bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorectal endoscopic submucosal dissection: Technical advantages compared to endoscopic mucosal resection and minimally invasive surgery
Authors: Saito Yutaka , Yamada Masayoshi , So Eriko , Abe Seiichiro , Sakamoto Taku , Nakajima Takeshi , Otake Yosuke , Ono Akiko , Matsuda Takahisa
Published: November 2013

Background and Aim

In recent years, the effectiveness of colorectal endoscopic submucosal dissection (ESD) has been increasingly reported. Herein, we highlight the most recent developments and technical advantages of colorectal ESD compared to EMR and minimally invasive surgery.

Methods

All candidate lesions for ESD were confirmed as being intramucosal tumors by colonoscopy. Presently, the indications for colorectal ESD approved by the Japanese government's medical insurance system are early colorectal cancers with a maximum tumor size of 2–5 cm; however, many early cancers >5 cm have been treated by ESD in referral centers.

Results

The primary advantage of ESD compared to endoscopic mucosal resection (EMR) is a higher en‐bloc resection rate for large colonic tumors that had previously been treated by surgery. ESD has several advantages compared to other therapeutic modalities, such as being a safer technique and providing better quality of life. For rectal cancer treatment, a longer procedure time is required for laparoscopic assisted colectomy, whereas trans‐anal resection and trans‐anal endoscopic microsurgery are more invasive than ESD with a significantly higher recurrence rate. Accordingly, ESD is the preferred choice for early colorectal cancers when there is no risk of lymph‐node metastasis.

Conclusion

ESD is an effective procedure for treating non‐invasive non‐polypoid colorectal tumors. These tumors may be difficult to resect en bloc by conventional EMR. The use of ESD results in a higher en‐bloc resection rate and is less invasive than surgery.
Randomized controlled trial comparing stylet‐free endoscopic ultrasound‐guided fine‐needle aspiration with 22‐G and 25‐G needles
Authors: Gimeno‐García Antonio Z. , Elwassief Ahmed , Paquin Sarto C. , Gariépy Gilles , Sahai Anand V.
Published: November 2013

Background and Aim

Previous studies comparing endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) results with different gauge needles have all been carried out with the stylet in place and show no clear advantage to the larger 22‐G needle. Similar data for stylet‐free EUS‐FNA (SF‐EUS‐FNA) are unavailable. The aim of the present study was to determine whether diagnostic yield and specimen adequacy is superior with the 22‐G needle as compared to the 25‐G needle.

Methods

All patients ≥18 years referred for solid‐lesion EUS‐FNA were eligible. Patients with suspected diagnosis of lymphoma, gastrointestinal stromal tumor, sarcoidosis, significant coagulopathy (international normalized ratio >1.5 or platelets <50 000/mm3), use of clopidogrel within 7 days of EUS, and pregnancy were excluded. The two needles were compared regarding diagnostic yield, sample adequacy, bloodiness, ease of puncture, visibility, number of passes, failures, and complications.

Results

One hundred and twenty consecutive patients were included and 126 lesions were sampled. Sensitivity, specificity, positive predictive value and negative predictive value for the 22‐G SF‐EUS‐FNA were 83%, 100%, 100% and 56%, respectively, and for the 25‐G SF‐EUS‐FNA were 88.8%, 100%, 100% and 76.5%, respectively (P = NS). There were no significant differences between the 22‐G and the 25‐G FNA needles in sample adequacy, bloodiness, ease of puncture, FNA failure, visibility, number of passes and complications; and no significant differences between either needle were found in relation to lesion site.

Conclusion

For SF‐EUS‐FNA, the larger 22‐G needle offers no advantage over the smaller 25‐G needle.
Patch size but not short‐term isolation influences occurrence of westslope cutthroat trout above human‐made barriers
Authors: Peterson Douglas P. , Rieman Bruce E. , Horan Dona L. , Young Michael K.
Published: November 2013

Habitat fragmentation in aquatic systems has led to widespread isolation of stream fishes. Metapopulation theory predicts that persistence is directly related to local patch size and its characteristics, but because these relationships tend to be taxon‐specific, empirical data are important. We assembled 246 observations of occurrence of westslope cutthroat trout (WCT), a taxon of concern in the western U.S. and Canada, in stream networks isolated for up to 100 years (median 40 years) above human‐made barriers, mostly culverts, at road crossings within U.S. National Forests. We used logistic regression to analyse how WCT occurrence varied with patch size, isolation time and stream‐level covariates. Occurrence was positively related to stream length and habitat quality within the isolated stream network and negatively related to elevation and channel gradient. Unexpectedly, the probability of occurrence was not related to how long a habitat patch had been isolated. At the median elevation (1354 m) and channel gradient (14%), and where habitat quality was poor, WCT were likely to occur (probability >0.5) if an isolated stream network was at least 1.7 km. If habitat quality was high, about 0.2 km of habitat produced the same probability. Although there are important limitations, this analysis provides the first empirical estimate for how patch size and patch‐level characteristics influence persistence of WCT in isolated stream networks.
Dural arteriovenous fistulas presenting with reversible dementia are associated with a specific venous drainage
Authors: Labeyrie M. A. , Lenck S. , Saint‐Maurice J. P. , Bresson D. , Houdart E.
Published: November 2013

Background and purpose

Venous drainage of dural arteriovenous fistula (DAVF) with dementia has never been reported. The aim of this study was to discover if specific vascular conditions exist to develop dementia in patients with DAVF.

