bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites
Authors: Seo Yeon Seok , Park Soo Young , Kim Moon Young , Kim Sang Gyune , Park Jun Yong , Yim Hyung Joon , Jang Byoung Kuk , Park Seung Ha , Kim Ji Hoon , Suk Ki Tae , Kim Jin Dong , Kim Tae Yeob , Cho Eun Young , Lee Jun Sung , Jung Soung Won , Jang Jae Young , An Hyonggin , Tak Won Young , Baik Soon Koo , Hwang Jae Seok , Kim Young Seok , Sohn Joo Hyun , Um Soon Ho
Published: September 2017

Background and Aim

Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites.

Methods

Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS‐1).

Results

In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS‐1. Serum creatinine level was not significantly associated with mortality and development of HRS‐1 on multivariate analysis.

Conclusion

Serum cystatin C level was an independent predictor of mortality and development of HRS‐1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites.
Prognosis Communication in Late‐Life Disability: A Mixed Methods Study
Authors: Wong Theresa W. , Lang‐Brown Sean , Romo Rafael D. , Au‐Yeung Alvin , Lee Sei J. , Moran Patricia J. , Karlawish Jason , Sudore Rebecca , Clayton Josephine , Smith Alexander K.
Published: September 2017

Importance

Long‐term prognosis informs clinical and personal decisions for older adults with late‐life disability. However, many clinicians worry that telling patients their prognosis may cause harm.

Objective

To explore the safety of and reactions to prognosis communication in late‐life disability.

Design

Participants estimated their own life expectancy and were then presented their calculated life expectancy using a validated prognostic index. We used a semi‐structured interview guide to ask for their reactions. Qualitative data were analyzed using constant comparative analysis. Potential psychological and behavioral outcomes in response to receiving one's calculated prognosis were recorded and re‐assessed 2–4 weeks later.

Setting

Community‐dwelling older adults age 70+ residing in the San Francisco Bay Area.

Participants

Thirty five older adults with a median age of 80 requiring assistance with ≥1 Activity of Daily Living.

Results

Self‐estimates of life expectancy were similar to calculated results for 16 participants. 15 estimated their life expectancy to be longer than their calculated life expectancy by >2 years, while 4 shorter by >2 years. An overarching theme of, “fitting life expectancy into one's narrative” emerged from qualitative analysis. Discussing life expectancy led participants to express how they could alter their life expectancy (subtheme “locus of control”), how they saw their present health (subtheme “perceived health”), and their hopes and fears for the remaining years of their lives (subtheme “outlook on remaining years”). Feelings of anxiety and sadness in reaction to receiving calculated prognosis were rare.

Conclusions and Relevance

About half of the disabled older adults' self‐estimates of prognosis were similar to calculated estimates. Evidence of sadness or anxiety was rare. These data suggest that in most cases, clinicians may offer to discuss prognosis.
Long‐term community change: bryophytes are more responsive than vascular plants to nitrogen deposition and warming
Authors: Becker Scarpitta Antoine , Bardat Jacques , Lalanne Arnault , Vellend Mark
Published: September 2017

Aims

Many studies of vegetation change over multiple decades have focused on vascular plants, but very few on bryophytes, despite the importance of bryophytes for overall plant biodiversity and ecosystem functioning. Using a repeated survey of vascular plants and bryophytes in a forest ecosystem, we tested predictions of the hypotheses that: (1) vegetation change has been driven by N deposition and climate warming, and (2) bryophytes are more responsive to environmental change than vascular plants.

Location

Lowland temperate forest, northwest France.

Methods

In forest plots initially surveyed in 1976, we re‐surveyed both vascular plants and bryophytes in 2009 and 2012, respectively. We analysed changes in α‐diversity, β‐diversity, and species composition, and we used community‐weighted mean values of species affinities for temperature, light, pH, soil moisture and N to assess the temporal responses potentially caused by warming, N deposition, or possibly a changing light regime.

Results

We observed significantly increased species richness of bryophytes and decreased richness of vascular plants. Community affinities to N, pH and temperature increased significantly for bryophytes, but not for vascular plants, although the change over time in N affinities for vascular plants was qualitatively in the predicted direction. Bryophytes showed a higher magnitude of temporal community change than vascular plants, both in terms of overall species composition and environmental affinities, indicating a higher responsiveness of bryophytes to environmental change.

Conclusion

Overall, the result of more marked temporal community change for bryophytes suggests that the many studies of changes in vascular plant communities over time might underestimate the sensitivity of the broader plant community (including cryptogams) to environmental change.
Actinorhodin is a redox‐active antibiotic with a complex mode of action against Gram‐positive cells
Authors: Mak Stefanie , Nodwell Justin R.
Published: September 2017

