bluuebunny/crossref_metadata_2025 huggingface dataset:
First evidence of Beauvais’ hypothesis in a plant model
Authors: Gleiss Andreas , Kratky Karl Wilhelm , Frass Michael , Thieves Karin
Published: July 2016

Introduction:
Beauvais presented the application of a so-called ‘quantum-like model of homeopathy’ by introducing the idea of a type of randomization/unblinding which he called ‘in situ’. He predicted that randomized studies based on this type of randomization/unblinding lead to more pronounced effects in placebo controlled randomized homeopathic trials. We designed an experiment regarding wheat germination and stalk length to investigate Beauvais’ idea of ‘in situ randomization/unblinding’ using a homeopathic dilution of sulphur (LM VI) as compared to placebo as well as to water.

Aim and method:
The primary aim of this double-blind randomized controlled experiment was to investigate whether there are differences of ‘in situ randomization/unblinding’ vs ‘central randomization/unblinding’ with respect to the effect of a homeopathic substance compared to placebo. The secondary aim of our study was to examine possible differences between the sulphur and the placebo group in the ‘in situ’ arm regarding germination and/or stalk growth of wheat seedlings measured after a seven days exposure. Wheat was treated either with sulphur LM VI, placebo, or water. The wheat grains were placed on glass lids and treatment was performed following the ‘in situ randomization/unblinding’ as well as ‘central randomization/unblinding’ method. Germination was measured and classified into three categories.

Results:
Under ‘in situ’ randomization/unblinding the odds of a seed not to germinate is 40% lower if treated with sulphur compared to placebo (p = 0.004). In contrast, these odds are practically equal in the ‘central’ meta-group (OR = 1.01, p = 0.954). Under ‘in situ’ randomization/unblinding the odds of a seed to germinate with a length ≥1 mm is practically equal if treated with sulphur or with placebo (OR = 0.96, p = 0.717). In contrast, these odds are 21% higher under sulphur compared to placebo in the ‘central’ meta-group (OR = 1.21, p = 0.062). In summary, we found a sulphur effect that is significantly different between ‘in situ’ and ‘central’ randomization/unblinding relating to all three stages of germination.
Fertility of patients with polycystic ovary syndrome undergoing in vitro fertilization by age
Authors: Hwang Yu‐Im , Cha Sun‐Wha , Song In‐Ok , Yang Kwang‐Moon , Min Eung‐Gi , Kim Hye‐Ok
Published: July 2016

Objective

To evaluate outcomes of in vitro fertilization (IVF) among patients with polycystic ovary syndrome (PCOS) by age.

Methods

In a retrospective study, data were retrieved for patients with PCOS (Rotterdam 2003 criteria) and individuals with tubal factor infertility who underwent IVF at a center in Seoul, South Korea, between January 2003 and August 2012. IVF outcomes were compared by age group (A: 30–32 years; B: 33–35 years; C: 36–38 years; D: 39–41 years).

Results

The analysis included 307 women with PCOS and 364 with tubal factor infertility. There was a significant difference between women with PCOS and those with tubal infertility factor in the live birth rate in group B (41.3% vs 28.6%, P = 0.038) and in group C (40.4% vs 15.1%, P = 0.002). Among women with PCOS, no significant differences in number of retrieved oocytes were observed between the age groups (18.8 ± 9.6, 19.1 ± 10.0, 17.7 ± 7.5, and 17.0 ± 13.8). However, the clinical pregnancy rate was significantly lower in group D than in group C (47.2% vs 18.8%, P = 0.042).

Conclusion

Fertility in patients with PCOS was maintained until age 38 years using IVF. Thereafter, the pregnancy rate decreased, although the number of oocytes retrieved by IVF remained stable.
Sleep disorders in children with chronic kidney disease
Authors: Darwish Amira H. , Abdel-Nabi Hend
Published: July 2016

Background and Objectives:

This case-control study assessed the prevalence of sleep disorders among Egyptian children with chronic kidney disease (CKD), either maintained or not maintained on hemodialysis (HD), and compared them with healthy age and sex-matched children.

Patients and methods:

The total study population included 95 children, 54 of whom were CKD patients, 22 maintained on HD and 32 not maintained on HD; 41 healthy children of matched age and sex composed the control group.

Subjective impairment of sleep quality was assessed using the Arabic version of the Children's Sleep Habits Questionnaire (CSHQ). Daytime sleepiness and restless leg syndrome (RLS) were assessed using a pediatric modification of the Epworth sleepiness scale (ESS) and RLS Questionnaire, respectively.

Results:

Sleep disturbances were detected in 75.9% of the studied children with CKD: 81.8% in children with CKD undergoing dialysis, and 71.8% in children with CKD not on dialysis. Excessive daytime sleepiness (EDS) and RLS symptoms were reported in 22% and 20.4% of the studied children with CKD, respectively.

