bluuebunny/crossref_metadata_2025 huggingface dataset:
A SYSTEMATIC APPROACH FOR ASSESSING, IN THE ABSENCE OF FULL EVIDENCE, WHETHER MULTICOMPONENT INTERVENTIONS CAN BE MORE COST-EFFECTIVE THAN SINGLE COMPONENT INTERVENTIONS
Authors: Mewes Janne C. , Steuten Lotte M.G. , IJzerman Maarten J. , van Harten Wim H.
Published: September 2017

Objectives:Multicomponent interventions (MCIs), consisting of at least two interventions, are common in rehabilitation and other healthcare fields. When the effectiveness of the MCI versus that of its single interventions is comparable or unknown, evidence of their expected incremental cost-effectiveness can be helpful in deciding which intervention to recommend. As such evidence often is unavailable this study proposes an approach to estimate what is more cost-effective; the MCI or the single intervention(s).

Methods:We reviewed the literature for potential methods. Of those identified, headroom analysis was selected as the most suitable basis for developing the approach, based on the criteria of being able to estimate the cost-effectiveness of the single interventions versus that of the MCI (a) within a limited time frame, (b) in the absence of full data, and (c) taking into account carry-over and interaction effects. We illustrated the approach with an MCI for cancer survivors.

Results:The approach starts with analyzing the costs of the MCI. Given a specific willingness-to-pay-value, it is analyzed how much effectiveness the MCI would need to generate to be considered cost-effective, and if this is likely to be attained. Finally, the cost-effectiveness of the single interventions relative to the potential of the MCI for being cost-effective can be compared.

Conclusions:A systematic approach using headroom analysis was developed for estimating whether an MCI is likely to be more cost effective than one (or more) of its single interventions.
Spatiotemporal risk mapping of hand, foot and mouth disease and its association with meteorological variables in children under 5 years
Authors: XU C. D. , XIAO G. X.
Published: September 2017

Hand, foot and mouth disease (HFMD) risk has become an increasing concern in the Beijing–Tianjin–Hebei region, which is the biggest urban agglomeration in north-eastern Asia. In the study, spatiotemporal epidemiological features of HFMD were analysed, and a Bayesian space–time hierarchy model was used to detect local spatial relative risk (RR) and to assess the effect of meteorological factors. From 2009 to 2013, there was an obvious seasonal pattern of HFMD risk. The highest risk period was in the summer, with an average monthly incidence of 4·17/103, whereas the index in wintertime was 0·16/103. Meteorological variables influenced temporal changes in HFMD. A 1 °C rise in air temperature was associated with an 11·5% increase in HFMD (corresponding RR 1·122). A 1% rise in relative humidity was related to a 9·51% increase in the number of HFMD cases (corresponding RR 1·100). A 1 hPa increment in air pressure was related to a 0·11% decrease in HFMD (corresponding RR 0·999). A 1 h increase in sunshine was associated with a 0·28% rise in HFMD cases (corresponding RR 1·003). A 1 m/s rise in wind speed was related to a 6·2% increase in HFMD (corresponding RR 1·064). High-risk areas were mainly large cities, such as Beijing, Tianjin, Shijiazhuang and their neighbouring areas. These findings can contribute to risk control and implementation of disease-prevention policies.
Prevalence ofClostridium difficileinfection and colonization in a tertiary hospital and elderly community of North-Eastern Peninsular Malaysia
Authors: ZAINUL N. H. , MA Z. F. , BESARI A. , SITI ASMA H. , RAHMAN R. A. , COLLINS D. A. , HAMID N. , RILEY T. V. , LEE Y. Y.
Published: September 2017

Little is known aboutClostridium difficileinfection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage ofC. difficileamong the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n= 76) and healthy community members (n= 138),C. difficileantigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenicC. difficilecolonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22C. difficilestrains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis,C. difficilecolonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (bothP< 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey.C. difficilecolonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.
‘Art’ in Archaeology and Anthropology: An Overview of the Concept
Authors: Robb John
Published: September 2017

The concept of art has proved controversial in archaeology and anthropology. Many feel that the concept, developed to fit high art in modern Western society, is inappropriate for objects made for other uses, in other times, or in other cultures. Yet there is no widely agreed critique or alternative concept. This introduction reviews responses to this dilemma, ranging from using the concept uncritically, using the term ‘art’ simply as an archaeological convenience to refer to things such as petroglyphs and figurines, and treating art simply as material culture. It then explores the recent concepts of art as affective material culture, as socially defined networks, and as locally defined aesthetic action. Finally, it raises the possibility that art is our local category of the kind of powerful objects found in many cultures.
How to Cope with Working in an Open-space Lab?
Authors: Pautasso Marco , Van Der Werf Wopke
Published: September 2017

