bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Risk Factors for Community and Hospital Acquisition of Clostridium difficile Infection in the Tel Aviv Sourasky Medical Center
Authors: Na’amnih Wasef , Adler Amos , Miller-Roll Tamar , Cohen Dani , Carmeli Yehuda
Published: May 2017

OBJECTIVES

To estimate the incidence and identified risk factors for community-acquired (CA) and hospital-acquired (HA) Clostridium difficile infection (CDI)

METHODS

We conducted 2 parallel case-control studies at Tel Aviv Sourasky Medical Center from January 1, 2011, to December 31, 2014. We identified persons with CDI, determined whether infection was community or hospital acquired, and calculated incidence rates from 2007 to 2014. We collected demographic, clinical, and epidemiological information for CDI cases and hospitalized control cases and estimated the odds ratio with 95% confidence interval using conditional logistic regression.

RESULTS

In total, 1,563 CDI cases were identified in the study. The incidence rate of CA-CDI and HA-CDI increased by 1.6-fold and 1.2-fold, respectively, during 2012–2014. However, the incidence rate of CA-CDI was 0.84 per 100,000 (95% CI, 0.52–1.30), the rate for HA-CDI was 4.7 per 10,000 patient days (95% CI, 4.08–5.38), respectively, in 2014. We identified several factors as independent variables significantly associated with HA-CDI: functional disability, presence of nasogastric tube, antibiotic use, chemotherapy, infection by extended-spectrum β-lactamases, and mean of albumin values. Risk factors independently associated with CA-CDI were close contact with a family member who had been hospitalized in the previous 6 months, inflammatory bowel disease, and home density index (adjusted odds ratio, 25.7; 95% confidence interval, 3.99–165.54; P=.001).

CONCLUSIONS

The identification of the main modifiable risk factors for HA-CDI (antibiotic exposure and hypoalbuminemia) and for CA-CDI (close contact with a family member who had been hospitalized in the previous 6 months) is likely to optimize prevention efforts; these factors are critical in preventing the spread of CDI.

Infect Control Hosp Epidemiol 2017;38:912–920
Measuring Antibiotic Appropriateness for Urinary Tract Infections in Nursing Home Residents
Authors: Eure Taniece , LaPlace Lisa L. , Melchreit Richard , Maloney Meghan , Lynfield Ruth , Whitten Tory , Warnke Linn , Dumyati Ghinwa , Quinlan Gail , Concannon Cathleen , Thompson Deborah , Stone Nimalie D. , Thompson Nicola D.
Published: May 2017

We assessed the appropriateness of initiating antibiotics in 49 nursing home (NH) residents receiving antibiotics for urinary tract infection (UTI) using 3 published algorithms. Overall, 16 residents (32%) received prophylaxis, and among the 33 receiving treatment, the percentage of appropriate use ranged from 15% to 45%. Opportunities exist for improving UTI antibiotic prescribing in NH.

Infect Control Hosp Epidemiol 2017;38:998–1001
TELL KHAIBER: AN ADMINISTRATIVE CENTRE OF THE SEALAND PERIOD
Authors: Campbell Stuart , Moon Jane , Killick Robert , Calderbank Daniel , Robson Eleanor , Shepperson Mary , Slater Fay
Published: May 2017

Excavations at Tell Khaiber in southern Iraq by the Ur Region Archaeological Project have revealed a substantial building (hereafter the Public Building) dating to the mid-second millenniumb.c. The results are significant for the light they shed on Babylonian provincial administration, particularly of food production, for revealing a previously unknown type of fortified monumental building, and for producing a dated archive, in context, of the little-understood Sealand Dynasty. The project also represents a return of British field archaeology to long-neglected Babylonia, in collaboration with Iraq's State Board for Antiquities and Heritage. Comments on the historical background and physical location of Tell Khaiber are followed by discussion of the form and function of the Public Building. Preliminary analysis of the associated archive provides insights into the social milieu of the time. Aspects of the material culture, including pottery, are also discussed.
AT MOST 64 LINES ON SMOOTH QUARTIC SURFACES (CHARACTERISTIC 2)
Authors: RAMS SŁAWOMIR , SCHÜTT MATTHIAS
Published: May 2017

