bluuebunny/crossref_metadata_2025 huggingface dataset:
Expressivité et contenus implicites
Authors: Gavrilova Elena , Frison Philippe
Published: November 2018

L’expressivité, qui va de pair avec l’énoncé, est un aspect permanent de la traduction. Elle constitue une dimension, implicite ou non, ajoutée au texte en tant que tel. Cependant, les chercheurs divergent sur une définition appropriée. Après en avoir proposé une, nous avons entrepris de montrer à l’aide d’exemples comment ce concept peut aider les traducteurs à mieux adapter leur stratégie aux types de textes à rendre dans la langue d’arrivée.
Translators’ image in Iranian feature films
Authors: Khoshsaligheh Masood , Kafi Mohsen , Narges Noorani Seyede
Published: November 2018

Drawing on the significant influence of audiovisual media on people’s conceptions of any given phenomenon, the current qualitative study
was an attempt to identify the social dimensions of the Iranian translator, represented in feature films in Iran. Specifically,
the study aimed to explore the identity, socioeconomic status and lifestyle of the translator characters depicted in Iranian
feature films. Therefore, 16 Iranian films, involving interlingual translation, were selected. The thematic analysis revealed five
sociological aspects of the Iranian translator reflected in Iranian films: identity of the translator, socioeconomic status of the
translator, lifestyle and attitude of the translator, attitudes of other characters towards the translator, and the role of
translation in the turn of events. The results indicated that translators are generally shown as self-disciplined and dissociable
individuals who are devoted to their work. The translator characters mostly had minor roles in the plot and turn of events.
Conflict in corpora
Authors: Clancy Brian
Published: November 2018

The analysis of conflict in family discourse has often been characterised by ethnographic approaches and/or fine-grained analysis of unique conflict episodes. This article, by contrast, uses a c.175,000-word spoken corpus of Irish family discourse, in conjunction with a corpus pragmatic approach, to explore specific linguistic aspects of conflict discourse. Conflict episodes are identified and analysed in the corpus using a range of linguistic “hooks” (Rühlemann 2010) that have been previously associated with prefacing disagreement such as the markerwell, mitigators (I think, I mean, I guess) or the counterargument strategyyes but. The analysis reveals that the family members most frequently use theyeah butstrategy in conflict episodes which facilitates immediate disagreement. This strategy is often accompanied by a range of mitigators, predominantly in turn final position, some of which have not been previously identified as indexing conflict sequences.
Accusations and interpersonal conflict in televised multi-party interactions amongst speakers of (Argentinian and
Peninsular) Spanish
Authors: Haugh Michael , Sinkeviciute Valeria
Published: November 2018

While there is a growing body of research on impoliteness and conflict talk, the role of accusations in interpersonal conflict has
been only addressed in passing. In this paper, we focus on accusations in conflict talk amongst interactants who are in a
situation demanding the formation of intimate relationships within a relatively short span of time, namely, the television reality
show Big Brother. We examine, in particular, accusation sequences arising in multi-party interactions from the
Argentinian and Spanish versions of the show. We analyse the ways in which assertions of fault or wrongdoing are construed as
accusations through such responses as denials, counter-accusations and challenges, and the ways in which participants explicitly
evaluate each other’s behaviour through such sequences. We conclude that accusations are designed primarily to enact moral
denunciation or condemnation of another party, and so almost invariably occasion interpersonal disputes.
Basque-Spanish bilingual children’s expressive and receptive grammatical abilities
Authors: Anderson Rhiannon M. , Giezen Marcel R. , Pourquié Marie
Published: November 2018

Expressive-receptive gaps in lexical abilities have been documented for bilingual children, but few studies have investigated whether a similar gap is observed at the grammatical level. The current study assessed grammatical abilities through sentence production and comprehension tasks in both languages in 17 Basque-Spanish simultaneous bilingual 6- through 9-year-olds (both languages acquired before three years of age). The children scored lower in Basque than Spanish for sentence production, but no significant differences were found for sentence comprehension. While an expressive-receptive gap was found for both languages, this gap was larger in Basque than in Spanish. Object-verb agreement errors were especially prevalent in Basque production, possibly because verbs in Spanish only agree with the subject. These results demonstrate that expressive-receptive gaps are also observed in bilingual children’s grammatical abilities and may vary depending on the structural similarity between the two languages.
Commodification of women’s breasts
Authors: Correa Doris , Shohamy Elana
Published: November 2018

