bluuebunny/crossref_metadata_2025 huggingface dataset:
Profile of the unfolded protein response in rat cerebellar cortical development
Authors: Naughton Michelle , McMahon Jill , Healy Sinéad , FitzGerald Una
Published: May 2019

The unfolded protein response (UPR) has been reported during normal development of cortical neurons and cerebellar white matter and may also contribute to the pathogenesis of neurological conditions, such as Marinesco‐Sjogren syndrome and Borna virus infection, which result in cerebellar defects. The UPR is initiated when the processing capacity of the endoplasmic reticulum (ER) is overwhelmed. Misfolded proteins accumulate and can activate ER stress sensors; PKR‐like endoplasmic reticulum kinase (PERK), inositol‐requiring enzyme 1 (IRE1), activated transcription factor 6 (ATF6) and their downstream targets glucose‐regulated protein 78 (GRP78), glucose‐regulated protein 94 (GRP94) and protein disulfide isomerase (PDI). In order to provide a fuller appreciation of the possible importance of ER stress‐associated proteins in the context of cerebellar disease, we have profiled the expression of ER stress sensors and their downstream targets in the developing cerebellar cortex in postnatal rat. Activation of PERK and IRE1 stress sensors was observed for the first time in normally developing granule cell precursors. A second proliferative pPERK‐positive population was also detected in the internal granular layer (IGL). In general, the density of UPR protein‐positive cells was found to decrease significantly when profiles in early and late postnatal ages were compared. These data may be relevant to studies of medulloblastoma and warrant further investigation.
Upper Bounds on Liouville First‐Passage Percolation and Watabiki's Prediction
Authors: Ding Jian , Goswami Subhajit
Published: May 2019

Given a planar continuum Gaussian free field h𝒰 in a domain 𝒰 with Dirichlet boundary condition and any δ > 0, we let be a real‐valued smooth Gaussian process where is the average of h𝒰 along a circle of radius δ with center v. For γ > 0, we study the Liouville first‐passage percolation (in scale δ), i.e., the shortest path distance in 𝒰 where the weight of each path P is given by . We show that the distance between two typical points is for all sufficiently small but fixed γ > 0 and some constant c* > 0. In addition, we obtain similar upper bounds on the Liouville first‐passage percolation for discrete Gaussian free fields, as well as the Liouville graph distance, which roughly speaking is the minimal number of euclidean balls with comparable Liouville quantum gravity measure whose union contains a continuous path between two endpoints. Our results contradict some reasonable interpretations of Watabiki's prediction (1993) on the random distance of Liouville quantum gravity at high temperatures.© 2019 Wiley Periodicals, Inc.
Effects of mindfulness training on the default mode network in borderline personality disorder
Authors: Carmona i Farrés Cristina , Elices Matilde , Soler Joaquim , Domínguez‐Clavé Elisabet , Martín‐Blanco Ana , Pomarol‐Clotet Edith , Salvador Raymond , Martinez‐Horta Saül , Pascual Juan C.
Published: May 2019

Patients with borderline personality disorder (BPD) present dysfunctions of the default mode network (DMN). Mindfulness training has proven effective to improve the symptoms of BPD. The present study examines the effect of mindfulness training on BPD symptomatology and DMN activity during the performance of a working memory task in patients with BPD. Sixty‐five individuals with BPD were randomized to receive psychotherapy with either the mindfulness module of dialectical behavioural therapy (DBT‐M) or with interpersonal effectiveness module (DBT‐IE). The impact of treatments was evaluated with clinical and mindfulness variables as well as with functional magnetic resonance imaging during performance of the task. Both groups showed improvement in BPD symptoms and other clinical variables after treatment. Unexpectedly, there were no between‐group differences in DMN activation or deactivation. However, activation of the left anterior insula increased in both groups after the intervention. Compared with the control group, participants in the DBT‐M group presented higher deactivation in a cluster extending bilaterally from the calcarine to the cuneus and superior occipital gyri.
Thermodynamic Investigation of Ternary Delafossite Crystals
Authors: Wolff Nora , Klimm Detlef , Ganschow Steffen , Siche Dietmar
Published: May 2019

The ternary phase diagram of copper–iron–aluminium delafossite is established with FactSage calculations to improve the conditions for solution growth and the electrical conductivity of the transparent p‐type semiconductor copper–aluminium delafossite by addition of iron oxide. Initial growth experiments with the optical float zone method show that the growth of single crystals with commercially relevant dimensions is not expected in the near future.
The value relevance of environmental, social, and governance disclosure: Evidence from Dow Jones Sustainability World Index listed companies
Authors: Aureli Selena , Gigli Sabrina , Medei Renato , Supino Enrico
Published: May 2019

The relationship between a company's sustainability practices and its financial performance has been investigated with different methods and from different theoretical perspectives. This study aims to answer the following questions: (a) Do investors react to the publication of sustainability reports on company websites? (b) Has the market reaction to the publication of the sustainability report increased in the last few years? In this study, 170 report disclosures were considered from 55 listed companies from all over the world in the period from 2009 to 2016. To analyze the impact of the report publications on the security returns, 33 different event windows were analyzed. Results show two significant event windows and an increasing level of significance in the reports released after 2013.
Corporate social responsibility activities and firm performance: The moderating role of strategic emphasis and industry competition
Authors: Jia Xingping
Published: May 2019