Let $k$ be a field of characteristic $2$. We give a geometric proof that there are no smooth quartic surfaces $S\subset \mathbb{P}_{k}^{3}$ with more than 64 lines (predating work of Degtyarev which improves this bound to 60). We also exhibit a smooth quartic containing 60 lines which thus attains the record in characteristic $2$.
Probiotic yogurt and acidified milk similarly reduce postprandial inflammation and both alter the gut microbiota of healthy, young men
Authors: Burton Kathryn J. , Rosikiewicz Marta , Pimentel Grégory , Bütikofer Ueli , von Ah Ueli , Voirol Marie-Jeanne , Croxatto Antony , Aeby Sébastien , Drai Jocelyne , McTernan Philip G. , Greub Gilbert , Pralong François P. , Vergères Guy , Vionnet Nathalie
Published: May 2017

Probiotic yogurt and milk supplemented with probiotics have been investigated for their role in ‘low-grade’ inflammation but evidence for their efficacy is inconclusive. This study explores the impact of probiotic yogurt on metabolic and inflammatory biomarkers, with a parallel study of gut microbiota dynamics. The randomised cross-over study was conducted in fourteen healthy, young men to test probiotic yogurt compared with milk acidified with 2 %d-(+)-glucono-δ-lactone during a 2-week intervention (400 g/d). Fasting assessments, a high-fat meal test (HFM) and microbiota analyses were used to assess the intervention effects. Baseline assessments for the HFM were carried out after a run-in during which normal milk was provided. No significant differences in the inflammatory response to the HFM were observed after probiotic yogurt compared with acidified milk intake; however, both products were associated with significant reductions in the inflammatory response to the HFM compared with the baseline tests (assessed by IL6, TNFαand chemokine ligand 5) (P<0·001). These observations were accompanied by significant changes in microbiota taxa, including decreased abundance ofBilophila wadsworthiaafter acidified milk (log 2-fold-change (FC)=–1·5,Padj=0·05) and probiotic yogurt intake (FC=–1·3,Padj=0·03), increased abundance ofBifidobacteriumspecies after acidified milk intake (FC=1·4,Padj=0·04) and detection ofLactobacillus delbrueckiispp.bulgaricus(FC=7·0,Padj<0·01) andStreptococcus salivariusspp.thermophilus(FC=6·0,Padj<0·01) after probiotic yogurt intake. Probiotic yogurt and acidified milk similarly reduce postprandial inflammation that is associated with a HFM while inducing distinct changes in the gut microbiota of healthy men. These observations could be relevant for dietary treatments that target ‘low-grade’ inflammation.
Interpreting Pedagogical Acts: Acts 8.26–40 and Narrative Reflexivity as Pedagogy
Authors: Dinkler Michal Beth
Published: May 2017

This article foregrounds a fact so basic that it often goes unnoticed: stories frequently depict the acts of reading and/or interpreting stories; many narratives are themselves concerned with proper modes of narrative interpretation. I contend that such scenes work rhetorically to inculcate particular kinds of hermeneutical skills in their audiences, and thus can be read as pedagogical scenarios vis-à-vis implied readers. I begin the article by introducing the contemporary notion of narrative reflexivity and situating that concept within the broader literary sub-field of rhetorical narratology. Then, I turn to Acts 8.26–40 as a brief case study in order to demonstrate how narrative reflexivity can help us to think in fresh ways about the pedagogical force of ancient narratives. Specifically, I argue that this story in Acts reflexively commends the following hermeneutical principle for its readers: because reading is not synonymous with understanding, one ought to have an authoritative interpretive guide, and embrace a hermeneutic of hospitality towards the received narrative. Finally, I highlight several examples from ancient literature that demonstrate why my proposed reading coheres with ancient views about pedagogy and textual interpretation more broadly.
The influence of communication mode on written language processing and beyond
Authors: Barca Laura , Pezzulo Giovanni
Published: May 2017