Conclusions:

Sleep disturbances are very common among children with CKD. Sleep disturbances in patients with CKD include restless legs syndrome (RLS), excessive daytime sleepiness (EDS), sleep-disordered breathing (SDB), behavioral insomnias, and parasomnias.
Gravito-inertial waves in a differentially rotating spherical shell
Authors: Mirouh G. M. , Baruteau C. , Rieutord M. , Ballot J.
Published: July 2016

The gravito-inertial waves propagating over a shellular baroclinic flow inside a rotating spherical shell are analysed using the Boussinesq approximation. The wave properties are examined by computing paths of characteristics in the non-dissipative limit, and by solving the full dissipative eigenvalue problem using a high-resolution spectral method. Gravito-inertial waves are found to obey a mixed-type second-order operator and to be often focused around short-period attractors of characteristics or trapped in a wedge formed by turning surfaces and boundaries. We also find eigenmodes that show a weak dependence with respect to viscosity and heat diffusion just like truly regular modes. Some axisymmetric modes are found unstable and likely destabilized by baroclinic instabilities. Similarly, some non-axisymmetric modes that meet a critical layer (or corotation resonance) can turn unstable at sufficiently low diffusivities. In all cases, the instability is driven by the differential rotation. For many modes of the spectrum, neat power laws are found for the dependence of the damping rates with diffusion coefficients, but the theoretical explanation for the exponent values remains elusive in general. The eigenvalue spectrum turns out to be very rich and complex, which lets us suppose an even richer and more complex spectrum for rotating stars or planets that own a differential rotation driven by baroclinicity.
Exact solutions to non-classical steady nozzle flows of Bethe–Zel’dovich–Thompson fluids
Authors: Guardone Alberto , Vimercati Davide
Published: July 2016

Steady nozzle flows of Bethe–Zel’dovich–Thompson fluids – substances exhibiting non-classical gasdynamic behaviour in a finite vapour-phase thermodynamic region in close proximity to the liquid–vapour saturation curve – are examined. Non-classical flow features include rarefaction shock waves, shock waves with either upstream or downstream sonic states and split shocks. Exact solutions for a mono-component single-phase fluid expanding from a reservoir into a stationary atmosphere through a conventional converging–diverging nozzle are determined within the quasi-one-dimensional inviscid flow approximation. The novel analytical approach makes it possible to elucidate the connection between the adiabatic, possibly non-isentropic flow field and the underlying local isentropic-flow features, including the possible qualitative alterations in passing through shock waves. Contrary to previous predictions based on isentropic-flow inspection, shock disintegration is found to occur also from reservoir states corresponding to a single sonic point. The global layout of the flow configurations produced by a monotonic decrease in the ambient pressure, namely the functioning regime, is examined for reservoir conditions resulting in single-phase flows. Accordingly, a classification of steady nozzle flows into 10 different functioning regimes is proposed. Flow conditions determining the transition between the different classes of flow are investigated and each functioning regime is associated with the corresponding thermodynamic region of reservoir states.
Interaction forces between microfluidic droplets in a Hele-Shaw cell
Authors: Sarig I. , Starosvetsky Y. , Gat A. D.
Published: July 2016

Various microfluidic systems, such as chemical and biological lab-on-a-chip devices, involve motion of multiple droplets within an immersing fluid in shallow microchannels. Modelling the dynamics of such systems requires calculation of the forces of interaction between the moving droplets. These forces are commonly approximated by superposition of dipole solutions, which requires an assumption of sufficiently large distance between the droplets. In this work we obtain exact solutions (in the Hele-Shaw limit) for two moving droplets, and a droplet within a droplet, located within a moving immersing fluid, without limitation on the distance between the droplets. This is achieved by solution of the pressure field in a bipolar coordinate system and calculation of the force in Cartesian coordinates. Our results are compared with numerical computations, experimental data and the existing dipole-based models. We utilize the results to calculate the dynamics of a droplet within a droplet, and of two close droplets, located within an immersing fluid with oscillating speed. Overall, the obtained results establish the solid base for the rather important future extensions for modelling the complex, long-range interdroplet interactions in the limit of dense droplet media.
Molecular Line Emission Towards High-Mass Clumps: The MALT90 Catalogue
Authors: Rathborne J. M. , Whitaker J. S. , Jackson J. M. , Foster J. B. , Contreras Y. , Stephens I. W. , Guzmán A. E. , Longmore S. N. , Sanhueza P. , Schuller F. , Wyrowski F. , Urquhart J. S.
Published: July 2016