This study extends the literature on the relationship between corporate social responsibility (CSR) activities and firm performance by incorporating the role of strategic emphasis, defined as the resources that firms allocate to value appropriation (with the emphasis on advertising expenditure) versus value creation (with the emphasis on research and development investment), and how industry competition creates a three‐way interaction with CSR and strategic emphasis to affect firm performance. Using data from 3,401 publicly traded firm‐year observations in China for the years 2009–2015, the study demonstrates that CSR enhances firm performance when the firm's strategy emphasizes value appropriation over value creation. The interaction effect of CSR and strategic emphasis is also shown to vary with the level of competition in the industry. The results not only contribute to the literature on the relationship between CSR and firm performance, but can also inform firms' resource allocation decisions, enabling them to gain instrumental value from CSR initiatives.
Invasive Galega officinalis (Goat's rue) plants in Canada form a symbiotic association with strains of Neorhizobium galegae sv. officinalis originating from the Old World
Authors: Bromfield Eden S. P. , Cloutier Sylvie , Robidas Catherine , Tran Thi Thu Van , Darbyshire Stephen J.
Published: May 2019

The toxic legume plant, Galega officinalis, is native to the Eastern Mediterranean and Black Sea regions. This legume is considered to be a noxious weed, and its establishment in Canada may have resulted from ornamental planting and/or field trials. In its native range, a highly specific nitrogen‐fixing symbiosis with the bacterium, Neorhizobium galegae symbiovar (sv.) officinalis, is required for normal growth. In North America, nothing is known about the bacterial symbionts of G. officinalis. Our purpose was to determine the species and symbiovar identity of symbiotic bacteria associated with invasive plants of G. officinalis at five sites in the province of Ontario, Canada.  Sequence analysis of four housekeeping (16S rRNA, atpD, glnII, and recA) and two symbiosis (nodC and nifH) genes showed that all 50 bacterial isolates from root nodules of G. officinalis at the five Canadian sites were identical to strains of N. galegae sv. officinalis originating either from Europe or the Caucasus. Plant tests indicated that soils collected from four Canadian sites without a history of agriculture or presence of G. officinalis were deficient in symbiotic bacteria capable of eliciting nodules on this plant. Collectively our data support the hypothesis of anthropogenic co‐introduction of G. officinalis and its specific symbiotic bacterium into Canada from the Old World. Factors that may limit the spread of G. officinalis in new environments are discussed.
Spatial differences in genetic diversity and northward migration suggest genetic erosion along the boreal caribou southern range limit and continued range retraction
Authors: Thompson Laura M. , Klütsch Cornelya F. C. , Manseau Micheline , Wilson Paul J.
Published: May 2019

With increasing human activities and associated landscape changes, distributions of terrestrial mammals become fragmented. These changes in distribution are often associated with reduced population sizes and loss of genetic connectivity and diversity (i.e., genetic erosion) which may further diminish a species' ability to respond to changing environmental conditions and lead to local population extinctions. We studied threatened boreal caribou (Rangifer tarandus caribou) populations across their distribution in Ontario/Manitoba (Canada) to assess changes in genetic diversity and connectivity in areas of high and low anthropogenic activity. Using data from >1,000 caribou and nine microsatellite loci, we assessed population genetic structure, genetic diversity, and recent migration rates using a combination of network and population genetic analyses. We used Bayesian clustering analyses to identify population genetic structure and explored spatial and temporal variation in those patterns by assembling networks based onRSTandFSTas historical and contemporary genetic edge distances, respectively. The Bayesian clustering analyses identified broad‐scale patterns of genetic structure and closely aligned with theRSTnetwork. TheFSTnetwork revealed substantial contemporary genetic differentiation, particularly in areas presenting contemporary anthropogenic disturbances and habitat fragmentation. In general, relatively lower genetic diversity and greater genetic differentiation were detected along the southern range limit, differing from areas in the northern parts of the distribution. Moreover, estimation of migration rates suggested a northward movement of animals away from the southern range limit. The patterns of genetic erosion revealed in our study suggest ongoing range retraction of boreal caribou in central Canada.
How a measure of tree structural complexity relates to architectural benefit‐to‐cost ratio, light availability, and growth of trees
Authors: Seidel Dominik , Annighöfer Peter , Stiers Melissa , Zemp Clara Delphine , Burkardt Katharina , Ehbrecht Martin , Willim Katharina , Kreft Holger , Hölscher Dirk , Ammer Christian
Published: May 2019

Aboveground tree architecture is neither fully deterministic nor random. It is likely the result of mechanisms that balance static requirements and light‐capturing efficiency. Here, we used terrestrial laser scanning data to investigate the relationship between tree architecture, here addressed using the box‐dimension (Db), and the architectural benefit‐to‐cost ratio, the light availability, and the growth of trees. We detected a clear relationship betweenDband the benefit‐to‐cost ratio for the tested three temperate forest tree species (Fagus sylvaticaL.,Fraxinus excelsiorL., andAcer pseudoplatanusL.). In addition, we could also show thatDbis positively related to the growth performance of several tropical tree species. Finally, we observed a negative relationship between the strength of competition enforced on red oak (Quercus rubraL.) trees and theirDb.We therefore argue thatDbis a meaningful and integrative measure that describes the structural complexity of the aboveground compartments of a plant as well as its relation to structural efficiency (benefit‐to‐cost ratio), productivity, and growing conditions (competition or availability of light).
A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain
Authors: Larrosa Pardo Fabian , Bondesson Elisabeth , Schelin Maria E. C. , Jöud Anna
Published: May 2019