Empirical evidence suggests a broad impact of communication mode on cognition at large, beyond language processing. Using a sign language since infancy might shape the representation of words and other linguistic stimuli – for example, incorporating in it the movements and signs used to express them. Once integrated into linguistic representations, this visuo-motor content can affect deaf signers’ linguistic and cognitive processing.
Where does (sign) language begin?
Authors: Berent Iris , Dupuis Amanda
Published: May 2017

Goldin-Meadow & Brentari (G-M&B) outline several criteria for delineating the boundaries between (discrete) signs and (continuous) gestures. However, the complex links between linguistics forms and their phonetic realizations defy such heuristics. A systematic exploration of language structure by mouth and by hand may help get us closer to answering the important challenge outlined in this target article.
The physiognomic unity of sign, word, and gesture
Authors: Cornejo Carlos , Musa Roberto
Published: May 2017

Goldin-Meadow & Brentari (G-M&B) are implicitly going against the dominant paradigm in language research, namely, the “speech as written language” metaphor that portrays vocal sounds and bodily signs as means of delivering stable word meanings. We argue that Heinz Werner's classical research on the physiognomic properties of language supports and complements their view of sign and gesture as a unified system.
Perspectives on gesture from autism spectrum disorder: Alterations in timing and function
Authors: Eigsti Inge-Marie , de Marchena Ashley
Published: May 2017

The target article highlights the utility of new technology to study sign language and gesture. Research in special populations – specifically, individuals with autism spectrum disorder, ASD – may further illuminate sign/gesture similarities and differences and lead to a deeper understanding of the mechanisms of growth and change. Even verbally fluent speakers with ASD display distinctive qualities in sign and gesture.
Emoticons in text may function like gestures in spoken or signed communication
Authors: Feldman Laurie Beth , Aragon Cecilia R. , Chen Nan-Chen , Kroll Judith F.
Published: May 2017

We draw parallels between emoticons in textual communication and gesture in signed language with respect to the interdependence of codes by describing two contexts under which the behavior of emoticons in textual communication resembles that of gesture in speech. Generalizing from those findings, we propose that gesture is likely characterized by a nuanced interdependence with language whether signed, spoken or texted.
Good things come in threes: Communicative acts comprise linguistic, imagistic, and modifying components
Authors: Kästner Lena , Newen Albert
Published: May 2017

Gesture and sign form an integrated communication system, as do gesture and speech. Communicative acts in both systems combine categorical linguistic (words or signs) with imagistic (gestures) components. Additionally, both sign and speech can employ modifying components that convey iconic information tied to a linguistic base morpheme. An accurate analysis of communicative acts must take this third category into account.
Gesture or sign? A categorization problem
Authors: Occhino Corrine , Wilcox Sherman
Published: May 2017

Goldin-Meadow & Brentari (G-M&B) rely on a formalist approach to language, leading them to seek objective criteria by which to distinguish language and gesture. This results in the assumption that gradient aspects of signs are gesture. Usage-based theories challenge this view, maintaining that all linguistic units exhibit gradience. Instead, we propose that the distinction between language and gesture is a categorization problem.
Vocal laughter punctuates speech and manual signing: Novel evidence for similar linguistic and neurological mechanisms
Authors: Provine Robert R.
Published: May 2017

Vocal laughter fills conversations between speakers with normal hearing and between deaf users of American Sign Language, but laughter rarely intrudes on the phrase structure of spoken or signed conversation, being akin to punctuation in written text. This punctuation effect indicates that language, whether vocal or signed, is dominant over laughter, and that speech and manual signing involve similar mechanisms.
Toward true integration
Authors: Rosselló Joana , Mattos Otávio , Hinzen Wolfram
Published: May 2017