Open-space labs and research environments are increasingly common worldwide. They are supposed to facilitate interactions among researchers, but can be disruptive to those who need to be in a quiet environment in order to concentrate. This problem is increasingly felt across the natural, medical and social sciences, has a clear interdisciplinary and cross-cultural relevance, but has been the focus of limited attention. We propose some simple suggestions for researchers struggling in an open-space lab, based on a literature review and our experience in open spaces in various labs and countries (Australia, China, France, Italy, the Netherlands, Switzerland, the UK and the USA) as undergrads, PhD students, postdocs, researchers and (W. van der Werf) professors. Our aim is to help researchers working in open-space offices and labs with some straightforward solutions that will make their lives and work easier.
A Soil Probe System to Evaluate Weed Seed Survival in Soil Disinfestation Trials
Authors: Hoffmann Mark , Fennimore Steven A.
Published: September 2017

Weed seed viability is an important parameter to assess the efficacy of soil disinfestation methods like fumigation and steam. In field experiments, seed samples are commonly placed in permeable bags and buried at several depths in soil before the application of soil disinfestation treatments. The seed samples are recovered several days to weeks after treatment and then seed viability is determined in the laboratory. The process of sample installation and recovery is time consuming and may expose personnel to hazardous conditions such as heat or fumigants. Described is a custom soil probe system, developed to simplify installation and recovery of weed seeds from soil. Each soil probe is capable of holding weed seed samples at three different depths up to 30 cm. The following hypothesis was tested: viability of weed seeds is similarly affected by soil disinfestation treatments whether the seeds were contained in the soil probe system or seed bag assays. Two different soil disinfestation trials were conducted: (1) a repeated micro-plot study (USDA Salinas, 1 m-2), using steam as a soil disinfestation treatment and (2) a field study in a commercial strawberry field with 1,3-dicloropropene plus chloropicrin (Pic-Clor 60) as soil disinfestation method. In both studies, seed viability of burning nettle, common knotweed, and common purslane (tetrazolium assay) and germination rates of yellow nutsedge tubers were assessed. Results indicate that the soil probe system can be used as an alternative to the seed bag assay to assess weed control efficacy of described soil disinfestation methods.
„Glück in Herz und Beinen“
Authors: Hanefeld Ruth , Koch Sabine C.
Published: September 2017

Zusammenfassung. Ziel der vorliegenden Studie war zu überprüfen, ob Swingtanz glücklich macht und wenn ja, welche Faktoren dafür verantwortlich sind. Konkret wurde betrachtet, inwieweit er 1) eine Steigerung des subjektiven Wohlbefindens bewirkt sowie 2) ob und welcher der drei Wirkfaktoren am stärksten ist: die Swing-Musik, die Tanzbewegung des „Bouncings“ oder das Einheitserleben mit dem Partner. Um Wirkung und Wirkfaktoren zu ermitteln, füllten 115 Personen der Swingtanz-Community vor und nach dem Tanzen in zehn natürlichen Settings einen Fragebogen zur Befindlichkeit aus. Die Resultate zeigten eine signifikante Steigerung der Befindlichkeit nach dem Swingtanz. Es konnte jedoch keine Hierarchie zwischen den drei Faktoren festgestellt werden: alle drei schienen den Tänzern ähnlich wichtig, mit einem leichten Vorsprung von Musik und „Bouncing“. Aufgrund der fehlenden Kontrollgruppe war eine Mediationsanalyse nicht möglich. Elemente des Swingtanzes könnten für die Tanztherapie nützlich sein. Deshalb wären Studien in klinischem Kontext der nächste Schritt.
Analyzing Organizational Growth in Repeated Cross-Sectional Designs	Using Multilevel Structural Equation Modeling
Authors: Hochweber Jan , Hartig Johannes
Published: September 2017

Abstract. In repeated cross-sections of organizations, different individuals are sampled from the same set of organizations at each time point of measurement. As a result, common longitudinal data analysis methods (e.g., latent growth curve models) cannot be applied in the usual way. In this contribution, a multilevel structural equation modeling approach to analyze data from repeated cross-sections is presented. Results from a simulation study are reported which aimed at obtaining guidelines on appropriate sample sizes. We focused on a situation where linear growth occurs at the organizational level, and organizational growth is predicted by a single organizational level variable. The power to identify an effect of this organizational level variable was moderately to strongly positively related to number of measurement occasions, number of groups, group size, intraclass correlation, effect size, and growth curve reliability. The Type I error rate was close to the nominal alpha level under all conditions.
Investigation of Parameter Estimation Accuracy for Growth Curve	Modeling With Categorical Indicators
Authors: Finch W. Holmes
Published: September 2017

Abstract. Growth curve modeling (GCM) is an important and commonly used methodology in the social sciences for examining change over time in a variable value. While much of the empirical research examining the performance of various estimators under a variety of conditions has focused on continuous (and typically normally distributed) observed indicators, in practice researchers frequently make use of categorical indicators with anywhere from two to as many as seven categories. Given the popularity of GCMs, along with the frequent use of categorical indicators, and the relative dearth of simulation research focusing on estimation of these models with such variables, the current study focused on the issue of parameter estimation accuracy as related to the number of categorical indicators, and the number of categories per indicator. Results of this research found that for models with only a linear component, parameter estimation was very accurate for as few as four indicators with two categories each and a sample size of 200. On the other hand, when the underlying model included both linear and quadratic terms, parameter estimation accuracy suffered for a small number of dichotomous indicators unless the sample size was 1,000 or more. However, with six or more indicator variables, and/or at least three categories, parameter estimation accuracy remained high.
Similarities Between Ranking and Rating Measures of Values	Preferences
Authors: Moors Guy , Vriens Ingrid , Gelissen John
Published: September 2017