Background

Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by pain resulting from the underlying disease that has provoked a state of central sensitization. However, this argument is currently limited by evidence that has insufficiently captured the temporal nature of the relationship between diagnosis of the underlying disease and onset of widespread pain. The aim of this study was to investigate if patients with rheumatoid arthritis (RA), endometriosis or inflammatory bowel disease (IBD), have a higher risk of developing widespread pain (fibromyalgia or chronic widespread pain [CWP]).

Methods

Using the Swedish Skåne Healthcare register on health care consultation, a cohort of 889,938 adult patients were followed from 2007 to 2016 and incident cases of RA, endometriosis or IBD and of fibromyalgia and CWP were identified by registered diagnoses. Using Poisson regression, we calculated incidence rate ratios (IRR) adjusted for sex, age, education and propensity to seek health care.

Results

For patients with RA the IRR for later fibromyalgia was 3.64 (95% CI: 2.75–4.81) compared to patients without RA, for CWP it was 2.96 (95% CI: 1.81–4.86). For endometriosis patients the IRR for fibromyalgia was 2.83 (95% CI: 1.96–4.08) and for CWP 5.02 (95% CI: 3.10–8.13). IBD patients had an IRR = 2.32 (95% CI: 1.58–3.42) for fibromyalgia and 1.42 (95% CI: 0.93–2.17) for CWP.

Conclusions

This study shows that RA, endometriosis and IBD are all risk factors for later fibromyalgia and CWP, consistent with a hypothesis of central sensitization as an effect of a painful underlying condition.

Significance

We show that RA, endometriosis and IBD predisposes for later fibromyalgia and CWP, a common hypothesis previously difficult to verify due to lack of longitudinal data. The results inform further research regarding the aetiology of fibromyalgia and CWP and stress the need of clinical focus on the pain itself in chronic diseases with pain as a symptom.
Pine cone pyrolysis: Optimization of temperature for energy recovery
Authors: Boutaieb Mouzaina , Guiza Monia , Román Silvia , Nogales Sergio , Ledesma Beatriz , Ouederni Abdelmottaleb
Published: May 2019

In this work, the pine cones pyrolysis (a mixture of both scales and axis) was investigated under different temperature (500–800°C) at a bench scale fixed bed reactor operating in batch mode. It was found that operating temperature had a slight or more marked influence on the product phase distribution as a consequence of the enhancement of biomass decomposition and also the greater prominence of cracking reactions especially at highest temperatures, yielding a greater gas production. It was found that increasing temperature led to decreasing biochar yields (from 29.4% to 20.4%) and increasing gas yields (from 34.4 to 44.4%), whereas the bio‐oil yield passed through a maximum 37.6% at 600°C. The biochars were characterized in terms of proximate and elemental analysis, thermal degradation profiles, high heating value and surface chemistry and morphology. In addition, the composition of gases was determined by gas chromatography. Apart from the changes induced by increasing temperature on the biochar properties such as greater pore volumes at 700°C (used in activated carbon manufacture), it was found that gas production was enhanced, and H2 and CH4 yields were the highest at 800°C. Finally, at 600°C biochar showed the highest heating value of 30.95 MJ kg−1, allowing its use briquette biofuels.
Assessment of the physicochemical characteristics of soil planted with elephant grass—Cenchrus purpureus (Schumach.) Morrone—following application of biosolid and chemical fertilization
Authors: Neves Talles I. , Abrahão Raphael , Uyeda Claudio A. , de Souza Silva Cleiton , de Deus Alex S.
Published: May 2019

Biosolids are dehydrated sludge derived from effluent treatment plants. These biosolids may be used as agricultural fertilizers due to their characteristically high organic matter and nutrient contents. Thus, alternative uses for biosolids must be identified, and agriculture is one such potential alternative. The present study aimed to assess the soil physicochemical gains and losses resulting from the application of textile industrial biosolid and chemical fertilization recommended for elephant grass crops. To this end, physicochemical and biological soil analyses were carried out. A field experiment was conducted using a randomized block design with three blocks and the following treatments: without fertilization; with conventional fertilization; and with 1×, 2×, 4×, and 8× biosolid based on the Recommendation from the Brazilian National Council for the Environment. The results were analyzed using the Tukey test, which showed the viability of using biosolids. That is, the biosolids caused an increase even higher than that resulting from some fertilizing elements such as phosphorus, calcium, and sodium in treatments with chemical fertilization and without causing soil contamination, either with heavy metals, pathogenic microorganisms, or nitrogen. This provides an environmentally friendly way of disposing of this otherwise unusable waste.
Energy savings in convective drying of various materials using variable temperature conditions
Authors: Doder Đorđije D. , Đaković Damir D.
Published: May 2019