Cosmetic surgery has become a widespread phenomenon in the last decades, especially in Colombia where a large number of women
undergo it every year. This surgical boom is reflected in several Linguistic Landscape resources including the internet,
where a growing number of cosmetic surgery centers advertise their procedures. Particularly common among these procedures is
breast augmentation, which many Colombian women have at a young age. This article reports on a study which drew on critical linguistic landscape and feminist theories to explore how local cosmetic surgery websites contribute to the commodification of women’s breasts, and its
implications for users of these websites. Data collected for this study included text and images from 12 local websites
advertising cosmetic surgery in Colombia, including breast augmentation. Data analysis showed that these websites contributed to
the commodification of women’s bodies by using a series of ideological mechanisms. Implications for users of these
public spaces include asking critical questions about these websites and becoming more socially active in their consumption.
Gender assignment to Spanish-English mixed DPs
Authors: Casielles-Suárez Eugenia
Published: November 2018

Previous studies on gender assignment to Spanish-English mixed Determiner Phrases (DPs) have noticed a tendency to default to the masculine gender (e.g.el store). However, some studies have revealed that other factors such as the gender of the Spanish translation equivalent (analogical criterion) are also relevant, particularly in written discourse (e.g.la conference). Further, it has been hypothesized that feminine-marked mixed DPs in oral discourse, which are viewed as exceptions to the default gender strategy, should be highly restricted to singleton switches (Valdés Kroff 2016). This paper investigates if feminine-marked mixed DPs are restricted to singleton switches in written discourse by analyzing a mixed-language text, which contains both types of switches (singleton and multiword). The results confirm the importance of the analogical criterion in written discourse and show that feminine-marked DPs are not restricted to singleton switches, and that the analogical criterion is relevant to both singleton and multiword switches.
Selling cheese online
Authors: Ramón Noelia , Labrador Belén
Published: November 2018

This paper is a corpus-based study of certain key nouns used in promotional texts describing cheese in English. A corpus of online cheese descriptions was compiled to extract lexical information regarding the characterization of cheese. All in all, 37 key nouns were identified and classified into 7 semantic categories: appearance, part, colour, aroma, texture, taste and quality ranking. All the occurrences of each key noun were analysed to obtain an exhaustive inventory of the phraseological patterns in which they occur. The results show both objective characteristics (size, shape and colour) and subjective features which tend to be described positively in this promotional subgenre (aroma, texture and taste). Additionally, this text type includes key nouns related to the quality ranking of the cheeses promoted. The main aim of this paper is to gain insight into one particular subgenre – promotional cheese descriptions – through the major lexical co-occurrences used to convey positive evaluation of cheeses.
Towards finding a difficulty index for English grammatical terminology
Authors: Yousefpoori-Naeim Mehrdad , Baleghizadeh Sasan
Published: November 2018

Despite going through some ups and downs, grammar teaching has always been one of the central issues in the history of second
language teaching. In order to teach grammar, teachers frequently get involved in metalanguage, which has grammatical terminology
as one of its major components. Since the nature and use of grammatical terminology in language teaching has remained a
considerably under-researched area to the day, the present study, originally a doctoral dissertation, was an attempt to find a
difficulty index for a more or less comprehensive list of English grammatical terms, collected from various sources of English
grammar. For this purpose, frequency of terms in a researcher-built corpus of EFL/ESL pedagogic grammar textbooks and English
students’ familiarity with the terms were used as the two main criteria for calculating the difficulty index. A corpus of 14
grammatical textbooks was created, and then each of the 459 terms in the list was searched for in the textbooks to calculate their
frequencies as well as ranks in the corpus. Student familiarity with the terms in the list was also measured through a productive
test of grammatical terminology administered to 72 BA students of English at Shahid Beheshti University in Iran. Based on the
results, the traditional dichotomy of scientific versus pedagogic terminology was questioned, arguing for an additional category,
non-pedagogic term. Accordingly, 173 (37.7%) of the terms in the list never appeared in the corpus and thus
were labelled non-pedagogic. Terms with a large corpus/test rank were reanalyzed to find out about the reasons for the gap.
Furthermore, the distribution of terms across the corpus textbooks revealed that as the level of the books rises, the number of
terms also increases, indicating the direct relationship between second language proficiency and metalingual knowledge. Most
importantly, more than 10 major and minor trends in the use of grammatical terminology in pedagogy were explored and suggested.
Finally, as the output of the study, 6 equivalent objective tests of pedagogic grammatical terminology were developed for the
first time in the literature.
Conceptualization and theorization of terminology translation in humanities and social sciences
Authors: Wei Xiangqing
Published: November 2018

In recent decades, the scope of terminology research has been extended. The peculiarities and complexities of terminology are
further ascertained by the exploration into the practice of terminology translation in the field of humanities and social
sciences. The cultural functions that terminology in this research field (H&SS terms) fulfill and the intrinsic difficulties
involved in translating them are worth further investigation. This paper based on some reflections of the development of the
NUTermBank discusses the legitimacy of terminology translation as independent research and makes an initial attempt to theorize
about how the research can be actually carried out. A holistic view of terminology translation is taken and a 3-M research model
is proposed in this paper.
Effect of regulatory modes on work performance: the moderating role of job familiarity and job complexity / El efecto del modo de regulación en el rendimiento laboral: el rol moderador de la familiaridad con el trabajo y la complejidad de la tarea
Authors: Lo Destro Calogero , Chernikova Marina , Pierro Antonio , Kruglanski Arie W. , Higgins E. Tory
Published: November 2018