Abstract. The form-resistant hypothesis states that alternative ways of measuring the same values should be small if method-specific features are taken into account. However, previous research that compared rating and ranking questionnaires for measuring values has shown mixed results. We suggest that adopting a latent class segmentation approach helps to explain these mixed results by identifying segments with similar item preference structures and segments linked to one format only. Our approach is applied to a Dutch survey on work values. In both ranking and rating mode, we find two similar segments reflecting the intrinsic and extrinsic preference structure, while other segments differed between modes. In line with the modified form-resistant hypothesis, the results suggest the same latent preference structure has guided particular segments in a population to respond similarly to rating and ranking questions.
A key role for IL‐7R in the generation of microenvironments required for thymic dendritic cells
Authors: Moore Amanda J , In Tracy SH , Trotman‐Grant Ashton , Yoganathan Kogulan , Montpellier Bertrand , Guidos Cynthia J , Zúñiga‐Pflücker Juan Carlos , Anderson Michele K
Published: September 2017

Interleukin‐7 receptor (IL‐7R) signaling is critical for multiple stages of T‐cell development, but a role in the establishment of the mature thymic architecture needed for T‐cell development and thymocyte selection has not been established. Crosstalk signals between developing thymocytes and thymic epithelial cell (TEC) precursors are critical for their differentiation into cortical TECs (cTECs) and medullary TECs (mTECs). In addition, mTEC‐derived factors have been implicated in the recruitment of thymic dendritic cells (DCs) and intrathymic DC development. We therefore examined corticomedullary structure and DC populations in the thymus of Il7r−/− mice. Analysis of TEC phenotype and spatial organization revealed a striking shift in the mTEC to cTEC ratio, accompanied by disorganized corticomedullary structure. Several of the thymic subsets known to have DC potential were nearly absent, accompanied by reductions in DC cell numbers. We also examined chemokine expression in the Il7r−/− thymus, and found a significant decrease in mTEC‐derived CCR7 ligand expression, and high levels of cTEC‐derived chemokines, including CCL25 and CXCL12. Although splenic DCs were similarly affected, bone marrow (BM) precursors capable of giving rise to DCs were unperturbed. Finally, BM chimeras showed that there was no intrinsic need for IL‐7R signaling in the development or recruitment of thymic DCs, but that the provision of wild‐type progenitors enhanced reconstitution of thymic DCs from Il7r−/− progenitors. Our results are therefore supportive of a model in which Il7r‐dependent cells are required to set up the microenvironments that allow accumulation of thymic DCs.
Nanoparticle assembly enabled by EHD-printed monolayers
Authors: Porter Benjamin Francis , Mkhize Nhlakanipho , Bhaskaran Harish
Published: September 2017

Augmenting existing devices and structures at the nanoscale with unique functionalities is an exciting prospect. So is the ability to eventually enable at the nanoscale, a version of rapid prototyping via additive nanomanufacturing. Achieving this requires a step-up in manufacturing for industrial use of these devices through fast, inexpensive prototyping with nanoscale precision. In this paper, we combine two very promising techniques—self-assembly and printing—to achieve additively nanomanufactured structures. We start by showing that monolayers can drive the assembly of nanoparticles into pre-defined patterns with single-particle resolution; then crucially we demonstrate for the first time that molecular monolayers can be printed using electrohydrodynamic (EHD)-jet printing. The functionality and resolution of such printed monolayers then drives the self-assembly of nanoparticles, demonstrating the integration of EHD with self-assembly. This shows that such process combinations can lead towards more integrated process flows in nanomanufacturing. Furthermore, in-process metrology is a key requirement for any large-scale nanomanufacturing, and we show that Dual-Harmonic Kelvin Probe Microscopy provides a robust metrology technique to characterising these patterned structures through the convolution of geometrical and environmental constraints. These represent a first step toward combining different additive nanomanufacturing techniques and metrology techniques that could in future provide additively nanomanufactured devices and structures.
Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children
Authors: Wendel Ben S. , He Chenfeng , Qu Mingjuan , Wu Di , Hernandez Stefany M. , Ma Ke-Yue , Liu Eugene W. , Xiao Jun , Crompton Peter D. , Pierce Susan K. , Ren Pengyu , Chen Keke , Jiang Ning
Published: September 2017

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12–47 months old) with 4−8 ml of blood. Here, we show this accurate and high-coverage repertoire-sequencing method can use as few as 1000 naive B cells. Unexpectedly, we discover high levels of somatic hypermutation in infants as young as 3 months old. Antibody clonal lineage analysis reveals that somatic hypermutation levels are increased in both infants and toddlers upon infection, and memory B cells isolated from individuals who previously experienced malaria continue to induce somatic hypermutations upon malaria rechallenge. These results highlight the potential of antibody repertoire diversification in infants and toddlers.
Tricritical wings and modulated magnetic phases in LaCrGe3 under pressure
Authors: Kaluarachchi Udhara S. , Bud’ko Sergey L. , Canfield Paul C. , Taufour Valentin
Published: September 2017