Convective drying process is among the most energy‐intensive ones; therefore, every kind of its improvement may result in a significant reduction of energy consumption, which contributes to sustainable energy planning. Intermittent drying, often accomplished by periodical temperature lowering and/or stopping the air flow completely, is one of the most popular measures for energy saving. Herein, intermittent regime was carried out only by temperature variation, keeping the heater turned on for 60 min, and then turned off for another 30 min, while the fan was turned on all the time. Temperature lowering in certain periods saves energy, but some extension of total drying time is also expected. The aim of the article was to explore the possibility of energy saving with no significant time extension and the influence of different effective diffusivities in that context. Hence, the drying materials with different properties were chosen—walnuts, chestnuts with and without shell, pumpkin, and potatoes. Drying of walnuts was described in more detail to briefly explain the basic idea of the analysis, whereas other materials were analyzed only in terms of energy saving. The research showed the noticeable effective diffusivity influence on energy saving, and only materials with its high value are suitable for such a treatment
Excessive apoptosis of podocytes caused by dysregulation of microRNA‐182‐5p and CD2AP confers to an increased risk of diabetic nephropathy
Authors: Ming Lei , Ning Jing , Ge Yuan , Zhang Ying , Ruan Zhen
Published: May 2019

The functions of miR‐182‐5p in the pathogenesis of diabetic nephropathy (DN) remain largely unclear. Here, we studied the roles and relationship between miR‐182‐5p and CD2AP in the development of DN. We used real‐time polymerase chain reaction (PCR) to compare miR‐182‐5p expression between DN and control groups, while computational analysis and luciferase assays were used to confirm CD2AP as a miR‐182‐5p target. Western blot and real‐time PCR were then used to measure the messenger RNA (mRNA) and protein expression of CD2AP in the presence of miR‐182‐5p. The results showed that miR‐182‐5p was highly expressed in cells isolated from people with DN. In addition, the luciferase activity of cells transfected with wild‐type/mutant CD2AP confirmed CD2AP as a direct target of miR‐182‐5p. The expression levels of CD2AP mRNA and protein were much lower in the DN group compared with that in the normal group. In addition, the expression levels of CD2AP mRNA and protein were evidently increased by a miR‐182‐5p inhibitor, but notably downregulated by miR‐182‐5p mimics or CD2AP small interfering RNA (siRNA). Furthermore, miR‐182‐5p and CD2Ap siRNA significantly reduced the survival rate and viability of transfected cells, while the miR‐182‐5p inhibitor exhibited an opposite effect. These findings indicated the presence of a negative regulatory relationship between miR‐182‐5p and CD2AP in podocytes cells and suggested that the overexpression of miR‐182‐5p contributes to the pathogenesis of DN.
Performance evaluation of serum PIVKA‐II measurement using HISCL‐5000 and a method comparison of HISCL‐5000, LUMIPULSE G1200, and ARCHITECT i2000
Authors: Ryu Mi Ra , Kang Eun‐Suk , Park Hyung‐Doo
Published: May 2019

Background

Protein induced by vitamin K antagonist‐II (PIVKA‐II), in addition to alpha‐fetoprotein, is a useful tumor marker for diagnosis of hepatocellular carcinoma (HCC). We evaluated the analytical performance of the HISCL‐5000 analyzer (Sysmex Corporation) in the measurement of serum PIVKA‐II.

Methods

We evaluated the precision and linearity of PIVKA‐II assays using the HISCL‐5000 analyzer. Methods using HISCL‐5000, LUMIPULSE G1200 (Fujirebio Diagnostics), and ARCHITECT i2000 (Abbott Diagnostics) were compared according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 501 subjects (median age 59 years, age range 24‐90 years) were enrolled. Among them, 335 were HCC patients, 46 were patients with non‐HCC liver disease, and 120 were healthy individuals. Non‐HCC liver disease included liver cirrhosis, chronic hepatitis, HBV or HCV carrier, hepatic adenoma, and intrahepatic cholangiocarcinoma.

Results

Repeatability (%CV) in low‐ and high‐level controls and pooled serum was 2.81%‐10.30%, and within‐laboratory precision was 4.24%‐8.86%. In a linearity test, the coefficient of determination (R2) was 0.9957, ranging from 11 to 69 897 mAU/mL. In comparison, the coefficient of correlation (r) was 0.9561‐0.9644, agreement was 93.4%‐97.6%, and the κ value was 0.855‐0.945 among the three analyzers. About 99.2% of healthy individuals and 84.8% of non‐HCC liver disease patients were below the cutoff value (40 mAU/mL) on HISCL‐5000.

Conclusions

A PIVKA‐II assay using HISCL‐5000 showed acceptable analytical performance including precision, linearity, and method comparison. This indicates that HISCL‐5000 can be potentially helpful in clinical laboratories.
Effects of blood sample handling procedures on measurable interleukin 6 in plasma and serum
Authors: Gong Yan , Liang Shaocong , Zeng Lei , Ni Yanli , Zhou Shaosong , Yuan Xiaopeng
Published: May 2019

Introduction

Interleukin‐6(IL‐6) measurement is used as a biomarker in medical diagnosis, therapy, and prognosis in various diseases. However, several pre‐analytical factors may yield a false IL‐6 result. In this study, we set out to investigate the effects of corrected blood sample handling procedures on measurable IL‐6.

