bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis
Authors: Sergin Ismail , Evans Trent D. , Zhang Xiangyu , Bhattacharya Somashubhra , Stokes Carl J. , Song Eric , Ali Sahl , Dehestani Babak , Holloway Karyn B. , Micevych Paul S. , Javaheri Ali , Crowley Jan R. , Ballabio Andrea , Schilling Joel D. , Epelman Slava , Weihl Conrad C. , Diwan Abhinav , Fan Daping , Zayed Mohamed A. , Razani Babak
Published: June 2017

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy–lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy–lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy–lysosomal biogenesis and show trehalose’s ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease.
Tightening of tropical ascent and high clouds key to precipitation change in a warmer climate
Authors: Su Hui , Jiang Jonathan H. , Neelin J. David , Shen T. Janice , Zhai Chengxing , Yue Qing , Wang Zhien , Huang Lei , Choi Yong-Sang , Stephens Graeme L. , Yung Yuk L.
Published: June 2017

The change of global-mean precipitation under global warming and interannual variability is predominantly controlled by the change of atmospheric longwave radiative cooling. Here we show that tightening of the ascending branch of the Hadley Circulation coupled with a decrease in tropical high cloud fraction is key in modulating precipitation response to surface warming. The magnitude of high cloud shrinkage is a primary contributor to the intermodel spread in the changes of tropical-mean outgoing longwave radiation (OLR) and global-mean precipitation per unit surface warming (dP/dTs) for both interannual variability and global warming. Compared to observations, most Coupled Model Inter-comparison Project Phase 5 models underestimate the rates of interannual tropical-mean dOLR/dTs and global-mean dP/dTs, consistent with the muted tropical high cloud shrinkage. We find that the five models that agree with the observation-based interannual dP/dTs all predict dP/dTs under global warming higher than the ensemble mean dP/dTs from the ∼20 models analysed in this study.
Derivation and Validation of a Mortality Risk Score for Severe Hand, Foot and Mouth Disease in China
Authors: Qiu Jun , Lu Xiulan , Liu Xiao , Zang Ping , Zhao Wenjiao , Liu Pingping , Xiao Zhenghui
Published: June 2017

Outbreaks of hand, foot and mouth disease (HFMD) have increased recently, as has the case fatality rate in severe cases. No scoring system currently exists to predict mortality risk for severe HFMD in previous study. We retrospectively collected laboratory parameters for 546 patients with severe HFMD (a derivation and a validation cohort) at Hunan Children’s Hospitals between January 2012 and December 2014. We developed a mortality risk score comprising four laboratory parameters: blood glucose (GLU), white blood cells (WBC), lactate (LAC), and N-terminal-probrain natriuretic peptide (NT-proBNP). Using an “optimal” cutoff score of 4, the sensitivity, specificity, positive predictive value and negative predictive value was 88.00%, 96.14%, 62.86% and 99.08%, respectively, in the derivation cohort. Among severe HFMD patients with low- and high-risk scores in the validation cohort, case fatality rates were 1.49% and 74.07%, respectively. According to the “optimal” cut-off in the derivation cohort, the sensitivity, specificity, positive predictive value, and negative predictive value were 80.95%, 93.83%, 62.96% and 97.44%, respectively, in the derivation cohort. The mortality risk score demonstrated good discrimination (AUC > 0.9) and calibration (P > 0.05) in both cohorts. The mortality risk score, comprising WBC, GLU, LAC and NT-proBNP, has been demonstrated good discrimination and calibration in the both cohorts.
Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
Authors: Buñay Julio , Larriba Eduardo , Moreno Ricardo D. , del Mazo Jesús
Published: June 2017

Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis “miRNome” (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3 mg/kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP) and 0.05 mg/kg-BW/day of each alkylphenol (NP, OP), from conception to adulthood. The testis “miRNome” was characterised using next-generation sequencing (NGS). Expression levels of genes involved in miRNA biogenesis were measured by RT-qPCR, as well as several physiological and cytological parameters. We found two up-regulated, and eight down-regulated miRNAs and thirty-six differentially expressed isomiRs along with an over-expression ofDrosha,AdarandZcchc11. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation ofmiR-18a-5pwithNr1h2involved in the deregulation of the steroidogenesis pathway. Here, we present the first association between miRNA/isomiRs deregulation, their mechanisms of biogenesis and histopathological and hormonal alterations in testes of adult mice exposed to a mixture of low-dose EDCs, which can play a role in male infertility.
Pancreatic adenocarcinoma response to chemotherapy enhanced with non-invasive radio frequency evaluated via an integrated experimental/computational approach
Authors: Ware Matthew J. , Curtis Louis T. , Wu Min , Ho Jason C. , Corr Stuart J. , Curley Steven A. , Godin Biana , Frieboes Hermann B.
Published: June 2017

