bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease
Authors: Davies Danielle S. , Ma Jolande , Jegathees Thuvarahan , Goldsbury Claire 
Published: November 2016

AbstractChanges in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52–98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged‐matched control microglia. In AD cases, on average, 49%–64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged‐matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging‐related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural‐glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease.
A novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes
Authors: Kindt Frances , Hammer Elke , Kemnitz Stefan , Blumenthal Antje , Klemm Paul , Schlüter Rabea , Quaggin Susan E , van den Brandt Jens , Fuellen Georg , Völker Uwe , Endlich Karlhans , Endlich Nicole 
Published: November 2016

Background and PurposeTherapeutic options for treating glomerulopathies, the main cause of chronic kidney disease, are limited. Podocyte dedifferentiation is a major event in the pathogenesis of glomerulopathies. The goal of the present study was, therefore, to develop an assay to monitor podocyte differentiation suitable for compound screening.Experimental ApproachWe isolated and cultured glomeruli from transgenic mice, expressing cyan fluorescent protein (CFP) under the control of the promoter of nephrin, a marker of podocyte differentiation. Mean CFP fluorescence intensity per glomerulus (MFG) was determined by summation of all glomerular voxels from confocal z‐stacks in the absence and presence of pharmaceutical compounds.Key ResultsIn untreated cultured glomeruli, MFG remained fairly stable during the first 5 days, when foot processes were already effaced, and the level of many podocyte‐specific proteins was only mildly affected, as revealed by proteomics. Between day 6 and 9, MFG decreased to almost zero. The decrease in MFG was paralleled by a decrease in CFP and nephrin expression, as determined by RT‐PCR, western blots and proteomics. Puromycin aminonucleoside (PAN), which damages podocytes, concentration‐dependently induced a complete loss of MFG. Dexamethasone (25 μM) and pioglitazone (10 μM) markedly attenuated the effect of 0.6 μg·mL−1 PAN on MFG.Conclusion and ImplicationsIn summary, we established a novel assay to assess the effect of pharmaceutical compounds on the differentiation of podocytes in situ. Our assay is suitable for compound screening to identify drugs for the treatment of glomerulopathies.
Afzelin ameliorates D‐galactosamine and lipopolysaccharide‐induced fulminant hepatic failure by modulating mitochondrial quality control and dynamics
Authors: Lee Sang‐Bin , Kang Jung‐Woo , Kim So‐Jin , Ahn Jongmin , Kim Jinwoong , Lee Sun‐Mee 
Published: November 2016

Background and PurposeFulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti‐inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D‐galactosamine (GalN)/LPS induced FHF, particularly focusing on mitochondrial quality control and dynamics.Experimental ApproachMice were administered afzelin i.p. 1 h before receiving GalN (800 mg·kg−1)/LPS (40 μg·kg−1), and they were then killed 5 h after GalN/LPS treatment.Key ResultsAfzelin improved the survival rate and reduced the serum levels of alanine aminotransferase and pro‐inflammatory cytokines in GalN/LPS‐treated mice. Afzelin attenuated the mitochondrial damage, as indicated by diminished mitochondrial swelling and mitochondrial glutamate dehydrogenase activity in GalN/LPS‐treated mice. Afzelin enhanced mitochondrial biogenesis, as indicated by increased levels of PPAR‐γ coactivator 1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. Afzelin also decreased the level of mitophagy‐related proteins, parkin and PTEN‐induced putative kinase 1. Furthermore, while GalN/LPS significantly increased the level of fission‐related protein, dynamin‐related protein 1, and decreased the level of fusion‐related protein, mitofusin 2; these effects were attenuated by afzelin.Conclusions and ImplicationsOur findings demonstrated that afzelin protects against GalN/LPS‐induced liver injury by enhancing mitochondrial biogenesis, suppressing excessive mitophagy and balancing mitochondrial dynamics.
Flower‐visiting bat species contribute unequally toward agricultural pollination ecosystem services in southern Thailand
Authors: Stewart Alyssa B. , Dudash Michele R. 
Published: November 2016