Method

EDTA plasma and serum samples were collected from 45 healthy individuals. The participants were divided into three groups to perform different handling procedures. Different centrifugal timing, storage temperature, and time were executed on the samples. The changed trends of IL‐6 levels were analyzed.

Results

At baseline, while the paired plasma and serum IL‐6 values had a good correlation, the plasma levels were higher than serum. In general, the unseparated EDTA plasma kept steady with time. With the increase in storage temperature and time, a more pronounced rise in unseparated serum IL‐6 was observed. Nevertheless, the samples in Group 3 which centrifuged and separated immediately kept stable after a different temperature and longtime storage.

Conclusion

Sample types, centrifugal timing, storage temperature, and time may affect the IL‐6 levels. A standard blood sample handling procedure should be performed to ensure the accuracy and stability of IL‐6 values.
Association between miRNA‐196a2 rs11614913 T>C polymorphism and Kawasaki disease susceptibility in southern Chinese children
Authors: Wang Jinxin , Li Jiawen , Qiu Huixian , Zeng Lanlan , Zheng Hao , Rong Xing , Jiang Zhiyong , Gu Xueping , Gu Xiaoqiong , Chu Maoping
Published: May 2019

Background

miRNAs play important roles in a variety of diseases. Thus, the association between miRNA‐196a2 rs11614913 T>C polymorphism and Kawasaki disease susceptibility is still unknown.

Methods

We included 532 children with Kawasaki disease and 623 healthy children from South China, and their DNA was extracted for genotyping by TaqMan methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association.

Results

No significant associations were observed between the miRNA‐196a2 rs11614913 T>C polymorphisms and Kawasaki disease risk (TC vs TT: adjusted OR = 1.04, 95% CI = 0.79‐1.37; CC vs TT: adjusted OR = 0.87, 95% CI = 0.63‐1.21; dominant model: adjusted OR = 0.99, 95% CI = 0.76‐1.27; and recessive model: adjusted OR = 0.85, 95% CI = 0.64‐1.13). There was also no significant correlation found in stratified analyses.

Conclusion

This study suggests that miRNA‐196a2 rs11614913 T>C may not be associated with Kawasaki disease susceptibility in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions.
Modulation of renin angiotensin system components by high glucose levels in the culture of collecting duct cells
Authors: Leite A. P. O. , Aragão Danielle S. , Nogueira Marie D. , Pereira Renata O. , Jara Zaira P. , Fiorino Patricia , Casarini Dulce E. , Farah Vera
Published: May 2019

Diabetes mellitus and its complications have become a major health concern in Western countries. Increased activity of the intrarenal renin–angiotensin system (RAS) contributes to diabetic nephropathy (DN). We previously reported that in mesangial cells, the high glucose concentration (HG) leads to upregulation of angiotensin‐converting enzyme (ACE) messenger RNA, suggesting that ACE was modulated by angiotensin II (Ang II) release. However, this relation in the collecting duct has not yet been studied. We, therefore, aimed to evaluate RAS modulation in inner medullary collecting duct cells (IMCD) exposed to HG. The IMCD were divided into normal glucose (5 mM D‐glucose, NG), high glucose (30 mM, HG), and mannitol (30 mM, M) groups. The cells were cultured 48 hr in their respective media. The intracellular and extracellular ACE activity was measured using hippuryl‐His‐Leu as substrate via a fluorimetric assay and expression was analyzed using western blot analysis. ACE activity, intracellular (27%) and extracellular (22%), was significantly lower in the HG group than in NG and M. ACE2 activity and Ang 1–7 levels were higher in the intracellular compartment. Our data suggest that the HG cannot modify ACE synthesis in IMCD cells but can modulate its activity. The decrease in ACE activity may result in decreased levels of Ang II to protect the IMCD against proliferative and inflammatory deleterious effects of this peptide. Conversely, the increase of ACE2 generating high levels of Ang 1–7, a vasodilator peptide, suggesting that this peptide can induce glucose uptake and protect cells against oxidative stress, which can elicit insulin resistance.
microRNA‐124 attenuates isoflurane‐induced neurological deficits in neonatal rats via binding to EGR1
Authors: Yang Wenqian , Guo Qulian , Li Jingyi , Wang Ximei , Pan Bingbing , Wang Yunjiao , Wu Lei , Yan Jianqin , Cheng Zhigang
Published: May 2019