Experimental and theoretical investigations on itinerant ferromagnetic systems under pressure have shown that ferromagnetic quantum criticality is avoided either by a change of the transition order, becoming of the first order at a tricritical point, or by the appearance of modulated magnetic phases. In the first case, the application of a magnetic field reveals a wing-structure phase diagram as seen in itinerant ferromagnets such as ZrZn2 and UGe2. In the second case, no tricritical wings have been observed so far. Here, we report on the discovery of wing-structure as well as the appearance of modulated magnetic phases in the temperature-pressure-magnetic field phase diagram of LaCrGe3. Our investigation of LaCrGe3 reveals a double-wing structure indicating strong similarities with ZrZn2 and UGe2. But, unlike these simpler systems, LaCrGe3 also shows modulated magnetic phases similar to CeRuPO. This finding provides an example of an additional possibility for the phase diagram of metallic quantum ferromagnets.
Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life
Authors: Parks Donovan H. , Rinke Christian , Chuvochina Maria , Chaumeil Pierre-Alain , Woodcroft Ben J. , Evans Paul N. , Hugenholtz Philip , Tyson Gene W.
Published: September 2017

Challenges in cultivating microorganisms have limited the phylogenetic diversity of currently available microbial genomes. This is being addressed by advances in sequencing throughput and computational techniques that allow for the cultivation-independent recovery of genomes from metagenomes. Here, we report the reconstruction of 7,903 bacterial and archaeal genomes from >1,500 public metagenomes. All genomes are estimated to be ≥50% complete and nearly half are ≥90% complete with ≤5% contamination. These genomes increase the phylogenetic diversity of bacterial and archaeal genome trees by >30% and provide the first representatives of 17 bacterial and three archaeal candidate phyla. We also recovered 245 genomes from the Patescibacteria superphylum (also known as the Candidate Phyla Radiation) and find that the relative diversity of this group varies substantially with different protein marker sets. The scale and quality of this data set demonstrate that recovering genomes from metagenomes provides an expedient path forward to exploring microbial dark matter.
Cytokine-based Predictive Models to Estimate the Probability of Chronic Periodontitis: Development of Diagnostic Nomograms
Authors: Tomás I. , Arias-Bujanda N. , Alonso-Sampedro M. , Casares-de-Cal M. A. , Sánchez-Sellero C. , Suárez-Quintanilla D. , Balsa-Castro C.
Published: September 2017

Although a distinct cytokine profile has been described in the gingival crevicular fluid (GCF) of patients with chronic periodontitis, there is no evidence of GCF cytokine-based predictive models being used to diagnose the disease. Our objectives were: to obtain GCF cytokine-based predictive models; and develop nomograms derived from them. A sample of 150 participants was recruited: 75 periodontally healthy controls and 75 subjects affected by chronic periodontitis. Sixteen mediators were measured in GCF using the Luminex 100™ instrument: GMCSF, IFNgamma, IL1alpha, IL1beta, IL2, IL3, IL4, IL5, IL6, IL10, IL12p40, IL12p70, IL13, IL17A, IL17F and TNFalpha. Cytokine-based models were obtained using multivariate binary logistic regression. Models were selected for their ability to predict chronic periodontitis, considering the different role of the cytokines involved in the inflammatory process. The outstanding predictive accuracy of the resulting smoking-adjusted models showed that IL1alpha, IL1beta and IL17A in GCF are very good biomarkers for distinguishing patients with chronic periodontitis from periodontally healthy individuals. The predictive ability of these pro-inflammatory cytokines was increased by incorporating IFN gamma and IL10. The nomograms revealed the amount of periodontitis-associated imbalances between these cytokines with pro-inflammatory and anti-inflammatory effects in terms of a particular probability of having chronic periodontitis.
Softening non-metallic crystals by inhomogeneous elasticity
Authors: Howie P. R. , Thompson R. P. , Korte-Kerzel S. , Clegg W. J.
Published: September 2017

High temperature structural materials must be resistant to cracking and oxidation. However, most oxidation resistant materials are brittle and a significant reduction in their yield stress is required if they are to be resistant to cracking. It is shown, using density functional theory, that if a crystal’s unit cell elastically deforms in an inhomogeneous manner, the yield stress is greatly reduced, consistent with observations in layered compounds, such as Ti3SiC2, Nb2Co7, W2B5, Ta2C and Ta4C3. The mechanism by which elastic inhomogeneity reduces the yield stress is explained and the effect demonstrated in a complex metallic alloy, even though the electronegativity differences within the unit cell are less than in the layered compounds. Substantial changes appear possible, suggesting this is a first step in developing a simple way of controlling plastic flow in non-metallic crystals, enabling materials with a greater oxidation resistance and hence a higher temperature capability to be used.
Erratum: Identification of Na+/K+-ATPase inhibition-independent proarrhythmic ionic mechanisms of cardiac glycosides
Authors: Koh Cai Hong , Wu Jianjun , Chung Ying Ying , Liu Zhenfeng , Zhang Rong-Rong , Chong Ketpin , Korzh Vladimir , Ting Sherwin , Oh Steve , Shim Winston , Tian Hai-Yan , Wei Heming
Published: September 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Cofilin-mediated Neuronal Apoptosis via p53 Translocation and PLD1 Regulation
Authors: Liu Tian , Wang Fang , LePochat Patrick , Woo Jung-A. A. , Bukhari Mohammed Zaheen , Hong Kyung Woo , Trotter Courtney , Kang David E.
Published: September 2017