Actinorhodin is a blue‐pigmented, redox‐active secondary metabolite that is produced by the bacterium Streptomyces coelicolor. Although actinorhodin has been used as a model compound for studying secondary metabolism, its biological activity is not well understood. Indeed, redox‐active antibiotics in general have not been widely investigated at the mechanistic level. In this work, we have conducted a comprehensive chemical genetic investigation of actinorhodin's antibacterial effect on target organisms. We find that actinorhodin is a potent, bacteriostatic, pH‐responsive antibiotic. Cells activate at least three stress responses in the presence of actinorhodin, including those responsible for managing oxidative damage, protein damage and selected forms of DNA damage. We find that mutations in the Staphylococcus aureus walRKHI operon can confer low‐level resistance to actinorhodin, indicating possible targeting of the cell envelope. Our study indicates a complex mechanism of action, involving multiple molecular targets, that is distinct from other antibiotics.
The role of genomic location and flanking 3′UTR in the generation of functional levels of variant surface glycoprotein in Trypanosoma brucei
Authors: Ridewood Sophie , Ooi Cher‐Pheng , Hall Belinda , Trenaman Anna , Wand Nadina Vasileva , Sioutas Georgios , Scherwitzl Iris , Rudenko Gloria
Published: September 2017

Trypanosoma brucei faces relentless immune attack in the mammalian bloodstream, where it is protected by an essential coat of Variant Surface Glycoprotein (VSG) comprising ∼10% total protein. The active VSG gene is in a Pol I‐transcribed telomeric expression site (ES). We investigated factors mediating these extremely high levels of VSG expression by inserting ectopic VSG117 into VSG221 expressing T. brucei. Mutational analysis of the ectopic VSG 3′UTR demonstrated the essentiality of a conserved 16‐mer for mRNA stability. Expressing ectopic VSG117 from different genomic locations showed that functional VSG levels could be produced from a gene 60 kb upstream of its normal telomeric location. High, but very heterogeneous levels of VSG117 were obtained from the Pol I‐transcribed rDNA. Blocking VSG synthesis normally triggers a precise precytokinesis cell‐cycle checkpoint. VSG117 expression from the rDNA was not adequate for functional complementation, and the stalled cells arrested prior to cytokinesis. However, VSG levels were not consistently low enough to trigger a characteristic ‘VSG synthesis block’ cell‐cycle checkpoint, as some cells reinitiated S phase. This demonstrates the essentiality of a Pol I‐transcribed ES, as well as conserved VSG 3′UTR 16‐mer sequences for the generation of functional levels of VSG expression in bloodstream form T. brucei.
Characterization of microRNAs from Arabidopsis galls highlights a role for miR159 in the plant response to the root‐knot nematode Meloidogyne incognita
Authors: Medina Clémence , da Rocha Martine , Magliano Marc , Ratpopoulo Alizée , Revel Benoît , Marteu Nathalie , Magnone Virginie , Lebrigand Kevin , Cabrera Javier , Barcala Marta , Silva Ana Cláudia , Millar Anthony , Escobar Carolina , Abad Pierre , Favery Bruno , Jaubert‐Possamai Stéphanie
Published: September 2017

Root knot nematodes (RKN) are root parasites that induce the genetic reprogramming of vascular cells into giant feeding cells and the development of root galls. MicroRNAs (miRNAs) regulate gene expression during development and plant responses to various stresses.

Disruption of post‐transcriptional gene silencing in Arabidopsis ago1 or ago2 mutants decrease the infection rate of RKN suggesting a role for this mechanism in the plant‐nematode interaction. By sequencing small RNAs from uninfected Arabidopsis roots and from galls 7 and 14 d post infection with Meloidogyne incognita, we identified 24 miRNAs differentially expressed in gall as putative regulators of gall development. Moreover, strong activity within galls was detected for five miRNA promoters.

Analyses of nematode development in an Arabidopsis miR159abc mutant had a lower susceptibility to RKN, suggesting a role for the miR159 family in the plant response to M. incognita. Localization of mature miR159 within the giant and surrounding cells suggested a role in giant cell and gall. Finally, overexpression of miR159 in galls at 14 d post inoculation was associated with the repression of the miR159 target MYB33 which expression is restricted to the early stages of infection.

Overall, these results implicate the miR159 in plant responses to RKN.
Dose‐dependent interactions between two loci trigger altered shoot growth in BG‐5 × Krotzenburg‐0 (Kro‐0) hybrids of Arabidopsis thaliana
Authors: Alhajturki Dema , Muralidharan Subhashini , Nurmi Markus , Rowan Beth A. , Lunn John E. , Boldt Helena , Salem Mohamed A. , Alseekh Saleh , Jorzig Christian , Feil Regina , Giavalisco Patrick , Fernie Alisdair R. , Weigel Detlef , Laitinen Roosa A. E.
Published: September 2017

Hybrids occasionally exhibit genetic interactions resulting in reduced fitness in comparison to their parents. Studies of Arabidopsis thaliana have highlighted the role of immune conflicts, but less is known about the role of other factors in hybrid incompatibility in plants. Here, we present a new hybrid incompatibility phenomenon in this species.

We have characterized a new case of F1 hybrid incompatibility from a cross between the A. thaliana accessions Krotzenburg‐0 (Kro‐0) and BG‐5, by conducting transcript, metabolite and hormone analyses, and identified the causal loci through genetic mapping.

The F1 hybrids showed arrested growth of the main stem, altered shoot architecture, and altered concentrations of hormones in comparison to parents. The F1 phenotype could be rescued in a developmental‐stage‐dependent manner by shifting to a higher growth temperature. These F1 phenotypes were linked to two loci, one on chromosome 2 and one on chromosome 3. The F2 generation segregated plants with more severe phenotypes which were linked to the same loci as those in the F1.