AbstractThe large majority of angiosperm species depend on animals for pollination, including many agricultural crops, and plant‐pollinator interactions have been extensively studied. However, not all floral visitors actually transfer pollen, and efforts to distinguish true pollinators from mere visitors are particularly scarce among the bat pollination literature. To determine whether Old World bat species are equally effective pollinators in mixed‐agricultural areas of southern Thailand, we examined six night‐blooming plant taxa and quantified pollinator importance (PI) of seven common nectarivorous bat species. PI was calculated as the product of nightly bat visitation rate (obtained from mist‐netting data) and pollen transfer efficiency (estimated from bat pollen loads). We found that PI varied by both bat species and plant species. In general, the nectar‐specialist bat species were more important pollinators, yet their order of importance differed across our focal plant species. In addition, PI was dictated more by pollen transfer effectiveness than visitation rate. Our findings highlight the importance of Old World bat pollinators within southern Thailand's mixed‐agricultural landscape and illustrate how seemingly similar floral visitors can have very different contributions toward plant pollination success.
Affective Parenting Behaviors, Adolescent Depression, and Brain Development: A Review of Findings From the Orygen Adolescent Development Study
Authors: Schwartz Orli S. , Simmons Julian G. , Whittle Sarah , Byrne Michelle L. , Yap Marie B. H. , Sheeber Lisa B. , Allen Nicholas B. 
Published: November 2016

AbstractParenting plays a multifaceted role in adolescent development. In this article, we review studies based on an observational assessment of affective parenting behaviors collected as part of the longitudinal Orygen Adolescent Development Study and explore three ways that parenting may predict adolescent‐onset depression. Specifically, we review findings that observed affective parental behaviors prospectively predict depressive symptoms and the onset of depressive disorder, predict adolescent depression indirectly via emotion regulation, and interact with brain development to predict adolescent depression. Parents who express higher frequencies of aggression or lower frequencies of positivity, or who are more likely to respond negatively to their adolescents’ positive and aggressive behaviors, tend to have adolescents at greater risk for depression and suboptimal brain development. Accounting for the direct, indirect, and moderating effects of parenting may enable us to characterize more accurately the trajectories of adolescent development, which can inform prevention and early intervention efforts.
Longitudinal Changes in Social Brain Development: Processing Outcomes for Friend and Self
Authors: Braams Barbara R. , Crone Eveline A. 
Published: November 2016

Adolescence is an important time for social development during which friendships become more intimate and complex. In this functional magnetic resonance imaging (fMRI) study we tested how outcomes for friends are processed on the neural level across adolescence. Participants between 8 and 27 years of age were tested twice with a 2‐year difference between the first (N = 299) and second (N = 254) time points. Participants performed a task in which they could win and lose money for themselves and their best friend. Mixed linear models revealed a linear decrease in activity in social brain regions for friend > self over development. These results confirm changes in the social brain network across adolescent development, we further show that individual differences are related to these neural changes.
Cost‐effectiveness analysis of the atraumatic restorative treatment‐based approach to managing early childhood caries
Authors: Tonmukayakul Utsana , Arrow Peter 
Published: November 2016