Isoflurane anesthesia induces neuroapoptosis in the development of the brain. In this study, neonatal rats and hippocampal neurons were subjected to isoflurane exposure, in which the effect of miR‐124 on the neurological deficits induced by isoflurane was evaluated. Isoflurane anesthesia models were induced in neonatal SD rats aged 7 days and then treated with miR‐124 agomir, miR‐124 antagomir, or LV‐CMV‐early growth response 1 (EGR1) plasmids. Then, the spatial learning and memory ability of rats were evaluated by Morris water maze. Furthermore, primary hippocampal neurons cultured 7 days were also exposed to isoflurane and transfected with miR‐124 agomir, miR‐124 antagomir, or LV‐CMV‐EGR1 plasmids. The targeting relationship of miR‐124 and EGR1 was verified by the dual‐luciferase reporter gene assay. To identify the effect of miR‐124 on neuron activities, the viability and apoptosis of hippocampal neurons were assessed. In response to isoflurane exposure, miR‐124 expression was reduced and EGR1 expression was increased in the hippocampal tissues and neurons. The isoflurane anesthesia damaged rats' spatial learning and memory ability, and reduced viability, and promoted apoptosis of hippocampal neurons. EGR1 was targeted and negatively regulated by miR‐124. The treatment of miR‐124 agomir improved rats' spatial learning and memory ability and notably increased hippocampal neuron viability and resistance to apoptosis, corresponding to an increased brain‐derived neurotrophic factor (BDNF) expression, inhibited expression of proapoptotic factors (cleaved‐Caspase‐3 and Bax), and enhanced the expression of antiapoptotic factor (Bcl‐2). Upregulated miR‐124 inhibited the expression of EGR1, by which mechanism miR‐124 reduced the neurological deficits induced by isoflurane in neonatal rats through inhibiting apoptosis of hippocampal neurons.
Melatonin: A new inhibitor agent for cervical cancer treatment
Authors: Shafabakhsh Rana , Reiter Russel J. , Mirzaei Hamed , Teymoordash Somayyeh Noei , Asemi Zatollah
Published: May 2019

Cervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms.
STAT3 directly regulates NKp46 transcription in NK cells of HBeAg-negative CHB patients
Authors: Zheng Bingqing , Yang Yinli , Han Qiuju , Yin Chunlai , Pan Zhaoyi , Zhang Jian
Published: May 2019

NK cells play an important role in early control of HBV infection. The function of NK cells is inhibited in chronic hepatitis B virus (CHB) infection, although the underlying mechanism remains unknown. We found that the expression of STAT3 decreased in peripheral NK cells of CHB patients, and was associated with low levels of degranulation and IFN-γ secretion. In addition, STAT3 levels were positively correlated with cytolysis-associated molecules and antiviral cytokines, such as CD107a, granzyme B, perforin, and IFN-γ. HBsAg directly inhibited the expression and activation of STAT3 in NK cells, and knocking down STAT3 expression in NK cells inhibited proliferation, decreased cyclin d1 levels, and suppressed responsiveness to IL-21 stimulation. Furthermore, STAT3 directly bound to the promoter of NKp46, an important activating receptor of NK cells, to regulate its transcription and expression. Taken together, our findings indicate that STAT3 is an important positive regulator of NK cells, and provide a new mechanism of NK cell dysfunction in CHB.
Kinetics of oxidation of benzyl alcohols with molecular oxygen catalyzed by N‐hydroxyphthalimide: Role of hydroperoxyl radicals
Authors: Opeida I. A. , Sheparovych R. B. , Hrynda Yu. M. , Khavunko O. Yu. , Kompanets M. O. , Shendryk A. N.
Published: May 2019

A kinetic study of the initiated oxidation of benzyl alcohol and cumene by molecular oxygen was performed. The oxidation rate was more enhanced with N‐hydroxyphthalimide (NHPI) in the case of cumene than that of benzyl alcohol. HOOH inhibits cumene oxidation and does not affect the rate of oxidation of benzyl alcohol. It was shown that termination chain reactions of phthalimid‐N‐oxyl radicals (PINO•) does not occur with RОО• and proceeds with HOO•. A kinetic scheme of the process and an equation describing the kinetics of oxidation of benzyl alcohol in the presence of NHPI are proposed. Using the PM7 method, the thermodynamic characteristics of elementary steps of oxidation explaining the obtained results were calculated.
Kinetics of esterification of the levulinic acid with n‐hexanol, n‐octanol, and n‐decanol in the presence of dodecatungstophosphoric acid as a catalyst
Authors: Hamryszak Łukasz , Grzesik Mirosław
Published: May 2019

Levulinic acid was esterified with n‐hexanol, n‐octanol, and n‐decanol at 393–413 K and at molar ratios of between 3:1 and 10:1 (alcohol: acid) in the presence of the dodecatungstophosphoric acid (H3PW12O40) as catalyst (0.1 wt%) to study the reaction kinetics. The results of such study are the precise form of kinetic equation, which is indispensable in design and optimization of industrial‐scale chemical reactors. The authors stated that reactions were of second order and that the activation energy (E) decreased from 66 to 53 kJ/mol in the following alcohol sequence: n‐hexanol > n‐octanol > n‐decanol.
Medium‐Bandgap Conjugated Polymer Donors for Organic Photovoltaics
Authors: Sun Liya , Xu Xiangfei , Song Shan , Zhang Yangqian , Miao Chunyang , Liu Xiang , Xing Guichuan , Zhang Shiming
Published: May 2019