This study provides novel insights into how previously unknown mechanisms controlling shoot branching and stem growth can result in hybrid incompatibility.
Target of rapamycin signaling orchestrates growth–defense trade‐offs in plants
Authors: De Vleesschauwer David , Filipe Osvaldo , Hoffman Gena , Seifi Hamed Soren , Haeck Ashley , Canlas Patrick , Van Bockhaven Jonas , De Waele Evelien , Demeestere Kristof , Ronald Pamela , Hofte Monica
Published: September 2017

Plant defense to microbial pathogens is often accompanied by significant growth inhibition. How plants merge immune system function with normal growth and development is still poorly understood. Here, we investigated the role of target of rapamycin (TOR), an evolutionary conserved serine/threonine kinase, in the plant defense response.

We used rice as a model system and applied a combination of chemical, genetic, genomic and cell‐based analyses.

We demonstrate that ectopic expression of TOR and Raptor (regulatory‐associated protein of mTOR), a protein previously demonstrated to interact with TOR in Arabidopsis, positively regulates growth and development in rice. Transcriptome analysis of rice cells treated with the TOR‐specific inhibitor rapamycin revealed that TOR not only dictates transcriptional reprogramming of extensive gene sets involved in central and secondary metabolism, cell cycle and transcription, but also suppresses many defense‐related genes. TOR overexpression lines displayed increased susceptibility to both bacterial and fungal pathogens, whereas plants with reduced TOR signaling displayed enhanced resistance. Finally, we found that TOR antagonizes the action of the classic defense hormones salicylic acid and jasmonic acid.

Together, these results indicate that TOR acts as a molecular switch for the activation of cell proliferation and plant growth at the expense of cellular immunity.
WHO standards for biotherapeutics, including biosimilars: an example of the evaluation of complex biological products
Authors: Knezevic Ivana , Griffiths Elwyn
Published: September 2017

The most advanced regulatory processes for complex biological products have been put in place in many countries to provide appropriate regulatory oversight of biotherapeutic products in general, and similar biotherapeutics in particular. This process is still ongoing and requires regular updates to national regulatory requirements in line with scientific developments and up‐to‐date standards. For this purpose, strong knowledge of and expertise in evaluating biotherapeutics in general and similar biotherapeutic products, also called biosimilars, in particular is essential. Here, we discuss the World Health Organization's international standard‐setting role in the regulatory evaluation of recombinant DNA–derived biotherapeutic products, including biosimilars, and provide examples that may serve as models for moving forward with nonbiological complex medicinal products. A number of scientific challenges and regulatory considerations imposed by the advent of biosimilars are described, together with the lessons learned, to stimulate future discussions on this topic. In addition, the experiences of facilitating the implementation of guiding principles for evaluation of similar biotherapeutic products into regulatory and manufacturers’ practices in various countries over the past 10 years are briefly explained, with the aim of promoting further developments and regulatory convergence of complex biological and nonbiological products.
Thiamine content of F‐75 therapeutic milk for complicated severe acute malnutrition: time for a change?
Authors: Hiffler Laurent , Adamolekun Bola , Fischer Philip R. , Fattal‐Vavleski Aviva
Published: September 2017

Since community‐based management of severe acute malnutrition has become the standard of care, the clinical profile of severe acutely malnourished patients admitted to hospitals or inpatient therapeutic feeding centers has changed significantly. These patients are usually very ill and often present with several comorbidities, such as shock, sepsis, and pneumonia. Complicated severe acute malnutrition patients are at risk of thiamine insufficiency, and critically ill patients have higher thiamine requirements. The thiamine content of F‐75, the therapeutic milk formula used in the early stabilization phase of refeeding in patients with severe acute malnutrition, seems insufficient. Here, we discuss the need and rationale for a substantial increase in the thiamine content of F‐75.
TALEN‐mediated targeted mutagenesis of more than 100 COMT copies/alleles in highly polyploid sugarcane improves saccharification efficiency without compromising biomass yield
Authors: Kannan Baskaran , Jung Je Hyeong , Moxley Geoffrey W. , Lee Sun‐Mi , Altpeter Fredy
Published: September 2017

Sugarcane is the world's most efficient feedstock for commercial production of bioethanol due to its superior biomass production and accumulation of sucrose in stems. Integrating first‐ and second‐generation ethanol conversion processes will enhance the biofuel yield per unit area by utilizing both sucrose and cell wall‐bound sugars for fermentation. RNAi suppression of the lignin biosynthetic gene caffeic acid O‐methyltransferase (COMT) has been demonstrated to improve bioethanol production from lignocellulosic biomass. Genome editing has been used in a number of crops for creation of loss of function phenotypes but is very challenging in sugarcane due to its highly polyploid genome. In this study, a conserved region of COMT was targeted with a single‐transcription activator‐like effector nuclease (TALEN) pair for multi‐allelic mutagenesis to modify lignin biosynthesis in sugarcane. Field‐grown TALEN‐mediated COMT mutants showed up to 19.7% lignin reduction and significantly decreased syringyl to guaiacyl (S/G) ratio resulting in an up to 43.8% improved saccharification efficiency. Biomass production of COMT mutant lines with superior saccharification efficiency did not differ significantly from the original cultivar under replicated field conditions. Sanger sequencing of cloned COMT amplicons (1351–1657 bp) revealed co‐editing of 107 of the 109 unique COMT copies/alleles in vegetative progeny of line CB6 using a single TALEN pair. Line CB6 combined altered cell wall composition and drastically improved saccharification efficiency with good agronomic performance. These findings confirm the feasibility of co‐mutagenesis of a very large number of target alleles/copies for improvement in crops with complex genomes.
A double EPSPS gene mutation endowing glyphosate resistance shows a remarkably high resistance cost
Authors: Han Heping , Vila‐Aiub Martin M. , Jalaludin Adam , Yu Qin , Powles Stephen B.
Published: September 2017