AbstractObjectivePaediatric dental care under general anaesthesia among preschool children in Western Australia is increasing and costly. This study assessed cost‐effectiveness of the atraumatic restorative treatment‐based (ART‐based) approach against the standard care (SC) approach to managing early childhood caries in a primary care setting based on a 1‐year pragmatic randomized controlled trial.MethodsCost‐effectiveness analysis, from the service provider perspective, was conducted. Outcomes include number of referral to specialists and dental treatments. One‐way and probabilistic sensitivity analyses were undertaken to test the robustness of the cost‐effectiveness estimates.ResultsSix children in theART‐based group and 62 children in theSCgroup (n= 127 each group) were referred for paediatric dental specialist care. Children in theART‐based group received more dental services than those allocated to theSCgroup (mean = 3.8,SD2.0 and mean = 1.8,SD1.8, respectively, Wilcoxon rank‐sum test,P< 0.01). Total costs of theART‐based approach and theSCgroup were $137 860 and $178 217, respectively. Based on probabilistic sensitivity analysis, $654 was saved per referral to specialist avoided and $36 was saved per additional dental treatment. The probability that theART‐based approach is cost‐saving was 63%. Specialist dental treatment fees had a big impact on the cost‐effectiveness estimates.ConclusionTheART‐based approach appears to be a worthwhile intervention because it resulted in fewer referred cases and enabled more treatments to be provided with cost‐savings.
The effect of intranasal sodium citrate on olfaction in post‐infectious loss: results from a prospective, placebo‐controlled trial in 49 patients
Authors: Whitcroft K.L. , Ezzat M. , Cuevas M. , Andrews P. , Hummel T. 
Published: November 2016

ObjectivesFree calcium plays an integral role in peripheral olfactory processing, including feedback inhibition. It has therefore been suggested that reduction of intranasal free calcium with buffer solutions such as sodium citrate may improve olfactory function in patients with smell impairment. Several previous studies have supported this hypothesis, particularly in post‐infectious olfactory loss. We therefore aimed to determine whether treatment with intranasal sodium citrate improves olfactory function in patients with post‐infectious impairment.DesignProspective, single‐blind, placebo‐controlled trial.SettingInterdisciplinary Smell and Taste Clinic, TU Dresden (tertiary referral centre).ParticipantsForty‐nine adult participants with post‐infectious olfactory impairment (M : F = 11 : 38, mean age 58.71 ± 11.03 years).Main outcome measuresOlfactory function (odour threshold and identification) before and after treatment as determined using “Sniffin' Sticks”. Patients were treated monorhinally with 1 mL sodium citrate solution. The contralateral nasal cavity was treated with 1 mL physiological sodium chloride solution, which acted as internal control. Clinical improvement was assumed where threshold or identification score increased by ≥2.5 or 3 points, respectively, or ≥5.5 points together.ResultsWe demonstrated a statistically significant improvement in composite threshold + identification scores following treatment with sodium citrate, compared with placebo. This was true for all patients (mean improvement 0.87 ± 2.68 points, P = 0.04), and on subgroup analysis in those with hyposmia (mean improvement 1.15 ± 2.37 points, P = 0.02). However, the effect size did not reach clinical significance.ConclusionsFurther basic and clinical work is required to fully delineate the effect of intranasal sodium citrate in the treatment of post‐infectious olfactory loss.
Newborn hearing screening in prematurity: fate of screening failures and auditory maturation
Authors: Yang H.C. , Sung C.M. , Shin D.J. , Cho Y.B. , Jang C.H. , Cho H.‐H. 
Published: November 2016

ObjectivesThe purpose of this study was to identify delayed auditory maturation and the fate of premature infants who failed the newborn hearing screening (NHS) in neonatal intensive care unit.Materials and methodsA total of 1375 neonates underwent NHS using the transient evoked otoacoustic emission (TEOAE) in a tertiary hospital between 2007 and 2010 according to the Joint Committee on Infant Hearing guidelines. In addition, a structured telephone survey was given to caregivers of infants who were lost to follow‐up NHS. Auditory steady‐state response (ASSR) threshold and the threshold change in diagnostic test failures were analysed.ResultAmong the 1375 NICU babies, 344 (25.0%) babies, 111 (9.7%) babies and 64 (4.6%) babies failed to pass the first TEOAE, second TEOAE and diagnostic ASSR, respectively. However, at the age of about 5 years, 12 (0.9%) infants showed permanent hearing loss (PHL). The ASSR threshold improved from 69.0 ± 19.7 dB to 52.9 ± 21.6 dB in <4 months (P < 0.001). Premature infants of <29 weeks of gestational age at birth showed higher referral (P = 0.003) rate at the first OAE test compared to the others, and the difference continued until the last follow‐up. The odds ratio for the initial ASSR threshold >67.5 dB for PHL was 9.00 (95% confidence interval, 1.7–46.7).ConclusionMost of first TEOAE screening failures (91.3%) showed normal hearing and speech development. Hearing levels in premature infants can improve over time, particularly in neonates with initial ASSR threshold <67.5 dB.
Significance of epidermal mitoses in challenging melanocytic proliferations
Authors: Minca Eugen C. , Billings Steven D. , Elson Paul , Tetzlaff Michael T. , Andea Aleodor A. , Ko Jennifer S. 
Published: November 2016