Whether in sign or speech, language is more integrative than the target article suggests. A more integrative view embraces not only sign/speech and co-sign/speech gesture, but also indicative gestures irrespective of modality, and locations along with movements in the signed modality, as suggested by both linguistic acquisition and pathologies. An extended integrative view also proves advantageous in terms of conceptual coherence.
The categorical role of structurally iconic signs
Authors: Strickland Brent , Aristodemo Valentina , Kuhn Jeremy , Geraci Carlo
Published: May 2017

Goldin-Meadow & Brentari (G-M&B) argue that, for sign language users, gesture – in contrast to linguistic sign – is iconic, highly variable, and similar to spoken language co-speech gesture. We discuss two examples (telicity and absolute gradable adjectives) that challenge the use of these criteria for distinguishing sign from gesture.
Analysing real-world visual search tasks helps explain what the functional visual field is, and what its neural mechanisms are
Authors: Campion John
Published: May 2017

Rejecting information-processing-based theory permits the merging of a top-down analysis of visual search tasks with a bottom-up analysis of brain structure and function. This reveals the true nature of the functional visual field and its precise role in the conduct of visual search tasks. The merits of such analyses over the traditional methods of the authors are described.
Eye movements are an important part of the story, but not the whole story
Authors: Cave Kyle R.
Published: May 2017

Some previous accounts of visual search have emphasized covert attention at the expense of eye movements, and others have focused on eye movements while ignoring covert attention. Both selection mechanisms are likely to contribute to many searches, and a full account of search will probably need to explain how the two interact to find visual targets.
Why the item will remain the unit of attentional selection in visual search
Authors: Eimer Martin
Published: May 2017

Hulleman & Olivers (H&O) reject item-based serial models of visual search, and they suggest that items are processed equally and globally during each fixation period. However, neuroscientific studies have shown that attentional biases can emerge in parallel but in a spatially selective item-based fashion. Even within a parallel architecture for visual search, the item remains the critical unit of selection.
Oh, the number of things you will process (in parallel)!
Authors: Lleras Alejandro , Cronin Deborah A. , Madison Anna M. , Wang Marshall , Buetti Simona
Published: May 2017

We highlight the importance of considering the variance produced during the parallel processing stage in vision and present a case for why it is useful to consider the “item” as a meaningful unit of study when investigating early visual processing in visual search tasks.
Those pernicious items
Authors: Rosenholtz Ruth
Published: May 2017

Hulleman & Olivers (H&O) identify a number of problems with item-based thinking and its impact on our understanding of visual search. I detail ways in which item-thought is worse than the authors suggest. I concur with the broad strokes of the theory they set out, and also clarify the relationship between their view and our recent theory of visual search.
Just learning
Authors: Larsen-Freeman Diane
Published: May 2017

I have always been interested in learning. I chose to study psychology as an undergraduate because it was in my psychology courses that I got to study theories of learning. I learned that the psychologists couldn't agree on what theexplanandumwas. Some thought it was human behavior; others argued for mental competence. It was only later that I found my own focus: I became interested in understanding the learning oflanguage(although the issue of behavior versus mental competence persisted).
Pronunciation assessment
Authors: Isaacs Talia , Harding Luke
Published: May 2017