Amyloid β (Aβ) accumulation is an early event in the pathogenesis of Alzheimer’s disease (AD), leading to mitochondrial and synaptic dysfunction, tau accumulation, and eventual neuronal death. While the p53 apoptotic pathway has clearly been associated with Aβ deposits and neuronal apoptosis, the critical upstream factors contributing to p53 activation in AD are not well understood. We have previously shown that cofilin activation plays a pivotal role in Aβ-induced mitochondrial and synaptic dysfunction. In this study, we show that activated cofilin (S3A) preferentially forms a complex with p53 and promotes its mitochondrial and nuclear localization, resulting in transcription of p53-responsive genes and promotion of apoptosis. Conversely, reduction of endogenous cofilin by knockdown or genetic deficiency inhibits mitochondrial and nuclear translocation of p53 in cultured cells and in APP/PS1 mice. This cofilin-p53 pro-apoptotic pathway is subject to negative regulation by PLD1 thorough cofilin inactivation and inhibition of cofilin/p53 complex formation. Finally, activated cofilin is unable to induce apoptosis in cells genetically lacking p53. These findings taken together indicate that cofilin coopts and requires the nuclear and mitochondrial pro-apoptotic p53 program to induce and execute apoptosis, while PLD1 functions in a regulatory multi-brake capacity in this pathway.
Acute interaction between hydrocortisone and insulin alters the plasma metabolome in humans
Authors: Alwashih Mohammad A. , Stimson Roland H. , Andrew Ruth , Walker Brian R. , Watson David G.
Published: September 2017

With the aim of identifying biomarkers of glucocorticoid action and their relationship with biomarkers of insulin action, metabolomic profiling was carried out in plasma samples from twenty healthy men who were administered either a low or medium dose insulin infusion (n = 10 each group). In addition, all subjects were given metyrapone (to inhibit adrenal cortisol secretion) + /− hydrocortisone (HC) in a randomised crossover design to produce low, medium and high glucocorticoid levels. The clearest effects of insulin were to reduce plasma levels of the branched chain amino acids (BCAs) leucine/isoleucine and their deaminated metabolites, and lowered free fatty acids and acylcarnitines. The highest dose of hydrocortisone increased plasma BCAs in both insulin groups but increased free fatty acids only in the high insulin group, however hydrocortisone did not affect the levels of acyl carnitines in either group. The clearest interaction between HC and insulin was that hydrocortisone produced an elevation in levels of BCAs and their metabolites which were lowered by insulin. The direct modulation of BCAs by glucocorticoids and insulin may provide the basis for improved in vivo monitoring of glucocorticoid and insulin action.
Genesis of ultra-high-Ni olivine in high-Mg andesite lava triggered by seamount subduction
Authors: Nishizawa Tatsuji , Nakamura Hitomi , Churikova Tatiana , Gordeychik Boris , Ishizuka Osamu , Haraguchi Satoru , Miyazaki Takashi , Vaglarov Bogdan Stefanov , Chang Qing , Hamada Morihisa , Kimura Jun-Ichi , Ueki Kenta , Toyama Chiaki , Nakao Atsushi , Iwamori Hikaru
Published: September 2017

The Kamchatka Peninsula is a prominent and wide volcanic arc located near the northern edge of the Pacific Plate. It has highly active volcanic chains and groups, and characteristic lavas that include adakitic rocks. In the north of the peninsula adjacent to the triple junction, some additional processes such as hot asthenospheric injection around the slab edge and seamount subduction operate, which might enhance local magmatism. In the forearc area of the northeastern part of the peninsula, monogenetic volcanic cones dated at <1 Ma were found. Despite their limited spatiotemporal occurrence, remarkable variations were observed, including primitive basalt and high-Mg andesite containing high-Ni (up to 6300 ppm) olivine. The melting and crystallization conditions of these lavas indicate a locally warm slab, facilitating dehydration beneath the forearc region, and a relatively cold overlying mantle wedge fluxed heterogeneously by slab-derived fluids. It is suggested that the collapse of a subducted seamount triggered the ascent of Si-rich fluids to vein the wedge peridotite and formed a peridotite–pyroxenite source, causing the temporal evolution of local magmatism with wide compositional range.
Transfer of labile organic matter and microbes from the ocean surface to the marine aerosol: an experimental approach
Authors: Rastelli Eugenio , Corinaldesi Cinzia , Dell’Anno Antonio , Lo Martire Marco , Greco Silvestro , Cristina Facchini Maria , Rinaldi Matteo , O’Dowd Colin , Ceburnis Darius , Danovaro Roberto
Published: September 2017