Recently, an increasing number of researchers have begun to focus on developing nonfullerene acceptors, so it is very important to synthesize new polymers that are compatible with nonfullerene acceptors. Besides, wide‐ or medium‐bandgap polymer donors could be better to match narrow nonfullerene acceptors. The design of medium‐bandgap (MBG) polymer donors and their application in organic photovoltaics (OPVs) play an important part in the improvement of OPV device performance. This review summarizes the photovoltaic performance of MBG polymers that have been reported during the last decade. Furthermore, their structure–property relationships and device performance are discussed. On the basis of analyzing many polymer structures, guidance toward the design of novel photovoltaic materials might be helpful to understand the basic OPV mechanism and the path towards commercialization.
Genetic testing becoming critical for patients, clinicians
Authors: Canady Valerie A.
Published: May 2019

Information to help clinicians determine which medications or other treatment options for various mental health conditions are better suited for patients based on their genetics is continuing to gain traction in the field.
Reliability of tumor segmentation in glioblastoma: Impact on the robustness of MRI‐radiomic features
Authors: Tixier Florent , Um Hyemin , Young Robert J , Veeraraghavan Harini
Published: May 2019

Purpose

The use of radiomic features as biomarkers of treatment response and outcome or as correlates to genomic variations requires that the computed features are robust and reproducible. Segmentation, a crucial step in radiomic analysis, is a major source of variability in the computed radiomic features. Therefore, we studied the impact of tumor segmentation variability on the robustness of MRI radiomic features.

Method

Fluid‐attenuated inversion recovery (FLAIR) and contrast‐enhanced T1‐weighted (T1WICE) MRI of 90 patients diagnosed with glioblastoma were segmented using a semiautomatic algorithm and an interactive segmentation with two different raters. We analyzed the robustness of 108 radiomic features from five categories (intensity histogram, gray‐level co‐occurrence matrix, gray‐level size‐zone matrix (GLSZM), edge maps, and shape) using intra‐class correlation coefficient (ICC) and Bland and Altman analysis.

Results

Our results show that both segmentation methods are reliable with ICC ≥ 0.96 and standard deviation (SD) of mean differences between the two raters (SDdiffs) ≤ 30%. Features computed from the histogram and co‐occurrence matrices were found to be the most robust (ICC ≥ 0.8 and SDdiffs ≤ 30% for most features in these groups). Features from GLSZM were shown to have mixed robustness. Edge, shape, and GLSZM features were the most impacted by the choice of segmentation method with the interactive method resulting in more robust features than the semiautomatic method. Finally, features computed from T1WICEand FLAIR images were found to have similar robustness when computed with the interactive segmentation method.

Conclusion

Semiautomatic and interactive segmentation methods using two raters are both reliable. The interactive method produced more robust features than the semiautomatic method. We also found that the robustness of radiomic features varied by categories. Therefore, this study could help motivate segmentation methods and feature selection in MRI radiomic studies.
Ultra‐low‐dose PET reconstruction using generative adversarial network with feature matching and task‐specific perceptual loss
Authors: Ouyang Jiahong , Chen Kevin T. , Gong Enhao , Pauly John , Zaharchuk Greg
Published: May 2019

Purpose

Our goal was to use a generative adversarial network (GAN) with feature matching and task‐specific perceptual loss to synthesize standard‐dose amyloid Positron emission tomography (PET) images of high quality and including accurate pathological features from ultra‐low‐dose PET images only.

Methods

Forty PET datasets from 39 participants were acquired with a simultaneous PET/MRI scanner following injection of 330 ± 30 MBq of the amyloid radiotracer 18F‐florbetaben. The raw list‐mode PET data were reconstructed as the standard‐dose ground truth and were randomly undersampled by a factor of 100 to reconstruct 1% low‐dose PET scans. A 2D encoder‐decoder network was implemented as the generator to synthesize a standard‐dose image and a discriminator was used to evaluate them. The two networks contested with each other to achieve high‐visual quality PET from the ultra‐low‐dose PET. Multi‐slice inputs were used to reduce noise by providing the network with 2.5D information. Feature matching was applied to reduce hallucinated structures. Task‐specific perceptual loss was designed to maintain the correct pathological features. The image quality was evaluated by peak signal‐to‐noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) metrics with and without each of these modules. Two expert radiologists were asked to score image quality on a 5‐point scale and identified the amyloid status (positive or negative).

Results

With only low‐dose PET as input, the proposed method significantly outperformed Chen et al.'s method (Chen et al. Radiology. 2018;290:649–656) (which shows the best performance in this task) with the same input (PET‐only model) by 1.87 dB in PSNR, 2.04% in SSIM, and 24.75% in RMSE. It also achieved comparable results to Chen et al.'s method which used additional magnetic resonance imaging (MRI) inputs (PET‐MR model). Experts' reading results showed that the proposed method could achieve better overall image quality and maintain better pathological features indicating amyloid status than both PET‐only and PET‐MR models proposed by Chen et al.