A novel glyphosate resistance double point mutation (T102I/P106S, TIPS) in the 5‐enolpyruvylshikimate‐3‐phosphate synthase (EPSPS) gene has been recently identified for the first time only in the weed species Eleusine indica. Quantification of plant resistance cost associated with the TIPS and the often reported glyphosate resistance single P106S mutation was performed. A significant resistance cost (50% in seed number currency) associated with the homozygous TIPS but not the homozygous P106S EPSPS variant was identified in E. indica plants. The resistance cost associated with the TIPS mutation escalated to 85% in plants under resource competition with rice crops. The resistance cost was not detected in nonhomozygous TIPS plants denoting the recessive nature of the cost associated with the TIPS allele. An excess of 11‐fold more shikimate and sixfold more quinate in the shikimate pathway was detected in TIPS plants in the absence of glyphosate treatment compared to wild type, whereas no changes in these compounds were observed in P106S plants when compared to wild type. TIPS plants show altered metabolite levels in several other metabolic pathways that may account for the expression of the observed resistance cost.
Inclusion of sepsis and hypoxaemia in mortality prediction of hospitalized patients with community‐acquired pneumonia
Authors: Berk Takir Huriye , Esquinas Antonio M. , Glossop Alastair J.
Published: September 2017

See Reply
Rescue therapy within the UK Cystic Fibrosis Registry: An exploration of predictors of intravenous antibiotic use amongst adults with CF
Authors: Hoo Zhe Hui , Wildman Martin J. , Curley Rachael , Walters Stephen J. , Campbell Michael J.
Published: September 2017

ABSTRACT

Background and objective

Intravenous (i.v.) antibiotics are needed for rescue when preventative therapy fails to achieve stability among adults with cystic fibrosis (CF). Understanding the distribution of i.v. days can provide insight into the care that adults with CF need. We aim to determine the baseline characteristics that are associated with higher i.v. use, in particular to test the hypothesis that prior‐year i.v. use is associated with future‐year i.v. use.

Methods

This is a cross‐sectional analysis of the 2013–2014 UK CF registry data. Stepwise logistic regression was performed using current‐year i.v. days as the dependent variable, and demographic variables including prior‐year i.v. days as the covariates. Based on these results, study sample was divided into clinically meaningful subgroups using analysis similar to tree‐based method.

Results

Data were available for 4269 adults in 2013 and 4644 adults in 2014. Prior‐year i.v. use was the strongest predictor for current‐year i.v. use followed by forced expiratory volume in 1 s (FEV1). Adults with high prior‐year i.v. use (>14 days) continued to require high levels of i.v., regardless of FEV1. Those with high prior‐year i.v. use and FEV1 ≥70% had higher current‐year i.v. days compared to adults with low prior‐year i.v. use and FEV1 <40% (28 days, interquartile range (IQR): 11–41 days vs 14 days, IQR: 0–28 days; Mann–Whitney P‐value <0.001 in 2013).

Conclusion

CF people with prior high levels of rescue often continue to need high levels of rescue even if they have good FEV1. The reasons for this require further investigations.
Father group leaders' experiences of creating an arena for father support – A qualitative study
Authors: Kerstis Birgitta , Wells Michael B. , Andersson Ewa
Published: September 2017

Background

Parental classes consisting of only fathers, hereafter referred to as father groups, have existed in Sweden since the mid‐1990s.

Objective

To describe the father group leaders' perspectives on and experiences of father groups.

Method

A qualitative study was conducted using content analysis. Eleven individual interviews with father group leaders were conducted. An interview guide was used.

Settings and participants

The study was set in different parts of Sweden. The participants were eleven men who are father group leaders. They were recruited using the snowball method.

