bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of regioselective starch‐based macroinitiators at molecular level
Authors: Wang Leli , Qu Lin , Wu Ying , Men Yongjun , Liu Zhengping
Published: June 2017

Regioselective starch‐based macroinitiators, such as 2,3,6‐O‐macroinitiator (2,3,6‐O‐starch‐2‐bromoisobutyrate), 2‐O‐macroinitiator (2‐O‐starch chloroacetate), 6‐O‐macroinitiator (6‐O‐starch‐3‐chloropivalate), 3‐O‐macroinitiator (3‐O‐starch‐2‐bromoisobutyrate), 3,6‐O‐macroinitiator (3,6‐O‐starch‐2‐bromoisobutyrate), and 2,3‐O‐macroinitiator (2,3‐O‐starch‐2‐bromoisobutyrate), were successfully synthesized at the molecular level. 13C NMR spectra were employed to certify the structures of these regioselective macroinitiators. Their thermal behaviors characterized by TGA and DSC indicated the destruction of hydrogen bonds and the crystalline structure during the dissolution and reaction processes. The solubility of macroinitiators depended on their degree of substitution (DS).
Cover Image, Volume 7, Issue 4
Authors: Hermans Susanne M.A. , Pfleger Christopher , Nutschel Christina , Hanke Christian A. , Gohlke Holger
Published: June 2017

The front cover image, by Susanne M.A. Hermans et al., is based on the Advanced Review Rigidity theory for biomolecules: concepts, software, and applications, DOI: 10.1002/wcms.1311.

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Cover Image, Volume 7, Issue 4
Authors: Chen Yang , Wang Zhong‐yi , Yuan Gang , Huang Lan
Published: June 2017

The cover image, by Yang Chen et al., is based on the Overview An overview of online based platforms for sharing and analyzing electrophysiology data from big data perspective, DOI: 10.1002/widm.1206.

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Cover Image, Volume 9, Issue 4
Authors: Cui Yi , Liu Jing , Irudayaraj Joseph
Published: June 2017

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The front cover image, by Yi Cui et al., is based on the Advanced Review Beyond quantification: in situ analysis of transcriptome and pre‐mRNA alternative splicing at the nanoscale, DOI: 10.1002/wnan.1443.
A new micro X‐ray fluorescence spectrometer for in vivo elemental analysis in plants
Authors: Fittschen U.E.A. , Kunz H.‐H. , Höhner R. , Tyssebotn I.M.B. , Fittschen A.
Published: June 2017

In vivo micro X‐ray fluorescence (micro‐XRF) on plants is aimed at mapping spatial ion accumulation, eg. in plant leaves to minimize artifacts arising from sample preparation and to be able to detect changes occurring under environmental stress. To obtain reliable results, a spectrometer and sample setup that maintain the plant in good physiological condition are necessary. We have built a micro‐XRF spectrometer, in which analyses are performed in air, thereby allowing for in vivo micro‐XRF measurements in plants. Mapping is performed with full spectrum acquisition in each pixel and is automated and controlled by computer software developed for this micro‐XRF unit. Limits of detection were found to be comparable to those found previously at second‐generation synchrotron facilities using a freestanding film reference from 0.04 ng/mm2 for Fe to 0.20 ng/mm2 for Pb. The spot size was determined to be less than 14 μm at Rh Kα line (20.214 keV). Relative sensitivities were determined for elements from S to Pb using the freestanding film reference and a 13‐element standard dried droplet deposition. For in vivo measurements, a dedicated sample holder was developed by 3‐D printing. Here, we present the in vivo elemental analysis capabilities of our micro‐XRF spectrometer by mapping elements in Arabidopsis thaliana plants and by assessing their physiological state before and after scanning. Copyright © 2017 John Wiley & Sons, Ltd.
Making Flow-Based Security Detection Parallel
Authors: Švepeš Marek , Čejka Tomáš
Published: June 2017

Flow based monitoring is currently a standard approach suitable for large networks of ISP size. The main advantage of flow processing is a smaller amount of data due to aggregation. There are many reasons (such as huge volume of transferred data, attacks represented by many flow records) to develop scalable systems that can process flow data in parallel. This paper deals with splitting a stream of flow data in order to perform parallel anomaly detection on distributed computational nodes. Flow data distribution is focused not only on uniformity but mainly on successful detection. The results of an experimental analysis show that the proposed approach does not break important semantic relations between individual flow records and therefore it preserves detection results. All experiments were performed using real data traces from Czech National Education and Research Network.
Visual Analytics for Network Security and Critical Infrastructures
Authors: Burská Karolína , Ošlejšek Radek
Published: June 2017