Although chemotherapy combined with radiofrequency exposure has shown promise in cancer treatment by coupling drug cytotoxicity with thermal ablation or thermally-induced cytotoxicity, limited access of the drug to tumor loci in hypo-vascularized lesions has hampered clinical application. We recently showed that high-intensity short-wave capacitively coupled radiofrequency (RF) electric-fields may reach inaccessible targets in vivo. This non-invasive RF combined with gemcitabine (Gem) chemotherapy enhanced drug uptake and effect in pancreatic adenocarcinoma (PDAC), notorious for having poor response and limited therapeutic options, but without inducing thermal injury. We hypothesize that the enhanced cytotoxicity derives from RF-facilitated drug transport in the tumor microenvironment. We propose an integrated experimental/computational approach to evaluate chemotherapeutic response combined with RF-induced phenotypic changes in tissue with impaired transport. Results show that RF facilitates diffusive transport in 3D cell cultures representing hypo-vascularized lesions, enhancing drug uptake and effect. Computational modeling evaluates drug vascular extravasation and diffusive transport as key RF-modulated parameters, with transport being dominant. Assessment of hypothetical schedules following current clinical protocol for Stage-IV PDAC suggests that unresponsive lesions may be growth-restrained when exposed to Gem plus RF. Comparison of these projections to experiments in vivo indicates that synergy may result from RF-induced cell phenotypic changes enhancing drug transport and cytotoxicity, thus providing a potential baseline for clinically-focused evaluation.
Smart pH-sensitive nanoassemblies with cleavable PEGylation for tumor targeted drug delivery
Authors: Zhao Guanren , Long Ling , Zhang Lina , Peng Mingli , Cui Ting , Wen Xiaoxun , Zhou Xing , Sun Lijun , Che Ling
Published: June 2017

A new acidly sensitive PEGylated polyethylenimine linked by Schiff base (PEG-s-PEI) was designed to render pH-sensitive PEGylation nanoassemblies through multiple interactions with indomethacin and docetaxel (DTX). DTX nanoassemblies driven by PEG-s-PEI thus formulated exhibited an excellent pH-sensitivity PEGylation cleavage performance at extracellular pH of tumor microenvironment, compared to normal tissues, thereby long circulated in blood but were highly phagocytosed by tumor cells. Consequently, this smart pH-sensitive PEGylation cleavage provided an efficient strategy to target tumor microenvironment, in turn afforded superior therapeutic outcome in anti-tumor activity.
Bias–selectable nBn dual–band long–/very long–wavelength infrared photodetectors based on InAs/InAs1−xSbx/AlAs1−xSbx type–II superlattices
Authors: Haddadi Abbas , Dehzangi Arash , Chevallier Romain , Adhikary Sourav , Razeghi Manijeh
Published: June 2017

Type–II superlattices (T2SLs) are a class of artificial semiconductors that have demonstrated themselves as a viable candidate to compete with the state–of–the–art mercury–cadmium–telluride material system in the field of infrared detection and imaging. Within type–II superlattices, InAs/InAs1−xSbx T2SLs have been shown to have a significantly longer minority carrier lifetime. However, demonstration of high–performance dual–band photodetectors based on InAs/InAs1−xSbx T2SLs in the long and very long wavelength infrared (LWIR & VLWIR) regimes remains challenging. We report the demonstration of high–performance bias–selectable dual–band long–wavelength infrared photodetectors based on new InAs/InAs1−xSbx/AlAs1−xSbx type–II superlattice design. Our design uses two different bandgap absorption regions separated by an electron barrier that blocks the transport of majority carriers to reduce the dark current density of the device. As the applied bias is varied, the device exhibits well–defined cut–off wavelengths of either ∼8.7 or ∼12.5 μm at 77 K. This bias–selectable dual–band photodetector is compact, with no moving parts, and will open new opportunities for multi–spectral LWIR and VLWIR imaging and detection.
Learning and Timing of Voluntary Blink Responses Match Eyeblink Conditioning
Authors: Rasmussen Anders , Jirenhed Dan-Anders
Published: June 2017

Can humans produce well-timed blink responses to a neutral stimulus voluntarily, without receiving any blink-eliciting, unconditional, stimulus? And if they can, to what degree does classical eyeblink conditioning depend on volition? Here we show that voluntary blink responses learned in two paradigms that did not involve any unconditional blink-eliciting stimuli, display timing that is as good, or better than, the timing of blink responses learned in a standard eyeblink conditioning paradigm. The exceptional timing accuracy likely stems from the fact that, in contrast to previous studies, we challenged our participants to blink in a timed manner, and not merely to blink so as to avoid the corneal air puff. These results reveal a remarkable level of voluntary control over a simple movement, and they challenge the view that learning during eyeblink conditioning is necessarily automatic and involuntary.
Aberrant plasticity of peripheral sensory axons in a painful neuropathy
Authors: Hirai Takashi , Mulpuri Yatendra , Cheng Yanbing , Xia Zheng , Li Wei , Ruangsri Supanigar , Spigelman Igor , Nishimura Ichiro
Published: June 2017

Neuronal cells express considerable plasticity responding to environmental cues, in part, through subcellular mRNA regulation. Here we report on the extensive changes in distribution of mRNAs in the cell body and axon compartments of peripheral sensory neurons and the 3′ untranslated region (3′UTR) landscapes after unilateral sciatic nerve entrapment (SNE) injury in rats. Neuronal cells dissociated from SNE-injured and contralateral L4 and L5 dorsal root ganglia were cultured in a compartmentalized system. Axonal and cell body RNA samples were separately subjected to high throughput RNA sequencing (RNA-Seq). The injured axons exhibited enrichment of mRNAs related to protein synthesis and nerve regeneration. Lengthening of 3′UTRs was more prevalent in the injured axons, including the newly discovered alternative cleavage and polyadenylation of NaV1.8 mRNA. Alternative polyadenylation was largely independent from the relative abundance of axonal mRNAs; but they were highly clustered in functional pathways related to RNA granule formation in the injured axons. These RNA-Seq data analyses indicate that peripheral nerve injury may result in highly selective mRNA enrichment in the affected axons with 3′UTR alterations potentially contributing to the mechanism of neuropathic pain.
Features of electron gas in InAs nanowires imposed by interplay between nanowire geometry, doping and surface states
Authors: Degtyarev V. E. , Khazanova S. V. , Demarina N. V.
Published: June 2017