The Millimetre Astronomy Legacy Team 90 GHz survey aims to characterise the physical and chemical evolution of high-mass clumps. Recently completed, it mapped 90 GHz line emission towards 3 246 high-mass clumps identified from the ATLASGAL 870 μm Galactic plane survey. By utilising the broad frequency coverage of the Mopra telescope’s spectrometer, maps in 16 different emission lines were simultaneously obtained. Here, we describe the first catalogue of the detected line emission, generated by Gaussian profile fitting to spectra extracted towards each clumps’ 870 μm dust continuum peak. Synthetic spectra show that the catalogue has a completeness of > 95%, a probability of a false-positive detection of < 0.3%, and a relative uncertainty in the measured quantities of < 20% over the range of detection criteria. The detection rates are highest for the (1–0) transitions of HCO+, HNC, N2H+, and HCN (~77–89%). Almost all clumps (~95%) are detected in at least one of the molecular transitions, just over half of the clumps (~53%) are detected in four or more of the transitions, while only one clump is detected in 13 transitions. We find several striking trends in the ensemble of properties for the different molecular transitions when plotted as a function of the clumps’ evolutionary state as estimated from Spitzer mid-IR images, including (1) HNC is relatively brighter in colder, less evolved clumps than those that show active star formation, (2) N2H+ is relatively brighter in the earlier stages, (3) that the observed optical depth decreases as the clumps evolve, and (4) the optically thickest HCO+ emission shows a ‘blue-red asymmetry’ indicating overall collapse that monotonically decreases as the clumps evolve. This catalogue represents the largest compiled database of line emission towards high-mass clumps and is a valuable data set for detailed studies of these objects.
Temporal and Spatial Variations of Freshwater Reservoir Ages in the Loire River Watershed
Authors: Coularis C , Tisnérat-Laborde N , Pastor L , Siclet F , Fontugne M
Published: July 2016

In order to map the freshwater reservoir effect (FRE) variability of the Loire River and its tributaries, spatial and temporal carbon isotope (13C and 14C) analyses of the dissolved inorganic carbon (DIC) were conducted. Sites were selected to represent the diversity of geological settings, soil type, and land use. Results show a large spatial variability of 14C FRE ranging between 135 and 2251±30 yr, objectively correlated to DIC contents and alkalinity. Deeper investigations of the relationship between 14C activity of DIC and environmental variables show that the geological substrate is the dominant factor in the 14C reservoir effect, and far more influential than the river flow discharge.
High intake of fatty fish, but not of lean fish, affects serum concentrations of TAG and HDL-cholesterol in healthy, normal-weight adults: a randomised trial
Authors: Hagen Ingrid V. , Helland Anita , Bratlie Marianne , Brokstad Karl A. , Rosenlund Grethe , Sveier Harald , Mellgren Gunnar , Gudbrandsen Oddrun A.
Published: July 2016

The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat.
Asian snake farms: conservation curse or sustainable enterprise?
Authors: Aust Patrick W. , Van Tri Ngo , Natusch Daniel J.D. , Alexander Graham J.
Published: July 2016

Snake farming in Asia has increased over the past decade, and conservationists have expressed concerns that farms may foster overexploitation of wild populations and create legal conduits for illegally harvested wild individuals. We conducted face-to-face interviews with snake farmers in Viet Nam and China, with the aim of describing the basic models under which snakes are farmed for meat. We synthesized this information to assess the feasibility of farming snakes for human consumption, drawing conclusions about the impact of this industry on the conservation of wild snake populations. The most commonly farmed snakes include the monocled cobraNaja kaouthia, the Chinese cobraNaja atra, the oriental rat snakePtyas mucosusand the king cobraOphiophagus hannah. These species have life histories that are compatible with the demands of intensive livestock production, including early maturity, rapid growth rates, high reproductive output, efficient food assimilation rates and undemanding space requirements. Snake farmers appear to be capitalizing on the unique energy-efficiency of snakes to produce meat for human consumption. We conclude that the ease and profitability of farming snakes in China and Viet Nam make farming a viable substitute for harvesting wild snakes, with apparently minimal threat to wild populations. Snake farming offers a range of novel agricultural opportunities and has the potential to play a pivotal role in sustainable development.
Are orthographic effects language specific? The influence of second language orthography on second language phoneme awareness
Authors: PYTLYK CAROLYN
Published: July 2016

This research investigated first language (L1) and second language (L2) orthographic effects on L2 phoneme perception. Twenty-five native English learners of Russian (n = 13) and Mandarin (n = 12) participated in an auditory phoneme counting task, using stimuli organized along two parameters: consistency and homophony. The learners more successfully counted phonemes in L2 words with consistent letter–phoneme correspondences (e.g., всё /fsʲɔ/, three letters/three phonemes) than in words with inconsistent correspondences (e.g., звать /zvatʲ/, five letters/four phonemes), indicating that L2 phoneme awareness is influenced by L2 orthography and that orthographic effects are not limited to the L1. In addition, the lack of any L1 homophone effects suggests that L2 orthographic effects overrode any potential L1 orthographic interference for these intermediate-level learners, suggesting orthographic effects may be language specific.
Children who stutter exchange linguistic accuracy for processing speed in sentence comprehension
Authors: FORTUNATO-TAVARES TALITA , HOWELL PETER , SCHWARTZ RICHARD G. , DE ANDRADE CLAUDIA R. FURQUIM
Published: July 2016