Prior research has shown that the combination of assessment and locomotion regulatory modes leads to the best performance-related outcomes. The aim of the current study was to analyse how familiarity and complexity moderate this relationship between the two regulatory modes and job performance. Participants’ locomotion and assessment tendencies were measured, and they were asked to rate the familiarity and complexity of their daily work tasks, as well as their job performance over the last year. Results showed that when job tasks were unfamiliar and more complex, high locomotion and high assessment were both needed for optimal performance. However, when both familiarity and job complexity were low, high locomotion alone led to the best performance. A similar result was obtained when task familiarity was high: regardless of task complexity, the best performance was shown by employees high in locomotion, no matter the assessment. In conclusion, the present study furnishes useful suggestions for employers who wish to maximize employees’ performance.
Drp1-dependent mitochondrial fission regulates p62-mediated autophagy in LPS-induced activated microglial cells
Authors: Chae Unbin , Kim Han Seop , Lee Hyun-Shik , Lee Sang-Rae , Lee Dong-Seok
Published: November 2018

Microglial activation is known to be an important event during innate immunity, but microglial inflammation is also thought to play a role in the etiology of neurodegenerative diseases. Recently, it was reported that autophagy could influence inflammation and activation of microglia. However, little is known about the regulation of autophagy during microglial activation. In this study, we demonstrated that mitochondrial fission-induced ROS can promote autophagy in microglia. Following LPS-induced autophagy, GFP-LC3 puncta were increased, and this was suppressed by inhibiting mitochondrial fission and mitochondrial ROS. Interestingly, inhibition of mitochondrial fission and mitochondrial ROS also resulted in decreased p62 expression, but Beclin1 and LC3B were unaffected. Taken together, these results indicate that ROS induction due to increased LPS-stimulated mitochondrial fission triggers p62 mediated autophagy in microglial cells. Our findings provide the first important clues towards understanding the correlation between mitochondrial ROS and autophagy.

Abbreviations: Drp1; Dynamin related protein 1, LPS; Lipopolysaccharide, ROS; Reactive Oxygen Species, GFP; Green Fluorescent Protein, CNS; Central Nervous System, AD; Alzheimer’s Disease, PD; Parkinson’s Disease, ALIS; Aggresome-like induced structures, iNOS; inducible nitric oxide synthase, Cox-2; Cyclooxygenase-2, MAPK; Mitogen-activated protein kinase; SODs; Superoxide dismutase, GPXs; Glutathione Peroxidase, Prxs; Peroxiredoxins
Pantothenate auxotrophy of Methylobacterium spp. isolated from living plants
Authors: Yoshida Yusuke , Iguchi Hiroyuki , Sakai Yasuyoshi , Yurimoto Hiroya
Published: November 2018

A number of pink-pigmented facultative methylotrophs (PPFMs) belonging to Methylobacterium spp. isolated from living plant samples were found to require B vitamins for their growth in minimal medium, and most B vitamin-auxotrophic PPFMs required pantothenate (vitamin B5). Further investigation of pantothenate auxotrophy using the representative strain Methylobacterium sp. OR01 demonstrated that this strain cannot synthesize β-alanine, one of the precursors of pantothenate. β-alanine and several precursors of pantothenate restored the growth of Methylobacterium sp. OR01 in minimal medium. Furthermore, this strain could colonize leaves of Arabidopsis thaliana cultivated in medium without pantothenate or its precursors. Pantothenate, β-alanine and several precursors were detected in the suspension of A. thaliana leaves. These results suggest that pantothenate-auxotrophic PPFMs can symbiotically colonize the surface of plant leaves by acquiring β-alanine and other precursors, in addition to pantothenate. Finally, the fitness advantage of B vitamin auxotrophy of PPFMs in the phyllosphere environment is discussed.
Class groups of Kummer extensions via cup products in Galois cohomology
Authors: Schaefer Karl , Stubley Eric
Published: November 2018

We use Galois cohomology to study the

p
p

-rank of the class group of

Q

(

N

1

/

p

)

\mathbf {Q}(N^{1/p})

, where

N
≡
1
mod

p

N \equiv 1 \bmod {p}

is prime. We prove a partial converse to a theorem of Calegari–Emerton, and provide a new explanation of the known counterexamples to the full converse of their result. In the case

p
=
5

p = 5

, we prove a complete characterization of the

5
5

-rank of the class group of

Q

(

N

1

/

5

)

\mathbf {Q}(N^{1/5})

in terms of whether or not

∏

k
=
1

(
N
−
1
)