Methods

Venous drainage in patients embolized in our centre between 1996 and 2012 for a DAVF with dementia were qualitatively analyzed and compared with a control group without dementia.

Results

Eight patients with dementia and 45 control patients were included. The prevalence of dementia was 4%. Diffuse hemispheric white matter lesions on magnetic resonance imaging (MRI) were consistently associated with dementia. Cognitive symptoms dramatically improved after embolization. The consistent angiographic feature in patients with dementia was drainage of the DAVF into both the straight sinus and the superior sagittal sinuses. Only two patients in the control group had similar abnormalities.

Conclusions

The association of a reflux from the fistula into the straight sinus and the superior sagittal sinuses is a necessary condition to develop such a reversible dementia in DAVF. Venous hypertension in the territory of transparenchymal veins may explain this reversal phenomenon. A rapidly progressive dementia with diffuse white matter lesions on MRI should evoke this diagnosis to the physician.
Colon cancer surveillance in inflammatory bowel disease: unclear gain but no psychological pain?
Authors: Mountifield R. , Bampton P. , Prosser R. , Mikocka‐Walus A. , Andrews J. M.
Published: November 2013

Background

Surveillance for colorectal neoplasia in inflammatory bowel disease (IBD) is widely practised despite a lack of convincing mortality reduction. The psychological impact of this approach is largely unexplored.

Aim

To examine psychological well‐being among IBD subjects undergoing colonoscopic surveillance for colorectal cancer (CRC).

Methods

A cross‐sectional study was performed by interrogating an IBD database for subjects currently enrolled in colonoscopic surveillance programmes. Identified surveillance subjects were age‐ and gender‐matched with IBD control subjects not meeting surveillance criteria. Subjects were mailed a questionnaire including demographic details, the Short Form 36 (SF‐36) survey to assess quality of life, the Spielberger State‐Trait Personality Inventory, the Multidimensional Health Locus of Control, and a Risk Perception Questionnaire.

Results

One hundred and thirty‐nine of 286 (49%) subjects responded, 53% male, 46% Crohn disease. Fifty‐six per cent respondents were in the surveillance group. Surveillance subjects were older (55.4 vs 51.1 years; P = .048) with longer disease duration, but otherwise had comparable demographics with controls. Overall, quality of life was not significantly different between cohorts (mean SF‐36 63.82 vs 65.48; P = 0.70). Groups did not differ on any locus of control classification (P = 0.52), nor was there any difference between mean scores on ‘state’ subscales of the Spielberger State‐Trait Personality Inventory: anxiety (P = 0.91), curiosity (P = 0.12), anger (P = 0.81) or depression (P = 0.70). Both groups grossly overestimated their perceived lifetime risk of CRC at 50%, with no difference between surveillance and control subjects (P = 1.0).

Conclusions

Enrolment in colonoscopic colon cancer surveillance does not appear to impair psychological well‐being in individuals with IBD despite longer disease duration. IBD patients overestimate their risk of CRC.
Pulmonary hypertension and breathlessness: is it a combination we can ignore?
Authors: Strange G. , Williams T. , Kermeen F. , Whyte K. , Keogh A.
Published: November 2013

On 5 May 2013 it was World Pulmonary Hypertension (PHT) Day marking three decades on from the first reported deaths in an epidemic because of toxic rapeseed (canola) oil. This epidemic provided the impetus to the first World Health Organization to set up a world symposia. World leaders of PHT met for the fifth time in Nice, France in February 2013. Although we wait the official proceedings, this meeting provides us opportunity to reflect on the current situation in Australia and New Zealand, and examine the implications for our two countries. PHT remains difficult to identify, delays in patient diagnosis persist, and breathlessness remains dominant in the diagnosis of all causes of PHT. This review examines some of the recent changes in diagnosis, our understanding of the emerging expanding epidemiology data and the patient's journeys through the healthcare system. We also review the current treatment options on monotherapy and in poly‐pharmacy or combination therapy, along with the strategic management implications of the lack of funded combination therapy associated with prognosis.
International flight‐related transmission of pandemic influenza A(H1N1)pdm09: an historical cohort study of the first identified cases in the United Kingdom
Authors: Young Nicholas , Pebody Richard , Smith Gillian , Olowokure Babatunde , Shankar Giri , Hoschler Katja , Galiano Monica , Green Helen , Wallensten Anders , Hogan Angela , Oliver Isabel
Published: November 2013

Background

Transporting over two billion passengers per year, global airline travel has the potential to spread emerging infectious diseases, both via transportation of infectious cases and through in‐flight transmission. Current World Health Organization (WHO) guidance recommends contact tracing of passengers seated within two rows of a case of influenza during air travel.

Objectives

The objectives of this study were to describe flight‐related transmission of influenza A(H1N1)pdm09 during a commercial flight carrying the first cases reported in the United Kingdom and to test the specific hypothesis that passengers seated within two rows of an infectious case are at greater risk of infection.

Methods

An historical cohort study, supplemented by contact tracing, enhanced surveillance data and laboratory testing, was used to establish a case status for passengers on board the flight.