Comprehension of predicates and reflexives was examined in children who stutter (CWS) and children who do not stutter (CWNS) who were between 9 years, 7 months and 10 years, 2 months. Demands on working memory and manual reaction time were also assessed in two experiments that employed a four-choice picture-selection sentence comprehension task. CWS were less accurate than CWNS on the attachment of predicates. For reflexives, there was no between-group difference in accuracy, but there was a difference in speed. The two constructions induced processing at different points on a speed–accuracy continuum with CWS sacrificing accuracy to respond fast with predicates, while they maintained accuracy of reflexives by responding slower relative to CWNS. Predicates made more demands on language than nonspeech motor reaction time, whereas the reverse was the case with reflexives for CWS compared to CWNS.
Riemannian surfaces with torsion as homogenization limits of locally Euclidean surfaces with dislocation-type singularities
Authors: Kupferman Raz , Maor Cy
Published: July 2016

We reconcile two classical models of edge dislocations in solids. The first, from the early 1900s, models isolated edge dislocations as line singularities in locally Euclidean manifolds. The second, from the 1950s, models continuously distributed edge dislocations as smooth manifolds endowed with non-symmetric affine connections (equivalently, endowed with torsion fields). In both models, the solid is modelled as a Weitzenböck manifold. We prove, using a weak notion of convergence, that the second model can be obtained rigorously as a homogenization limit of the first model as the density of singular edge dislocation tends to infinity.
Nodal vector solutions with clustered peaks for nonlinear elliptic equations in ℝ3
Authors: He Qihan , Wang Chunhua
Published: July 2016

We study the following coupled nonlinear Schr¨odinger system in ℝ3:

where μ1 > 0, μ2 > 0 and β ∈ ℝ is a coupling constant. Irrespective of whether the system is repulsive or attractive, we prove that it has nodal semi-classical segregated or synchronized bound states with clustered spikes for sufficiently small ε under some additional conditions on P(x), Q(x) and β. Moreover, the number of this type of solutions will go to infinity as ε → 0+.
Neurodevelopmental Disorders (ASD and ADHD): DSM-5, ICD-10, and ICD-11
Authors: Doernberg Ellen , Hollander Eric
Published: July 2016

Neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have undergone considerable diagnostic evolution in the past decade. In the United States, the current system in place is the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), whereas worldwide, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) serves as a general medical system. This review will examine the differences in neurodevelopmental disorders between these two systems. First, we will review the important revisions made from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) to the DSM-5, with respect to ASD and ADHD. Next, we will cover the similarities and differences between ASD and ADHD classification in the DSM-5 and the ICD-10, and how these differences may have an effect on neurodevelopmental disorder diagnostics and classification. By examining the changes made for the DSM-5 in 2013, and critiquing the current ICD-10 system, we can help to anticipate and advise on the upcoming ICD-11, due to come online in 2017. Overall, this review serves to highlight the importance of progress towards complementary diagnostic classification systems, keeping in mind the difference in tradition and purpose of the DSM and the ICD, and that these systems are dynamic and changing as more is learned about neurodevelopmental disorders and their underlying etiology. Finally this review will discuss alternative diagnostic approaches, such as the Research Domain Criteria (RDoC) initiative, which links symptom domains to underlying biological and neurological mechanisms. The incorporation of new diagnostic directions could have a great effect on treatment development and insurance coverage for neurodevelopmental disorders worldwide.
Faith and the Free Market: Evangelicals, the Tea Party, and Economic Attitudes
Authors: Deckman Melissa , Cox Dan , Jones Robert , Cooper Betsy
Published: July 2016

We argue that concerted efforts by Tea Party leaders, Republican politicians, and leading Christian Right figures to establish and promote a connection between Christian faith and the free-market system has helped shift the economic attitudes of white evangelical Protestants in a more conservative direction. Our analysis of Public Religion Research Institute survey data finds that white evangelical Protestants express greater skepticism about an active role of government in society and believe economic growth is more likely to be spurred by a reduction in taxes rather than in public investments. Moreover, we find that identifying with the Tea Party has a conservatizing influence on their economic issue positions. While we find that partisanship, class, and in some cases, age, serve to modify the views of some evangelicals, by and large, evangelicals have come to embrace the conservative fiscal message promoted by both the Republican Party and the Tea Party movement.
Controllable optical activity with non-chiral plasmonic metasurfaces
Authors: Yu Ping , Li Jianxiong , Tang Chengchun , Cheng Hua , Liu Zhaocheng , Li Zhancheng , Liu Zhe , Gu Changzhi , Li Junjie , Chen Shuqi , Tian Jianguo
Published: July 2016