/

2

k

k

\prod _{k=1}^{(N-1)/2} k^{k}

and

5

−
1

2

\frac {\sqrt {5} - 1}{2}

are

5
5

th powers mod

N
N

.
Rigidity of marginally outer trapped (hyper)surfaces with negative 𝜎-constant
Authors: Mendes Abraão
Published: November 2018

In this paper we generalize a result of Galloway and Mendes in two different situations: in the first case for marginally outer trapped surfaces (MOTSs) of genus greater than

1
1

and, in the second case, for MOTSs of high dimension with negative

σ
\sigma

-constant. In both cases we obtain a splitting result for the ambient manifold when it contains a stable closed MOTS which saturates a lower bound for the area (in dimension

2
2

) or for the volume (in dimension

≥
3

\ge 3

). These results are extensions of theorems of Nunes and Moraru to general (non-time-symmetric) initial data sets.
Local and non-local Dirichlet forms on the Sierpiński carpet
Authors: Grigor’yan Alexander , Yang Meng
Published: November 2018

We give a purely analytic construction of a self-similar local regular Dirichlet form on the Sierpiński carpet using approximation of stable-like non-local closed forms which gives an answer to an open problem in analysis on fractals.
Stem cell models of human synapse development and degeneration
Authors: Wilson Emily S. , Newell-Litwa Karen
Published: November 2018

Many brain disorders exhibit altered synapse formation in development or synapse loss with age. To understand the complexities of human synapse development and degeneration, scientists now engineer neurons and brain organoids from human-induced pluripotent stem cells (hIPSC). These hIPSC-derived brain models develop both excitatory and inhibitory synapses and functional synaptic activity. In this review, we address the ability of hIPSC-derived brain models to recapitulate synapse development and insights gained into the molecular mechanisms underlying synaptic alterations in neuronal disorders. We also discuss the potential for more accurate human brain models to advance our understanding of synapse development, degeneration, and therapeutic responses.
Homeolog expression quantification methods for allopolyploids
Authors: Kuo Tony C Y , Hatakeyama Masaomi , Tameshige Toshiaki , Shimizu Kentaro K , Sese Jun
Published: November 2018

Genome duplication with hybridization, or allopolyploidization, occurs in animals, fungi and plants, and is especially common in crop plants. There is an increasing interest in the study of allopolyploids because of advances in polyploid genome assembly; however, the high level of sequence similarity in duplicated gene copies (homeologs) poses many challenges. Here we compared standard RNA-seq expression quantification approaches used currently for diploid species against subgenome-classification approaches which maps reads to each subgenome separately. We examined mapping error using our previous and new RNA-seq data in which a subgenome is experimentally added (synthetic allotetraploid Arabidopsis kamchatica) or reduced (allohexaploid wheat Triticum aestivum versus extracted allotetraploid) as ground truth. The error rates in the two species were very similar. The standard approaches showed higher error rates (>10% using pseudo-alignment with Kallisto) while subgenome-classification approaches showed much lower error rates (<1% using EAGLE-RC, <2% using HomeoRoq). Although downstream analysis may partly mitigate mapping errors, the difference in methods was substantial in hexaploid wheat, where Kallisto appeared to have systematic differences relative to other methods. Only approximately half of the differentially expressed homeologs detected using Kallisto overlapped with those by any other method in wheat. In general, disagreement in low-expression genes was responsible for most of the discordance between methods, which is consistent with known biases in Kallisto. We also observed that there exist uncertainties in genome sequences and annotation which can affect each method differently. Overall, subgenome-classification approaches tend to perform better than standard approaches with EAGLE-RC having the highest precision.
BlendMol: advanced macromolecular visualization in Blender
Authors: Durrant Jacob D
Published: November 2018

Programs such as VMD and PyMOL are excellent tools for analyzing macromolecular structures, but they do not implement many of the advanced rendering techniques common in the film and video-game industries. In contrast, the open-source program Blender is a general-purpose tool for industry-standard rendering/visualization, but its user interface is poorly suited for rigorous scientific analysis. We present BlendMol, a Blender plugin that imports VMD or PyMOL scenes into Blender. BlendMol-generated images are well suited for use in manuscripts, outreach programs, websites and classes.

Availability and implementation

BlendMol is available free of charge from http://durrantlab.com/blendmol/. It is written in Python.