We present a study of electron gas properties in InAs nanowires determined by interaction between nanowire geometry, doping and surface states. The electron gas density and space distribution are calculated via self-consistent solution of coupled Schroedinger and Poisson equations in the nanowires with a hexagonal cross-section. We show that the density of surface states and the nanowire width define the spatial distribution of the electrons. Three configurations can be distinguished, namely the electrons are localized in the center of the wire, or they are arranged in a uniform tubular distribution, or finally in a tubular distribution with additional electron accumulation at the corners of the nanowire. The latter one is dominating for most experimentally obtained nanowires. N-type doping partly suppresses electron accumulation at the nanowire corners. The electron density calculated for both, various nanowire widths and different positions of the Fermi level at the nanowire surface, is compared with the experimental data for intrinsic InAs nanowires. Suitable agreement is obtained by assuming a Fermi level pinning at 60 to 100 meV above the conduction band edge, leading to a tubular electron distribution with accumulation along the corners of the nanowire.
Identification of an in vivo orally active dual-binding protein-protein interaction inhibitor targeting TNFα through combined in silico/in vitro/in vivo screening
Authors: Mouhsine Hadley , Guillemain Hélène , Moreau Gabriel , Fourati Najla , Zerrouki Chouki , Baron Bruno , Desallais Lucille , Gizzi Patrick , Ben Nasr Nesrine , Perrier Julie , Ratsimandresy Rojo , Spadoni Jean-Louis , Do Hervé , England Patrick , Montes Matthieu , Zagury Jean-François
Published: June 2017

TNFα is a homotrimeric pro-inflammatory cytokine, whose direct targeting by protein biotherapies has been an undeniable success for the treatment of chronic inflammatory diseases. Despite many efforts, no orally active drug targeting TNFα has been identified so far. In the present work, we identified through combined in silico/in vitro/in vivo approaches a TNFα direct inhibitor, compound 1, displaying nanomolar and micromolar range bindings to TNFα. Compound 1 inhibits the binding of TNFα with both its receptors TNFRI and TNFRII. Compound 1 inhibits the TNFα induced apoptosis on L929 cells and the TNFα induced NF-κB activation in HEK cells. In vivo, oral administration of compound 1 displays a significant protection in a murine TNFα-dependent hepatic shock model. This work illustrates the ability of low-cost combined in silico/in vitro/in vivo screening approaches to identify orally available small-molecules targeting challenging protein-protein interactions such as homotrimeric TNFα.
Investigation of Electric Field Induced Mixing in Silicon Micro Ring Resonators
Authors: De Leonardis Francesco , Soref Richard A. , Passaro Vittorio M. N.
Published: June 2017

In this paper we present a detailed theoretical investigation of the electric field induced mixing effect, in which the up and down frequency-conversion processes are obtained by inducing an effective second order susceptibility via the periodic spatial distribution of reversed biased p-i-n junctions. The possibility of realizing a frequency generation process within an integrated microring resonator is demonstrated here, by simulations, in the silicon on insulator platform. Furthermore, general physical features have been investigated by means of a comparative analysis of the frequency generation performance as a function of the input pump power, the linear and nonlinear losses, and the coupling factors. A conversion efficiency of 627.5 %/W has been obtained for the second harmonic generation process. Therefore, an improvement of 4 to 50 times with respect to the straight waveguides is achieved, depending on the cavity ring radius. Finally, for the up/down conversion, from telecom idler to mid-IR and from Mid-IR to telecom signal, respectively, an efficiency of 85.9%/W and 454.4 %/W has been obtained in the silicon microring resonator, respectively.
Presence of caffeine reversibly interferes with efficacy of acupuncture-induced analgesia
Authors: Fujita Takumi , Feng Changyong , Takano Takahiro
Published: June 2017

Acupuncture is an alternative treatment for wide spectrum chronic pain. However, its validity remains controversial due to the disputed efficacy assessed in various clinical studies. Moreover, variability amongst individuals complicates the predictability of outcome, which impedes the integration of acupuncture into mainstream pain management programs. In light of our previous finding that the analgesic effect of acupuncture is mediated by adenosine A1 receptor activation at the acupuncture point, we here report that in acute and chronic animal pain models, oral intake of caffeine, a potent adenosine receptor antagonist, interferes with acupuncture analgesia, even at a low dose. Local administration of caffeine at the acupuncture point was sufficient to eliminate the analgesic effect, dismissing the systemic action of caffeine. Such interference was reversible, as caffeine withdrawal fully restored the efficacy of acupuncture by the next day, and long-term exposure to caffeine did not alter A1 receptor expression at the acupuncture point. Combined, these data indicate that a trace amount of caffeine can reversibly block the analgesic effects of acupuncture, and controlling caffeine consumption during acupuncture may improve pain management outcomes.
High-order exceptional points in optomechanics
Authors: Jing H. , Özdemir Ş. K. , Lü H. , Nori Franco
Published: June 2017