Results

Data were available for 239 of 278 (86·0%) of passengers on the flight, of whom six were considered infectious in‐flight and one immune. The attack rate (AR) was 10 of 232 (4·3%; 95% CI 1·7–6·9%). There was no evidence that the AR for those seated within two rows of an infectious case was different from those who were not (relative risk 0·9; 95% CI 0·2–3·1; P = 1·00). Laboratory testing using PCR and/or serology, available for 118 of 239 (49·4%) of the passengers, was largely consistent with clinically defined case status.

Conclusions

This study of A(H1N1)pdm09 does not support current WHO guidance regarding the contact tracing of passengers seated within two rows of an infectious case of influenza during air travel.
Peramivir and laninamivir susceptibility of circulating influenza A and B viruses
Authors: Leang Sook‐Kwan , Kwok Simon , Sullivan Sheena G. , Maurer‐Stroh Sebastian , Kelso Anne , Barr Ian G. , Hurt Aeron C.
Published: November 2013

Influenza viruses collected from regions of Asia, Africa and Oceania between 2009 and 2012 were tested for their susceptibility to two new neuraminidase inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir inhibition. However, 3·2% (19/599) of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B viruses had reduced or highly reduced peramivir inhibition, with single occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a combined G145R+Y142H mutation. These data demonstrate that despite an increase in H275Y variants in 2011, there was no marked change in the frequency of peramivir‐ or laninamivir‐resistant variants following the market release of the drugs in Japan in 2010.
Crevicular fluid biomarkers and periodontal disease progression
Authors: Kinney Janet S. , Morelli Thiago , Oh Min , Braun Thomas M. , Ramseier Christoph A. , Sugai Jim V. , Giannobile William V.
Published: November 2013

Aim

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP).

Materials and methods

In this study, 100 individuals participated in a 12‐month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi‐monthly. Subgingival plaque and serum were collected bi‐annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP‐8, MMP‐9, Osteoprotegerin, C‐reactive Protein and IL‐1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing.

Results

Eighty‐three individuals completed the 6‐month monitoring phase. With the exception of GCF C‐reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86).

Conclusions

Signature of GCF fluid‐derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745).
Maternal investment increases with altitude in a frog on the Tibetan Plateau
Authors: Chen W. , Tang Z. H. , Fan X. G. , Wang Y. , Pike D. A.
Published: November 2013

Reproducing females can allocate energy between the production of eggs or offspring of different size or number, both of which can strongly influence fitness. The physical capacity to store developing offspring imposes constraints on maximum clutch volume, but individual females and populations can trade off whether more or fewer eggs or offspring are produced, and their relative sizes. Harsh environments are likely to select for larger egg or offspring size, and many vertebrate populations compensate for this reproductive investment through an increase in female body size. We report a different trade‐off in a frog endemic to the Tibetan Plateau, Rana kukunoris. Females living at higher altitudes (n = 11 populations, 2000–3500 m) produce larger eggs, but without a concomitant increase in female body size or clutch size. The reduced diel and seasonal activity at high altitudes may impose constraints on the maximum body size of adult frogs, by limiting the opportunity for energy accumulation. Simultaneously, producing larger eggs likely helps to increase the rate of embryonic development, causing tadpoles to hatch earlier. The gelatinous matrix surrounding eggs, more of which is produced by large females, may help buffer developing embryos from temperature fluctuations or offer protection from ultraviolet radiation. High‐altitude frogs on the Tibetan Plateau employ a reproductive strategy that favours large egg size independent of body size, which is unusual in amphibians. The harsh and unpredictable environmental conditions at high altitudes can thus impose strong and opposing selection pressures on adult and embryonic life stages, both of which can simultaneously influence fitness.
Systematic reviews: Work that needs to be done and not to be done
Authors: Adams Clive E , Polzmacher Stefanie , Wolff Annabelle
Published: November 2013

Systematic reviews are researches requiring great attention to detail. They may well necessitate considerable investment of effort to ensure relevant data are identified, extracted, synthesized, written up and disseminated. These tasks have already been greatly refined and, in some cases, simplified, by machines. The last two decades have seen remarkable progress in machine‐assisted production of reviews – the next two should see much more.
A Relational Response toNewman's Objection toRussell's Causal Theory of Perception
Authors: Eilan Naomi
Published: November 2013

The causal theory of perception (CTP) has come under a great deal of critical scrutiny from philosophers of mind interested in the nature of perception.M. H. Newman's set‐theoretic objection to Russell's structuralist version of theCTP, in his 1928 paper “MrRussell's Causal Theory of Perception” has not, to my knowledge, figured in these discussions. In this paper I aim to show that it should:Newman's objection can be generalized to yield a particularly powerful and incisive challenge to all versions of theCTP. In effect it says that if theCTPis true, at least one of the following claims must be false. (1) Our perception‐based judgements are made true or false by the state of mind independent objects. (2) The concepts we use in such judgments refer to the intrinsic, mind‐independent properties of such objects. (3) Experience provides us with knowledge of these properties. The paper sets out the structure of the problem asNewman saw it, extends it to current debates in theory of perception and considers various responses to it. The response I argue for involves jettisoning theCTPin favour of a relational account of perceptual experience, in a way that allows us to hold onto all three claims.
Rhizobial infection does not require cortical expression of upstream common symbiosis genes responsible for the induction of Ca2+ spiking
Authors: Hayashi Teruyuki , Shimoda Yoshikazu , Sato Shusei , Tabata Satoshi , Imaizumi‐Anraku Haruko , Hayashi Makoto
Published: November 2013