Supplementary information

Supplementary data are available at Bioinformatics online.
Computational modeling reveals MAP3K8 as mediator of resistance to vemurafenib in thyroid cancer stem cells
Authors: Gianì Fiorenza , Russo Giulia , Pennisi Marzio , Sciacca Laura , Frasca Francesco , Pappalardo Francesco
Published: November 2018

Motivation

Val600Glu (V600E) mutation is the most common BRAF mutation detected in thyroid cancer. Hence, recent research efforts have been performed trying to explore several inhibitors of the V600E mutation-containing BRAF kinase as potential therapeutic options in thyroid cancer refractory to standard interventions. Among them, vemurafenib is a selective BRAF inhibitor approved by Food and Drug Administration for clinical practice. Unfortunately, vemurafenib often displays limited efficacy in poorly differentiated and anaplastic thyroid carcinomas probably because of intrinsic and/or acquired resistance mechanisms. In this view, cancer stem cells (CSCs) may represent a possible mechanism of resistance to vemurafenib, due to their self-renewal and chemo resistance properties.

Results

We present a computational framework to suggest new potential targets to overcome drug resistance. It has been validated with an in vitro model based upon a spheroid-forming method able to isolate thyroid CSCs that may mimic resistance to vemurafenib. Indeed, vemurafenib did not inhibit cell proliferation of BRAF V600E thyroid CSCs, but rather stimulated cell proliferation along with a paradoxical over-activation of ERK and AKT pathways. The computational model identified a fundamental role of mitogen-activated protein kinase 8 (MAP3K8), a serine/threonine kinase expressed in thyroid CSCs, in mediating this drug resistance. To confirm model prediction, we set a suitable in vitro experiment revealing that the treatment with MAP3K8 inhibitor restored the effect of vemurafenib in terms of both DNA fragmentation and poly (ADP-ribose) polymerase cleavage (apoptosis) in thyroid CSCs. Moreover, MAP3K8 expression levels may be a useful marker to predict the response to vemurafenib.

Availability and implementation

The model is available in GitHub repository visiting the following URL: https://github.com/francescopappalardo/MAP3K8-Thyroid-Spheres-V-3.0.

Supplementary information

Supplementary data are available at Bioinformatics online.
Aging-Related Changes in Cognition and Cortical Integrity are Associated With Serum Expression of Candidate MicroRNAs for Alzheimer Disease
Authors: Maldonado-Lasuncion Ines , Atienza Mercedes , Sanchez-Espinosa Mayely P , Cantero Jose L
Published: November 2018

Evidence has shown that microRNAs (miRNAs) are involved in molecular pathways responsible for aging and prevalent aging-related chronic diseases. However, the lack of research linking circulating levels of miRNAs to changes in the aging brain hampers clinical translation. Here, we have investigated if serum expression of brain-enriched miRNAs that have been proposed as potential biomarkers in Alzheimer’s disease (AD) (miR-9, miR-29b, miR-34a, miR-125b, and miR-146a) are also associated with cognitive functioning and changes of the cerebral cortex in normal elderly subjects. Results revealed that candidate miRNAs were linked to changes in cortical thickness (miR-9, miR-29b, miR-34a, and miR-125b), cortical glucose metabolism (miR-29b, miR-125b, and miR-146a), and cognitive performance (miR-9, miR-34a, and miR-125b). While both miR-29b and miR-125b were related to aging-related structural and metabolic cortical changes, only expression levels of miR-125b were associated with patterns of glucose consumption shown by cortical regions that correlated with executive function. Together, these findings suggest that serum expression of AD-related miRNAs are biologically meaningful in aging and may play a role as biomarkers of cerebral vulnerability in late life.
A Mellin transform approach to barrier option pricing
Authors: Guardasoni Chiara , Rodrigo Marianito R , Sanfelici Simona
Published: November 2018

A barrier option is an exotic path-dependent option contract that, depending on terms, automatically expires or can be exercised only if the underlying asset ever reaches a predetermined barrier price. Using a partial differential equation approach, we provide an integral representation of the barrier option price via the Mellin transform. In the case of knock-out barrier options, we obtain a decomposition of the barrier option price into the corresponding European option value minus a barrier premium. The integral representation formula can be expressed in terms of the solution to a system of coupled Volterra integral equations of the first kind. Moreover, we suggest some possible numerical approaches to the problem of barrier option pricing.
Minimal Asymptotic Translation Lengths of Torelli Groups and Pure Braid Groups on the Curve Graph
Authors: Baik Hyungryul , Shin Hyunshik
Published: November 2018

In this paper, we show that the minimal asymptotic translation length of the Torelli group ${\mathcal{I}}_g$ of the surface $S_g$ of genus $g$ on the curve graph asymptotically behaves like $1/g$, contrary to the mapping class group ${\textrm{Mod}}(S_g)$, which behaves like $1/g^2$. We also show that the minimal asymptotic translation length of the pure braid group ${\textrm{PB}}_n$ on the curve graph asymptotically behaves like $1/n$, contrary to the braid group ${\textrm{B}}_n$, which behaves like $1/n^2$.
Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Authors: Chung Arlene E , Shoenbill Kimberly , Mitchell Sandra A , Dueck Amylou C , Schrag Deborah , Bruner Deborah W , Minasian Lori M , St. Germain Diane , O’Mara Ann M , Baumgartner Paul , Rogak Lauren J , Abernethy Amy P , Griffin Ashley C , Basch Ethan M
Published: November 2018

Objective

The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies.