Surface ocean bubble-bursting generates aerosols composed of microscopic salt-water droplets, enriched in marine organic matter. The organic fraction profoundly influences aerosols’ properties, by scattering solar radiations and nucleating water particles. Still little is known on the biochemical and microbiological composition of these organic particles. In the present study, we experimentally simulated the bursting of bubbles at the seawater surface of the North-Eastern Atlantic Ocean, analysing the organic materials and the diversity of the bacteria in the source-seawaters and in the produced aerosols. We show that, compared with seawater, the sub-micron aerosol particles were highly enriched in organic matter (up to 140,000x for lipids, 120,000x for proteins and 100,000x for carbohydrates). Also DNA, viruses and prokaryotes were significantly enriched (up to 30,000, 250 and 45x, respectively). The relative importance of the organic components in the aerosol did not reflect those in the seawater, suggesting their selective transfer. Molecular analyses indicate the presence of selective transfers also for bacterial genotypes, highlighting higher contribution of less abundant seawater bacterial taxa to the marine aerosol. Overall, our results open new perspectives in the study of microbial dispersal through marine aerosol and provide new insights for a better understanding of climate-regulating processes of global relevance.
New molecular insights into the tyrosyl-tRNA synthase inhibitors: CoMFA, CoMSIA analyses and molecular docking studies
Authors: Li Shengrong , Fan Jilin , Peng Chengkang , Chang Yiqun , Guo Lianxia , Hou Jinsong , Huang Miaoqi , Wu Biyuan , Zheng Junxia , Lin Longxin , Xiao Gaokeng , Chen Weimin , Liao Guochao , Guo Jialiang , Sun Pinghua
Published: September 2017

Drug resistance caused by excessive and indiscriminate antibiotic usage has become a serious public health problem. The need of finding new antibacterial drugs is more urgent than ever before. Tyrosyl-tRNA synthase was proved to be a potent target in combating drug-resistant bacteria. In silico methodologies including molecular docking and 3D-QSAR were employed to investigate a series of newly reported tyrosyl-tRNA synthase inhibitors of furanone derivatives. Both internal and external cross-validation were conducted to obtain high predictive and satisfactory CoMFA model (q2 = 0.611, r2
pred
 = 0.933, r2
m
 = 0.954) and CoMSIA model (q2 = 0.546, r2
pred
 = 0.959, r2
m
 = 0.923). Docking results, which correspond with CoMFA/CoMSIA contour maps, gave the information for interactive mode exploration. Ten new molecules designed on the basis of QSAR and docking models have been predicted more potent than the most active compound 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (15) in the literatures. The results expand our understanding of furanones as inhibitors of tyrosyl-tRNA synthase and could be helpful in rationally designing of new analogs with more potent inhibitory activities.
Oxytocin Receptor Polymorphisms are Differentially Associated with Social Abilities across Neurodevelopmental Disorders
Authors: Baribeau Danielle A. , Dupuis Annie , Paton Tara A. , Scherer Stephen W. , Schachar Russell J. , Arnold Paul D. , Szatmari Peter , Nicolson Rob , Georgiades Stelios , Crosbie Jennifer , Brian Jessica , Iaboni Alana , Lerch Jason , Anagnostou Evdokia
Published: September 2017

Oxytocin is a pituitary neuropeptide that affects social behaviour. Single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR) have been shown to explain some variability in social abilities in control populations. Whether these variants similarly contribute to the severity of social deficits experienced by children with neurodevelopmental disorders is unclear. Social abilities were assessed in a group of children with autism spectrum disorder (ASD, n = 341) or attention deficit hyperactivity disorder (ADHD, n = 276) using two established social measures. Scores were compared by OXTR genotype (rs53576, rs237887, rs13316193, rs2254298). Unexpectedly, the two most frequently studied OXTR SNPs in the general population (rs53576 and rs2254298) were associated with an increased severity of social deficits in ASD (p < 0.0001 and p = 0.0005), yet fewer social deficits in ADHD (p = 0.007 and p < 0.0001). We conclude that these genetic modifier alleles are not inherently risk-conferring with respect to their impact on social abilities; molecular investigations are greatly needed.
Y Chromosome, Mitochondrial DNA and Childhood Behavioural Traits
Authors: Howe Laurence J. , Erzurumluoglu A. Mesut , Davey Smith George , Rodriguez Santiago , Stergiakouli Evie
Published: September 2017

Many psychiatric traits are sexually dimorphic in terms of prevalence, age of onset, progression and prognosis; sex chromosomes could play a role in these differences. In this study we evaluated the association between Y chromosome and mitochondrial DNA haplogroups with sexually-dimorphic behavioural and psychiatric traits. The study sample included 4,211 males and 4,009 females with mitochondrial DNA haplogroups and 4,788 males with Y chromosome haplogroups who are part of the Avon Longitudinal Study of Parents and Children (ALSPAC) based in the United Kingdom. Different subsets of these populations were assessed using measures of behavioural and psychiatric traits with logistic regression being used to measure the association between haplogroups and the traits. The majority of behavioural traits in our cohort differed between males and females; however Y chromosome and mitochondrial DNA haplogroups were not associated with any of the variables. These findings suggest that if there is common variation on the Y chromosome and mitochondrial DNA associated with behavioural and psychiatric trait variation, it has a small effect.
Evolution of T Cell Responses during Measles Virus Infection and RNA Clearance
Authors: Nelson Ashley N. , Putnam Nicole , Hauer Debra , Baxter Victoria K. , Adams Robert J. , Griffin Diane E.
Published: September 2017