For the establishment of an effective root nodule symbiosis, a coordinated regulation of the infection processes between the epidermis and cortex is required. However, it remains unclear whether the symbiotic genes identified so far are involved in epidermal and/or cortical infection, e.g. epidermal and cortical infection thread formation or cortical cell division. To analyze the symbiotic gene requirements of the infection process, we have developed an epidermis‐specific expression system (pEpi expression system) and examined the symbiotic genes NFR1, NFR5, NUP85, NUP133, CASTOR, POLLUX, CCaMK, CYCLOPS, NSP1 and NSP2 for involvement in the infection process in the epidermis and cortex. Our study shows that expression of the upstream common symbiosis genes CASTOR, POLLUX, NUP85 and NUP133 in the epidermis is sufficient to induce formation of infection threads and cortical cell division, leading to the development of fully effective nodules. Our system also shows a requirement of CCaMK, CYCLOPS, NSP1 and NSP2 for the entire nodulation process, and the different contributions of NFR1 and NFR5 to cortical infection thread formation. Based on these analyses using the pEpi expression system, we propose a functional model of symbiotic genes for epidermal and cortical infection.
Stable transformation and reverse genetic analysis of Penium margaritaceum: a platform for studies of charophyte green algae, the immediate ancestors of land plants
Authors: Sørensen Iben , Fei Zhangjun , Andreas Amanda , Willats William G. T. , Domozych David S. , Rose Jocelyn K. C.
Published: November 2013

The charophyte green algae (CGA, Streptophyta, Viridiplantae) occupy a key phylogenetic position as the immediate ancestors of land plants but, paradoxically, are less well‐studied than the other major plant lineages. This is particularly true in the context of functional genomic studies, where the lack of an efficient protocol for their stable genetic transformation has been a major obstacle. Observations of extant CGA species suggest the existence of some of the evolutionary adaptations that had to occur for land colonization; however, to date, there has been no robust experimental platform to address this genetically. We present a protocol for high‐throughput Agrobacterium tumefaciens‐mediated transformation of Penium margaritaceum, a unicellular CGA species. The versatility of Penium as a model for studying various aspects of plant cell biology and development was illustrated through non‐invasive visualization of protein localization and dynamics in living cells. In addition, the utility of RNA interference (RNAi) for reverse genetic studies was demonstrated by targeting genes associated with cell wall modification (pectin methylesterase) and biosynthesis (cellulose synthase). This provided evidence supporting current models of cell wall assembly and inter‐polymer interactions that were based on studies of land plants, but in this case using direct observation in vivo. This new functional genomics platform has broad potential applications, including studies of plant organismal biology and the evolutionary innovations required for transition from aquatic to terrestrial habitats.
The potential for manipulating RNA with pentatricopeptide repeat proteins
Authors: Yagi Yusuke , Nakamura Takahiro , Small Ian
Published: November 2013

The pentatricopeptide repeat (PPR) protein family, which is particularly prevalent in plants, includes many sequence‐specific RNA‐binding proteins involved in all aspects of organelle RNA metabolism, including RNA stability, processing, editing and translation. PPR proteins consist of a tandem array of 2‐30 PPR motifs, each of which aligns to one nucleotide in the RNA target. The amino acid side chains at two or three specific positions in each motif confer nucleotide specificity in a predictable and programmable manner. Thus, PPR proteins appear to provide an extremely promising opportunity to create custom RNA‐binding proteins with tailored specificity. We summarize recent progress in understanding RNA recognition by PPR proteins, with a particular focus on potential applications of PPR‐based tools for manipulating RNA, and on the challenges that remain to be overcome before these tools may be routinely used by the scientific community.
Sewer Networks Optimization Using Cellular Automata
Authors: Rohani Maryam , Hadi Afshar Mohammad
Published: November 2013

The Hybrid Cellular Automata (HCA) method is used in this paper for the optimal design of sewer network problems with the fixed layout. The HCA method decomposes the problem into two sub-problems with considering the pipe diameters and nodal cover depths as decision variables. Two stages are solved iteratively for determining the decision variables in a manner to minimize the total cost of the sewer network subject to the operational constraints. The HCA method is used to optimally solve three benchmark examples with different sizes and the results are presented and compared to those of the existing methods. The results indicate that the HCA method is more efficient and effective than the alternative methods.
Effect of Temperature Dependent Fluid Properties on Heat Transfer in Turbulent Mixed Convection
Authors: Zonta Francesco , Soldati Alfredo
Published: November 2013