Materials and Methods

Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission.

Results

Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term.

Discussion

Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting.

Conclusions

Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative.
Dppa3 is critical for Lin28a-regulated ES cells naïve–primed state conversion
Authors: Sang Hui , Wang Dan , Zhao Shuang , Zhang Jinxin , Zhang Yan , Xu Jia , Chen Xiaoniao , Nie Yan , Zhang Kaiyue , Zhang Shuaiqiang , Wang Yuebing , Wang Na , Ma Fengxia , Shuai Ling , Li Zongjin , Liu Na
Published: November 2018

Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naïve to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naïve–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naïve–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naïve versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naïve–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.
The effect of maintaining high hemoglobin levels on long-term kidney function in kidney transplant recipients: a randomized controlled trial
Authors: Tsujita Makoto , Kosugi Tomoki , Goto Norihiko , Futamura Kenta , Nishihira Morikuni , Okada Manabu , Hiramitsu Takahisa , Narumi Shunji , Uchida Kazuharu , Takeda Asami , Morozumi Kunio , Maruyama Shoichi , Watarai Yoshihiko
Published: November 2018

Background

Posttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial.

Methods

A 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5–13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5–11.5 g/dL, n = 63).

Results

The mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, −5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (−1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not.

Conclusion

This prospective study suggests that correcting anemia to the target Hb level range (12.5–13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.
111. Increasing Duration of Surgical Prophylaxis Increases Antimicrobial-Associated Adverse Events but Does Not Decrease Surgical Site Infections: An Opportunity for Stewardship
Authors: Strymish Judith M , Branch-Elliman Westyn , O’Brien William , Itani Kamal , Gupta Kalpana
Published: November 2018

Background

The benefits of surgical antimicrobial prophylaxis are limited to the first 24 hours postoperatively. However, little is known about the harms associated with prophylaxis lasting for greater than 24 hours. Thus, we sought to characterize the relationship between duration of prophylaxis and key post-operative outcomes, including surgical site infections (SSI), acute kidney injuries (AKI), and C. difficile infections (CDI) using a large, multi-center national cohort.

Methods

All patients who underwent cardiac, orthopedic total joint, vascular, and colorectal procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI within the national VA healthcare system during the period from FY08 to FY13 were included. The primary exposure variable of interest was duration of postoperative prophylaxis (<24 hours, 24–48 hours, and 48+ hours). Outcomes evaluated included SSI, AKI, and CDI. ORs were calculated using log binomial regression models adjusted for known risk factors for each clinical syndrome selected a priori.

Results

Out of a total cohort of 79,092, all patients had SSI and C. difficile outcomes available and 67,729 patients had AKI outcome available. After stratification by type of surgery and adjusting for age, sex, race, diabetes, smoking, pre-operative MRSA colonization status, mupirocin receipt, and type of prophylaxis, there was no significant association between SSI and duration of prophylaxis; longer durations did not lead to additional SSI reduction. Odds of AKI increased with each additional day of prophylaxis among cardiac and noncardiac surgeries. Similarly, the odds of C. difficile increased with each additional day of prophylaxis across all types of surgery (P < 0.01) (see figure).

Conclusion

Increasing duration of postoperative antimicrobial prophylaxis is associated with higher odds of AKI and C. difficile infection in a dose-dependent manner. Additional days of prophylaxis are not associated with reduced odds of SSI. These findings suggest that stewardship efforts to limit duration have the potential to reduce antimicrobial-associated adverse events without leading to increases in SSI.

Disclosures

K. Itani, sanofi: Grant Investigator, Grant recipient. Pfizer: Grant Investigator, Grant recipient.
117. Effect of Nasopharyngeal Pneumococcal Carriage on RSV and hMPV Illness Severity in Infants in Nepal
Authors: Murray Alastair , Englund Janet , Kuypers Jane , Tielsch James , Katz Joanne , Shrestha Laxman , Khatry Subarna , Leclerq Steven C , Steinhoff Mark C , Chu Helen Y
Published: November 2018

Background

Pneumococcal pneumonia after a preceding respiratory viral illness is associated with morbidity and mortality in infants. Our study sought to determine how pneumococcal carriage impacted illness severity due to respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in infants 0–6 months in a low resource setting in South Asia without pneumococcal vaccination. Previous studies in this population found an overall 79.4% prevalence of pneumococcal carriage in ages 1–36 months with higher rates of carriage among healthy controls when compared with those with respiratory illness.

