
Early genetic aberrations in patients with sporadic colorectal cancer
Authors: Druliner Brooke R. , Ruan Xiaoyang , Sicotte Hugues , O'Brien Daniel , Liu Hongfang , Kocher Jean‐Pierre A. , Boardman Lisa
Published: September 2017

Chromosome instability (CIN) is widely observed in both sporadic and hereditary colorectal cancer (CRC). Defects in APC and WNT signaling are primarily associated with CIN in hereditary CRC, but the genetic causes for CIN in sporadic CRC remain elusive. Using high‐density SNP array and exome data from The Cancer Genome Atlas (TCGA), we characterized loss of heterozygosity (LOH) and copy number variation (CNV) in the peripheral blood, normal colon, and corresponding tumor tissue in 15 CRC patients with proficient mismatch repair (MMR) and 24 CRC patients with deficient MMR. We found a high frequency of 18q LOH in tumors and arm‐specific enrichment of genetic aberrations on 18q in the normal colon (primarily copy neutral LOH) and blood (primarily copy gain). These aberrations were specific to the sporadic, pMMR CRC. Though in tumor samples genetic aberrations were observed for genes commonly mutated in hereditary CRC (eg, APC, CTNNB1, SMAD4, BRAF), none of them showed LOH or CNV in the normal colon or blood. DCC located on 18q21.1 topped the list of genes with genetic aberrations in the tumor. In an independent cohort of 13 patients subjected to Whole Genome Sequencing (WGS), we found LOH and CNV on 18q in adenomatous polyp and tumor tissues. Our data suggests that patients with sporadic CRC may have genetic aberrations preferentially enriched on 18q in their blood, normal colon epithelium, and non‐malignant polyp lesions that may prove useful as a clinical marker for sporadic CRC detection and risk assessment.