bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of elbasvir/grazoprevir therapy in patients with chronic HCV infection: Results from the Spanish HEPA‐C real‐world cohort
Authors: Hernández‐Conde Marta , Fernández Inmaculada , Perelló Christie , Gallego Adolfo , Bonacci Martin , Pascasio Juan M. , Romero‐Gómez Manuel , Llerena Susana , Fernández‐Rodríguez Conrado , Castro Urda José L. , García Buey Luisa , Carmona Isabel , Morillas Rosa M. , García Nuria Domínguez , Gea Francisco , Carrión José A. , Castellote Jose , Moreno‐Planas Jose M. , Piqueras Alcol Belén , Molina Esther , Diago Moises , Montoliu Silvia , de la Vega Juan , Menéndez Fernando , Sánchez Ruano Juan J. , García‐Samaniego Javier , Rosales‐Zabal Jose M. , Anton María D. , Badia Ester , Souto‐Rodríguez Raquel , Salmeron Francisco J. , Fernández‐Bermejo Miguel , Figueruela Blanca , Moreno‐Palomares Jose J. , Calleja Jose L.
Published: September 2018

In randomized controlled trials of patients with chronic HCV infection, elbasvir/grazoprevir (EBR/GZR) demonstrated high cure rates and a good safety profile. This study assessed the effectiveness and safety of EBR/GZR, with and without ribavirin, in a real‐world HCV patient cohort. HEPA‐C is a collaborative, monitored national registry of HCV patients directed by the Spanish Association for the Study of the Liver and the Networked Biomedical Research Centre for Hepatic and Digestive Diseases. Patients entered into HEPA‐C between December 2016 and May 2017, and treated with EBR/GZR with at least end‐of‐treatment response data, were included. Demographic, clinical and virologic data were analysed, and adverse events (AEs) recorded. A total of 804 patients were included in the study. The majority were male (57.9%), with a mean age of 60 (range, 19‐92) years. Genotype (GT) distribution was GT 1, 86.8% (1a, 14.3%; 1b, 72.5%); GT 4, 13.2% and 176 patients (21.9%) were cirrhotic. Overall, among 588 patients with available data, 570 (96.9%) achieved sustained virologic response at 12 weeks post‐treatment (SVR12). SVR12 rates by genotype were GT 1a, 97.7%; GT 1b, 98.6%; and GT 4, 98.1%. No significant differences in SVR12 according to fibrosis stage were observed. Eighty patients experienced an AE, resulting in treatment discontinuation in three. In this large cohort of patients with chronic HCV managed in a real‐world setting in Spain, EBR/GZR achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with a similarly good safety profile.
Genetic drift shaped MHC IIB diversity of an endangered anuran species within the Italian glacial refugium
Authors: Talarico L. , Babik W. , Marta S. , Mattoccia M.
Published: September 2018

Highly polymorphic genes of the major histocompatibility complex (MHC) encode proteins involved in the immune response that protect vertebrates from parasites and pathogen infections. MHC variation is shaped by a complex and poorly understood interplay of selective and demographic forces. Studies of MHC variation provide biologically meaningful insights useful for conservation of threatened taxa such as amphibians, which are globally declining partly due to the impact of emerging infectious diseases (e.g. chytridiomycosis). Here, we characterized MHC class IIB variation in the Apennine yellow‐bellied toad (Bombina pachypus), an endangered anuran, across its whole distribution range within the Italian peninsula. We compared MHC IIB diversity between refugial (REF) and post‐glacial expansion (PGE) areas and tested for the correlation between MHC and neutral variation to quantify the role of drift in shaping MHC diversity. Overall MHC polymorphism was limited compared to other amphibian species. Despite the clear evidence of historical positive selection acting on antigen‐binding sites, we found a significant correlation between the diversity of MHC and that of putatively neutral microsatellite markers, which suggests that genetic drift has contributed extensively to shaping MHC variation. MHC diversity was higher in the REF populations and decreased northwards into the PGE area, in accordance with the ‘southern richness and northern purity’ pattern. Past demographic events likely determined the reduction of MHC variation in the PGE area; in particular, the northern populations appeared to survive for a long time with a depleted MHC variation. We discussed recent population declines of B. pachypus in light of our findings.
Promoting NQT linguistic awareness of dialogic teaching practices: a dialogic model of professional development
Authors: Bignell Carole
Published: September 2018

This study offers an insight into the experiences of three newly qualified English primary teachers and their pupils as they sought to develop dialogic teaching in lessons. It draws upon a range of literature from the field of classroom talk, with a particular focus on the work of Robin Alexander to underpin teacher/researcher professional discussion and analysis of periodic video recordings of talk in these classrooms. Supplemented by teacher interviews, the research examines the extent to which a dialogic approach to teacher professional development might facilitate teacher self‐evaluation as a means of developing a more dialogic classroom. In doing so, it seeks to exemplify key talk moves (dialogic bids) that these teachers used to open up dialogic spaces in lessons. The research concludes that raising teacher awareness of such talk moves through professional discussion and reflection upon teaching can provide teachers with a metacognitive resource for talking about and furthering dialogic teaching practices.
The soybean Rhg1 amino acid transporter gene alters glutamate homeostasis and jasmonic acid‐induced resistance to soybean cyst nematode
Authors: Guo Wei , Zhang Feng , Bao Aili , You Qingbo , Li Zeyu , Chen Jingsheng , Cheng Yihui , Zhao Wei , Shen Xinjie , Zhou Xinan , Jiao Yongqing
Published: September 2018