After an extended period of being on the periphery, numerous advancements in the field of second language (L2) pronunciation over the past decade have led to increased activity and visibility for this subfield within applied linguistics research. As Derwing (2010) underscored in her 2009 plenary at the first annualPronunciation in Second Language Learning and Teaching(PSLLT) conference, a record number of graduate students researching L2 pronunciation and subsequently launching into academic positions at international universities assures L2 pronunciation a bright future in research and teacher training. Other indicators of momentum include the focus of aLanguage Teachingtimeline on the topic of pronunciation (Munro & Derwing 2011), the appearance of multiple encyclopedia volumes or handbooks of pronunciation (e.g. Levis & Munro 2013; Reed & Levis 2015), and the establishment of the specializedJournal of Second Language Pronunciationin 2015, which constitutes a milestone in the professionalization of the field and ‘an essential step toward a disciplinary identity’ (Levis 2015: 1).
DISCOUNTING FOR PUBLIC POLICY: A SURVEY
Authors: Greaves Hilary
Published: May 2017

This article surveys the debate over the social discount rate. The focus is on the economics rather than the philosophy literature, but the survey emphasizes foundations in ethical theory rather than highly technical details. I begin by locating the standard approach to discounting within the overall landscape of ethical theory. The article then covers the Ramsey equation and its relationship to observed interest rates, arguments for and against a positive rate of pure time preference, the consumption elasticity of utility, and the effect of various sorts of uncertainty on the discount rate. Climate change is discussed as an application.
The lack of exponential stability for a class of second-order systems with memory
Authors: Danese Valeria , Dell'Oro Filippo
Published: May 2017

We analyse the decay properties of the solution semigroup S(t) generated by the linear integrodifferential equation

where the operator A is strictly positive self-adjoint with A–1 not necessarily compact. The asymptotic stability of S(t) is investigated in terms of the dependence of the parameter γ ∈ ℝ. In particular, we show that S(t) is not exponentially stable when γ ≠ 1.
Bifurcation values of families of real curves
Authors: Joiţa Cezar , Tibăr Mihai
Published: May 2017

The detection of the bifurcation set of polynomial mapping ℝn → ℝp, n ⩾ p, in more than two variables remains an unsolved problem. In this note we provide a solution for n = p + 1 ⩾ 3.
PUBLIC RITUAL AND INTERREGIONAL INTERACTIONS: EXCAVATIONS OF THE CENTRAL PLAZA OF GROUP A, CEIBAL
Authors: Inomata Takeshi , Pinzón Flory , Palomo Juan Manuel , Sharpe Ashley , Ortíz Raúl , Méndez María Belén , Román Otto
Published: May 2017

The probable E-Group assemblage was a primary focus of our investigation at the lowland Maya center of Ceibal. Tunnel excavation into Structure A-20 (the western structure of this complex) demonstrated that the Ceibal residents built the earliest version (Structure Ajaw) by carving natural marl around 950b.c.The earliest version of the eastern platform (Structure Xa'an) was also made at the same time out of the natural marl layer. Through a series of renovations, the western structure grew into a pyramidal shape, and later versions of the eastern platform were moved further to the east. In addition, excavations revealed numerous caches, many with greenstone axes, along the center line of the E-Group assemblage. These results show that a formal ceremonial complex was established at the beginning of occupation at Ceibal, and its construction and public events held there played an important role in the creation of a new community.
CO2emissions and militarization in G7 countries: panel cointegration and trivariate causality approaches
Authors: Bildirici Melike
Published: May 2017

This paper aims to test the relation among militarization, CO2emissions, economic growth and energy consumption in G7 countries from 1985 to 2015 via panel methods. Long- and short-run coefficients and the causal relationship between the variables are important for G7 countries' energy policies and strategy. Cointegration among CO2emissions, militarization, energy consumption and economic growth was determined by using panel Johansen and panel autoregressive distributed lag (PARDL) methods. Further, the panel trivariate causality test was applied and unidirectional causalities from militarization to CO2emissions and from energy consumption to CO2emissions were found. The evidence of bidirectional causality between per capita GDP and militarization, between per capita GDP and energy consumption, and between energy consumption and militarization was determined. The paper recommends that environmental and energy policies must recognize the differences in the relation between militarization, energy consumption and economic growth in order to maintain sustainable economic growth in the G7 countries.
Organic food consumption during pregnancy is associated with different consumer profiles, food patterns and intake: the KOALA Birth Cohort Study
Authors: Simões-Wüst Ana Paula , Moltó-Puigmartí Carolina , van Dongen Martien CJM , Dagnelie Pieter C , Thijs Carel
Published: May 2017

Objective

To find out how the consumption of organic food during pregnancy is associated with consumer characteristics, dietary patterns and macro- and micronutrient intakes.