The effect of the uniform fluid properties approximation (Oberbeck-Boussinesq (OB)) in turbulent mixed convection is investigated via direct numerical simulation (DNS) of water flows with viscosity (μ) and thermal expansion coefficient (β) both independently and simultaneously varying with temperature (non-Oberbeck-Boussinesq conditions (NOB)). Mixed convection is analyzed for the prototypical case of Poiseuille-Rayleigh-Bénard (PRB) turbulent channel flow. In PRB flows, the combination of buoyancy driven (Rayleigh-Bénard) with pressure driven (Poiseuille) effects produce a complex flow structure, which depends on the relative intensity of the flow parameters (i.e., the Grashof number, Gr, and the shear Reynolds number, Reτ). In liquids, however, temperature variations induce local changes of fluid properties which influence the macroscopic flow field. We present results for different absolute values of the shear Richardson numbers (Riτ=|Gr/Reτ2|) under constant temperature boundary conditions. As Riτ is increased buoyant thermal plumes are generated, which induce large scale thermal convection that increases momentum and heat transport efficiency. Analysis of friction factor (Cf) and Nusselt number (Nu) for NOB conditions shows that the effect of viscosity is negligible, whereas the effect of thermal expansion coefficient is significant. Statistics of mixing show that (i) mixing increases for increasing Riτ (and decreases for increasing Reτ) and (ii) the effect of thermal expansion coefficient on mixing increases for increasing Riτ (and decreases for increasing Reτ). A simplified phenomenological model to predict heat transfer rates in PRB flows has also been developed.
Dynamic rotating‐shield brachytherapy
Authors: Liu Yunlong , Flynn Ryan T. , Kim Yusung , Yang Wenjun , Wu Xiaodong
Published: November 2013

Purpose:

To present dynamic rotating shield brachytherapy (D‐RSBT), a novel form of high‐dose‐rate brachytherapy (HDR‐BT) with electronic brachytherapy source, where the radiation shield is capable of changing emission angles during the radiation delivery process.

Methods:

A D‐RSBT system uses two layers of independently rotating tungsten alloy shields, each with a 180° azimuthal emission angle. The D‐RSBT planning is separated into two stages: anchor plan optimization and optimal sequencing. In the anchor plan optimization, anchor plans are generated by maximizing theD90 for the high‐risk clinical‐tumor‐volume (HR‐CTV) assuming a fixed azimuthal emission angle of 11.25°. In the optimal sequencing, treatment plans that most closely approximate the anchor plans under the delivery‐time constraint will be efficiently computed. Treatment plans for five cervical cancer patients were generated for D‐RSBT, single‐shield RSBT (S‐RSBT), and 192Ir‐based intracavitary brachytherapy with supplementary interstitial brachytherapy (IS + ICBT) assuming five treatment fractions. External beam radiotherapy doses of 45 Gy in 25 fractions of 1.8 Gy each were accounted for. The high‐risk clinical target volume (HR‐CTV) doses were escalated such that the D2cc of the rectum, sigmoid colon, or bladder reached its tolerance equivalent dose in 2 Gy fractions (EQD2 with α/β = 3 Gy) of 75 Gy, 75 Gy, or 90 Gy, respectively.

Results:

For the patients considered, IS + ICBT had an average total dwell time of 5.7 minutes/fraction (min/fx) assuming a 10 Ci192 Ir source, and the average HR‐CTV D90 was 78.9 Gy. In order to match the HR‐CTV D90 of IS + ICBT, D‐RSBT required an average of 10.1 min/fx more delivery time, and S‐RSBT required 6.7 min/fx more. If an additional 20 min/fx of delivery time is allowed beyond that of the IS + ICBT case, D‐RSBT and S‐RSBT increased the HR‐CTV D90 above IS + ICBT by an average of 16.3 Gy and 9.1 Gy, respectively.

Conclusions:

For cervical cancer patients, D‐RSBT can boost HR‐CTVD90 over IS + ICBT and S‐RSBT without violating the tolerance doses to the bladder, rectum, or sigmoid. The D90 improvements from D‐RSBT depend on the patient, the delivery time budget, and the applicator structure.
Asymmetric Distribution of Lunar Impact Basins Caused by Variations in Target Properties
Authors: Miljković Katarina , Wieczorek Mark A. , Collins Gareth S. , Laneuville Matthieu , Neumann Gregory A. , Melosh H. Jay , Solomon Sean C. , Phillips Roger J. , Smith David E. , Zuber Maria T.
Published: November 2013

Which Side of the Moon?

The far- and nearsides of the Moon are geologically different. Using high-precision crustal thickness maps derived from NASA's Gravity Recovery and Interior Laboratory (GRAIL) mission,

Miljković
et al.

(p.
724
) show that the distribution of lunar impact basins is also highly asymmetrical. Numerical simulations of impact basin formation coupled with three-dimensional simulations of the Moon's asymmetric thermal evolution suggest that lateral variations in temperature within the Moon's crust have a large effect on the final size of an impact basin.
Fusion for Moving
Authors: Clawson Gary A.
Published: November 2013

Tumor cell fusion with white blood cells has been a long-standing theory of metastasis—is there sufficient evidence yet?
The Joy and Fear in Space Exploration

Europa Report
Sebastián Cordero, director

Start Motion Pictures and Misher Films, USA, 2013. 90 minutes. http://start-media.com/start-motion-pictures/new-release/europa-report

Gravity
Alfonso Cuarón, director

Warner Brothers, USA, 2013. 91 minutes. http://gravitymovie.warnerbros.com
Authors: Hameed Salman
Published: November 2013

Despite plots based on things gone wrong, the films
Europa Report
and
Gravity
celebrate the idealism of human space exploration.
Quantum Mechanics Tackles Mechanics
Authors: Hammerer Klemens
Published: November 2013

A micromechanical oscillator can only be described with quantum mechanics after it is entangled with microwave fields.