Rhg1 (resistance to Heterodera glycines 1) is an important locus that contributes to resistance against soybean cyst nematode (SCN; Heterodera glycines Ichinohe), which is the most economically damaging disease of soybean worldwide. Simultaneous overexpression of three genes encoding a predicted amino acid transporter, an α‐soluble N‐ethylmaleimide‐sensitive factor attachment protein (α‐SNAP) and a predicted wound‐induced protein resulted in resistance to SCN provided by this locus. However, the roles of two of these genes (excluding α‐SNAP) remain unknown. Here, we report the functional characterization of Glyma.18G022400, a gene at the Rhg1 locus that encodes the predicted amino acid transporter Rhg1‐GmAAT. Although the direct role of Rhg1‐GmAAT in glutamate transport was not demonstrated, multiple lines of evidence showed that Rhg1‐GmAAT impacts glutamic acid tolerance and glutamate transportation in soybean. Transcriptomic and metabolite profiling indicated that overexpression of Rhg1‐GmAAT activated the jasmonic acid (JA) pathway. Treatment with a JA biosynthesis inhibitor reduced the resistance provided by the Rhg1‐containing PI88788 to SCN, which suggested that the JA pathway might play a role in Rhg1‐mediated resistance to SCN. Our results could be helpful for the clarification of the mechanism of resistance to SCN provided by Rhg1 in soybean.
Middle‐range theories as models: New criteria for analysis and evaluation
Authors: Risjord Mark
Published: September 2018

This essay argues for a new perspective on the analysis and evaluation of middle‐range theory. The commonly used criteria for theory evaluation in nursing are not as useful as they should be, and the root of the problem is an inappropriate understanding of middle‐range theory. In spite of their name, middle‐range theories should not be analysed and evaluated as concrete or limited versions of more general theories. Rather, they are best understood as models. The latter sections of this essay present a new method for analysing middle‐range theories and new criteria for their evaluation. Analysing and evaluating theories relevant to nursing as models has the capacity to increase their scholarly and clinical usefulness.
AV hysteresis causing initiation of recurrent atrial arrhythmias
Authors: Monkhouse Christopher , Dillon Terry , Chow Anthony W. C. , Behar Jonathan M.
Published: September 2018

A 73‐year‐old male with dual‐chamber implantable cardioverter defibrillator (Teligen, Boston Scientific, Marlborough, MA, USA) had multiple episodes of automatic mode switch (AMS) during clinical follow‐up. Over 50% of these demonstrated a similar pattern of initiation. AV Search+ in combination with sensor rate pacing can cause short‐coupled atrial paced intervals that can be proarrhythmic. After programming changes were made AMS burden has significantly decreased.
Medical students’ action plans are not specific
Authors: Hart Jo , Byrne‐Davis Lucie , Wass Val , Harrison Chris
Published: September 2018

Background

Action plans have been shown to be important in changing behaviour. In learners, action plans have been proposed as a mechanism by which feedback leads to an increase in expertise: feedback leads to action plans, which lead to changes in learning behaviours and finally to improvement. Little is known about the extent to which students are able to make specific actions plans that relate to the feedback they are given, however. We explored whether medical students created action plans after being given feedback, the quality of those plans and whether the action plans were related to the feedback given.

Action plans have been shown to be important in changing behaviour

Methods

We collected data from a communication session for Year‐1 medical students on the feedback they were given and the action plans they made for improvement.

Results

Most students (185/196, 94%) made one or more action plans, but only 31/196 (16%) made one or more action plans that were directly related to the feedback given to them.

Conclusions

Although educators may include action planning in education, students are not making specific enough action plans to effect change. Future work should include support for students in making better‐quality action plans.

…students are not making specific enough action plans to effect change
Transfusion‐associated graft‐versus‐host disease reexamined: potential for improved prevention using a universally applied intervention
Authors: Kleinman Steven , Stassinopoulos Adonis
Published: September 2018

BACKGROUND

Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a rare, often fatal complication of blood transfusion that can occur in immunocompromised or immunocompetent recipients and is the result of viable T cells present in the blood components transfused.

STUDY DESIGN AND METHODS

We examined the TA‐GVHD clinical case literature including numerous original clinical case reports and several comprehensive case series. We also evaluated recent in vitro experimental data on the inhibition of T cell proliferation, comparing the effect of a specific pathogen inactivation (PI) technology to that of the Food and Drug Administration–recommended gamma irradiation dose of 2500 cGy.

RESULTS

We identified 12 published TA‐GVHD cases with atypical/milder or delayed symptom presentations and/or an atypical clinical course; these included cases attributed to leukoreduced or suboptimally irradiated units. We summarize recent in vitro data using a sensitive limiting dilution assay that establish that, compared to irradiation at the recommended 2500 cGy dose, PI using amotosalen/ultraviolet A, or amustaline/glutathione achieves a greater degree of inhibition of T cell proliferation.