Methods

Infants were enrolled at the time of birth in a maternal influenza immunization trial conducted in rural Nepal from 2011 to 2014. Weekly household-based active surveillance was performed from birth to 6 months to assess for infant respiratory illness, defined as fever, cough, difficulty breathing, wheeze, or otorrhea. Mid-nasal swabs were collected and tested by PCR for RSV, hMPV, and streptococcus pneumoniae with inclusion of first illness episode in the surveillance period. Disease severity was defined using the World Health Organization Integrated Management of Childhood Illness criteria.

Results

Altogether, 247 (73.5%) of 336 infants with RSV and 154 (83.7%) of 184 infants with hMPV had S. pneumoniae detected. Mean age at RSV illness with concurrent pneumococcal carriage was 97.0 days (91.3–102.6) versus 72.8 days (63.3–82.4) for infants without carriage (P < 0.001). Mean age at hMPV illness with concurrent pneumococcal carriage was 101.3 days (93.9–108.7) versus 77.2 days (56.5–98.0) for infants without carriage (P = 0.01). Frequency of reported lower respiratory tract infection did not differ with or without carriage (RSV: 64.4% vs. 65.2% respectively; P = 0.89, hMPV: 52.6% vs. 50.0% P = 0.79). S. pneumoniae PCR cycle threshold value did not differ by duration or severity of RSV or hMPV illness episode.

Conclusion

High rates of pneumococcal carriage were observed with RSV and hMPV illness episodes in a birth cohort of infants in rural Nepal. The majority of infants with RSV or hMPV illness had pneumococcus detected at the time of first observed illness. However, no increase in RSV or hMPV illness severity or duration was seen with pneumococcal carriage.

Disclosures

H. Y. Chu, sanofi pasteur: Grant Investigator, Grant recipient. Novavax: Grant Investigator, Grant to co-investigator’s institution.
121. Improving Predictive Value of Phase 2a TB Drug Development Models Through PET/CT Imaging (NexGen EBA)
Authors: Xie Yingda , Via Laura , Chen Ray , Dodd Lori , Cai Ying , Paripati Paveen , Goldfeder Lisa , Winter Jill , Arora Kriti , Wang Jing , De Jagar Veronique , Malherbe Stephanus , Song Taeksun , Walzl Gerhard , Diacon Andreas , III Clifton Barry
Published: November 2018

Background

Current Phase 2a methods in tuberculosis (TB) drug development are severely limited in capturing a drug candidate’s sterilizing activity (ability to prevent TB relapse). We hypothesize that sputum-based measurements of current methods fail to capture drug activity in deep TB lesion compartments, where recalcitrant TB populations are sequestered. In our recent marmoset study, we found complementary 14-day PET/CT delta signatures across different TB lesion compartments that distinguish drugs with long-term sterilizing activity (e.g., rifampin and pyrazinamide) versus drugs with primarily early bactericidal activity (e.g., isoniazid) (Figure 1). We proceeded to evaluate this novel PET/CT Phase 2a approach among TB patients, benchmarked by drugs that are well-characterized clinically and pharmacokinetically.

Methods

HIV-negative patients with smear-positive pulmonary tuberculosis from Cape Town, South Africa were enrolled and randomized to receive a single drug [isoniazid (H), rifampin (R), pyrazinamide (Z), moxifloxacin (M)], a 2-drug regimen (HZ, RZ), or a 4-drug regimen (HRZE, MRZE) for 14 days in an inpatient facility. Primary data points were PET/CT scans evaluated at pretreatment baseline and treatment day 14 (and day 28 in the HRZE arm), and daily overnight sputum for early bactericidal activity measurements.

Results

From December 2015 to September 2017, 160 participants completed the study, from whom 340 PET/CT scans and 2,238 overnight sputum samples were collected. PET/CT scans from participants demonstrate diversity of lesion architecture and inter-individual variation in PET/CT changes over 14 days of treatment (Figure 2). A preliminary computational algorithm and first- and second-order PET/CT statistics have been developed for initial segmentation and TB lesion categorization of all study scans. Derivation of radiologic signatures by analysis of 14-day PET/CT changes across each lesion type is ongoing; blinded prediction of each participant’s treatment arm based on these signatures is expected by third-quarter 2018.

Conclusion

If successful, these signatures may be applied within a 14-day Phase 2a framework to evaluate new TB drug candidates and construct TB drug regimens with complementary lesion pharmacokinetics.

Disclosures

All authors: No reported disclosures.
151. Evaluation of Pneumococcal Vaccine Effectiveness Against Invasive Pneumococcal Disease Among US Medicare Beneficiaries ≥65 Years Old
Authors: Pilishvili Tamara , Almendares Olivia M , Nanduri Srinivas , Warnock Rob , Wu Xiyuan , McKean Stephen , Kelman Jeffrey , Farley Monica M , Schaffner William , Thomas Ann , Reingold Arthur , Harrison Lee H , Holtzman Corinne , Rowlands Jemma V , Petit Susan , Barnes Meghan , Torres Salina , Beall Bernard , Whitney Cynthia
Published: November 2018

Background

Pneumococcal conjugate vaccine (PCV13) was recommended in series with PPSV23 for all US adults ≥65 years in late 2014. We evaluated effectiveness of PCV13 against invasive pneumococcal disease (IPD) among Medicare beneficiaries ≥65 years old to assess this new policy.