Findings

The father group leaders described how participants often have high education levels and orderly social circumstances. The leaders described that the groups increased the fathers' reflection about parenthood, which could benefit the whole family in both the short and long term. The father group leaders reported that some of the topics in the sessions directly influenced fathers to discuss issues regarding equality and their co‐parenting relationship. They also argued that participating in father groups might help convince fathers to take more parental leave and build stronger relationships with their partner and child.
Reactive oxygen species generated in chloroplasts contribute to tobacco leaf infection by the necrotrophic fungus Botrytis cinerea
Authors: Rossi Franco R. , Krapp Adriana R. , Bisaro Fabiana , Maiale Santiago J. , Pieckenstain Fernando L. , Carrillo Néstor
Published: September 2017

Reactive oxygen species (ROS) play fundamental roles in plant responses to pathogen infection, including modulation of cell death processes and defense‐related gene expression. Cell death triggered as part of the hypersensitive response enhances resistance to biotrophic pathogens, but favors the virulence of necrotrophs. Even though the involvement of ROS in the orchestration of defense responses is well established, the relative contribution of specific subcellular ROS sources to plant resistance against microorganisms with different pathogenesis strategies is not completely known. The aim of this work was to investigate the role of chloroplastic ROS in plant defense against a typical necrotrophic fungus, Botrytis cinerea. For this purpose, we used transgenic Nicotiana tabacum (tobacco) lines expressing a plastid‐targeted cyanobacterial flavodoxin (pfld lines), which accumulate lower chloroplastic ROS in response to different stresses. Tissue damage and fungal growth were significantly reduced in infected leaves of pfld plants, as compared with infected wild‐type (WT) counterparts. ROS build‐up triggered by Botrytis infection and associated with chloroplasts was significantly decreased (70–80%) in pfld leaves relative to the wild type. Phytoalexin accumulation and expression of pathogenesis‐related genes were induced to a lower degree in pfld plants than in WT siblings. The impact of fungal infection on photosynthetic activity was also lower in pfld leaves. The results indicate that chloroplast‐generated ROS play a major role in lesion development during Botrytis infection. This work demonstrates that the modulation of chloroplastic ROS levels by the expression of a heterologous antioxidant protein can provide a significant degree of protection against a canonical necrotrophic fungus.
Effects of a 24 Week Multifaceted Sports Training Program on Some Physical Characteristics of 5 to 9 Year-Old Children
Authors: Bağcı Emre
Published: September 2017

This study was conducted to investigate the effects of a 24-week multifaceted sport training program on some physical and performance characteristics of 5-9 year old children. There are many researches about the necessities for children to start physical activity at an early age. According to the characteristics of different physical activities to be performed, children can endow with different developments. Multifaceted development in the motor properties of an unbranched individual will also benefit him/her in the branching phase. A branch that will be applied to children will develop the characteristics of that branch in the child. This study aims to determine the effects of the implementation of a training program consisting of the basic characteristics of different branches on the physical characteristics of children.A group of children with a mean age of 6.4 (SD 1.34) (n = 98) residing in Ankara participated in the study. A training program including basic techniques of many sports branches was applied to children in the form of 2 lesson hours per day for 2 days in each week. Lessons are scheduled for 45 minutes. During the 24-week training period, children were tested and measured three times; at the beginning, in the middle and at the end of the study. All physical characteristics of the children within the scope of the study has improved, and the differences in the test of vertical jump, throwing medicine ball, right foot balance posture, left hand grip force, shuttle, horizontal jump and 10x5m running were found to be statistically significant (p<0.05).
Aspects of a Hybrid Analytical Finite Element Method Approach for Ultrasonic Guided Wave Inspection Design
Authors: Rose Joseph L.
Published: September 2017

A strategy is presented here to develop guided wave inspection systems using short-range ultrasonic guided waves. A hybrid analytical finite element method (FEM) is presented. The importance of dispersion curve computation, wave structure analysis in the test part, actuator design, the establishment of appropriate boundary conditions from the actuator design to be used in any FEM computations leading to key experiments, and aspects of system design are discussed. Several interesting problems reported by the author in previous publications are used here to stress the importance of mode and frequency choice when solving guided wave problems.
Case report of a rare glomus jugulare tumor extended within the extracranial internal jugular vein: emphasis on initial ultrasound findings and literature review
Authors: Deng Qing , Wang Yijia , Chen Xiaoyi , Zhou Qing
Published: September 2017

Glomus jugulare tumor (GJT) is a rare benign neoplasm that is located in the skull base; it is impossible for ultrasonography to detect it in most cases. In this article, we present the case of a rare giant GJT, which extended into the internal jugular vein in the neck, initially detected by ultrasonography and confirmed by MRI and pathology. We highlight the initial ultrasonography findings and review the literature to summarize the ultrasonographic features of GJT.
Patterning of electrically tunable light-emitting photonic structures demonstrating bound states in the continuum
Authors: Penzo Erika , Romano Silvia , Wang Yu , Dhuey Scott , Dal Negro Luca , Mocella Vito , Cabrini Stefano
Published: September 2017

The authors report a scalable process to fabricate electrically tunable light-emitting photonic structures made of optically active and electrically conductive erbium-doped zinc oxide (Er:ZnO) deposited by magnetron sputtering. Such structures are expected to produce a dramatic amplification of the erbium fluorescence due to enhanced light-matter coupling at topologically protected states called bound states in the continuum (BIC). Our patterning approach circumvents roughening of the Er:ZnO during plasma etching by employing a metallic mask and a lift-off process. Etching with a polymer mask resulted in an unacceptable increase of the surface roughness, from a root mean square (RMS) roughness of 0.5 nm for the as-deposited sample to a RMS roughness of 25 nm after etching. Such surface roughness proves detrimental to the photonic crystal resonances and to the BIC mode in particular. Using a metallic mask instead allowed for the etching of Er:ZnO with a modest roughness increase (RMS value 4.1 nm). This patterning approach produced a photonic structure demonstrating a BIC mode close to the expected frequency of 1540 nm at normal incidence, in accordance with our simulations.
A pressure-induced topological phase with large Berry curvature in Pb