CONCLUSION

We propose that TA‐GVHD has a spectrum of disease severity indicating that additional mild cases may still occur but be undiagnosed and/or underreported, opening up the possibility, supported by in vitro experimental data, that irradiation at the currently established dose may not be fully protective. Furthermore, since many US institutions use component irradiation selectively only for immunocompromised patients, immunocompetent recipients are not fully protected. PI technologies appear to be at least equal to, if not better than, gamma irradiation in abrogating the ability of T cells to proliferate, and if applied to all blood components, protection against TA‐GVHD would be an additional benefit that would allow for the elimination of component irradiation.
The Relationship Between Physical Fitness Levels and Digit Ratio (2D:4D) of High School Students Engaged Actively in Sports
Authors: Gümüş Mustafa , Tutkun Erkut
Published: September 2018

The aim of this study is to examine the association between physical fitness and 2D:4D finger ratio of high school students engaged actively in sports. 23 licensed male athletes and 23 sedentary (n=46) high school students participated in the study voluntarily. The participants age, body weight, body mass index, 2D:4D finger measurement values were recorded and 20 meter shuttle run, 30 meter sprint, sit and reach test, standing long jump and hand grip strength tests were applied on the participants. The data obtained were assessed in SPSS 21 program and the results were assessed at p˂0.05 significance level. While the average age of athletes was 15.82±1.11 years, the average age of sedentary group was 15.13±0.96 years. While statistically significant difference was found between sedentary and athlete groups in terms of VO2max, right and left hand grip strength and long jump average values (p<0.05), no statistically significant difference was found between speed and flexibility measurement results (p>0.05). When the 2D:4D averages of sedentary and athlete groups were compared, statistically significant difference was found between right hand averages (p<0.05). When right and left hand 2D:4D was compared, no statistically significant difference was found in sedentary group (p>0.05), while significant difference was found in athletes (p<0.05). Statistically significant difference was found between 2D:4D averages of both hands with all physical fitness parameters (p<0.05). In the present study, finger ratio of the groups were found to be associated with some motoric and functional dominance parameters.
Athletes’ Body Talk: The Role of Contextual Body Image in Eating Disorders as Seen Through the Eyes of Elite Women Athletes
Authors: de Bruin A.P. (Karin) , Oudejans Raôul R.D.
Published: September 2018

The aim of the study was to investigate if and how body image, taken from a contextual perspective, contributes to the eating disorder history. This qualitative study investigated the process of eating disorder development in eight elite women athletes in at-risk sports. The results showed that the relationship between eating disorder symptomatology and the sports environment was clearly recognized by the elite women athletes. Contextual body image, more specifically negative body-evaluations and upward body comparisons, appeared as an important factor in the development of eating disorders, particularly in the athletic context. It became clear that the two aesthetic and two endurance athletes as well as the two weight-class athletes in rowing described quite negative body evaluations in the context of sport, while some of them also recognized an impact of body image experiences in daily life. However, for both judokas, their eating disorder had nothing to do with their body image but was attributed to the weight-classes in their sport and accompanying weight making. Several unique trajectories and individual eating disorder histories were distinguished which confirms the value of taking a qualitative approach in investigating eating disorders in sport. We also discovered links between what the athletes had reported as contributors to their eating disorder history and how they told their stories by combining content analysis and narrative inquiry. Furthermore, the present study also highlights several critical aspects for prevention and treatment that should support sport federations and clinical sport psychologists in taking appropriate actions to deal more effectively with eating disorders in athletes.
Unprecedented high irreversibility line in the nontoxic cuprate superconductor (Cu,C)Ba
2
Ca
3
Cu
4
O
11+δ
Authors: Zhang Yue , Liu Wenhao , Zhu Xiyu , Zhao Haonan , Hu Zheng , He Chengping , Wen Hai-Hu
Published: September 2018

The nontoxic superconductor (Cu,C)Ba
2
Ca
3
Cu
4
O
11+δ
has the highest irreversibility line for possible applications above the LN
2
temperature.
An “ideal lignin” facilitates full biomass utilization
Authors: Li Yanding , Shuai Li , Kim Hoon , Motagamwala Ali Hussain , Mobley Justin K. , Yue Fengxia , Tobimatsu Yuki , Havkin-Frenkel Daphna , Chen Fang , Dixon Richard A. , Luterbacher Jeremy S. , Dumesic James A. , Ralph John
Published: September 2018

The structural homogeneity and acid stability of linear
C
-lignins allow their deconstruction to useful monomers in high yield.
The probacterial effect of type I interferon signaling requires its own negative regulator USP18
Authors: Shaabani Namir , Honke Nadine , Nguyen Nhan , Huang Zhe , Arimoto Kei-ichiro , Lazar Daniel , Loe Taylor K. , Lang Karl S. , Prinz Marco , Knobeloch Klaus-Peter , Zhang Dong-Er , Teijaro John R.
Published: September 2018

USP18 acts as a key effector molecule downstream of IFN-I signaling to promote primary and secondary bacterial infections.
Divergent Nrf Family Proteins and MtrCAB Homologs Facilitate Extracellular Electron Transfer in Aeromonas hydrophila
Authors: Conley Bridget E. , Intile Peter J. , Bond Daniel R. , Gralnick Jeffrey A.
Published: September 2018