A comprehensive analysis of cyber attacks is important for better understanding of their nature and their origin. Providing a sufficient insight into such a vast amount of diverse (and sometimes seemingly unrelated) data is a task that is suitable neither for humans nor for fully automated algorithms alone. Not only a combination of the two approaches but also a continuous reasoning process that is capable of generating a sufficient knowledge base is indispensable for a better understanding of the events. Our research is focused on designing new exploratory methods and interactive visualizations in the context of network security. The knowledge generation loop is important for its ability to help analysts to refine the nature of the processes that continuously occur and to offer them a better insight into the network security related events. In this paper, we formulate the research questions that relate to the proposed solution.
Cost‐Effectiveness of Two Decision Strategies for Shunt Use During Carotid Endarterectomy
Authors: Kolkert Joe L. P. , Groenwold Rolf H. H. , Leijdekkers Vanessa J. , ter Haar Joep , Zeebregts Clark J. , Vahl Anco
Published: June 2017

Background

Arterial shunting during carotid endarterectomy (CEA) is essential in some patients because of insufficient cerebral perfusion during cross‐clamping. However, the optimal diagnostic modality identifying these patients is still debated. None of the currently used modalities has been proved superior to another. The aim of this study was to assess the cost‐effectiveness of two modalities, stump pressure measurement (SPM) versus electroencephalography (EEG) combined with transcranial Doppler (TCD) during CEA.

Methods

Two retrospective cohorts of consecutive patients undergoing CEA with different intraoperative neuromonitoring strategies (SPM vs. EEG/TCD) were analyzed. Clinical data were collected from patient hospital records. Primary clinical outcome was in‐hospital stroke or death. Total admission costs were calculated based on volumes of healthcare resources. Analyses of effects and costs were adjusted for clinical differences between patients by means of a propensity score, and cost‐effectiveness was estimated.

Results

A total of 503 (239 SPM; 264 EEG/TCD) patients were included, of whom 19 sustained a stroke or died during admission (3.3 vs. 4.2%, respectively, adjusted risk difference 1.3% (95% CI −2.3–4.8%)). Median total costs were €4946 (IQR 4424–6173) in the SPM group versus €7447 (IQR 6890–8675) in the EEG/TCD group. Costs for neurophysiologic assessments were the main determinant for the difference.

Conclusions

Given the evidence provided by this small retrospective study, SPM would be the favored strategy for intraoperative neuromonitoring if cost‐effectiveness was taken into account when deciding which strategy to adopt.
“If It Helps, It's Worth a Try”: an Investigation of Perceptions and Attitudes about Genetic Counseling among Southern Manitoba Hutterites
Authors: Gemmell Amber P. , Veach Patricia McCarthy , MacFarlane Ian , Riesgraf Rachel , LeRoy Bonnie S.
Published: June 2017

Few studies have explored the public's views of genetic counseling services, and even fewer focus on founder populations with high prevalence of genetic disease, such as Hutterites. The Hutterites are an Anabaptist religious group grounded in a strong Christian faith. The primary aim of this study was to assess Hutterites’ views of genetic counseling services. A secondary aim was to compare their views to those obtained in a study of rural Midwestern U.S. residents (Riesgraf et al., Journal of Genetic Counseling, 24(4), 565‐579, 2015). One‐hundred eleven individuals from southern Manitoba Hutterite colonies completed an anonymous survey assessing familiarity with and attitudes about genetic counseling; perceptions of its purpose, scope and practice; and willingness to use genetic counseling services. Although many respondents were not familiar with genetic counseling, most had accurate perceptions and positive attitudes. For instance, mean ratings showed endorsement of trust in information provided by genetic counselors and agreement that genetic counseling aligns with their values. Logistic regression indicated reported willingness to use genetic counseling services increased if respondents: had a higher self‐rated familiarity with genetic counseling; were younger; agreed with the statement: I would trust the information provided by a genetic counselor; and disagreed with the statements: Genetic counseling is only useful for a small group of people with rare diseases, and Genetic counselors help expectant parents choose the eye color of their child. Thematic analysis of comments regarding willingness to use genetic counseling services yielded themes of personal/family risk, pragmatism (genetic counseling is sensible and practical for managing health concerns), and desire to prevent genetic conditions in the Hutterite population. Comparison of the present findings to those of Riesgraf et al. suggests predictors of Hutterites’ willingness to use genetic counseling are unique and culturally‐based. Limited replication of Riesgraf et al. was achieved. Additional findings, practice implications and research recommendations are presented.
Hypoglycemic Event Frequency and the Effect of Continuous Glucose Monitoring in Adults with Type 1 Diabetes Using Multiple Daily Insulin Injections
Authors: Riddlesworth Tonya , Price David , Cohen Nathan , Beck Roy W.
Published: June 2017

Introduction

The benefits of continuous glucose monitoring (CGM) in type 1 diabetes have been established among adults using insulin pumps. The DIAMOND randomized clinical trial examined the effectiveness of using CGM in improving glycemic control in participants using insulin injections. The frequency of hypoglycemic events in this trial has not been previously examined.