[Also see Report by

Palomaki
et al.

]
The Serious Business of Play

Play, Playfulness, Creativity and Innovation
by Patrick Bateson and Paul Martin

Cambridge University Press, Cambridge, 2013. 165 pp. $85, £55. ISBN 9781107015135. Paper, $34.99, £21.99. ISBN 9781107689343.
Authors: Brown Gillian R.
Published: November 2013

Surveying the roles that playful behavior fills in development; Bateson and Martin pay particular attention to its influence on cognitive abilities.
Have Your PIC!
Authors: Malik Sohail , Roeder Robert G.
Published: November 2013

Structural analyses help to elucidate a key step in DNA transcription.

[Also see Research Article by

Murakami
et al.

]
Genetics Driving Epigenetics
Authors: Furey Terrence S. , Sethupathy Praveen
Published: November 2013

DNA sequence variants are associated with factors and epigenetic states that modify gene expression and contribute to quantitative differences in traits.

[Also see Reports by

Kilpinen
et al.

,

McVicker
et al.

, and

Kasowski
et al.

]
California Moves Shake Up Prenatal Gene Testing Market
Authors: Marshall Eliot
Published: November 2013

A California court has rejected Sequenom's patent on noninvasive prenatal testing, worrying some investors but encouraging rival firms.
Soldier-Scientists Join Counterinsurgency in Afghanistan
Authors: Stone Richard
Published: November 2013

The U.S. military has been quietly deploying soldier-scientists on noncombat missions in Afghanistan—an unprecedented program, according to one geologist who served in it.
The Forgotten Malaria
Authors: Vogel Gretchen
Published: November 2013

Long considered "benign," the malaria parasite
Plasmodium vivax
threatens billions while eluding control measures. Now, scientists are going on the offensive.
Realizing the Promise of Robotic Leg Prostheses
Authors: Goldfarb Michael , Lawson Brian E. , Shultz Amanda H.
Published: November 2013

Robotic prosthetic legs promise to restore healthy biomechanical function if they are well interfaced to the human neuromuscular control system.
Discrimination of Mycobacterium abscessus subsp. massiliense from Mycobacterium abscessus subsp. abscessus in Clinical Isolates by Multiplex PCR
Authors: Nakanaga Kazue , Sekizuka Tsuyoshi , Fukano Hanako , Sakakibara Yumi , Takeuchi Fumihiko , Wada Shinpei , Ishii Norihisa , Makino Masahiko , Kuroda Makoto , Hoshino Yoshihiko
Published: November 2013

The rapidly growing mycobacterium
M. abscessus

sensu lato is the causative agent of emerging pulmonary and skin diseases and of infections following cosmetic surgery and postsurgical procedures.
M. abscessus
sensu lato

can be divided into at least three subspecies:
M. abscessus
subsp.
abscessus
,
M. abscessus
subsp.
massiliense
, and
M. abscessus
subsp.
bolletii
. Clinical isolates of rapidly growing mycobacteria were previously identified as
M. abscessus
by DNA-DNA hybridization. More than 30% of these 117 clinical isolates were differentiated as
M. abscessus
subsp.
massiliense
using combinations of multilocus genotyping analyses. A much more cost-effective technique to distinguish
M. abscessus
subsp.
massiliense
from
M. abscessus
subsp.
abscessus
, a multiplex PCR assay, was developed using the whole-genome sequence of
M. abscessus
subsp.
massiliense
JCM15300 as a reference. Several primer sets were designed for single PCR to discriminate between the strains based on amplicons of different sizes. Two of these single-PCR target sites were chosen for development of the multiplex PCR assay. Multiplex PCR was successful in distinguishing clinical isolates of
M. abscessus
subsp.
massiliense
from samples previously identified as
M. abscessus
. This approach, which spans whole-genome sequencing and clinical diagnosis, will facilitate the acquisition of more-precise information about bacterial genomes, aid in the choice of more relevant therapies, and promote the advancement of novel discrimination and differential diagnostic assays.
Clinical Comparison of Simplexa Universal Direct and BD GeneOhm Tests for Detection of Toxigenic Clostridium difficile in Stool Samples
Authors: Nolte Frederick S. , Ribeiro-Nesbitt Danielle G.
Published: November 2013

We compared the performance characteristics of the Simplexa universal direct (Focus Diagnostics, Cypress, CA) and BD GeneOhm (BD Diagnostics/GeneOhm Sciences, San Diego, CA) tests for detection of toxigenic
Clostridium difficile
in 459 stool samples (9.4% positive). The observed agreement for the results of the two tests with 452 samples with valid test results was 98.2% (kappa, 0.9;
P
value of 0.73 by the McNemar test). When samples with discordant or invalid results were retested, the agreement increased to 100%.
Isolation and Characterization of Porcine Epidemic Diarrhea Viruses Associated with the 2013 Disease Outbreak among Swine in the United States
Authors: Chen Qi , Li Ganwu , Stasko Judith , Thomas Joseph T. , Stensland Wendy R. , Pillatzki Angela E. , Gauger Phillip C. , Schwartz Kent J. , Madson Darin , Yoon Kyoung-Jin , Stevenson Gregory W. , Burrough Eric R. , Harmon Karen M. , Main Rodger G. , Zhang Jianqiang
Published: November 2013