1−
x

Sn

x

Te
Authors: Liang Tian , Kushwaha Satya , Kim Jinwoong , Gibson Quinn , Lin Jingjing , Kioussis Nicholas , Cava Robert J. , Ong N. Phuan
Published: September 2017

Under pressure, the semiconductor PbSnTe transitions from an insulator to a Weyl metal that displays a large Berry curvature.
Compliant substratum guides endothelial commitment from human pluripotent stem cells
Authors: Smith Quinton , Chan Xin Yi , Carmo Ana Maria , Trempel Michelle , Saunders Michael , Gerecht Sharon
Published: September 2017

Surface stiffness during the early stages of stem cell differentiation affects vascular fate under chemically defined conditions.
PAI-1 is a critical regulator of FGF23 homeostasis
Authors: Eren Mesut , Place Aaron T. , Thomas Paul M. , Flevaris Panagiotis , Miyata Toshio , Vaughan Douglas E.
Published: September 2017

Pharmacological inhibition of PAI-1 augments proteolytic clearance of FGF23.
Methylmercury uptake and degradation by methanotrophs
Authors: Lu Xia , Gu Wenyu , Zhao Linduo , Farhan Ul Haque Muhammad , DiSpirito Alan A. , Semrau Jeremy D. , Gu Baohua
Published: September 2017

Certain methanotrophs can take up and degrade methylmercury, signifying a potentially important demethylation pathway in the environment.
Active Pacific meridional overturning circulation (PMOC) during the warm Pliocene
Authors: Burls Natalie J. , Fedorov Alexey V. , Sigman Daniel M. , Jaccard Samuel L. , Tiedemann Ralf , Haug Gerald H.
Published: September 2017

The warm, ~400-ppmv CO
2
world of the Pliocene supported a northern-sourced meridional overturning cell in the Pacific.
Autogenic geomorphic processes determine the resolution and fidelity of terrestrial paleoclimate records
Authors: Foreman Brady Z. , Straub Kyle M.
Published: September 2017

Mesoscale geomorphic processes impose regularity in deposition, allowing quantitative resolution of proxy-based climate reconstructions.
A versatile 3D tissue matrix scaffold system for tumor modeling and drug screening
Authors: Rijal Girdhari , Li Weimin
Published: September 2017

Tissue matrix scaffold is an advanced tissue-mimicry 3D culture system for biomedical research and drug screening.
Ligand-induced twisting of nanoplatelets and their self-assembly into chiral ribbons
Authors: Jana Santanu , de Frutos Marta , Davidson Patrick , Abécassis Benjamin
Published: September 2017

Organic ligands can induce twist on nanometer-thin crystalline platelets and on their self-assembled ribbons.
A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea
Authors: Bergström Anders , Oppenheimer Stephen J. , Mentzer Alexander J. , Auckland Kathryn , Robson Kathryn , Attenborough Robert , Alpers Michael P. , Koki George , Pomat William , Siba Peter , Xue Yali , Sandhu Manjinder S. , Tyler-Smith Chris
Published: September 2017

The population structure in Papua New Guinea reflects a Neolithic transition with high present-day genetic differentiation.
Soft x-ray excitonics
Authors: Moulet A. , Bertrand J. B. , Klostermann T. , Guggenmos A. , Karpowicz N. , Goulielmakis E.
Published: September 2017

Consecutive attosecond pulses reveal the dynamics of excitons ensuing from core-electron excitation in silica.
Biological fabrication of cellulose fibers with tailored properties
Authors: Natalio Filipe , Fuchs Regina , Cohen Sidney R. , Leitus Gregory , Fritz-Popovski Gerhard , Paris Oskar , Kappl Michael , Butt Hans-Jürgen
Published: September 2017

Biological incorporation of functional molecules into cotton fibers adds magnetic or optical properties.
Highly efficient electrocaloric cooling with electrostatic actuation
Authors: Ma Rujun , Zhang Ziyang , Tong Kwing , Huber David , Kornbluh Roy , Ju Yongho Sungtaek , Pei Qibing
Published: September 2017

A flexible and lightweight device uses an electrocaloric polymer film to provide exceptional cooling power.
Microbial mass movements
Authors: Zhu Yong-Guan , Gillings Michael , Simonet Pascal , Stekel Dov , Banwart Steve , Penuelas Josep
Published: September 2017

Wastewater, tourism, and trade are moving microbes around the globe at an unprecedented scale
Paper of note in
Science
356
(6341)
Authors: VanHook Annalisa M.
Published: September 2017

This week’s article is about a lipid that stimulates or inhibits mTORC1 signaling depending on where in the cell the lipid is made.
Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children
Authors: Walters Elisabetta , Demers Anne-Marie , van der Zalm Marieke M. , Whitelaw Andrew , Palmer Megan , Bosch Corné , Draper Heather R. , Gie Robert P. , Hesseling Anneke C.
Published: September 2017