Measles is an acute viral disease associated both with immune suppression and development of life-long immunity. Clearance of measles virus (MeV) involves rapid elimination of infectious virus during the rash followed by slow elimination of viral RNA. To characterize cellular immune responses during recovery, we analyzed the appearance, specificity and function of MeV-specific T cells for 6 months after respiratory infection of rhesus macaques with wild type MeV. IFN-γ and IL-17-producing cells specific for the hemagglutinin and nucleocapsid proteins appeared in circulation in multiple waves approximately 2-3, 8 and 18–24 weeks after infection. IFN-γ-secreting cells were most abundant early and IL-17-secreting cells late. Both CD4+ and CD8+ T cells were sources of IFN-γ and IL-17, and IL-17-producing cells expressed RORγt. Therefore, the cellular immune response evolves during MeV clearance to produce functionally distinct subsets of MeV-specific CD4+ and CD8+ T cells at different times after infection.
Structural and dynamical characteristics of flow units in metallic glasses
Authors: Liu S. T. , Li F. X. , Li M. Z. , Wang W. H.
Published: September 2017

The metallic glasses (MGs) are conjectured to be heterogeneous—their microscopic structures are embedded with localized, soft and loosely packed atomic regions, which are termed as flow units (FUs). Detailed knowledges on the structure and dynamical features of FUs are essential for understanding the plasticity of MGs. In our study, by performing dynamical tests on MGs in molecular dynamics simulations, we show that mechanical hysteretic loops are formed in the strain-stress curves due to the undergoing plastic events. By analyzing the activated times of each atom in different dynamical tests, we map the exact locations of FUs and the distribution of their activation probability in the initial structure of MGs. More importantly, we demonstrate that the FUs are indeed liquid-like according to the Lindemann criterion of melting.
Predictive models of minimal hepatic encephalopathy for cirrhotic patients based on large-scale brain intrinsic connectivity networks
Authors: Jiao Yun , Wang Xun-Heng , Chen Rong , Tang Tian-Yu , Zhu Xi-Qi , Teng Gao-Jun
Published: September 2017

We aimed to find the most representative connectivity patterns for minimal hepatic encephalopathy (MHE) using large-scale intrinsic connectivity networks (ICNs) and machine learning methods. Resting-state fMRI was administered to 33 cirrhotic patients with MHE and 43 cirrhotic patients without MHE (NMHE). The connectivity maps of 20 ICNs for each participant were obtained by dual regression. A Bayesian machine learning technique, called Graphical Model-based Multivariate Analysis, was applied to determine ICN regions that characterized group differences. The most representative ICNs were evaluated by the performance of three machine learning methods (support vector machines (SVMs), multilayer perceptrons (MLP), and C4.5). The clinical significance of these potential biomarkers was further tested. The temporal lobe network (TLN), and subcortical network (SCN), and sensorimotor network (SMN) were selected as representative ICNs. The distinct functional integration patterns of the representative ICNs were significantly correlated with behavior criteria and Child-Pugh scores. Our findings suggest the representative ICNs based on GAMMA can distinguish MHE from NMHE and provide supplementary information to current MHE diagnostic criteria.
Development and Validation of a Nomogram for Predicting Survival in Patients with Advanced Pancreatic Ductal Adenocarcinoma
Authors: Deng Qing-Long , Dong Shu , Wang Lei , Zhang Chen-Yue , Ying Hai-Feng , Li Zhao-Shen , Shen Xiao-Heng , Guo Yuan-Bao , Meng Zhi-Qiang , Yu Jin-Ming , Chen Qi-Wen
Published: September 2017

This study aimed to develop and validate an effective prognostic nomogram for advanced PDAC patients. We conducted a prospective multicenter cohort study involving 1,526 advanced PDAC patients from three participating hospitals in China between January 1, 2004 and December 31, 2013. Two thirds of the patients were randomly assigned to the training set (n = 1,017), and one third were assigned to the validation set (n = 509). Multivariate cox regression analysis was performed to identify significant prognostic factors for overall survival to develop the nomogram. Internal and external validation using C-index and calibration curve were conducted in the training set and validation set respectively. As results, seven independent prognostic factors were identified: age, tumor stage, tumor size, ALT (alanine aminotransferase), ALB (albumin), CA 19-9, HBV infection status, and these factors were entered into the nomogram. The proposed nomogram showed favorable discrimination and calibration both in the training set and validation set. The C-indexes of the training set and validation set were 0.720 and 0.696 respectively, which were both significantly higher than that of the staging system (C-index = 0.613, P < 0.001). In conclusion, the proposed nomogram may be served as an effective tool for prognostic evaluation of advanced PDAC.
Inter-individual differences in heart rate variability are associated with inter-individual differences in mind-reading
Authors: Lischke Alexander , Lemke Daniela , Neubert Jörg , Hamm Alfons O. , Lotze Martin
Published: September 2017