Methods

Adults with type 1 diabetes using multiple daily insulin injections (MDI) with A1C values of 7.5% to 9.9% and not using CGM were randomized to adopt CGM (CGM group, n = 105) or continue with usual care (control group, n = 53). CGM data were collected from both groups at the beginning of the study and after 3 and 6 months. A hypoglycemic event was defined as a series of at least CGM values less than 3.0 mmol/L, separated by 20 min or more, with no intervening values of 3.0 mmol/L or more. Hypoglycemic event rates per 24 h were compared using a linear model adjusted for the baseline event rate per 24 h, baseline A1C, and site as a random effect.

Results

In the CGM group, the median hypoglycemic event rate fell by 30% (0.23 per 24 h at baseline and 0.16 per 24 h at follow-up) while in the control group the rate was nearly unchanged (0.31 per 24 h at baseline and 0.30 per 24 h at follow-up; p value = 0.03).

Conclusion

In the DIAMOND randomized controlled trial, participants in the CGM group experienced a greater reduction in hypoglycemic event rate than participants receiving usual care in the control group.

Trial Registration

Clinicaltrials.gov Identifier: NCT02282397.
Minimizing a Wireless Passive LC-Tank Sensor to Monitor Bladder Pressure: A Simulation Study
Authors: Melgaard Jacob , Struijk Johannes J. , Rijkhoff Nico J. M.
Published: June 2017

In this simulation study, a wireless passive LC-tank sensor system was characterized. Given the application of continuous bladder monitoring, a specific system was proposed in terms of coil geometries and electronic circuitry. Coupling coefficients were spatially mapped by simulation, as a function of both coil distance, and longitudinal and transverse translation of the sensor relative to the antenna. Further, two interrogation schemes were outlined. One was an auto-balancing bridge for computing the sensor-system impedance. In this case, the theoretical noise limit of the analogue part of the system was found by simulations. As the full system is not necessary for obtaining a pressure reading from the sensor, a simplified circuit more suited for an implantable system was deduced. For this system, both the analogue and digital parts were simulated. First, the required ADC resolution for operating the system at a given coupling was found by simulations in the noise-free case. Then, for one selected typical operational point, noise was added gradually, and through Monte-Carlo type simulations, the system performance was obtained. Combining these results, it was found that it at least is possible to operate the proposed system for distances up to 12 mm, or equivalently for coupling coefficients above 0.005. In this case a 14 bit ADC is required, and a carrier SNR of 27 dB can be tolerated.
Longitudinal study of religiosity and mental health of adolescents with psychiatric problems. The TRAILS study
Authors: van der Jagt-Jelsma W. , de Vries-Schot M. , Scheepers P. , van Deurzen P.A.M. , Klip H. , Buitelaar J.K.
Published: June 2017

Purpose:

This study used longitudinal data to examine the influence of the religiosity of pre-adolescents with psychiatric problems on the course of mental health during adolescence.

Methods:

In the TRAILS clinical cohort of 543 pre-adolescents (10–12 years), mental health problems were assessed using self-report at baseline, T2 (12–14 years), T3 (14–17 years), and T4 (17–21 years). The Youth Self Report (YSR) was used at baseline, T2, and T3, and the Adult Self Report (ASR) was used at T4. Religiosity was assessed at baseline using self-report and information from mothers and fathers, resulting in three categorical religiosity variables and six SOCON (Social Cultural Developments Questionnaire) religiosity scales that assess religiosity in greater detail. Repeated measure ANOVA analyses were performed for each independent religiosity variable with internalizing and externalizing problem behavior as dependent variables, gender as a factor and time (T1, T2, T3 and T4) as within factor. Results were adjusted for marital status of parents and socioeconomic status and corrected for multiple testing.

Results:

There were main effects of the self-report SOCON scale “Humanistic beliefs” and gender and gender “by Humanistic beliefs” interaction effect on internalizing problems. Follow-up tests revealed that among females “high” scores on “Humanistic beliefs” were associated with increased internalizing problems.