We study mechanical cooling in systems of coupled passive (lossy) and active (with gain) optical resonators. We find that for a driving laser which is red-detuned with respect to the cavity frequency, the supermode structure of the system is radically changed, featuring the emergence of genuine high-order exceptional points. This in turn leads to giant enhancement of both the mechanical damping and the spring stiffness, facilitating low-power mechanical cooling in the vicinity of gain-loss balance. This opens up new avenues of steering micromechanical devices with exceptional points beyond the lowest-order two.
Effects of transient high temperature treatment on the intestinal flora of the silkworm Bombyx mori
Authors: Sun Zhenli , Kumar Dhiraj , Cao Guangli , Zhu Liyuan , Liu Bo , Zhu Min , Liang Zi , Kuang Sulan , Chen Fei , Feng Yongjie , Hu Xiaolong , Xue Renyu , Gong Chengliang
Published: June 2017

The silkworm Bombyx mori is a poikilotherm and is therefore sensitive to various climatic conditions. The influence of temperature on the intestinal flora and the relationship between the intestinal flora and gene expression in the silkworm remain unknown. In the present study, changes of the intestinal flora at 48, 96 and 144 h following transient high temperature treatment (THTT) of 37 °C for 8 h were investigated. According to principal component analysis, the abundances of Enterococcus and Staphylococcus showed a negative correlation with other dominant genera. After THTT, the gene expression levels of spatzle-1 and dicer-2 were increased and decreased, respectively, which suggested that the Toll and RNAi pathways were activated and suppressed, respectively. The species-gene expression matrix confirmed that the spatzle-1 and dicer-2 gene expression levels were negatively and positively correlated, respectively, with the abundance of Enterococcus and Staphylococcus in the control. The abundance of Variovorax post-THTT was positively correlated with the spatzle-1 gene expression level, whereas the community richness of Enterococcus was negatively correlated with the spatzle-1 gene expression level and positively correlated with the dicer-2. The results of the present investigation provide new evidence for understanding the relationships among THTT, intestinal flora and host gene expression.
Sol-gel Autocombustion Synthesis of Nanocrystalline High-entropy Alloys
Authors: Niu Bo , Zhang Fan , Ping Hang , Li Na , Zhou Jieyang , Lei Liwen , Xie Jingjing , Zhang Jinyong , Wang Weimin , Fu Zhengyi
Published: June 2017

A reduction in the particle size is expected to improve the properties and increase the application potential of high-entropy alloys. Therefore, in this study, a novel sol–gel autocombustion technique was first used to synthesize high-entropy alloys. The average grain size of the prepared nanocrystalline CoCrCuNiAl high-entropy alloys showed was 14 nm with an excellent and uniform dispersion, exhibiting a distinct magnetic behavior similar to the superparamagnetic behavior. We show that the metal nitrates first form (Co,Cu,Mg,Ni,Zn)O high-entropy oxides, and then in situ reduce to CoCrCuNiAl high-entropy alloys by the reducing gases, and the chelation between citric acid and the metal ions and the in situ chemical reactions are the dominant reaction mechanisms. We demonstrate that the sol–gel autocombustion process is an efficient way to synthesize solid solution alloys eluding the restriction of a high mixing entropy.
Atrial fibrillation as a prognostic indicator of myocardial infarction and cardiovascular death: a systematic review and meta-analysis
Authors: He Wenqi , Chu Yingjie
Published: June 2017

This study aimed to investigate whether atrial fibrillation (AF) predicts myocardial infarction (MI) or cardiovascular (CV) death. AF is a well-established risk factor for thrombotic stroke and all-cause mortality. PubMed, EmBase, and Cochrane Central were searched for articles comparing the incidence rates of MI, CV death, or CV events between AF and non-AF patients. Relative risk ratio (RR) was used as effect estimate. Crude and adjusted RRs were calculated. Data were pooled using a random-effects model. The meta-analysis included 27 studies. In the unadjusted analysis, AF patients had a nonsignificant trend toward a higher risk of MI compared with non-AF patients; however, a significant association was found. The crude data analysis showed that AF was associated with increased risk of CV death (P < 0.05) and CV events (P < 0.05). These associations remained significant after pooling data from adjusted models (CV death: RR = 1.95, 95% CI 1.51–2.51, P < 0.05; CV events: RR = 2.10, 95% CI 1.50–2.95, P < 0.05). These results showed that AF is an independent risk factor for MI, CV death, and CV events.
Antibacterial and detoxifying activity of NZ17074 analogues with multi-layers of selective antimicrobial actions against Escherichia coli and Salmonella enteritidis
Authors: Yang Na , Liu Xuehui , Teng Da , Li Zhanzhan , Wang Xiumin , Mao Ruoyu , Wang Xiao , Hao Ya , Wang Jianhua
Published: June 2017

NZ17074 (N1), an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is cytotoxic. To reduce its cytotoxicity, seven N1 analogues with different structures were designed by changing their disulfide bonds, hydrophobicity, or charge. The “rocket” analogue-N2 and the “kite” analogue-N6 have potent activity and showed lower cytotoxicity in RAW264.7 cells than N1. The NMR spectra revealed that N1, N2, and N6 adopt β-sheet structures stabilized by one or two disulfide bonds. N2 and N6 permeabilized the outer/inner membranes of E. coli, but did not permeabilize the inner membranes of S. enteritidis. N2 and N6 induced E. coli and S. enteritidis cell cycle arrest in the I-phase and R-phase, respectively. In E. coli and in S. enteritidis, 18.7–43.8% of DNA/RNA/cell wall synthesis and 5.7–61.8% of DNA/RNA/protein synthesis were inhibited by the two peptides, respectively. Collapsed and filamentous E. coli cells and intact morphologies of S. enteritidis cells were observed after treatment with the two peptides. Body weight doses from 2.5–7.5 mg/kg of N2 and N6 enhanced the survival rate of peritonitis- and endotoxemia-induced mice; reduced the serum IL-6, IL-1β and TNF-α levels; and protected mice from lipopolysaccharide-induced lung injury. These data indicate that N2 and N6, through multiple selective actions, may be promising dual-function candidates as novel antimicrobial and anti-endotoxin peptides.
Evaluation of the immature platelet fraction contribute to the differential diagnosis of hereditary, immune and other acquired thrombocytopenias
Authors: Ferreira F. L. B. , Colella M. P. , Medina S. S. , Costa-Lima C. , Fiusa M. M. L. , Costa L. N. G. , Orsi F. A. , Annichino-Bizzacchi J. M. , Fertrin K. Y. , Gilberti M. F. P. , Ozelo M. C. , De Paula E. V.
Published: June 2017