Porcine epidemic diarrhea virus (PEDV) was detected in May 2013 for the first time in U.S. swine and has since caused significant economic loss. Obtaining a U.S. PEDV isolate that can grow efficiently in cell culture is critical for investigating pathogenesis and developing diagnostic assays and for vaccine development. An additional objective was to determine which gene(s) of PEDV is most suitable for studying the genetic relatedness of the virus. Here we describe two PEDV isolates (ISU13-19338E and ISU13-22038) successfully obtained from the small intestines of piglets from sow farms in Indiana and Iowa, respectively. The two isolates have been serially propagated in cell culture for over 30 passages and were characterized for the first 10 passages. Virus production in cell culture was confirmed by PEDV-specific real-time reverse-transcription PCR (RT-PCR), immunofluorescence assays, and electron microscopy. The infectious titers of the viruses during the first 10 passages ranged from 6 × 102to 2 × 10550% tissue culture infective doses (TCID50)/ml. In addition, the full-length genome sequences of six viruses (ISU13-19338E homogenate, P3, and P9; ISU13-22038 homogenate, P3, and P9) were determined. Genetically, the two PEDV isolates were relatively stable during the first 10 passages in cell culture. Sequences were also compared to those of 4 additional U.S. PEDV strains and 23 non-U.S. strains. All U.S. PEDV strains were genetically closely related to each other (≥99.7% nucleotide identity) and were most genetically similar to Chinese strains reported in 2011 to 2012. Phylogenetic analyses using different genes of PEDV suggested that the full-length spike gene or the S1 portion is appropriate for sequencing to study the genetic relatedness of these viruses.
Adeno-Associated Virus Capsid Proteins May Play a Role in Transcription and Second-Strand Synthesis of Recombinant Genomes
Authors: Salganik Maxim , Aydemir Fikret , Nam Hyun-Joo , McKenna Robert , Agbandje-McKenna Mavis , Muzyczka Nicholas
Published: November 2013

A group of four interacting amino acids in adeno-associated virus type 8 (AAV8) called the pH quartet has been shown to undergo a structural change when subjected to acidic pH comparable to that seen in endosomal compartments. We examined the phenotypes of mutants with mutations in these amino acids as well as several nearby residues in the background of AAV2. We found that three of the mutations in this region (Y704A, E562A, and E564A) produce normal titers of mature capsids but are extremely defective for transduction (>10
7
-fold). The remaining mutants were also defective for transduction, but the defect in these mutants (E563A, E561A, H526A, and R389A) is not as severe (3- to 22-fold). Two other mutants (Y700A and Y730A) were found to be defective for virus assembly. One of the extremely defective mutants (Y704A) was found to enter the cell, traffic to the nucleus, and uncoat its DNA nearly as efficiently as the wild type. This suggested that some step after nuclear entry and uncoating was defective. To see if the extremely defective mutants were impaired in second-strand synthesis, the Y704A, E562A, and E564A mutants containing self-complementary DNA were compared with virus containing single-stranded genomes. Two of the mutants (Y704A and E564A) showed 1-log and 3-log improvements in infectivity, respectively, while the third mutant (E562A) showed no change. This suggested that inhibition of second-strand synthesis was responsible for some but not most of the defect in these mutants. Comparison of Y704A mRNA synthesis with that of the wild-type capsid showed that accumulation of steady-state mRNA in the Y704A mutant was reduced 450-fold, even though equal genome numbers were uncoated. Our experiments have identified a novel capsid function. They suggest that AAV capsids may play a role in the initiation of both second-strand synthesis and transcription of the input genome.
A Targeted Mutation within the Feline Leukemia Virus (FeLV) Envelope Protein Immunosuppressive Domain To Improve a Canarypox Virus-Vectored FeLV Vaccine
Authors: Schlecht-Louf Géraldine , Mangeney Marianne , El-Garch Hanane , Lacombe Valérie , Poulet Hervé , Heidmann Thierry
Published: November 2013

We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagationin vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the “mechanical” function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressivein vivoand that this immunosuppressive activity can be “switched off” by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-γ)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-γ/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressivein vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.
Insights into Bacteriophage T5 Structure from Analysis of Its Morphogenesis Genes and Protein Components
Authors: Zivanovic Yvan , Confalonieri Fabrice , Ponchon Luc , Lurz Rudi , Chami Mohamed , Flayhan Ali , Renouard Madalena , Huet Alexis , Decottignies Paulette , Davidson Alan R. , Breyton Cécile , Boulanger Pascale
Published: November 2013

Bacteriophage T5 represents a large family of lytic
Siphoviridae
infecting Gram-negative bacteria. The low-resolution structure of T5 showed the T=13 geometry of the capsid and the unusual trimeric organization of the tail tube, and the assembly pathway of the capsid was established. Although major structural proteins of T5 have been identified in these studies, most of the genes encoding the morphogenesis proteins remained to be identified. Here, we combine a proteomic analysis of T5 particles with a bioinformatic study and electron microscopic immunolocalization to assign function to the genes encoding the structural proteins, the packaging proteins, and other nonstructural components required for T5 assembly. A head maturation protease that likely accounts for the cleavage of the different capsid proteins is identified. Two other proteins involved in capsid maturation add originality to the T5 capsid assembly mechanism: the single head-to-tail joining protein, which closes the T5 capsid after DNA packaging, and the nicking endonuclease responsible for the single-strand interruptions in the T5 genome. We localize most of the tail proteins that were hitherto uncharacterized and provide a detailed description of the tail tip composition. Our findings highlight novel variations of viral assembly strategies and of virion particle architecture. They further recommend T5 for exploring phage structure and assembly and for deciphering conformational rearrangements that accompany DNA transfer from the capsid to the host cytoplasm.
Viral MicroRNAs Targeting Virus Genes Promote Virus Infection in Shrimp
In Vivo
Authors: He Yaodong , Yang Kai , Zhang Xiaobo
Published: November 2013