Conclusion

Standard‐dose amyloid PET images can be synthesized from ultra‐low‐dose images using GAN. Applying adversarial learning, feature matching, and task‐specific perceptual loss are essential to ensure image quality and the preservation of pathological features.
Dude, Where's my Transmitter? Probability of Radio Transmitter Detections and Locational Errors for Tracking River Fish
Authors: Watkins Owen B. , Paul Andrew J. , Spencer Stephen C. , Sullivan Michael G. , Foote Lee
Published: May 2019

To simulate radio-location tracking of fish in a lotic system, we deployed 148-MHz radio transmitters and measured signals from three altitudes over a known location. We examined detection distance, location error, and detection probability for two transmitter types at seven transmitter depths. We found that transmitter type, altitude, flight direction, and depth affected both detectability of transmitters and accuracy of locations. Maximum observed detection distance was 5,614 m for the small-type transmitters at an altitude of 300 and 14,508 m for large-type transmitters at an altitude of 600 m. Detection distances declined rapidly with increasing transmitter depth for both transmitter types. Locational errors ranged from 8 to 842 m (x¯ = 177 m; SE = 15.2) and were biased with flight direction. Detection probabilities declined with increasing transmitter depth and with increasing number of scanned frequencies. Scanning five frequencies, at the optimal flight altitude for a given transmitter type, resulted in nearly a 50% loss of detection probability at a 5-m depth and a 90% decrease at a 7-m depth. We recommend that researchers model their probability of detection a priori, all transmitters transmit on a single frequency, and a receiver altitude of 300 m should be maintained.
The difficult challenge of modelling the non‐linear elastic behaviour of soils within a theoretically sound framework
Authors: Lagioia Rocco , Panteghini Andrea
Published: May 2019

Hypo‐elastic relations are often adopted to simulate the recoverable non‐linear behaviour of soils within elasto‐plastic constitutive models. In reality, they are unable to reproduce the elastic, ie, recoverable, response of materials; hence, they introduce severe inconsistencies in models based on the decomposition of the total strain tensor into its recoverable and permanent parts. Hyper‐elasticity should then be used. However, existing models developed within this framework do not satisfy a number of fundamental theoretical requirements. A new hyper‐elastic model is proposed, which is rigourously formulated by integrating some of the main relations which emerge from experimental results. The model satisfies all theoretical requirements and also possesses features that are fundamental for its numerical integration. The model can be considered as the correct hyper‐elastic version of the classical hypo‐elastic constitutive relation adopted in models based on the Critical State framework, such as the Modified Cam‐Clay, with a constant Poisson's ratio.
A tool for empirical equipoise assessment in multigroup comparative effectiveness research
Authors: Yoshida Kazuki , Solomon Daniel H. , Haneuse Sebastien , Kim Seoyoung C. , Patorno Elisabetta , Tedeschi Sara K. , Lyu Houchen , Hernández‐Díaz Sonia , Glynn Robert J.
Published: May 2019

Purpose

In observational research, equipoise concerns whether groups being compared aresimilar enoughfor valid inference.Empirical equipoisewas previously proposed as a tool to assess patient similarity based on propensity scores (PS). We extended this work for multigroup observational studies.

Methods

We modified the tool to allow for multinomial exposures such that the proposed definition reduces to the original when there are only two groups. We illustrated how the tool can be used as a method to assess study design within three‐group clinical examples. We then conducted three‐group simulations to assess how the tool performed in a setting with residual confounding after PS weighting.

Results

In a clinical example based on rheumatoid arthritis, 44.5% of the sample fell within the region of empirical equipoise when considering first‐line biologics, whereas 57.7% did so for second‐line biologics, consistent with the expectation that a second‐line design results in better equipoise. In a simulation where the unmeasured confounder had the same magnitude of association with the treatment as the measured confounders and a 25% greater association with the outcome, the tool crossed the proposed threshold for empirical equipoise at a residual confounding of 20% on the ratio scale. When the unmeasured variable had a twice larger association with treatment, the tool became less sensitive and crossed the threshold at a residual confounding of 30%.

Conclusion

Our proposed tool may be useful in guiding cohort identification in multigroup observational studies, particularly with similar effects of unmeasured and measured covariates on treatment and outcome.
Adverse drug reaction reporting by community pharmacists—The barriers and facilitators
Authors: Hughes Mary Louise , Weiss Marjorie
Published: May 2019

Purpose

The United Kingdom's “Yellow Card Scheme” for reporting of adverse drug reactions (ADRs) has been operating for 50 years, but reporting rates by community pharmacists remain low. The aim of the study was therefore to investigate the views and experiences of ADR reporting by community pharmacists in Wales, with a particular focus on the potential barriers and facilitators to reporting.

Methods

Following ethics approval and piloting, a self‐complete questionnaire was mailed to all registered community pharmacies in Wales, UK (n = 713). A follow‐up mailing was sent to nonresponders after 2 weeks.

Results

A response rate of 52% (n = 372) was achieved, of whom 57% had never submitted a yellow card. Key barriers to reporting were not seeing ADRs, difficulty identifying the causative drug, not being sure which ADRs to report, and lack of time. Key facilitators were being able to report through dispensary software and having clearer guidelines about what to report. Differences between those who had previously reported ADRs and those who had not suggested lack of confidence and uncertainty about what to report were more of a barrier for nonreporters. Conversely, reporters wanted feedback on reports, ability to keep reports on their dispensary records, and remuneration to aid them with reporting.

Conclusions

While the respondents generally expressed positive attitudes towards ADR reporting, a number of barriers and potential facilitators were nevertheless identified. Clearer support and guidance for reporting, such as through a “champions” scheme similar to that run in Welsh hospitals, may help current nonreporters to engage.