Optical activity is the rotation of the plane of linearly polarized light along the propagation direction as the light travels through optically active materials. In existing methods, the strength of the optical activity is determined by the chirality of the materials, which is difficult to control quantitatively. Here we numerically and experimentally investigated an alternative approach to realize and control the optical activity with non-chiral plasmonic metasurfaces. Through judicious design of the structural units of the metasurfaces, the right and left circular polarization components of the linearly polarized light have different phase retardations after transmitting through the metasurfaces, leading to large optical activity. Moreover, the strength of the optical activity can be easily and accurately tuned by directly adjusting the phase difference. The proposed approach based on non-chiral plasmonic metasurfaces exhibits large optical activity with a high controllable degree of freedom, which may provide more possibilities for applications in photonics.
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
Authors: Mitchell Jonathan S. , Li Ni , Weinhold Niels , Försti Asta , Ali Mina , van Duin Mark , Thorleifsson Gudmar , Johnson David C. , Chen Bowang , Halvarsson Britt-Marie , Gudbjartsson Daniel F. , Kuiper Rowan , Stephens Owen W. , Bertsch Uta , Broderick Peter , Campo Chiara , Einsele Hermann , Gregory Walter A. , Gullberg Urban , Henrion Marc , Hillengass Jens , Hoffmann Per , Jackson Graham H. , Johnsson Ellinor , Jöud Magnus , Kristinsson Sigurður Y. , Lenhoff Stig , Lenive Oleg , Mellqvist Ulf-Henrik , Migliorini Gabriele , Nahi Hareth , Nelander Sven , Nickel Jolanta , Nöthen Markus M. , Rafnar Thorunn , Ross Fiona M. , da Silva Filho Miguel Inacio , Swaminathan Bhairavi , Thomsen Hauke , Turesson Ingemar , Vangsted Annette , Vogel Ulla , Waage Anders , Walker Brian A. , Wihlborg Anna-Karin , Broyl Annemiek , Davies Faith E. , Thorsteinsdottir Unnur , Langer Christian , Hansson Markus , Kaiser Martin , Sonneveld Pieter , Stefansson Kari , Morgan Gareth J. , Goldschmidt Hartmut , Hemminki Kari , Nilsson Björn , Houlston Richard S.
Published: July 2016

Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
Postoperative autotransfusion drain after total hip arthroplasty: a meta-analysis of randomized controlled trials
Authors: Xie Hui , Pan Jian-Ke , Hong Kun-Hao , Guo Da , Fang Jian , Yang Wei-Yi , Liu Jun
Published: July 2016

The use of a postoperative autotransfusion drain (PATD) to reduce allogenic blood transfusions in total hip arthroplasty (THA) remains controversial. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of this technique. Randomized controlled trials (RCTs) were identified from PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). Thirteen RCTs (1,424 participants) were included in our meta-analysis. The results showed that PATD reduced the rate of allogenic transfusions (RR = 0.56; 95% CI [0.40, 0.77]) and total blood loss (MD = −196.04; 95% CI [−311.01, −81.07]). Haemoglobin (Hb) levels were higher in the PATD group on postoperative day 1 (MD = 0.28; 95% CI [0.06, 0.49]), but no significant differences on postoperative days 2 or 3 (MD = 0.29; 95% CI [−0.02, 0.60]; MD = 0.26; 95% CI [−0.04, 0.56]; respectively). There were no differences in length of hospital stay (MD = −0.18; 95% CI [−0.61, 0.25]), febrile reaction (RR = 1.26; 95% CI [0.95, 1.67]), infection (RR = 0.95; 95% CI [0.54, 1.65]), wound problems (RR = 1.07; 95% CI [0.87, 1.33]), or serious adverse events (RR = 0.59; 95% CI [0.10, 3.58]). Our findings suggest that PATD is effective in reducing the rate of allogenic transfusion. However, the included studies are inadequately powered to conclusively determine the safety of this technique.
Prognostic values of four Notch receptor mRNA expression in gastric cancer
Authors: Wu Xiaoyu , Liu Wentao , Tang Ding , Xiao Haijuan , Wu Zhenfeng , Chen Che , Yao Xuequan , Liu Fukun , Li Gang
Published: July 2016