Conclusions:

There were hardly any associations between religiosity and mental health in a clinical cohort of pre-adolescents up to adolescence. The exception being that among females strong humanistic beliefs were associated with internalizing problems. Implications of these findings are discussed.
Comparison of cyclophosphamide–thalidomide–dexamethasone to bortezomib–cyclophosphamide–dexamethasone as induction therapy for multiple myeloma patients in Brazil
Authors: Vigolo Suelen , Zuckermann Joice , Bittencourt Rosane Isabel , Silla Lúcia , Pilger Diogo André
Published: June 2017

Objective/background:

Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency.

Methods:

Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progressionfree survival, and overall survival of patients.

Results:

Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p = 0.023). Disease progression after autologous HSCT did not differ between the two groups.

Conclusion:

VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments.
Visual Style and Constructing Identity in the Hellenistic World
Authors: Versluys Miguel John
Published: June 2017

Located in the small kingdom of Commagene at the upper Euphrates, the late Hellenistic monument of Nemrud Dağ (c.50 BC) has been undeservedly neglected by scholars. Qualified as a Greco-Persian hybrid instigated by a lunatic king, this fascinating project of bricolage has been written out of history. This volume redresses that imbalance, interpreting Nemrud Dağ as an attempt at canon building by Antiochos I in order to construct a dynastic ideology and social order, and proving the monument's importance for our understanding of a crucial transitional phase from Hellenistic to Roman. Hellenistic Commagene therefore holds a profound significance for a number of discussions, such as the functioning of the Hellenistic koine and the genesis of Roman 'art', Hellenism and Persianism in antiquity, dynastic propaganda and the power of images, Romanisation in the East, the contextualising of the Augustan cultural revolution, and the role of Greek culture in the Roman world.
Treating Chronically Traumatised Children with the Sleeping Dogs Method: Don't Let Sleeping Dogs Lie!
Authors: Struik Arianne
Published: June 2017

Many traumatised children in Australia do not receive the type of trauma-focused treatment endorsed by international guidelines and, as such, they suffer from the consequences of intergenerational trauma. Even when trauma-focused treatment is available, there is a group of children who are difficult to engage in treatment and do not want to talk about their traumatic memories. Clinicians are often reluctant to address the trauma, for fear of ‘waking up sleeping dogs’. All children deserve a chance to heal from trauma and I believe we, as a society, have a responsibility to provide children with appropriate services and treatment methods to help them achieve this. This article describes the Sleeping Dogs method, a three-phased trauma-focused treatment method, based on a collaborative use of interventions by therapists, child-protection workers, residential staff, school and the child's network. A Six Test Form is used to analyse the possible reasons why the child is unable to talk about his or her traumatic memories, for which interventions are planned. Case examples with children who can be difficult to engage in trauma-focused treatment are used to illustrate interventions. Clinical experiences show the Sleeping Dogs method has been successfully used internationally, as well as remote communities in Australia.
Sociolinguistic research with endangered varieties: The case of Louisiana French
Authors: Blainey Darcie
Published: June 2017

This article outlines the differences in goals, methods and results that variationist researchers may encounter when exploring and/or documenting a threatened language variety, and underscores special considerations and aspects of the research program that linguists must work to control for when working with endangered varieties of Western languages. In particular, it examines questions and strategies for dealing with sparse data for longitudinal studies; fewer speakers for stratified samples; the inverse relation between linguistic fluency and age; social network constraints in small speech communities; literacy-centric exercises in oral language communities; and larger project protocols designed for stable linguistic communities. Throughout the paper, the collection and analysis of Louisiana French liaison data from 1939, 1977, and 2010 provide an application of the proposed methods.
Wind farm power fluctuations and spatial sampling of turbulent boundary layers
Authors: Bossuyt Juliaan , Meneveau Charles , Meyers Johan
Published: June 2017

The fluctuations in power output from wind farms display significantly reduced spectra compared to single wind turbines due to power smoothing and averaging. In order to better understand these spectral features and to relate them to properties of turbulent boundary layers, we perform a wind tunnel experiment in which we measure spatio-temporal characteristics of an experimental surrogate of the power output from a micro wind farm with 100 porous disk models. The experimental results show that the frequency spectrum of the total wind farm power follows a power law with a slope between $-5/3$ and $-2$, and up to lower frequencies than seen for any individual turbine model. In agreement with previous studies in the literature, peaks in the spectrum are observed at frequencies corresponding to the mean flow convection time between consecutive turbines. In the current work we interpret the sum of power extraction from an array of turbines as a discrete spatial filtering of a turbulent boundary layer and derive the associated transfer function. We apply it to an existing model for the wavenumber–frequency spectrum of turbulent boundary layers. This approach allows us to verify the individual roles of Doppler shift and broadening of frequencies on the resulting spatially sampled frequency spectrum. Comparison with the wind tunnel data confirms that the approach captures and explains the main features in the spectrum, indicating the crucial role of the interaction between the spatial sampling and the space–time correlations inherently present in the flow. The frequency spectrum of the aggregated power from a wind farm thus depends on both the spectrum of the incoming turbulence and its modulation by the spatial distribution of turbines in the boundary layer flow.
Suppression of Facial Mimicry of Negative Facial Expressions in an Incongruent Context
Authors: Philip Léonor , Martin Jean-Claude , Clavel Céline
Published: June 2017