Metal-reducing microorganisms are used for electricity production, bioremediation of toxic compounds, wastewater treatment, and production of valuable compounds. Despite numerous microorganisms being reported to reduce metals, the molecular mechanism has primarily been studied in two model systems,
Shewanella oneidensis
and
Geobacter sulfurreducens
. We have characterized the mechanism of extracellular electron transfer in
Aeromonas hydrophila
, which uses the well-studied
Shewanella
system, MtrCAB, to move electrons across the outer membrane; however, most
Aeromonas
spp. appear to use a novel mechanism to transfer electrons from the inner membrane through the periplasm and to the outer membrane. The conserved use of MtrCAB in
Shewanella
spp. and
Aeromonas
spp. for metal reduction and conserved genomic architecture of metal reduction genes in
Aeromonas
spp. may serve as genomic markers for identifying metal-reducing microorganisms from genomic or transcriptomic sequencing. Understanding the variety of pathways used to reduce metals can allow for optimization and more efficient design of microorganisms used for practical applications.
Towards a palliative care approach in psychiatry: do we need a new definition?
Authors: Lindblad Anna , Helgesson Gert , Sjöstrand Manne
Published: September 2018

Psychiatry today is mainly practised within a curative framework. However, many mental disorders are persistent and negatively affect quality of life as well as life expectancy. This tension between treatment goals and the actual illness trajectory has evoked a growing academic interest in ‘palliative psychiatry’, namely the application of a palliative care approach in patients with severe persistent mental illness. Recently, Trachselet alpresented a working definition of palliative psychiatry. This first official attempt to capture the concept is based on WHO’s widely accepted definition of palliative care but modified and limited to include only severe persistent psychiatric illness. While this is a welcome step in the discussion on palliative care approaches in psychiatry, it also opens up for new questions. One of the most evident is whether psychiatry actually needs its own definition of palliative care or, put differently, whether there is something about mental disorders that differs so radically from other medical conditions that it calls for a separate definition. We acknowledge the need to discuss the goals of psychiatric care in patients with severe persistent psychiatric illness. However, we question whether a separate definition of palliative care exclusive to psychiatry is the right way to go. In this paper, we discuss why.
Ian Calvert
Authors: Muckle Andy , West Nick , Allen Mike
Published: September 2018

Working for the BBC's Natural History Unit was a neat stepping stone to a veterinary degree for a man with an interest in exotic species. His enthusiasm and expertise were equalled by his skill and charm.
Passing lane optimum length on two-lane highways
Authors: Jafari Amirhossein , Al-Kaisy Ahmed , Washburn Scott
Published: September 2018

An investigation into the optimum length of passing lanes on rural two-lane highways is presented in this paper. A passing lane is a short length of added lane to improve passing opportunities on two-lane two-way highways. The study utilized field data and traffic simulation in this investigation, with field data primarily used in calibrating and validating the traffic simulation program. A sensitivity analysis was conducted using traffic level and length of passing lane as the primary variables. The level of association between the reduction in platooning and study variables was examined. Study results showed that, within the range of passing lane length investigated in this study (0.5 mi to 3.0 mi), traffic performance continued to improve with the increase in passing lane length. Moreover, for the same target improvement in performance, the required passing lane length increases with the increase in traffic volume. The passing lane optimum lengths developed in this study all varied in the range between 0.80 and 2.0 miles depending on traffic volume.
Developmental stage has a greater effect than Cry1Ac expression in transgenic cotton on the phyllosphere mycobiome
Authors: Pan Jiangang , Lv Xin , Jin Decai , Bai Zhihui , Qi Hongyan , Zhang Hongxun , Zhuang Guoqiang
Published: September 2018

Transgenic Bt cotton is widely cultivated, yet its impact on the phyllosphere mycobiome is poorly understood. Hence, the objective of this study was to investigate the effects resulting from the planting of Bt cotton on fungal diversity composition. The α diversity for the Bt cotton line SGK321 was lower than that of control plants at the budding stage and the blossoming and boll-forming stage, while an obvious increase in diversity for Bt cotton XP188 was observed at the same stage. The Cry1Ac levels were higher at the seedling stage than at the budding stage and the blossoming and boll-forming stage. There was no direct relationship between the expression of the Bt protein and variation in the fungal community for Bt cotton. However, PCoA and PCA results indicated that community structure differed among developmental stages. These results indicated that developmental stage rather than Cry1Ac expression was the key factor shaping the phyllosphere mycobiome in transgenic cotton.
Boltzmann enhancements of biquasile counting invariants
Authors: Choi WonHyuk , Needell Deanna , Nelson Sam
Published: September 2018

In this paper, we build on the biquasiles and dual graph diagrams introduced in [7]. We introduce biquasile Boltzmann weights that enhance the previous knot coloring invariant defined in terms of finite biquasiles and provide examples differentiating links with the same counting invariant, demonstrating that the enhancement is proper. We identify conditions for a linear function [Formula: see text] to be a Boltzmann weight for an Alexander biquasile [Formula: see text].
Weak reducing disks and disk surgery
Authors: Lee Jung Hoon
Published: September 2018

Let [Formula: see text] be an unknot in [Formula: see text]-bridge position in the [Formula: see text]-sphere. We give an example of a pair of weak reducing disks [Formula: see text] and [Formula: see text] for [Formula: see text] such that both disks obtained from [Formula: see text] ([Formula: see text]) by a surgery along any outermost disk in [Formula: see text], cut off by an outermost arc of [Formula: see text] in [Formula: see text], are not weak reducing disks, i.e. the property of weak reducibility of compressing disks is not preserved by a disk surgery.
Real characters, monolithic characters and the Taketa inequality
Authors: Çınarcı Burcu , Erkoç Temha
Published: September 2018