BackgroundAccurate diagnosis of melanoma remains histologically challenging. Dermal mitoses support malignancy, but are only occasionally seen in melanomas. As melanomagenesis is thought to begin at the dermal‐epidermal junction, we investigated the significance of epidermal melanocytic mitoses (EMM) in a spectrum of lesions with molecular characterization.MethodsEpidermal mitoses density (EMD) was evaluated in 46 straightforward lesions (24 benign and 22 malignant) and 30 challenging lesions with expert interpretation, fluorescence in situ hybridization and myPath‐score characterization (12 favor‐benign, 9 favor‐malignant and 9 ambiguous). EMD was correlated with clinicopathologic parameters and myPath.ResultsIn straightforward cases, 25% nevi and 77% melanomas had EM. Median EMD was significantly lower in nevi vs. melanomas (0/mm vs. 0.04/mm, p = 0.001). EMD (0.01/mm‐cutoff) had 77% sensitivity, 79% specificity discriminating melanomas from nevi. In challenging cases, 17% favor‐benign, 67% favor‐malignant and 78% ambiguous lesions had EM. EMD (0.01/mm‐cutoff) had 67% sensitivity, 82% specificity on 21 non‐ambiguous lesions, similar to myPath. EMD was less accurate in Spitzoid lesions, which have high EMD and dermal mitoses.ConclusionWhile EMD is not an adequate single criterion in diagnosing melanoma, our results validate its discriminatory potential, suggesting that EM should prompt closer investigation for malignancy. Expanded studies with clinical follow up are warranted to further assess the EM utility in classifying melanocytic lesions.
Changing Comparative Advantage, Real Exchange Rate Impact and Sino–Japanese Trade Fluctuations
Authors: Qiu Bin , Wu Feifei , Tang Baoqing , Liu Xiuyan 
Published: November 2016

AbstractChina, as an important source country in the global value chain, especially in the East Asian production networks, has exerted significant influence on Sino–Japanese trade fluctuations. This paper explores the real factors that lead to the fluctuations in Sino–Japanese trade. Using the Hodrick–Prescott filter technique and OECD–WTO Statistics on Trade in Value Added from 1995 to 2011, the impact of the changing comparative advantage between the two countries is also examined. The empirical results indicate that determinants of the fluctuations in Sino–Japapese trade include changing comparative advantages, the volatility of the real exchange rate and quite a few external shocks. Some policy suggestions are put forward in regards to the stability of trade between the two countries.
China's Anti‐dumping Problems and Mitigation through Regional Trade Agreements
Authors: Sun Yanlin , Whalley John 
Published: November 2016

AbstractThe present paper explores the opportunities for China's regional trade agreement (RTA) initiatives to mitigate its anti‐dumping problems. The paper highlights the severity and discriminatory nature of China's anti‐dumping problems. The high concentration of the share of anti‐dumping actions taken by the top 4 and top 8 anti‐dumping initiators is noted. Our finding of a weak effect of existing RTAs on mitigating China's anti‐dumping problems supports the argument that China could become more active in mitigating anti‐dumping problems through RTA negotiations. An RTA can include a higher level of openness in exchange for an improvement in regional anti‐dumping provisions. Case studies on RTAs involving the EU, the USA and India offer some precedents for offering inducements and modifying regional anti‐dumping provisions. The approaches for China may lie in obtaining market economy status from intensive anti‐dumping initiators at RTA levels and also altering regional anti‐dumping provisions that could be put in place in exchange for some potential concessions.
Change in pain status in children with cerebral palsy
Authors: Christensen Rhandi , MacIntosh Alexander , Switzer Lauren , Fehlings Darcy 
Published: November 2016