The differential diagnosis of immune (ITP) and hereditary macrothrombocytopenia (HM) is key to patient management. The immature platelet fraction (IPF) represents the subset of circulating platelets with higher RNA content, and has been shown to distinguish hypo- from hyperproliferative thrombocytopenias. Here we evaluated the diagnostic accuracy of IPF in the differential diagnosis between HM and other thrombocytopenias in a population of patients with post-chemotherapy thrombocytopenia (n = 56), bone marrow failure (n = 22), ITP (n = 105) and HM (n = 27). TPO levels were also measured in HM and ITP matched for platelet counts. Platelet counts were similar in all patient groups. Higher IPF values were observed in both ITP (12.3%; 2.4–65.6%) and HM (29.8%; 4.6–65.9%) compared to hypoproliferative thrombocytopenias. IPF values were also higher in HM compared to ITP, yielding a diagnostic accuracy of 0.80 (95%CI 0.70–0.90; P < 0.0001) to distinguish these two conditions. Intra- and inter-assays reproducibility of IPF in HM patients revealed that this is a stable parameter. In conclusion, IPF is increased in HM compared to both ITP and other thrombocytopenias and contributes to the differentiation between ITP and HM. Further studies are warranted to understand the biological rationale of these findings and to its incorporation in diagnostic algorithms of HM.
Linking optical and molecular signatures of dissolved organic matter in the Mediterranean Sea
Authors: Martínez-Pérez Alba María , Nieto-Cid Mar , Osterholz Helena , Catalá Teresa S. , Reche Isabel , Dittmar Thorsten , Álvarez-Salgado Xosé Antón
Published: June 2017

Dissolved organic matter (DOM) plays a key role in global biogeochemical cycles and experiences changes in molecular composition as it undergoes processing. In the semi-closed basins of the oligotrophic Mediterranean Sea, these gradual molecular modifications can be observed in close proximity. In order to extend the spatial resolution of information on DOM molecular composition available from ultrahigh resolution mass spectrometry in this area, we relate this data to optical (fluorescence and absorption spectroscopy) measurements. Covariance between molecular formulae signal intensities and carbon-specific fluorescence intensities was examined by means of Spearman’s rank correlations. Fifty two per cent of the assigned molecular formulae were associated with at least one optical parameter, accounting for 70% of the total mass spectrum signal intensity. Furthermore, we obtained significant multiple linear regressions between optical and intensity-weighted molecular indices. The resulting regression equations were used to estimate molecular parameters such as the double bond equivalent, degradation state and occurrence of unsaturated aliphatic compounds from optical measurements. The statistical linkages between DOM molecular and optical properties illustrate that the simple, rapid and cost-efficient optical spectroscopic measurements provide valuable proxy information on the molecular composition of open ocean marine DOM.
Silver Nanowire/Colorless-Polyimide Composite Electrode: Application in Flexible and Transparent Resistive Switching Memory
Authors: Yeom Seung-Won , You Banseok , Cho Karam , Jung Hyun Young , Park Junsu , Shin Changhwan , Ju Byeong-Kwon , Kim Jong-Woong
Published: June 2017

Improving the performance of resistive switching memories, while providing high transparency and excellent mechanical stability, has been of great interest because of the emerging need for electronic wearable devices. However, it remains a great challenge to fabricate fully flexible and transparent resistive switching memories because not enough research on flexible and transparent electrodes, for their application in resistive switching memories, has been conducted. Therefore, it has not been possible to obtain a nonvolatile memory with commercial applications. Recently, an electrode composed of a networked structure of Ag nanowires (AgNWs) embedded in a polymer, such as colorless polyimide (cPI), has been attracting increasing attention because of its high electrical, optical, and mechanical stability. However, for an intended use as a transparent electrode and substrate for resistive switching memories, it still has the crucial disadvantage of having a limited surface coverage of conductive pathways. Here, we introduce a novel approach to obtain a AgNWs/cPI composite electrode with a high figure-of-merit, mechanical stability, surface smoothness, and abundant surface coverage of conductive networks. By employing the fabricated electrodes, a flexible and transparent resistive memory could be successfully fabricated.
Domain wall motion in Pb(Zr0.20Ti0.80)O3 epitaxial thin films
Authors: Borderon C. , Brunier A. E. , Nadaud K. , Renoud R. , Alexe M. , Gundel H. W.
Published: June 2017