Abstract. People react with Rapid Facial Reactions (RFRs) when presented with human facial emotional expressions. Recent studies show that RFRs are not always congruent with emotional cues. The processes underlying RFRs are still being debated. In our study described herein, we manipulate the context of perception and its influence on RFRs. We use a subliminal affective priming task with emotional labels. Facial electromyography (EMG) (frontalis, corrugator, zygomaticus, and depressor) was recorded while participants observed static facial expressions (joy, fear, anger, sadness, and neutral expression) preceded/not preceded by a subliminal word (JOY, FEAR, ANGER, SADNESS, or NEUTRAL). For the negative facial expressions, when the priming word was congruent with the facial expression, participants displayed congruent RFRs (mimicry). When the priming word was incongruent, we observed a suppression of mimicry. Happiness was not affected by the priming word. RFRs thus appear to be modulated by the context and type of emotion that is presented via facial expressions.
How Will Climate Change Affect the California Current Upwelling?
Authors: Cook Terri
Published: June 2017

The results of new simulations that account for internal climate variability contrast with previous projections of how this vital West Coast current will respond to anthropogenic warming.
Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib
Authors: Kastritis E , Gavriatopoulou M , Roussou M , Fotiou D , Ziogas D C , Migkou M , Eleutherakis-Papaiakovou E , Panagiotidis I , Kanellias N , Psimenou E , Papadopoulou E , Pamboucas C , Manios E , Gakiopoulou H , Ntalianis A , Tasidou A , Giannouli S , Terpos E , Dimopoulos M A
Published: June 2017

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.
Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system
Authors: Kaur H. , Carvalho J. , Looso M. , Singh P. , Chennupati R. , Preussner J. , Günther S. , Albarrán-Juárez J. , Tischner D. , Classen S. , Offermanns S. , Wettschureck N.
Published: June 2017

G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.
Correction: Corrigendum: Hepatic p63 regulates steatosis via IKKβ/ER stress
Authors: Porteiro Begoña , Fondevila Marcos F. , Delgado Teresa C. , Iglesias Cristina , Imbernon Monica , Iruzubieta Paula , Crespo Javier , Zabala-Letona Amaia , Fernø Johan , González-Terán Bárbara , Matesanz Nuria , Hernández-Cosido Lourdes , Marcos Miguel , Tovar Sulay , Vidal Anxo , Sánchez-Ceinos Julia , Malagon Maria M. , Pombo Celia , Zalvide Juan , Carracedo Arkaitz , Buque Xabier , Dieguez Carlos , Sabio Guadalupe , López Miguel , Aspichueta Patricia , Martínez-Chantar María L. , Nogueiras Ruben
Published: June 2017

Nature Communications 8: Article number:15111 (2017); Published: 8 May 2017; Updated: 16 June 2017 The affiliation details for Paula Iruzubieta and Javier Crespo are incorrect in this Article. The correct affiliation details for these authors are given below: Department of Gastroenterology and Hepatology, Marqués de Valdecilla University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
Why do physicians lack engagement with smoking cessation treatment in their COPD patients? A multinational qualitative study
Authors: van Eerd Eva Anne Marije , Bech Risør Mette , Spigt Mark , Godycki-Cwirko Maciek , Andreeva Elena , Francis Nick , Wollny Anja , Melbye Hasse , van Schayck Onno , Kotz Daniel
Published: June 2017