AimTo identify factors associated with a change in pain over time in children with cerebral palsy (CP).MethodPain was assessed at two time‐points by physicians and caregiver‐rated Health Utilities Index 3 (HUI3) pain scores.ResultsOne hundred and forty‐eight children out of 179 approached from outpatient clinics (83% response; 104 males, 44 females mean age 8y 8mo, range 3y–16y) across all Gross Motor Function Classification System (GMFCS) levels were included. Fifty‐five percent had changes in caregiver‐reported HUI3 pain. A backward stepwise multiple linear regression retained HUI3 pain score at visit 1 and GMFCS level (F[2,144]=23.40, R2=0.35; p<0.001) as variables associated with a change in pain status (HUI3 pain at visit 1: β=0.61, p<0.001; GMFCS level: β=−0.17, p<0.015). The association between HUI3 pain at visit 1 and GMFCS level was significant (β=−0.15, p<0.036). There was an association between pain etiology and pain trajectory (F[3,144]=5.39, p=0.002). Post‐hoc testing revealed musculoskeletal pain had the greatest improvements compared with the no pain group (p=0.006).InterpretationChildren with CP with more severe initial pain and higher gross motor function have lower pain at follow‐up indicating an improvement in pain status over time.
Sustained influence of metformin therapy on circulating glucagon‐like peptide‐1 levels in individuals with and without type 2 diabetes
Authors: Preiss David , Dawed Adem , Welsh Paul , Heggie Alison , Jones Angus G. , Dekker Jacqueline , Koivula Robert , Hansen Tue H. , Stewart Caitlin , Holman Rury R. , Franks Paul W. , Walker Mark , Pearson Ewan R. , Sattar Naveed ,   the DIRECT consortium group
Published: November 2016

AimsTo investigate, in the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) trial (NCT00723307), whether the influence of metformin on the glucagon‐like peptide (GLP)‐1 axis in individuals with and without type 2 diabetes (T2DM) is sustained and related to changes in glycaemia or weight, and to investigate basal and post‐meal GLP‐1 levels in patients with T2DM in the cross‐sectional Diabetes Research on Patient Stratification (DIRECT) study.Materials and methods
CAMERA was a double‐blind randomized placebo‐controlled trial of metformin in 173 participants without diabetes. Using 6‐monthly fasted total GLP‐1 levels over 18 months, we evaluated metformin's effect on total GLP‐1 with repeated‐measures analysis and analysis of covariance. In the DIRECT study, we examined active and total fasting and 60‐minute post‐meal GLP‐1 levels in 775 people recently diagnosed with T2DM treated with metformin or diet, using Student's t‐tests and linear regression.ResultsIn CAMERA, metformin increased total GLP‐1 at 6 (+20.7%, 95% confidence interval [CI] 4.7‐39.0), 12 (+26.7%, 95% CI 10.3‐45.6) and 18 months (+18.7%, 95% CI 3.8‐35.7), an overall increase of 23.4% (95% CI 11.2‐36.9;
P
< .0001) vs placebo. Adjustment for changes in glycaemia and adiposity, individually or combined, did not attenuate this effect. In the DIRECT study, metformin was associated with higher fasting active (39.1%, 95% CI 21.3‐56.4) and total GLP‐1 (14.1%, 95% CI 1.2‐25.9) but not post‐meal incremental GLP‐1. These changes were independent of potential confounders including age, sex, adiposity and glycated haemoglobin.ConclusionsIn people without diabetes, metformin increases total GLP‐1 in a sustained manner and independently of changes in weight or glycaemia. Metformin‐treated patients with T2DM also have higher fasted GLP‐1 levels, independently of weight and glycaemia.