Methods

We linked records for IPD cases (pneumococcus isolated from sterile sites) in persons ≥65 years old identified through Active Bacterial Core surveillance with those of Medicare beneficiaries. Isolates were serotyped and classified as PCV13 (with or without cross-reacting type 6C), and nonvaccine types. We selected Medicare beneficiaries with no record of IPD or pneumonia as controls, and matched to cases on age, residence census tract, and length of Medicare enrollment; we included all eligible controls. Vaccination and medical histories were obtained through Medicare. We estimated vaccine effectiveness (VE) as 1 minus the IPD odds ratio for vaccinated (PCV13) vs. unvaccinated (no PCV13 or PPSV23) persons using conditional logistic regression, adjusted for sex and underlying conditions.

Results

From 2,246 IPD cases identified in 2015–2016, 1,017 (45%) were matched to Medicare beneficiaries. After excluding cases in persons residing in long-term care facilities or with <1 year of Medicare enrollment, we included 699 eligible cases and 10,152 controls in our analysis. PCV13-types (+6C) accounted for 164 (23%) cases, and serotype 3 was the most common PCV13-type. Case patients were more likely than controls to have one or more chronic (88% vs. 58%) or immunocompromising (54% vs. 32%) conditions present. Fourteen percent, 22%, and 8% of case patients, and 18%, 21%, and 8% of controls received PCV13 only, PPSV23 only, or both vaccines, respectively. PCV13-only VE against PCV13-types was 36% (95% CI −18, 65%). When we included type 6C with PCV13-types, VE was 67% (95% CI 11, 88%). PCV13 showed similar effectiveness against PCV13 type (+6C) IPD among adults >75 years of age (VE 61%, 95% CI 14, 82). VE was 26% (95% CI −58, 65%) against serotype 3 and 67% (95% CI 11, 88%) against other PCV13-types (+6C). PCV13 was not effective against nonvaccine types.

Conclusion

PCV13 was effective in preventing IPD caused by PCV13 types when excluding type 3; no effectiveness was demonstrated against serotype 3.

Disclosures

W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee.
159. Genomic Epidemiology of MRSA at Intake to a Large Inner-City Jail: Evidence for Community Transmission Networks?
Authors: Popovich Kyle J , Snitkin Evan S , Green Stefan J , Aroutcheva Alla , Schoeny Michael , Payne Darjai , Thiede Stephanie , Zawitz Chad , Hota Bala , Hayden Mary K , Weinstein Robert A
Published: November 2018

Background

USA300 is endemic in the community, with congregate settings potentially facilitating spread. The impact of community MRSA transmission networks on importation of MRSA into urban jails is unknown. We examined MRSA colonization isolates entering the jail and determined whether there are community transmission networks for MRSA that precede incarceration.

Methods

HIV-infected and HIV-negative males incarcerated at the Cook County Jail were enrolled within 72 hours of intake. Surveillance cultures (nares, throat, and groin) were collected to determine prevalence of MRSA colonization. A survey was administered to identify predictors of colonization. Whole-genome sequencing (WGS) and phylogenetic analysis were integrated with epidemiologic data to identify community transmission networks.

Results

A total of 800 males were enrolled (83% AA and 9% Hispanic); 58% were HIV-infected. The prevalence of MRSA colonization at intake was 19%. In multivariate analysis, methamphetamine use (METH), unstable housing, and prior jail incarceration were significant predictors of MRSA. Among HIV patients, injection drug use and HIV care at outpatient Clinic A that emphasize comprehensive care to the LGBTQ community were significant predictors of MRSA. Of the 31 (45%) patients with care at Clinic A, 14 had MRSA colonization. We sequenced 145 isolates from unique individuals, with 102 and 13 closely related to USA300 and USA500 reference genomes, respectively. USA300 strains from intake were diverse (median pairwise SNV distance = 109), with several small clusters noted. WGS revealed the high prevalence of MRSA in Clinic A was not due to clonal spread but rather an intermingling of distinct community transmission networks (strains were highly diverse; median pairwise SNV distance = 410). We did identify a 13-member community transmission network underlying spread of USA500 (figure). Members of this network were more likely to be HIV-infected (P < 0.004), MSM (P < 0.001), and METH (P < 0.001).

Conclusion

A high proportion of individuals enter jail already colonized with MRSA and colonization risk factors provide clues to community reservoirs for MRSA. WGS extended epidemiologic analysis and revealed community transmission networks that could be a potential focus for an intervention.

Disclosures

All authors: No reported disclosures.