Smoking cessation is the only effective intervention to slow down the accelerated decline in lung function in smokers with chronic obstructive pulmonary disease. Nevertheless, physicians often do not routinely provide evidence-based smoking cessation treatment to their patients. To understand underlying reasons, we explored how physicians engage in smoking cessation treatment in their chronic obstructive pulmonary disease patients. In total, 21 focus group discussions were held with general practitioners and pulmonologists in seven different countries in Europe and Asia. We generated three themes, whereby some of the issues concerned smokers in general: first, ‘physicians’ frustration with chronic obstructive pulmonary disease patients who smoke’. These frustrations interfered with the provision of evidence-based treatment and could result in this group of patients being treated unequally. Second: ‘physicians’ limited knowledge of, and negative beliefs about, smoking cessation treatment’. This hindered treating smokers effectively. Third: ‘healthcare organisational factors that influence the use of smoking cessation treatments’. Money and time issues, as well as the failure to regard smoking as a disease, influenced how physicians engaged in smoking cessation treatment. Our results indicate that there is a number of barriers to the provision of effective smoking cessation treatment in patients with chronic obstructive pulmonary disease and smokers in general. Introducing an informative smoking cessation programme, including communication skills and ethical issues, in the vocational and postgraduate medical training may help to address these barriers. This is important in order to increase engagement with smoking cessation treatment and to improve quality of chronic obstructive pulmonary disease care.
The traditional Chinese medicine Achyranthes bidentata and our de novo conception of its metastatic chemoprevention: from phytochemistry to pharmacology
Authors: Jiang Zhou , Qian Jun , Dong Haiyan , Yang Jingyi , Yu Xiaobo , Chen Jianzhong , Chen Hongning , Shi Qing , Jia Lee
Published: June 2017

Our recent biosystems analysis revealed similarities between embryonic implantation and cancer cell adhesion, which suggests that abortifacients may be good for safe and effective metastatic chemoprevention targeting circulating tumor cells (CTC). Here we test the hypothesis by using the well-known abortion herb Achyranthes bidentata Blume (A. bidentata). Five compounds were separated from the herb root. Among them, ginsenoside Ro was the most potent in inhibiting embryonic implantation within non-cytotoxic concentrations. It specifically inhibited the metastatic dissemination capability of colon cancer cells HT29, including the migration and invasion ability, and their adhesion to human endothelium through inhibiting integrin αvβ6, MMP-2, MMP-9, and ERK phosphorylation by HT29. Pretreatment of nude mice with oral ginsenoside Ro followed by HT29 intravenous inoculation and 40-day oral ginsenoside Ro significantly prevented lung metastasis with downregulation of integrin αvβ6 and no toxicity. The present study firstly introduces the new conception of utilizing safe and effective abortion botanic medicines for CTC-based metastatic chemoprevention.
Plasmonic opals: observation of a collective molecular exciton mode beyond the strong coupling
Authors: Fauché Pierre , Gebhardt Christian , Sukharev Maxim , Vallée Renaud A. L.
Published: June 2017

Achieving and controlling strong light-matter interactions in many-body systems is of paramount importance both for fundamental understanding and potential applications. In this paper we demonstrate both experimentally and theoretically how to manipulate strong coupling between the Bragg-plasmon mode supported by an organo-metallic array and molecular excitons in the form of J-aggregates dispersed on the hybrid structure. We observe experimentally the transition from a conventional strong coupling regime exhibiting the usual upper and lower polaritonic branches to a more complex regime, where a third nondispersive mode is seen, as the concentration of J-aggregates is increased. The numerical simulations confirm the presence of the third resonance. We attribute its physical nature to collective molecule-molecule interactions leading to a collective electromagnetic response. A simple analytical model is proposed to explain the physics of the third mode. The nonlinear dependence on molecular parameters followed from the model are confirmed in a set of rigorous numerical studies. It is shown that at the energy of the collective mode molecules oscillate completely out of phase with the incident radiation acting as an effictive thin metal layer.
Serum C3 and Renal Outcome in Patients with Primary Focal Segmental Glomerulosclerosis
Authors: Liu Jian , Xie Jingyuan , Zhang Xiaoyan , Tong Jun , Hao Xu , Ren Hong , Wang Weiming , Chen Nan
Published: June 2017

The role of complement (C) in the pathogenesis or progression of focal segmental glomerulosclerosis (FSGS) is uncertain. The present study assessed the relationship between serum C3, the baseline characteristics, and the progression of FSGS in the cohort and identified the clinical implications of serum C3 levels in patients with FSGS. Compared to the patients with C3 ≥ 85 mg/dL (N = 474), those with C3 < 85 mg/dL (N = 117) presented a higher level of serum creatinine, lower levels of eGFR, hemoglobin, proteinuria, triglyceride, cholesterol, IgA, as well as, severe tubulointerstitial injury (TI). Of the 221 patients with a mean follow-up of 53.3 months, the risk of reaching end-stage renal disease (ESRD) was significantly higher in patients with low serum C3 level (p < 0.001). An additional 40 patients with primary FSGS revealed a significant correlation between MAC and AP (p = 0.003), MAC and serum C3 (p = 0.018), and AP and serum C3 (p = 0.028). Compared to patients with none-to-mild TI, those with moderate-to-severe TI exhibited a lower level of serum C3 and AP, and a higher level of serum MAC. In conclusion, complement activation occurring in patients with FSGS is associated with clinical and histological severities. Low serum C3 was an independent risk factor for poor renal outcome in patients with FSGS.
Thermal stability and topological protection of skyrmions in nanotracks
Authors: Cortés-Ortuño David , Wang Weiwei , Beg Marijan , Pepper Ryan A. , Bisotti Marc-Antonio , Carey Rebecca , Vousden Mark , Kluyver Thomas , Hovorka Ondrej , Fangohr Hans
Published: June 2017