Two Pb(Zr0.20Ti0.80)O3 samples of different thickness and domain configuration have been studied. The c-domain sample was found to have a higher coercive field E
c
and higher dielectric losses than the other which presents approximately 60% of c-domains and 40% of a-domains as observed by piezo force microscopy (PFM) characterization. Hyperbolic law measurements reveal that the higher coercive field is due to domain wall pinning in deeper defects and hence a higher field E
th
is required for unpinning. The dissipation factors due to domain wall motion, however, are similar in both samples since the domain wall density is low and there is almost no interaction between domain walls. The higher dielectric losses in the c-domain oriented sample are a result of a greater contribution from the lattice and seem to be due to strain from the substrate, which is not relieved in a thin sample. PFM and dielectric characterization are complementary methods which provide a better understanding of the domain wall motion.
Correction: Corrigendum: Fractional Solitons in Excitonic Josephson Junctions
Authors: Hsu Ya-Fen , Su Jung-Jung
Published: June 2017

Scientific Reports 5: Article number: 15796; published online: 29 October 2015; updated: 07 June 2017 In this Article, an affiliation has been omitted for Ya-Fen Hsu. The correct affiliations are listed below: Department of Electrophysics, National Chiao Tung University, Hsinchu 300, Taiwan. PhysicsDivision, National Center for Theoretical Science, Hsinchu, 30013, Taiwan.
Correction: Corrigendum: Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation
Authors: Patel Yogi A. , Saxena Tarun , Bellamkonda Ravi V. , Butera Robert J.
Published: June 2017

Scientific Reports 7: Article number: 39810; published online: 05 January 2017; updated: 07 June 2017 This Article contains an error in Figure 3B where the y-axis label of the scale bar is missing. The correct Figure 3 appears below as Figure 1.
Pyridalthiadiazole acceptor-functionalized triarylboranes with multi-responsive optoelectronic characteristics
Authors: Yin Xiaodong , Liu Kanglei , Ren Yi , Lalancette Roger A. , Loo Yueh-Lin , Jäkle Frieder
Published: June 2017

The functionalization of triarylboranes with pyridalthiadiazole (PT) acceptor moieties gives Ar2B–π–PT dyads and PT–π–B(Ar)–π–PT triads with low-lying PT-centered LUMO orbitals. Addition of a fluoride source results in competing anion binding to boron and PT reduction, depending on the steric and electronic structure of the B-aryl group.
Determination of heavy metals in cigarettes using high-resolution continuum source graphite furnace atomic absorption spectrometry
Authors: Ren Ting , Chen Xi , Ge Yao , Zhao Lijiao , Zhong Rugang
Published: June 2017

Quantitative determination of toxic metals in tobacco, smoke, ash and butts of cigarettes using HR-CS GFAAS.
Balancing the utility and legality of implementing portable mass spectrometers coupled with ambient ionization in routine law enforcement activities
Authors: Bruno Alessandra M. , Cleary Scott R. , O'Leary Adam E. , Gizzi Michael C. , Mulligan Christopher C.
Published: June 2017

Ambient sampling, portable MS systems have the potential to allow field processing of forensic evidence, as well as serve as a flexible investigative tool during law enforcement activities. However, the underlying legal implications require the discretion of practitioners to ensure both lawful and ethical usage.
Mo@Pt overlayers as efficient catalysts for hydrodeoxygenation of guaiacol and anisole
Authors: Lai Qinghua , Zhang Chen , Holles Joseph H.
Published: June 2017

Silica alumina supported Mo@Pt overlayer catalysts were prepared via the directed deposition technique and evaluated for hydrodeoxygenation (HDO) of guaiacol and anisole.
Space-confined synthesis of multilayer Cu–N-doped graphene nanosheets for efficient oxygen electroreduction
Authors: Ni Yangyang , Chen Zhengyan , Kong Fantao , Qiao Yu , Kong Aiguo , Shan Yongkui
Published: June 2017

Cu–N-doped graphene nanosheets prepared by thermal conversion of montmorillonite-confined Cu(ii) 2,2′-bipyridines exhibit efficient catalytic performance for oxygen electroreduction.
Quantitative and correlative biodistribution analysis of 89Zr-labeled mesoporous silica nanoparticles intravenously injected into tumor-bearing mice
Authors: Kramer Larissa , Winter Gordon , Baur Benjamin , Kuntz Andrea J. , Kull Thomas , Solbach Christoph , Beer Ambros J. , Lindén Mika
Published: June 2017

The biodistribution of 89Zr-labeled mesoporous silica nanoparticles (MSNs) was evaluated in detail using a prostate cancer mouse model bearing LNCaP C4-2 and PC-3 tumor xenografts with focus on passive targeting.
Simple fluorescence sensing of extreme acidity based on inner filter effect of ascorbic acid to fluorescent Au nanoclusters
Authors: Zhou Ronghui , Li Yuqin , Tian Yuanyuan , Sun Qun , Deng Pengchi , Wu Lan , Hou Xiandeng
Published: June 2017

On the basis of the inner filter effect (IFE) between ascorbic acid (AA) and Au nanoclusters (AuNCs), a simple extreme acidity fluorescence sensor was developed without complex organic synthesis, which can be used to detect acidity within the pH range of 2.4–4.6.
The interaction of photoexcited carbon nanodots with metal ions disclosed down to the femtosecond scale
Authors: Sciortino A. , Madonia A. , Gazzetto M. , Sciortino L. , Rohwer E. J. , Feurer T. , Gelardi F. M. , Cannas M. , Cannizzo A. , Messina F.
Published: June 2017