In this paper, we prove that the Taketa inequality, namely the derived length of a finite solvable group [Formula: see text] is less than or equal to the number of distinct irreducible complex character degrees of [Formula: see text], is true under some conditions related to the real and the monolithic characters of [Formula: see text].
BIOMECHANICAL RATIONALE FOR CHOICE OF CEMENT MANTLE THICKNESS AROUND A FEMORAL STEM
Authors: LEVADNYI IEVGEN , AWREJCEWICZ JAN , SZYMANOWSKA OLGA , GRZELCZYK DARIUSZ , GUBAUA JOSÉ EDUARDO , PEREIRA JUCÉLIO TOMÁS , DICATI GABRIELA WESSLING OENING
Published: September 2018

The change in mechanical properties of the femoral bone tissue surrounding hip endoprosthesis stems during the post-operative period is one of the causes of implant instability, and the mathematical description of this phenomenon is the subject of much research. In the present study, a model of bone adaptation, based on isotropic Stanford theory, is created for further computer investigation. The results of implementation of such a mathematical model are presented regarding the choice of cement mantle rational thickness in cemented hip arthroplasties. The results show that for cement mantle thicknesses ranging from 1–1.5[Formula: see text]mm, a peak stress value in the proximal part of the mantle exceeds the limit of durability of bone cement. Moreover, results show that high reduction in the bone density of distal and proximal regions was observed in cases of cement mantle thicknesses varying from 1–3[Formula: see text]mm. No significant changes in bone density of the abovementioned regions were obtained for 4[Formula: see text]mm and 5[Formula: see text]mm. The outcome of numerical investigations can be treated as valuable and will lead to the improvement of cemented hip replacement surgery results.
Design and Preparation of Magnetic CTAB/Montmorillonite Nanocomposite for Phenols Removal
Authors: Shen Rong , Yu Yichang , Wang Yue , Xia Zhining
Published: September 2018

The cetyltrimethyl ammonium bromide (CTAB)-modified montmorillonite (MMT) was synthesized via a novel “dissolution and reassembly” method. To determine the optimal formula, the adsorption of C.I. Reactive Red 2 (X3B) with CTAB/MMT was investigated. The optimal CTAB/MMT nanocomposite was used to remove 2,6-dichlorophenol and p-nitrophenol from aqueous solutions. The adsorption results can be described by Langmuir isotherm, and the adsorption capacities were 200[Formula: see text]mg/g and 125[Formula: see text]mg/g for 2,6-dichlorophenol and p-nitrophenol, respectively. To realize the quick separation and recycle, the magnetic CTAB/MMT was further strategized and synthesized. The adsorption equilibrium time was 15[Formula: see text]min for both contaminants; the ions’ strength showed a little bit of influence on the adsorption performance. In addition, compared with acidic condition, neutral condition was more beneficial to the adsorption reaction. Due to the addition of Fe3O4, the adsorption capacities of this magnetic nanocomposite for 2,6-dichlorophenol and p-nitrophenol were a little bit decreased, which were 170[Formula: see text]mg/g and 91[Formula: see text]mg/g, respectively. However, the magnetic nanocomposite can be separated within 30[Formula: see text]s under an external magnetic field, which would be useful in the practical application.
The Effect of Plasma Gas Composition on the Nanostructures and Optical Properties of TiO2 Films Prepared by Helicon-PECVD
Authors: Li D. , Dai S. , Goullet A. , Granier A.
Published: September 2018

TiO2 films were deposited from oxygen/titanium tetraisopropoxide (TTIP) plasmas at low temperature by Helicon-PECVD at floating potential ([Formula: see text] or substrate self-bias of [Formula: see text]50[Formula: see text]V. The influence of titanium precursor partial pressure on the morphology, nanostructure and optical properties was investigated. Low titanium partial pressure ([TTIP] [Formula: see text] 0.013[Formula: see text]Pa) was applied by controlling the TTIP flow rate which is introduced by its own vapor pressure, whereas higher titanium partial pressure was formed through increasing the flow rate by using a carrier gas (CG). Then the precursor partial pressures [TTIP[Formula: see text]CG] [Formula: see text][Formula: see text]Pa and 0.093[Formula: see text]Pa were obtained. At [Formula: see text], all the films exhibit a columnar structure, but the degree of inhomogeneity is decreased with the precursor partial pressure. Phase transformation from anatase ([TTIP] [Formula: see text] 0.013[Formula: see text]Pa) to amorphous ([TTIP[Formula: see text]CG] [Formula: see text][Formula: see text]Pa) has been evidenced since the O[Formula: see text] ion to neutral flux ratio in the plasma was decreased and more carbon contained in the film. However, in the case of [Formula: see text]50[Formula: see text]V, the related growth rate for different precursor partial pressures is slightly ([Formula: see text] 15%) decreased. The columnar morphology at [TTIP] [Formula: see text] 0.013[Formula: see text]Pa has been changed into a granular structure, but still homogeneous columns are observed for [TTIP[Formula: see text]CG] [Formula: see text][Formula: see text]Pa and 0.093[Formula: see text]Pa. Rutile phase has been generated at [TTIP] [Formula: see text][Formula: see text]Pa. Ellipsometry measurements were performed on the films deposited at [Formula: see text]50[Formula: see text]V; results show that the precursor addition from low to high levels leads to a decrease in refractive index.
Global dynamics of deterministic and stochastic epidemic systems with nonmonotone incidence rate
Authors: Feng Tao , Qiu Zhipeng
Published: September 2018