Notch ligands and receptors are frequently deregulated in several human malignancies including gastric cancer. The activation of Notch signaling has been reported to contribute to gastric carcinogenesis and progression. However, the prognostic roles of individual Notch receptors in gastric cancer patients remain elusive. In the current study, we accessed the prognostic roles of four Notch receptors, Notch 1–4, in gastric cancer patients through “The Kaplan-Meier plotter” (KM plotter) database, in which updated gene expression data and survival information include a total of 876 gastric cancer patients. All four Notch receptors’ high mRNA expression was found to be correlated to worsen overall survival (OS) for all gastric cancer patients followed for 20 years. We further accessed the prognostic roles of individual Notch receptors in different clinicopathological features using Lauren classification, pathological grades, clinical grades, HER2 status and different choices of treatments of gastric cancer patients. These results indicate that there are critical prognostic values of the four Notch receptors in gastric cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of gastric cancer and to develop tools to more accurately predict their prognosis.
Indexing Effects of Copy Number Variation on Genes Involved in Developmental Delay
Authors: Uddin Mohammed , Pellecchia Giovanna , Thiruvahindrapuram Bhooma , D’Abate Lia , Merico Daniele , Chan Ada , Zarrei Mehdi , Tammimies Kristiina , Walker Susan , Gazzellone Matthew J. , Nalpathamkalam Thomas , Yuen Ryan K. C. , Devriendt Koenraad , Mathonnet Géraldine , Lemyre Emmanuelle , Nizard Sonia , Shago Mary , Joseph-George Ann M. , Noor Abdul , Carter Melissa T. , Yoon Grace , Kannu Peter , Tihy Frédérique , Thorland Erik C. , Marshall Christian R. , Buchanan Janet A. , Speevak Marsha , Stavropoulos Dimitri J. , Scherer Stephen W.
Published: July 2016

A challenge in clinical genomics is to predict whether copy number variation (CNV) affecting a gene or multiple genes will manifest as disease. Increasing recognition of gene dosage effects in neurodevelopmental disorders prompted us to develop a computational approach based on critical-exon (highly expressed in brain, highly conserved) examination for potential etiologic effects. Using a large CNV dataset, our updated analyses revealed significant (P < 1.64 × 10−15) enrichment of critical-exons within rare CNVs in cases compared to controls. Separately, we used a weighted gene co-expression network analysis (WGCNA) to construct an unbiased protein module from prenatal and adult tissues and found it significantly enriched for critical exons in prenatal (P < 1.15 × 10−50, OR = 2.11) and adult (P < 6.03 × 10−18, OR = 1.55) tissues. WGCNA yielded 1,206 proteins for which we prioritized the corresponding genes as likely to have a role in neurodevelopmental disorders. We compared the gene lists obtained from critical-exon and WGCNA analysis and found 438 candidate genes associated with CNVs annotated as pathogenic, or as variants of uncertain significance (VOUS), from among 10,619 developmental delay cases. We identified genes containing CNVs previously considered to be VOUS to be new candidate genes for neurodevelopmental disorders (GIT1, MVB12B and PPP1R9A) demonstrating the utility of this strategy to index the clinical effects of CNVs.
A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients
Authors: Liu Kehui , Xiang Xiaogang , Bao Rebecca , Chen Rong , Liu Yunye , Xie Jingdong , Guo Qing , Bao Shisan , Xie Qing , Wang Hui
Published: July 2016

Entecavir (ETV) is a potent viral replication inhibitor for chronic hepatitis B (CHB) patients. To investigate the efficacy of ETV in Chinese nucleos(t)ide(NA)-experienced CHB patients. Among 89 CHB patients with ETV monotherapy for ≥6 months, 33/89 (37%) or 56/89 (73%) were NA-naïve or NA-experienced. During a median follow-up of 5.75 years, all NA-naïve CHB patients achieved VR without genotypic ETV-resistance. However, VR was observed in 50/56 (~90%) of NA-experienced CHB patients during a median follow-up of 4.75 years. Antiviral efficacy was not reduced in patients with previous lamivudine (LAM) with/without LAM-resistance (HR 0.465; 95% CI 0.196–1.100; p > 0.05) (HR 0.472; 95% CI 0.205–1.091; p > 0.05). Patients with a primary treatment failure to adefovir (ADV) had a reduced probability of achieving VR compared to NA-naïve (HR 0.496; 95% CI 0.287–0.857; p < 0.01). Previous ADV-experienced patients with a partial VR (HR 1.253; 95% CI 0.429–3.665; p > 0.05) did not influence antiviral response to ETV. The antiviral efficacy of ETV is not influenced by previous treatment LAM with/without LAM-resistance. ETV may still be an option in ADV-experienced patients with a partial VR, but not advised in patients with a primary treatment failure to ADV.
The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti
Authors: Aliota Matthew T. , Peinado Stephen A. , Velez Ivan Dario , Osorio Jorge E.
Published: July 2016

Zika virus (ZIKV) is causing an explosive outbreak of febrile disease in the Americas. There are no effective antiviral therapies or licensed vaccines for this virus and mosquito control strategies have not been adequate to contain the virus. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against other arboviruses. At present, it is unknown whether or not ZIKV can infect, disseminate and be transmitted by Wolbachia-infected Ae. aegypti. Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for ZIKV. These results support the use of Wolbachia biocontrol as a multivalent strategy against Ae. aegypti-transmitted viruses.
Alpha-tubulin enhanced renal tubular cell proliferation and tissue repair but reduced cell death and cell-crystal adhesion
Authors: Manissorn Juthatip , Khamchun Supaporn , Vinaiphat Arada , Thongboonkerd Visith
Published: July 2016