We use a combination of steady state, nanosecond-resolved, and femtosecond-resolved optical spectroscopy to fully unravel the interactions of highly fluorescent carbon nanodots with transition metal ions.
WITHDRAWN: Correlations of CTLA-4 exon-1 rs231775A>G and promoter region rs5742909C>T polymorphisms with the therapeutic efficacy of 131I radionuclide in Graves' disease
Authors: Luan Sha , Gao Yue , Wang Chun , Pei Chun-Ying , Zhao Chang-Jiu
Published: June 2017

The Accepted Manuscript version of this article (published on 6 June 2017) was withdrawn on 16 November 2017 at the request of the authors.
Using Speech Analysis to Unmask Perceptual Bias: Dialect, Difference, and Tolerance
Authors: Dalton Jennifer C. , Keegan Louise C.
Published: June 2017

Students in pre-professional training in Communication Sciences and Disorders (CSD) demonstrate a novice ability to identify their own perceptual biases towards linguistic differences among individuals with English dialects that differ from their own. This paper describes the application of speech analysis software (e.g., Praat) to increase students' ability to discriminate and identify distinct dialectal differences between two dialects of English: Southern-American accented English and Irish-accented English. Students utilized both auditory-perceptual as well as acoustic data to reveal their own perceptual biases. They contextualized their findings by identifying potential cultural influences that were predictive of the accent differences. Students reported that this experience increased their awareness of cultural and linguistic differences and served as a precursor to their development of clinical expertise in determining dialectal difference versus disorder in individuals with potential communication disorders.
Highly Enantioselective Biginelli Reaction of Aliphatic Aldehydes Catalyzed by Chiral Phosphoric Acids
Authors: Guo Yongbiao , Zou Chuanpin , Gao Zhenhua , Meng Xiangyan , Huang Guilan , Zhong Hui , Yu Huilan , Ding Xiaoqin , Tang Hui
Published: June 2017

Several chiral phosphoric acids were evaluated as organocatalysts for the enantioselective Biginelli reaction of aliphatic aldehydes. With a chiral phosphoric acid derived from 3,3′-bis(3,5-di-tert-butyl-4-methoxyphenyl)-1,1′-binaphthalene-2,2′-diol, and after extensive optimization of the reaction conditions, the corresponding dihydropyrimidines were obtained in moderate to high yields with 73–87% ee by a three-component reaction of an aliphatic aldehyde, urea, and a β-keto ester.
Asymmetric Friedel–Crafts/Michael Reaction of Indoles and Pyrroles with Coumarin-3-carbonylates
Authors: Beletskaya Irina , Desyatkin Victor
Published: June 2017

Asymmetric Friedel–Crafts reactions of indoles or pyrroles with coumarin-3-carboxylates catalyzed by Cu(OTf)2 complexes with chiral bis(oxazoline) ligands have been developed. The highest ee (up to 82%) was achieved for indole with a nitro derivative of coumarin-3-carboxylate­.
Unusually High Rate of Early Failure of Tibial Component in ATTUNE Total Knee Arthroplasty System at Implant–Cement Interface
Authors: Khlopas Anton , Chughtai Morad , Cole Connor , Gwam Chukwuweike , Harwin Steven , Whited Brent , Omiyi Didi , Drumm Joshua , Bonutti Peter
Published: June 2017

A novel design total knee arthroplasty (TKA) system has been introduced to improve patient outcomes and increase longevity. However, we have encountered a high rate of debonding of tibial implant–cement interface. In addition, multiple reports have been filed in Manufacturer and User Facility Device Experience database (MAUDE) with the same mechanism of failure. Therefore, we evaluated: clinical, radiographic, and intraoperative findings of patients who received this system and required a revision surgery, and findings from MAUDE database compiled to this date. We reviewed three hospital databases for patients who had revision TKA for tibial loosening at the implant–cement interface. This yielded 15 cases with a mean age of 61 years (range, 47–84). All patients received a novel knee system at another institution. Radiographic analysis was performed by treating orthopaedist. The MAUDE database was reviewed for reports of aseptic failure. Patients presented with pain on weight bearing, effusion, and decreased range of motion (ROM) within 2 years after surgery. Radiographic evaluation demonstrated loosening of the tibial components in 2 of 15 knees. This included cruciate retaining, posterior stabilized, fixed bearing, and rotating platform bearing designs. Intraoperative findings demonstrated gross loosening of the tibial component at the implant–cement interface. Femoral and patellar components were well fixed. There were 21 reports of tibial loosening at the implant–cement interface in MAUDE database in the past 2 months alone. Numerous other tibial failures were reported; however, the mechanisms of failures were not specified. Tibial component loosening is a rare complication of cemented TKA at short-term follow-up. Several possible reasons include increased constraint, reduced cement pockets, and reduced keel rotational stabilizers. The tibial component, which has greater torsional loads, has lower surface roughness than femoral component. We believe that this complication is underreported due to failure of radiographs to assess loosening. In addition, MAUDE database reporting is not consistent and competing companies cannot provide data on the revised components. In patients who have negative workup for a painful joint, one must consider the diagnosis of debonding.
Depression, Schwindel und Tremor – ein Fall von Gelsemium sempervirens
Authors: Thiele Von Claudia
Published: June 2017

Kurzvorstellung der Geriatrischen Reha- Klinik Bethel Welzheim. Präsentation einer Patientin mit Schwindel, Tremor und fraglicher Depression, die mit einer Einzeldosis Gelsemium C30 deutlich
gebessert wurde.
Editorial
Authors: Teut Michael
Published: June 2017