This paper is devoted to studying the dynamics of a susceptible-infective-latent-infective (SILI) epidemic model that is subject to the combined effects of environmental noise and intervention strategy. We extend the classical SILI epidemic model from a deterministic framework to a stochastic one. For the deterministic case, the global stability analysis of the solution is carried out in terms of the basic reproduction number. For the stochastic case, sufficient conditions for the extinction of diseases are obtained. Then, the existence of stationary distribution and asymptotic behavior of the solution are further studied to illustrate the cycling phenomena of recurrent diseases. Numerical simulations are conducted to verify these analytical results. It is shown that both stochastic noise and intervention strategy contribute to the control of diseases.
Adaptive Optics for Extremely Large Telescopes
Authors: Hippler Stefan
Published: September 2018

Adaptive Optics (AO) has become a key technology for the largest ground-based telescopes currently under, or close to beginning of, construction. AO is an indispensable component and has basically only one task, that is to operate the telescope at its maximum angular resolution, without optical degradations resulting from atmospheric seeing. Based on three decades of experience using AO usually as an add-on component, all extremely large telescopes and their instrumentation are designed for diffraction limited observations from the very beginning. This paper illuminates various approaches of the ELT, the Giant Magellan Telescope (GMT), and the Thirty-Meter Telescope (TMT), to fully integrate AO in their designs. The paper concludes with a brief look into the requirements that high-contrast imaging poses on AO.
Open complex giant system and Traditional Chinese Medicine
Authors: Wang Shuyun , Liu Liyan , Zhu Wei , Cui Baiping , Zheng Yufan , Liang Qianqian , Xu Chen , Zhou Xinyan , Sun Ning
Published: September 2018

Contemporary medicine faces the dilemma of not being able to clearly understand and effectively treat many complex diseases. A major cause is that current medical studies weigh too much on looking into microscopic world and get lost in it. In 1989, Dr. Hsue-Shen Tsien, one of the founders of contemporary System Sciences, first proposed the concept of Open Complex Giant Systems. He also pointed out that humans, in nature, are actually one of the Open Complex Giant Systems. It is time for us to use the methodology of System Sciences which integrates both holism and reductionism to study lives and diseases, especially from the view of Open Complex Giant System. Developed from a holistic view of humans and diseases based on thousands of years of experiences in fighting against human diseases, Traditional Chinese Medicine will undoubtedly provide us many new concepts, ideas, theories, and useful methods in dealing with man and his diseases as an Open Complex Giant System.
Students’ Experience of Participation in a Discipline—A Longitudinal Study of Computer Science and IT Engineering Students
Authors: Peters Anne-Kathrin
Published: September 2018

This article concludes a longitudinal study with the broader aim to explore learner development as a long-term, social process. One goal has been to inform the endeavours of improving student engagement, retention, as well as under-representation of certain demographics in computing.

Students of two computer science--related study programmes (CS/IT) reflected on their engagement in their field of study at different times during the first three study years. Drawing on social identity theory, the focus has been to analyse and describe different ways in which the students experience participation in CS/IT, i.e., doing, thinking, and feeling, in relation to CS/IT, negotiated among different people. Insights into participation in CS/IT were used to discuss what it entails to fit in and become a computing professional.

Phenomenographic analysis yields an outcome space that describes increasingly broad ways in which first-, second-, and third-year students experience participation in CS/IT. Two further outcome spaces provide nuanced insights into experiences that are of increasing relevance as the students advance in their studies, participation as problem solving, and problem solving for others.

Participation as problem solving appears to be central in this learning environment and the students integrate such experiences into their histories of engagement in CS/IT. In study year 3, the students also reason about participation as problem solving for others that they encounter in the human computer interaction course. However, at that time several students perform a technical problem solver identity and reject such broader ways of participating in CS/IT.
Innate Sensing of DNA Virus Genomes
Authors: Ma Zhe , Ni Guoxin , Damania Blossom
Published: September 2018

DNA viruses are linked to many infectious diseases and contribute significantly to human morbidity and mortality worldwide. Moreover, DNA viral infections are usually lifelong and hard to eradicate. Under certain circumstances, these viruses can cause fatal disease, especially in children and immunocompromised patients. An efficient innate immune response against these viruses is critical, not only as the first line of host defense against viral infection but also for mounting more specific and robust adaptive immunity against the virus. Recognition of the viral DNA genome is the very first step of this whole process and is crucial for understanding viral pathogenesis as well as for preventing and treating DNA virus–associated diseases. This review focuses on the current state of our knowledge on how human DNA viruses are sensed by the host innate immune system and how viral proteins counteract this immune response.
My Life and Virus Research Journey
Authors: Ghabrial Said A.
Published: September 2018