Adhesion of calcium oxalate (CaOx) crystals on renal tubular epithelial cells is a critical event for kidney stone disease that triggers many cascades of cellular response. Our previous expression proteomics study identified several altered proteins in MDCK renal tubular cells induced by CaOx crystals. However, functional significance of those changes had not been investigated. The present study thus aimed to define functional roles of such proteome data. Global protein network analysis using STRING software revealed α-tubulin, which was decreased, as one of central nodes of protein-protein interactions. Overexpression of α-tubulin (pcDNA6.2-TUBA1A) was then performed and its efficacy was confirmed. pcDNA6.2-TUBA1A could maintain levels of α-tubulin and its direct interacting partner, vimentin, after crystal exposure. Also, pcDNA6.2-TUBA1A successfully reduced cell death to almost the basal level and increased cell proliferation after crystal exposure. Additionally, tissue repair capacity was improved in pcDNA6.2-TUBA1A cells. Moreover, cell-crystal adhesion was reduced by pcDNA6.2-TUBA1A. Finally, levels of potential crystal receptors (HSP90, HSP70 and α-enolase) on apical membrane were dramatically reduced to basal levels by pcDNA6.2-TUBA1A. These findings implicate that α-tubulin has protective roles in kidney stone disease by preventing cell death and cell-crystal adhesion, but on the other hand, enhancing cell proliferation and tissue repair function.
Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction
Authors: Powell Katie L. , Stevens Veronica , Upton Dannielle H. , McCracken Sharon A. , Simpson Ann M. , Cheng Yan , Tasevski Vitomir , Morris Jonathan M. , Ashton Anthony W.
Published: July 2016

Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPβ) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. Conversely, TPβ attenuated these functions and inhibited migration. Expression of the TPβ transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPα mediates normal placentation; however, TPβ impairs placentation and promotes the development of IUGR and represents an underappreciated pathogenic factor in humans.
Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift
Authors: Zhang Ying-Ming , Yang Yang , Zhang Yu-Hui , Liu Yu
Published: July 2016

Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host‒guest interactions of an adamantane-bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA’s diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin‒hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates.
Visualization of Neuregulin 1 ectodomain shedding reveals its local processing in vitro and in vivo
Authors: Kamezaki Aosa , Sato Fuminori , Aoki Kazuhiro , Asakawa Kazuhide , Kawakami Koichi , Matsuzaki Fumio , Sehara-Fujisawa Atsuko
Published: July 2016

Neuregulin1 (NRG1) plays diverse developmental roles and is likely involved in several neurological disorders including schizophrenia. The transmembrane NRG1 protein is proteolytically cleaved and released as a soluble ligand for ErbB receptors. Such post-translational processing, referred to as ‘ectodomain shedding’, is thought to be crucial for NRG1 function. However, little is known regarding the regulatory mechanism of NRG1 cleavage in vivo. Here, we developed a fluorescent probe, NRG1 Cleavage Indicating SenSOR (N-CISSOR), by fusing mCherry and GFP to the extracellular and intracellular domains of NRG1, respectively. N-CISSOR mimicked the subcellular localization and biochemical properties of NRG1 including cleavage dynamics and ErbB phosphorylation in cultured cells. mCherry/GFP ratio imaging of phorbol-12-myristate-13-acetate-stimulated N-CISSOR-expressing HEK293T cells enabled to monitor rapid ectodomain shedding of NRG1 at the subcellular level. Utilizing N-CISSOR in zebrafish embryos revealed preferential axonal NRG1 ectodomain shedding in developing motor neurons, demonstrating that NRG1 ectodomain shedding is spatially regulated at the subcellular level. Thus, N-CISSOR will be a valuable tool for elucidating the spatiotemporal regulation of NRG1 ectodomain shedding, both in vitro and in vivo.
First Person Perspective of Seated Participants Over a Walking Virtual Body Leads to Illusory Agency Over the Walking
Authors: Kokkinara Elena , Kilteni Konstantina , Blom Kristopher J. , Slater Mel
Published: July 2016

Agency, the attribution of authorship to an action of our body, requires the intention to carry out the action, and subsequently a match between its predicted and actual sensory consequences. However, illusory agency can be generated through priming of the action together with perception of bodily action, even when there has been no actual corresponding action. Here we show that participants can have the illusion of agency over the walking of a virtual body even though in reality they are seated and only allowed head movements. The experiment (n = 28) had two factors: Perspective (1PP or 3PP) and Head Sway (Sway or NoSway). Participants in 1PP saw a life-sized virtual body spatially coincident with their own from a first person perspective, or the virtual body from third person perspective (3PP). In the Sway condition the viewpoint included a walking animation, but not in NoSway. The results show strong illusions of body ownership, agency and walking, in the 1PP compared to the 3PP condition, and an enhanced level of arousal while the walking was up a virtual hill. Sway reduced the level of agency. We conclude with a discussion of the results in the light of current theories of agency.
ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells
Authors: Morandi E. M. , Verstappen R. , Zwierzina M. E. , Geley S. , Pierer G. , Ploner C.
Published: July 2016