Viral microRNAs (miRNAs), most of which are characterized in cell lines, have been found to play important roles in the virus life cycle to avoid attack by the host immune system or to keep virus in the latency state. Viral miRNAs targeting virus genes can inhibit virus infection. In this study,
in vivo
findings in
Marsupenaeus japonicus
shrimp revealed that the viral miRNAs could target virus genes and further promote the virus infection. The results showed that white spot syndrome virus (WSSV)-encoded miRNAs WSSV-miR-66 and WSSV-miR-68 were transcribed at the early stage of WSSV infection. When the expression of WSSV-miR-66 and WSSV-miR-68 was silenced with sequence-specific anti-miRNA oligonucleotides (AMOs), the number of copies of WSSV and the WSSV-infected shrimp mortality were significantly decreased, indicating that the two viral miRNAs had a great effect on virus infection. It was revealed that the WSSV
wsv094
and
wsv177
genes were the targets of WSSV-miR-66 and that the
wsv248
and
wsv309
genes were the targets of WSSV-miR-68. The data demonstrate that the four target genes play negative roles in the WSSV infection. The targeting of the four virus genes by WSSV-miR-66 and WSSV-miR-68 led to the promotion of virus infection. Therefore, our
in vivo
findings show a novel aspect of viral miRNAs in virus-host interactions.
Exceptionally Potent and Broadly Cross-Reactive, Bispecific Multivalent HIV-1 Inhibitors Based on Single Human CD4 and Antibody Domains
Authors: Chen Weizao , Feng Yang , Prabakaran Ponraj , Ying Tianlei , Wang Yanping , Sun Jianping , Macedo Camila D. S. , Zhu Zhongyu , He Yuxian , Polonis Victoria R. , Dimitrov Dimiter S.
Published: November 2013

Soluble forms of the human immunodeficiency virus type 1 (HIV-1) primary receptor CD4 (soluble CD4 [sCD4]) have been extensively characterized for a quarter of a century as promising HIV-1 inhibitors, but they have not been clinically successful. By combining a protein cavity-filling strategy and the power of library technology, we identified an engineered cavity-altered single-domain sCD4 (mD1.22) with a unique combination of excellent properties, including broad and potent neutralizing activity, high specificity, stability, solubility, and affinity for the HIV-1 envelope glycoprotein gp120, and small molecular size. To further improve its neutralizing potency and breadth, we generated bispecific multivalent fusion proteins of mD1.22 with another potent HIV-1 inhibitor, an antibody domain (m36.4) that targets the coreceptor-binding site on gp120. The fusion proteins neutralized all HIV-1 isolates tested, with potencies about 10-, 50-, and 200-fold higher than those of the broadly neutralizing antibody VRC01, the U.S. FDA-approved peptide inhibitor T20, and the clinically tested sCD4-Fc fusion protein CD4-Ig, respectively. In addition, they exhibited higher stability and specificity and a lower aggregation propensity than CD4-Ig. Therefore, mD1.22 and related fusion proteins could be useful for HIV-1 prevention and therapy, including eradication of the virus.
Development of Virus-Specific CD4
+
and CD8
+
Regulatory T Cells Induced by Human Herpesvirus 6 Infection
Authors: Wang Fang , Chi Jing , Peng Guangyong , Zhou Feng , Wang Jinfeng , Li Lingyun , Feng Dongju , Xie Fangyi , Gu Bin , Qin Jian , Chen Yun , Yao Kun
Published: November 2013

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus. The mechanisms by which HHV-6 establishes latency and immunosuppression in its host are not well understood. Here we characterized HHV-6-specific T cells in peripheral blood mononuclear cells (PBMCs) from HHV-6-infected donors. Our results showed that HHV-6 infection could induce both CD4
+
and CD8
+
HHV-6-specific regulatory T (Treg) cells. These HHV-6-specific Treg cells had potent suppressive activity and expressed high levels of Treg-associated molecules CD25, FoxP3, and GITR. Both CD4
+
and CD8
+
Treg cells secreted gamma interferon (IFN-γ) and interleukin-10 (IL-10) but little or no IL-2, IL-4, or transforming growth factor β (TGF-β). Furthermore, HHV-6-specifc Treg cells not only could suppress naive and HHV-6-specific CD4
+
effector T cell immune responses but also could impair dendritic cell (DC) maturation and functions. In addition, the suppressive effects mediated by HHV-6-specific Treg cells were mainly through a cell-to-cell contact-dependent mechanism but not through the identified cytokines. These results suggest that HHV-6 may utilize the induction of Treg cells as a strategy to escape antivirus immune responses and maintain the latency and immunosuppression in infected hosts.