My long career in virology has been a continuous learning exercise with a very modest start. Virology and related pertinent fields have changed significantly during my lifetime. Sometimes I wish that my career had just started and I could apply all available and state of the art technology to solving problems and explaining intriguing observations. I was always convinced that visiting growers’ fields is essential for researchers to get firsthand observations and knowledge of virus disease problems under field conditions. I never thought I would pursue so many avenues of research, yet it is true that research never ends. I enjoyed dissecting strain diversity in a very important plant pathogen like bean pod mottle virus (BPMV) and using BPMV-based vectors to address fundamental virology questions. Lastly, solving the enigma of the transmissible disease of Helminthosporium victoriae and attempting to gain an understanding of the molecular basis of disease in a plant pathogenic fungus were thrilling.
Host IDO2 Gene Status Influences Tumor Progression and Radiotherapy Response in KRAS-Driven Sporadic Pancreatic Cancers
Authors: Nevler Avinoam , Muller Alexander J. , Sutanto-Ward Erika , DuHadaway James B. , Nagatomo Kei , Londin Eric , O'Hayer Kevin , Cozzitorto Joseph A. , Lavu Harish , Yeo Theresa P. , Curtis Mark , Villatoro Tatiana , Leiby Benjamin E. , Mandik-Nayak Laura , Winter Jordan M. , Yeo Charles J. , Prendergast George C. , Brody Jonathan R.
Published: September 2018

Purpose:

Heritable genetic variations can affect the inflammatory tumor microenvironment, which can ultimately affect cancer susceptibility and clinical outcomes. Recent evidence indicates that IDO2, a positive modifier in inflammatory disease models, is frequently upregulated in pancreatic ductal adenocarcinoma (PDAC). A unique feature of IDO2 in humans is the high prevalence of two inactivating single-nucleotide polymorphisms (SNP), which affords the opportunity to carry out loss-of-function studies directly in humans. In this study, we sought to address whether genetic loss of IDO2 may influence PDAC development and responsiveness to treatment.

Experimental Design: Transgenic Ido2+/+ and Ido2−/− mice in which oncogenic KRAS is activated in pancreatic epithelial cells were evaluated for PDAC. Two patient data sets (N = 200) were evaluated for the two IDO2-inactivating SNPs together with histologic, RNA expression, and clinical survival data.

Results:

PDAC development was notably decreased in the Ido2−/− mice (30% vs. 10%, P < 0.05), with a female predominance similar to the association observed for one of the human SNPs. In patients, the biallelic occurrence of either of the two IDO2-inactivating SNPs was significantly associated with markedly improved disease-free survival in response to adjuvant radiotherapy (P < 0.01), a treatment modality that has been highly debated due to its variable efficacy.

Conclusions:

The results of this study provide genetic support for IDO2 as a contributing factor in PDAC development and argue that IDO2 genotype analysis has the immediate potential to influence the PDAC care decision-making process through stratification of those patients who stand to benefit from adjuvant radiotherapy.
αvβ3 Integrin Mediates Radioresistance of Prostate Cancer Cells through Regulation of Survivin
Authors: Wang Tao , Huang Jiayi , Vue Mai , Alavian Michael R. , Goel Hira Lal , Altieri Dario C. , Languino Lucia R. , FitzGerald Thomas J.
Published: September 2018

The αvβ3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of αvβ3 integrin on the radiosensitivity of prostate cancer cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with αvβ3 integrin and PC-3 cells that contain endogenous β3 integrin were used. This study demonstrated that αvβ3 integrin increases survival of αvβ3-LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of αvβ3 integrin in PC-3 cells sensitizes to radiation. Expression of αvβ3 integrin in LNCaP cells also enhances anchorage-independent cell growth while knockdown of αvβ3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The αvβ3 antagonist, cRGD, significantly increases radiosensitivity in both αvβ3-LNCaP and PC-3 cells. Moreover, αvβ3 integrin prevents radiation-induced downregulation of survivin. Inhibition of survivin expression by siRNA or shRNA enhances IR-induced inhibition of anchorage-independent cell growth. Overexpression of wild-type survivin in PC-3 cells treated with αvβ3 integrin shRNA increases survival of cells upon IR. These findings reveal that αvβ3 integrin promotes radioresistance and regulates survivin levels in response to IR.

Implications:

Future translational research on targeting αvβ3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.
MKRN3 Levels in Girls with Central Precocious Puberty during GnRHa Treatment: A Longitudinal Study
Authors: Grandone Anna , Cirillo Grazia , Sasso Marcella , Tornese Gianluca , Luongo Caterina , Festa Adalgisa , Marzuillo Pierluigi , Miraglia del Giudice Emanuele
Published: September 2018

Background: Recently, mutations of makorin RING finger protein 3 (MKRN3) have been identified in familial central precocious puberty (CPP). Serum levels of this protein decline before the pubertal onset in healthy girls and boys and are lower in patients with CPP compared to prepubertal matched pairs. The aim of our study was to investigate longitudinal changes in circulating MKRN3 levels in patients with CPP before and during GnRH analogs (GnRHa) treatment. Methods: We performed a longitudinal prospective study. We enrolled 15 patients with CPP aged 7.2 years (range: 2–8) with age at breast development onset < 8 years and 12 control girls matched for the time from puberty onset (mean age 11.8 ± 1.2 years). Serum values of MKRN3, gonadotropins, and 17β-estradiol were evaluated before and during treatment with GnRHa (at 6 and 12 months). The MKRN3 gene was genotyped in CPP patients. In the girls from the control group, only basal levels were analyzed. Results: No MKRN3 mutations were found among CPP patients. MKRN3 levels declined significantly from baseline to 6 months of GnRHa treatment (p = 0.0007) and from 6 to 12 months of treatment (p = 0.003); MKRN3 levels at 6 months were significantly lower than in the control girls (p < 0.0001). Conclusions: We showed that girls with CPP had a decline in peripheral levels of MKRN3 during GnRHa treatment. Our data suggest a suppression of MKRN3 by continuous pharmacological administration of GnRHa.
Diagnostic Performance of Radiolabeled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging in Newly Diagnosed Intermediate to High-Risk Prostate Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Kim Seong-Jang , Lee Sang-Woo , Ha Hong Koo
Published: September 2018