In the present study, we investigated whether inter-individual differences in vagally-mediated cardiac activity (high frequency heart rate variability, HF-HRV) would be associated with inter-individual differences in mind-reading, a specific aspect of social cognition. To this end, we recorded resting state HF-HRV in 49 individuals before they completed the Reading the Mind in the Eyes Test, a test that required the identification of mental states on basis of subtle facial cues. As expected, inter-individual differences in HF-HRV were associated with inter-individual differences in mental state identification: Individuals with high HF-HRV were more accurate in the identification of positive but not negative states than individuals with low HF-HRV. Individuals with high HF-HRV may, thus, be more sensitive to positive states of others, which may increase the likelihood to detect cues that encourage approach and affiliative behavior in social contexts. Inter-individual differences in mental state identification may, thus, explain why individuals with high HF-HRV have been shown to be more successful in initiating and maintaining social relationships than individuals with low HF-HRV.
Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer
Authors: Thomsen Mathilde Borg Houlberg , Nordentoft Iver , Lamy Philippe , Vang Søren , Reinert Line , Mapendano Christophe Kamungu , Høyer Søren , Ørntoft Torben F. , Jensen Jørgen Bjerggaard , Dyrskjøt Lars
Published: September 2017

Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease. Analysis of adjacent normal urothelium showed low frequency mutations in patients with multifocal disease. Expression profiling showed intra-tumour and intra-patient co-existence of basal- and luminal-like tumour regions, and patients with multifocal disease had a greater degree of genomic and transcriptomic ITH, as well as transformation of adjacent normal cells, compared to patients with unifocal disease. Analysis of the adjacent urothelium may pave the way for therapies targeting the field disease.
Pulse Transit Time Based Continuous Cuffless Blood Pressure Estimation: A New Extension and A Comprehensive Evaluation
Authors: Ding Xiaorong , Yan Bryan P. , Zhang Yuan-Ting , Liu Jing , Zhao Ni , Tsang Hon Ki
Published: September 2017

Cuffless technique enables continuous blood pressure (BP) measurement in an unobtrusive manner, and thus has the potential to revolutionize the conventional cuff-based approaches. This study extends the pulse transit time (PTT) based cuffless BP measurement method by introducing a new indicator – the photoplethysmogram (PPG) intensity ratio (PIR). The performance of the models with PTT and PIR was comprehensively evaluated in comparison with six models that are based on sole PTT. The validation conducted on 33 subjects with and without hypertension, at rest and under various maneuvers with induced BP changes, and over an extended calibration interval, respectively. The results showed that, comparing to the PTT models, the proposed methods achieved better accuracy on each subject group at rest state and over 24 hours calibration interval. Although the BP estimation errors under dynamic maneuvers and over extended calibration interval were significantly increased for all methods, the proposed methods still outperformed the compared methods in the latter situation. These findings suggest that additional BP-related indicator other than PTT has added value for improving the accuracy of cuffless BP measurement. This study also offers insights into future research in cuffless BP measurement for tracking dynamic BP changes and over extended periods of time.
Bacterial distributions and prognosis of bloodstream infections in patients with liver cirrhosis
Authors: Xie Yangxin , Tu Bo , Xu Zhe , Zhang Xin , Bi Jingfeng , Zhao Min , Chen Weiwei , Shi Lei , Zhao Peng , Bao Chunmei , Qin Enqiang , Xu Dongping
Published: September 2017

Bloodstream infections (BSIs) are a frequently observed complication in liver cirrhosis patients. This study aimed to investigate the microbiological characteristics and outcomes of BSIs in patients with liver cirrhosis. We retrospectively studied 852 patients with liver cirrhosis who developed a BSI. Patient outcome was evaluated using 30-day mortality and assessed using multivariate stepwise logistic regression analysis. Antibiotic sensitivity of the pathogens was tested. Gram-negative bacteria were responsible for 59.6% of BSIs, and Gram-positive bacteria caused 40.4% of the episodes among liver cirrhosis patients. The bacterial distribution significantly differed between hospital-acquired and community-acquired infections, especially in cases caused by Gram-negative pathogens. The results of the drug sensitivity test suggested that amikacin, cefoperazone/sulbactam, and piperacillin/tazobactam highly suppressed Gram-negative infections, while vancomycin and teicoplanin strongly inhibited Gram-positive BSIs. Liver failure, liver cancer, complications, Child-Pugh grade, septic shock, administration of appropriate antibiotics within 24 h, ICU admission, nosocomial infection, and Gram nature of the bacteria were independent risk factors for 30-day mortality (P < 0.05). The choice of initial empirical antibiotics should be based on the type, severity and origin of infection and on the local epidemiological data on antibiotic resistance. Accurate evaluation of risk factors for mortality may improve appropriate therapeutic choice.