Magnetic skyrmions are hailed as a potential technology for data storage and other data processing devices. However, their stability against thermal fluctuations is an open question that must be answered before skyrmion-based devices can be designed. In this work, we study paths in the energy landscape via which the transition between the skyrmion and the uniform state can occur in interfacial Dzyaloshinskii-Moriya finite-sized systems. We find three mechanisms the system can take in the process of skyrmion nucleation or destruction and identify that the transition facilitated by the boundary has a significantly lower energy barrier than the other energy paths. This clearly demonstrates the lack of the skyrmion topological protection in finite-sized magnetic systems. Overall, the energy barriers of the system under investigation are too small for storage applications at room temperature, but research into device materials, geometry and design may be able to address this.
Ultrasound-mediated piezoelectric differentiation of neuron-like PC12 cells on PVDF membranes
Authors: Hoop Marcus , Chen Xiang-Zhong , Ferrari Aldo , Mushtaq Fajer , Ghazaryan Gagik , Tervoort Theo , Poulikakos Dimos , Nelson Bradley , Pané Salvador
Published: June 2017

Electrical and/or electromechanical stimulation has been shown to play a significant role in regenerating various functionalities in soft tissues, such as tendons, muscles, and nerves. In this work, we investigate the piezoelectric polymer polyvinylidene fluoride (PVDF) as a potential substrate for wireless neuronal differentiation. Piezoelectric PVDF enables generation of electrical charges on its surface upon acoustic stimulation, inducing neuritogenesis of PC12 cells. We demonstrate that the effect of pure piezoelectric stimulation on neurite generation in PC12 cells is comparable to the ones induced by neuronal growth factor (NGF). In inhibitor experiments, our results indicate that dynamic stimulation of PVDF by ultrasonic (US) waves activates calcium channels, thus inducing the generation of neurites via a cyclic adenosine monophosphate (cAMP)-dependent pathway. This mechanism is independent from the well-studied NGF induced mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) pathway. The use of US, in combination with piezoelectric polymers, is advantageous since focused power transmission can occur deep into biological tissues, which holds great promise for the development of non-invasive neuroregenerative devices.
Mito-xenophagic killing of bacteria is coordinated by a metabolic switch in dendritic cells
Authors: Radomski Nadine , Kägebein Danny , Liebler-Tenorio Elisabeth , Karger Axel , Rufer Elke , Tews Birke Andrea , Nagel Stefanie , Einenkel Rebekka , Müller Anne , Rebbig Annica , Knittler Michael R.
Published: June 2017

Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival. Tubulin deacetylase/autophagy regulator HDAC6 associates with disintegrated inclusions, thereby further disrupting their subcellular localisation and stability. Bacterial remnants are decorated with defective mitochondria, mito-aggresomal structures, and components of the ubiquitin/autophagy machinery before they are degraded via mito-xenophagy. The mechanism depends on cytoprotective HSP25/27, the E3 ubiquitin ligase Parkin and HDAC6 and promotes chlamydial antigen generation for presentation on MHC I. We propose that this novel mito-xenophagic pathway linking innate and adaptive immunity is critical for effective DC-mediated anti-bacterial resistance.
Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters
Authors: Brynolfsson Patrik , Nilsson David , Torheim Turid , Asklund Thomas , Karlsson Camilla Thellenberg , Trygg Johan , Nyholm Tufve , Garpebring Anders
Published: June 2017

In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.
Proteome profiling reveals novel biomarkers to identify complicated parapneumonic effusions
Authors: Wu Kuo-An , Wu Chih-Ching , Chen Chi-De , Chu Chi-Ming , Shih Li-Jane , Liu Yu-Ching , Wang Chih-Liang , Lin Hsi-Hsien , Yang Chia-Yu
Published: June 2017