Introduction: We aimed to assess the diagnostic accuracy of radiolabeled prostate-specific membrane antigen positron emission tomography (PSMA PET) or positron emission tomography/computed tomography (PET/CT) for primary lymph node (LN) staging in newly diagnosed intermediate to high-risk prostate cancer (PCa) patients. Material and Methods: The MEDLINE, PubMed, EMBASE, and Cochrane Library database from the earliest available date of indexing through May 31, 2018, were searched for studies evaluating the diagnostic performance of radiolabeled PSMA PET or PET/CT for primary LN staging in newly diagnosed intermediate to high-risk PCa. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR–), and constructed summary receiver operating characteristic curves. Results: Across 6 studies (298 patients), the pooled sensitivity was 0.71 (95% CI 0.59–0.81) and a pooled specificity of 0.95 (95% CI 0.87–0.99). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 15.6 (95% CI 5.6–43.0) and negative likelihood ratio (LR–) of 0.30 (95% CI 0.21–0.43). The pooled diagnostic odds ratio (DOR) was 51 (95% CI 21–126). Conclusion: Radiolabeled PSMA PET/CT shows a moderate sensitivity and high specificity for the detection of metastatic LNs in patients with newly diagnosed intermediate to high-risk PCa.
Cellular and Subcellular Expression of the Monocarboxylate Transporter MCT1 in Rat Heart
Authors: Johannsson Erlingur , Nagelhus Erlend A. , McCullagh Karl J.A. , Sejersted Ole M. , Blackstad Theodor W. , Bonen Arend , Ottersen Ole P.
Published: September 2018

An antibody to the C-terminus of the monocarboxylate transporter MCT1 was used to study the precise cellular and subcellular distribution of this transporter in rat heart. Postembedding immunogold procedures revealed that the labeling in the heart was restricted to cardiomyocytes and concentrated along the plasma membrane, including the transverse tubules. Gold particles occurred with highest densities in intercalated disks, where they avoided desmosomes and gap junctions. Labeling was also associated with plasmalemmal invaginations having ultrastructural features typical of caveolae. Internal membrane compartments were unlabeled. Quantitative analyses following postembedding labeling showed that the distribution of gold particles across the plasma membrane was nearly symmetrical, indicating that the C-terminus of the transporter is situated very close to the cell membrane. In preembedding immunogold experiments, the gold particles were localized at the external aspect of the plasma membrane, suggesting that the C-terminus is extracellular. From the present data, it can be concluded that even under basal conditions the majority of the MCT1 molecules in heart is present in the myocyte plasma membrane, implying that there is a constitutive functional expression of this transporter. It follows that the increased transmembrane flux of lactate during exercise or in pathological conditions such as ischemia must be a result of altered substrate gradients rather than of translocation of MCT1 molecules to the plasma membrane.
Circulating Apoptotic Progenitor Cells
Authors: Schwartzenberg Shmuel , Deutsch Varda , Maysel-Auslender Sofia , Kissil Sarina , Keren Gad , George Jacob
Published: September 2018

Background—

Progenitor CD34 cells are capable of differentiating into endothelial cells and play a role in neoangiogenesis. Circulating CD34
+
cells and endothelial progenitor cells are increased in acute coronary syndrome (ACS) patients possibly because of peripheral mobilization. We tested the hypothesis that circulating apoptotic progenitors are detectable in healthy subjects and altered in ACS patients.

Methods and Results—

Peripheral blood mononuclear cells were isolated by Ficoll density gradient from 53 patients with ACS undergoing coronary angiography and 27 healthy subjects. Apoptosis in progenitor CD34
+
cells was assessed using the Annexin V-PE/7-AAD detection kit, and fluorescence-activated cell sorter analysis was performed with triple staining for CD34, annexin-V, and 7-AAD. The percentage of apoptotic CD34
+
progenitors was determined in the 2 subject groups and correlated with clinical characteristics. The percentage of apoptotic CD34
+
progenitor cells was significantly increased in patients with ACS as compared with healthy subjects and was associated with the extent of coronary stenosis by angiography. There was no significant correlation between apoptotic progenitor CD34
+
cells and the other parameters that we examined (age, smoking, hypertension, hyperlipidemia, diabetes mellitus, ejection fraction, creatinine levels, or taking any of the various medications, including beta blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium blockers, nitrates, or statins).

Conclusion—

We established for the first time to our knowledge an assay to detect circulating apoptotic progenitor cells using fluorescein isothiocyanate–anti-CD34 MAb, annexin V-PE, and 7-AAD and found that apoptotic CD34
+
cells are increased in ACS patients and in patients with more extensive coronary artery disease. This novel assay may shed new light on the factors governing the hemeostasis of progenitor CD34
+
cells.