Ein wildes Jahr 2016 ist für die Homöopathie abgelaufen. Die Homöopathie hat viele Attacken aus der Presse und aus Skeptikerkreisen einstecken müssen, der Deutsche Homöopathiekongress 2016 in Bremen ist von einem sehr kritischen Presseecho begleitet worden.
Littre Hernia: A Rare Case of an Incarcerated Meckel’s Diverticulum
Authors: Malling Brian , Karlsen Andreas , Hern Jesper
Published: June 2017

A Meckel’s diverticulum is a remnant of the vitelline duct, which leads to the formation of a true diverticulum containing all layers of the small intestine. The diverticulum can contain ectopic gastric, duodenal or pancreatic tissue and is the most common congenital anomaly of the gastrointestinal tract with estimates of prevalence ranging from 0.3% to 3%. The condition is usually clinically silent. In children the most common complication is gastrointestinal bleeding caused by ulceration due to the acid secretion by ectopic gastric mucosa.
Beeinflusst sportliche Aktivität die Revisionsrate nach Knietotalendoprothese? Analyse eines 12-Jahres-Follow-up
Authors: Valle Christina , Sperr Michael , Lemhöfer Christina , Bartel Karla , Schmitt-Sody Marcus
Published: June 2017

Hintergrund Der Anspruch von Patienten an Knietotalprothesen (KTEP) wächst zunehmend. Es stellt sich immer wieder die Frage, ob sportlich aktive Patienten nach Implantation einer KTEP ein erhöhtes Revisionsrisiko aufweisen im Vergleich zu Patienten ohne sportliche Aktivitäten.

Patienten/Material und Methoden In einer retrospektiven Studie wurden 130 Patienten mit einem Altersdurchschnitt von 69,2 Jahren zu Ihrer sportlichen Aktivität 22 Monate vor und nach KTEP Primärimplantation befragt. Die Patienten wurden aufgrund der Ergebnisse der Befragung in 2 Gruppen (A = Sport, B = No-Sport) eingeteilt. 7 Jahre postoperativ wurden dieselben Patienten erneut zu Ihrem Sportverhalten und 12 Jahre postoperativ zusätzlich zu stattgehabten Revisionsoperationen befragt.

Ergebnisse Von den 130 im Jahre 2005, ca. 2 Jahre nach KTEP-Implantation, befragten Patienten gaben 88 (67,7 %) an, regelmäßig Sport auszuüben (Gruppe A) während 42 Patienten (32,3 %) keinerlei Sport betrieben (Gruppe B). 2010 antworteten 87 der 130 Patienten auf die Befragung. 60 Patienten der Gruppe A waren weiterhin regelmäßig sportlich aktiv. 27 Patienten der Gruppe B gaben an, weiterhin keinerlei Sport zu betreiben. 2015 konnten von den 87 Patienten die 2010 befragt wurden immerhin noch 67 Patienten kontaktiert werden – davon 46 Patienten der Gruppe A und 21 Patienten der Gruppe B. In Gruppe A kam es 12 Jahre postoperativ bei 7 von 46 Patienten (15,2 %) zu Revisionsoperationen. In Gruppe B gaben 5 von 21 (23,8 %) Patienten Revisionsoperationen im Sinne von Wechseloperationen in den letzten Jahren an.

Schlussfolgerung Es konnte gezeigt werden, dass 12 Jahre nach Primärimplantation einer KTEP die Revisionsrate in der Gruppe der sportlich aktiven Patienten verglichen mit den Inaktiven deutlich reduziert war. Daher lässt sich schlussfolgern, dass moderate sportliche Aktivität nach künstlichem Kniegelenkersatz keinen negativen Einfluss auf die Standzeit einer Knietotalendoprothese hat, sondern sogar möglicherweise zu verbesserter Osteointegration und damit zu weniger osteolytischen Reaktionen mit daraus resultierender aseptischer Prothesenlockerung führen könnte.
Use of a novel shorter minimum caliber needle for creating endoscopic tattoos for preoperative localization: a comparative ex vivo study
Authors: Imai Kenichiro , Hotta Kinichi , Ito Sayo , Yamaguchi Yuichiro , Kawakami Takeshi , Wada Takuya , Igarashi Kimihiro , Kishida Yoshihiro , Kinugasa Yusuke , Kawata Noboru , Tanaka Masaki , Kakushima Naomi , Takizawa Kohei , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki
Published: June 2017

Background and study aims In colorectal cancer surgery, inadvertent deep injections during endoscopic tattooing can cause India ink leakage into the peritoneum, leading to complications or to poor visualization of the surgical plane. This ex vivo animal study compared the use of novel shorter, minimum caliber needles versus conventional injection needles for endoscopic tattooing.

Animals and methods Four endoscopists used the novel needles and conventional needles to make ten endoscopic tattoos (five tattoos/needle type/endoscopist) in harvested porcine rectum using a saline test-injection method. India ink leakage and the success of the tattoo (i. e. visible, < 40 mm, plus no India ink leakage) were compared.

Results India ink leakage was observed for 30 % (6/20) of the conventional needle tattoos but for none of the novel needle tattoos (P = 0.02). Tattoos created using the novel needles were more successful than those made with the conventional needles: 18/20 (90 %) vs. 11/20 (55 %); P = 0.01.

Conclusions The use of novel shorter minimum caliber needles may be safe and effective for endoscopic tattooing for preoperative localization prior to colorectal cancer surgery.