Bacteriological confirmation of
Mycobacterium tuberculosis
is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (
N
-acetyl-
l
-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for
M. tuberculosis
. Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with “unconfirmed TB.” Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for
M. tuberculosis
detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.
Thinking beyond the Common Candida Species: Need for Species-Level Identification of Candida Due to the Emergence of Multidrug-Resistant Candida auris
Authors: Lockhart Shawn R. , Jackson Brendan R. , Vallabhaneni Snigdha , Ostrosky-Zeichner Luis , Pappas Peter G. , Chiller Tom
Published: September 2017

Candida
species are one of the leading causes of nosocomial infections. Because much of the treatment for
Candida
infections is empirical, some institutions do not identify
Candida
to species level. With the worldwide emergence of the multidrug-resistant species
Candida auris
, identification of
Candida
to species level has new clinical relevance. Species should be identified for invasive candidiasis isolates, and species-level identification can be considered for selected noninvasive isolates to improve detection of
C. auris
.
Heterogeneity of the Epstein-Barr Virus (EBV) Major Internal Repeat Reveals Evolutionary Mechanisms of EBV and a Functional Defect in the Prototype EBV Strain B95-8
Authors: Ba abdullah Mohammed M. , Palermo Richard D. , Palser Anne L. , Grayson Nicholas E. , Kellam Paul , Correia Samantha , Szymula Agnieszka , White Robert E.
Published: September 2017

Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types of lymphoma and carcinoma. Like other herpesviruses, EBV has diversified through both coevolution with its host and genetic exchange between virus strains. Sequence analysis of the EBV genome is unusually challenging because of the large number and lengths of repeat regions within the virus. Here we describe the sequence assembly and analysis of the large internal repeat 1 of EBV (IR1; also known as the BamW repeats) for more than 70 strains. The diversity of the latency protein EBV nuclear antigen leader protein (EBNA-LP) resides predominantly within the exons downstream of IR1. The integrity of the putative BWRF1 open reading frame (ORF) is retained in over 80% of strains, and deletions truncating IR1 always spare BWRF1. Conserved regions include the IR1 latency promoter (Wp) and one zone upstream of and two within BWRF1. IR1 is heterogeneous in 70% of strains, and this heterogeneity arises from sequence exchange between strains as well as from spontaneous mutation, with interstrain recombination being more common in tumor-derived viruses. This genetic exchange often incorporates regions of <1 kb, and allelic gene conversion changes the frequency of small regions within the repeat but not close to the flanks. These observations suggest that IR1—and, by extension, EBV—diversifies through both recombination and breakpoint repair, while concerted evolution of IR1 is driven by gene conversion of small regions. Finally, the prototype EBV strain B95-8 contains four nonconsensus variants within a single IR1 repeat unit, including a stop codon in the EBNA-LP gene. Repairing IR1 improves EBNA-LP levels and the quality of transformation by the B95-8 bacterial artificial chromosome (BAC).

IMPORTANCE
Epstein-Barr virus (EBV) infects the majority of the world population but causes illness in only a small minority of people. Nevertheless, over 1% of cancers worldwide are attributable to EBV. Recent sequencing projects investigating virus diversity to see if different strains have different disease impacts have excluded regions of repeating sequence, as they are more technically challenging. Here we analyze the sequence of the largest repeat in EBV (IR1). We first characterized the variations in protein sequences encoded across IR1. In studying variations within the repeat of each strain, we identified a mutation in the main laboratory strain of EBV that impairs virus function, and we suggest that tumor-associated viruses may be more likely to contain DNA mixed from two strains. The patterns of this mixing suggest that sequences can spread between strains (and also within the repeat) by copying sequence from another strain (or repeat unit) to repair DNA damage.
Mutations in the Fusion Protein of Measles Virus That Confer Resistance to the Membrane Fusion Inhibitors Carbobenzoxy-
d
-Phe-
l
-Phe-Gly and 4-Nitro-2-Phenylacetyl Amino-Benzamide
Authors: Ha Michael N. , Delpeut Sébastien , Noyce Ryan S. , Sisson Gary , Black Karen M. , Lin Liang-Tzung , Bilimoria Darius , Plemper Richard K. , Privé Gilbert G. , Richardson Christopher D.
Published: September 2017

The inhibitors carbobenzoxy (Z)-
d
-Phe-
l
-Phe-Gly (fusion inhibitor peptide [FIP]) and 4-nitro-2-phenylacetyl amino-benzamide (AS-48) have similar efficacies in blocking membrane fusion and syncytium formation mediated by measles virus (MeV). Other homologues, such as Z-
d
-Phe, are less effective but may act through the same mechanism. In an attempt to map the site of action of these inhibitors, we generated mutant viruses that were resistant to the inhibitory effects of Z-
d
-Phe-
l
-Phe-Gly. These 10 mutations were localized to the heptad repeat B (HRB) region of the fusion protein, and no changes were observed in the viral hemagglutinin, which is the receptor attachment protein. Mutations were validated in a luciferase-based membrane fusion assay, using transfected fusion and hemagglutinin expression plasmids or with syncytium-based assays in Vero, Vero-SLAM, and Vero-Nectin 4 cell lines. The changes I452T, D458N, D458G/V459A, N462K, N462H, G464E, and I483R conferred resistance to both FIP and AS-48 without compromising membrane fusion. The inhibitors did not block hemagglutinin protein-mediated binding to the target cell. Edmonston vaccine/laboratory and IC323 wild-type strains were equally affected by the inhibitors. Escape mutations were mapped upon a three-dimensional (3D) structure modeled from the published crystal structure of parainfluenzavirus 5 fusion protein. The most effective mutations were situated in a region located near the base of the globular head and its junction with the alpha-helical stalk of the prefusion protein. We hypothesize that the fusion inhibitors could interfere with the structural changes that occur between the prefusion and postfusion conformations of the fusion protein.