The fate of human adipose tissue stem cells (ASCs) is largely determined by biochemical and mechanical cues from the extracellular matrix (ECM), which are sensed and transmitted by integrins. It is well known that specific ECM constituents influence ASC proliferation and differentiation. Nevertheless, knowledge on how individual integrins regulate distinct processes is still limited. We performed gene profiling of 18 alpha integrins in sorted ASCs and adipocytes, identifying downregulations of RGD-motif binding integrins integrin-alpha-V (ITGAV) and integrin-alpha-5 (ITGA5), upregulation of laminin binding and leukocyte-specific integrins and individual regulations of collagen and LDV-receptors in differentiated adipocytes in-vivo. Gene function analyses in in-vitro cultured ASCs unraveled differential functions of ITGA5 and ITGAV. Knockdown of ITGAV, but not ITGA5 reduced proliferation, caused p21Cip1 induction, repression of survivin and specific regulation of Hippo pathway mediator TAZ. Gene knockdown of both integrins promoted adipogenic differentiation, while transgenic expression impaired adipogenesis. Inhibition of ITGAV using cilengitide resulted in a similar phenotype, mimicking loss of pan-ITGAV expression using RNAi. Herein we show ASC specific integrin expression patterns and demonstrate distinct regulating roles of both integrins in human ASCs and adipocyte physiology suggesting a negative impact of RDG-motif signaling on adipogenic differentiation of ASCs via ITGA5 and ITGAV.
Oxidative DNA damage stalls the human mitochondrial replisome
Authors: Stojkovič Gorazd , Makarova Alena V. , Wanrooij Paulina H. , Forslund Josefin , Burgers Peter M. , Wanrooij Sjoerd
Published: July 2016

Oxidative stress is capable of causing damage to various cellular constituents, including DNA. There is however limited knowledge on how oxidative stress influences mitochondrial DNA and its replication. Here, we have used purified mtDNA replication proteins, i.e. DNA polymerase γ holoenzyme, the mitochondrial single-stranded DNA binding protein mtSSB, the replicative helicase Twinkle and the proposed mitochondrial translesion synthesis polymerase PrimPol to study lesion bypass synthesis on oxidative damage-containing DNA templates. Our studies were carried out at dNTP levels representative of those prevailing either in cycling or in non-dividing cells. At dNTP concentrations that mimic those in cycling cells, the replication machinery showed substantial stalling at sites of damage and these problems were further exacerbated at the lower dNTP concentrations present in resting cells. PrimPol, the translesion synthesis polymerase identified inside mammalian mitochondria, did not promote mtDNA replication fork bypass of the damage. This argues against a conventional role for PrimPol as a mitochondrial translesion synthesis DNA polymerase for oxidative DNA damage; however, we show that Twinkle, the mtDNA replicative helicase, is able to stimulate PrimPol DNA synthesis in vitro, suggestive of an as yet unidentified role of PrimPol in mtDNA metabolism.
CRISP-ID: decoding CRISPR mediated indels by Sanger sequencing
Authors: Dehairs Jonas , Talebi Ali , Cherifi Yacine , Swinnen Johannes V.
Published: July 2016

The advent of next generation gene editing technologies has revolutionized the fields of genome engineering in allowing the generation of gene knockout models and functional gene analysis. However, the screening of resultant clones remains challenging due to the simultaneous presence of different indels. Here, we present CRISP-ID, a web application which uses a unique algorithm for genotyping up to three alleles from a single Sanger sequencing trace, providing a robust and readily accessible platform to directly identify indels and significantly speed up the characterization of clones.
Unbreakable distributed storage with quantum key distribution network and password-authenticated secret sharing
Authors: Fujiwara M. , Waseda A. , Nojima R. , Moriai S. , Ogata W. , Sasaki M.
Published: July 2016

Distributed storage plays an essential role in realizing robust and secure data storage in a network over long periods of time. A distributed storage system consists of a data owner machine, multiple storage servers and channels to link them. In such a system, secret sharing scheme is widely adopted, in which secret data are split into multiple pieces and stored in each server. To reconstruct them, the data owner should gather plural pieces. Shamir’s (k, n)-threshold scheme, in which the data are split into n pieces (shares) for storage and at least k pieces of them must be gathered for reconstruction, furnishes information theoretic security, that is, even if attackers could collect shares of less than the threshold k, they cannot get any information about the data, even with unlimited computing power. Behind this scenario, however, assumed is that data transmission and authentication must be perfectly secure, which is not trivial in practice. Here we propose a totally information theoretically secure distributed storage system based on a user-friendly single-password-authenticated secret sharing scheme and secure transmission using quantum key distribution and demonstrate it in the Tokyo metropolitan area (≤90 km).