Patients with pneumonia and parapneumonic effusion (PPE) have elevated mortality and a poor prognosis. The aim of this study was to discover novel biomarkers to help distinguish between uncomplicated PPE (UPPE) and complicated PPE (CPPE). Using an iTRAQ-based quantitative proteomics, we identified 766 proteins in pleural effusions from PPE patients. In total, 45 of these proteins were quantified as upregulated proteins in CPPE. Four novel upregulated candidates (BPI, NGAL, AZU1, and calprotectin) were selected and further verified using enzyme-linked immunosorbent assays (ELISAs) on 220 patients with pleural effusions due to different causes. The pleural fluid levels of BPI, NGAL, AZU1, and calprotectin were significantly elevated in patients with CPPE. Among these four biomarkers, BPI had the best diagnostic value for CPPE, with an AUC value of 0.966, a sensitivity of 97%, and a specificity of 91.4%. A logistic regression analysis demonstrated a strong association between BPI levels > 10 ng/ml and CPPE (odds ratio = 341.3). Furthermore, the combination of pleural fluid BPI levels with LDH levels improved the sensitivity and specificity to 100% and 91.4%, respectively. Thus, our findings provided a comprehensive effusion proteome data set for PPE biomarker discovery and revealed novel biomarkers for the diagnosis of CPPE.
Masking of a circadian behavior in larval zebrafish involves the thalamo-habenula pathway
Authors: Lin Qian , Jesuthasan Suresh
Published: June 2017

Changes in illumination can rapidly influence behavior that is normally controlled by the circadian clock. This effect is termed masking. In mice, masking requires melanopsin-expressing retinal ganglion cells that detect blue light and project to the thalamus. It is not known whether masking is wavelength-dependent in other vertebrates, nor is it known whether the thalamus is also involved or how it influences masking. Here, we address these questions in zebrafish. We find that diel vertical migration, a circadian behavior in larval zebrafish, is effectively triggered by blue, but not by red light. Two-photon calcium imaging reveals that a thalamic nucleus and a downstream structure, the habenula, have a sustained response to blue but not to red light. Lesioning the habenula reduces light-evoked climbing. These data suggest that the thalamo-habenula pathway is involved in the ability of blue light to influence a circadian behavior.
A novel bZIP protein, Gsb1, is required for oxidative stress response, mating, and virulence in the human pathogen Cryptococcus neoformans
Authors: Cheon Seon Ah , Thak Eun Jung , Bahn Yong-Sun , Kang Hyun Ah
Published: June 2017

The human pathogen Cryptococcus neoformans, which causes life-threatening meningoencephalitis in immunocompromised individuals, normally faces diverse stresses in the human host. Here, we report that a novel, basic, leucine-zipper (bZIP) protein, designated Gsb1 (general stress-related bZIP protein 1), is required for its normal growth and diverse stress responses. C. neoformans gsb1Δ mutants grew slowly even under non-stressed conditions and showed increased sensitivity to high or low temperatures. The hypersensitivity of gsb1Δ to oxidative and nitrosative stresses was reversed by addition of a ROS scavenger. RNA-Seq analysis during normal growth revealed increased expression of a number of genes involved in mitochondrial respiration and cell cycle, but decreased expression of several genes involved in the mating-pheromone-responsive MAPK signaling pathway. Accordingly, gsb1Δ showed defective mating and abnormal cell-cycle progression. Reflecting these pleiotropic phenotypes, gsb1Δ exhibited attenuated virulence in a murine model of cryptococcosis. Moreover, RNA-Seq analysis under oxidative stress revealed that several genes involved in ROS defense, cell-wall remodeling, and protein glycosylation were highly induced in the wild-type strain but not in gsb1Δ. Gsb1 localized exclusively in the nucleus in response to oxidative stress. In conclusion, Gsb1 is a key transcription factor modulating growth, stress responses, differentiation, and virulence in C. neoformans.
Hemodynamics of speech production: An fNIRS investigation of children who stutter
Authors: Walsh B. , Tian F. , Tourville J. A. , Yücel M. A. , Kuczek T. , Bostian A. J.
Published: June 2017

Stuttering affects nearly 1% of the population worldwide and often has life-altering negative consequences, including poorer mental health and emotional well-being, and reduced educational and employment achievements. Over two decades of neuroimaging research reveals clear anatomical and physiological differences in the speech neural networks of adults who stutter. However, there have been few neurophysiological investigations of speech production in children who stutter. Using functional near-infrared spectroscopy (fNIRS), we examined hemodynamic responses over neural regions integral to fluent speech production including inferior frontal gyrus, premotor cortex, and superior temporal gyrus during a picture description task. Thirty-two children (16 stuttering and 16 controls) aged 7–11 years participated in the study. We found distinctly different speech-related hemodynamic responses in the group of children who stutter compared to the control group. Whereas controls showed significant activation over left dorsal inferior frontal gyrus and left premotor cortex, children who stutter exhibited deactivation over these left hemisphere regions. This investigation of neural activation during natural, connected speech production in children who stutter demonstrates that in childhood stuttering, atypical functional organization for speech production is present and suggests promise for the use of fNIRS during natural speech production in future research with typical and atypical child populations.