IMPORTANCE
Due to lapses in vaccination worldwide that have caused localized outbreaks, measles virus (MeV) has regained importance as a pathogen. Antiviral agents against measles virus are not commercially available but could be useful in conjunction with MeV eradication vaccine programs and as a safeguard in oncolytic viral therapy. Three decades ago, the small hydrophobic peptide Z-
d
-Phe-
l
-Phe-Gly (FIP) was shown to block MeV infections and syncytium formation in monkey kidney cell lines. The exact mechanism of its action has yet to be determined, but it does appear to have properties similar to those of another chemical inhibitor, AS-48, which appears to interfere with the conformational change in the viral F protein that is required to elicit membrane fusion. Escape mutations were used to map the site of action for FIP. Knowledge gained from these studies could help in the design of new inhibitors against morbilliviruses and provide additional knowledge concerning the mechanism of virus-mediated membrane fusion.
Paediatric optic neuritis: factors leading to unfavourable outcome and relapses
Authors: Averseng-Peaureaux Delphine , Mizzi Marie , Colineaux Helene , Mahieu Laurence , Pera Maria Carmela , Brassat David , Chaix Yves , Berard Emilie , Deiva Kumaran , Cheuret Emmanuel
Published: September 2017

Objectives

To identify prognostic factors associated with poor visual recovery and chronic relapsing diseases, for example, multiple sclerosis (MS), in children with optic neuritis (ON) at onset.

Methods

This multicentre retrospective study included 102 children with a first ON episode between 1990 and 2012. The primary criterion was poor visual recovery determined by visual acuity, and the secondary was relapses following ON.

Results

Median age was 11 years, 66% were girls and mean follow-up was 24 months. 58% of children were diagnosed with idiopathic isolated ON, 22% had MS, 5% had Devic’s neuromyelitis optica and 6% chronic relapsing inflammatory ON. Complete visual acuity recovery rate was 57% (95% CI=[46%-69%]) at 6 months and 71% (95% CI=[60%-81%]) at 1 and 2 years but was lower in MS (p<0.01), with recovery rate of only 27% (95% CI=[12%-54%]) at 1 year. Age ≥10 years, optic disc pallor at funduscopy and MS were the principal factors associated with poor visual recovery. Age ≥10 years, abnormal brain MRI at onset and oligoclonal banding were significantly associated with MS (p<0.01).

Conclusion

Age ≥10, optic disc pallor and MS were associated with poor recovery. Better identification of these patients may help to adapt treatment and lead to a prospective treatment study.
Enteric-coated mycophenolate sodium in the treatment of non-infectious intermediate uveitis: results of a prospective, controlled, randomised, open-label, early terminated multicentre trial
Authors: Deuter Christoph M E , Engelmann Katrin , Heiligenhaus Arnd , Lanzl Ines , Mackensen Friederike , Ness Thomas , Pleyer Uwe , Stuebiger Nicole , Wilhelm Barbara , Luedtke Holger , Zierhut Manfred , Doycheva Deshka
Published: September 2017

Background/aims

To evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (EC-MPS) in combination with low-dose corticosteroids compared with a monotherapy with low-dose corticosteroids in subjects with non-infectious intermediate uveitis (IU).

Methods

Open-label, prospective, controlled, randomised multicentre trial. Patients were randomised in a 1:1 ratio to either the treatment group (prednisolone plus EC-MPS) or control group (prednisolone monotherapy). Patients in the control group who relapsed within 6 months changed to the crossover group (prednisolone plus EC-MPS). Maximum treatment duration was 15 months. The primary endpoint was the time to first relapse in the treatment group and control group.

Results

Forty-one patients at eight sites were analysed. Twenty-two patients were allocated to the treatment group, with 19 patients in the control group. A first relapse occurred in 9 patients (40.9%) in the treatment group and 15 patients (78.9%) in the control group (p=0.03). The median time to the first relapse was >15 months for the treatment group and 2.8 months for the control group (p=0.07). The probability of relapse-free survival at month 15 was estimated to be 52.9% in the treatment group and 19.7% in the control group (p=0.01). 15 patients changed to the crossover group. Of these, only four patients developed a second relapse. No safety concerns arose during the trial. Only one patient had to discontinue EC-MPS due to increased liver enzymes.

Conclusion

EC-MPS can be considered an effective and well-tolerated immunosuppressive drug to prevent relapses in patients with chronic IU.

Trial registration number

EUDRACT number: 2009-009998-10, Results.