Design

Cross-sectional description of consumer characteristics, dietary patterns and macro- and micronutrient intakes associated with consumption of organic food during pregnancy.

Setting

Healthy, pregnant women recruited to a prospective cohort study at midwives’ practices in the southern part of the Netherlands; to enrich the study with participants adhering to alternative lifestyles, pregnant women were recruited through various specific channels.

Subjects

Participants who filled in questionnaires on food frequency in gestational week 34 (n2786). Participant groups were defined based on the share of organic products within various food types.

Results

Consumers of organic food more often adhere to specific lifestyle rules, such as vegetarianism or anthroposophy, than do participants who consume conventional food only (reference group). Consumption of organic food is associated with food patterns comprising more products of vegetable origin (soya/vegetarian products, vegetables, cereal products, bread, fruits, and legumes) and fewer animal products (milk and meat), sugar and potatoes than consumed in conventional diets. These differences translate into distinct intakes of macro- and micronutrients, including higher retinol, carotene, tocopherol and folate intakes, lower intakes of vitamin D and B12and specific types oftrans-fatty acids in the organic groups. These differences are seen even in groups with low consumption of organic food.

Conclusions

Various consumer characteristics, specific dietary patterns and types of food intake are associated with the consumption of organic food during pregnancy.
Response of Drought-Stressed Grafted and Nongrafted Tomato to Postemergence Metribuzin
Authors: Chaudhari Sushila , Jennings Katherine M. , Monks David W. , Jordan David L. , Gunter Christopher C. , Louws Frank J.
Published: May 2017

Tomato grafting is practiced worldwide as an innovative approach to manage stress from drought, waterlogging, insects, and diseases. Metribuzin is a commonly used herbicide in tomato but has potential to cause injury after application if plants are under stress. The influence of metribuzin on grafted tomato under drought-stress has not been studied. Greenhouse experiments were conducted in Raleigh, NC to determine the tolerance of drought-stressed grafted and non-grafted tomato to metribuzin. The tomato cultivar ‘Amelia’ was used as the scion in grafted tomato, and for the non-grafted control. Two hybrid tomato ‘Beaufort’ and ‘Maxifort’ were used as rootstocks for grafted plants. Drought-stress treatments included: no drought-stress; 3 d of drought-stress before metribuzin application with no drought-stress after application (3 d DSB); and 3 d of drought-stress before metribuzin application with 3 d of drought-stress after application (3 d DSBA). Metribuzin was applied at 550 g ai ha−1. No difference in injury from metribuzin was observed in grafted and non-grafted plants. However, at 7 and 14 d after metribuzin treatment (DMT), less injury was observed on tomato in the 3 d DSBA treatment (5 and 2% injury, respectively) than on plants in the 3 d DSB treatment (15 and 8% injury, respectively) or those that were never drought-stressed (18 and 11% injury, respectively). Photosynthesis and stomatal conductance measured prior to metribuzin application were reduced similarly in grafted and non-grafted tomato subjected to drought-stress. Photosynthesis and stomatal conductance of grafted and non-grafted tomato at 7 DMT was not different among drought-stress treatments or metribuzin treatments. Grafted and non-grafted tomato plants under drought-stress exhibit similar tolerance to metribuzin. The risk of metribuzin injury to grafted tomato under drought-stress is similar to non-grafted tomato.
A Plunge into the Depths of Italy’s Lake Garda
Authors: Toffolon Marco , Piccolroaz Sebastiano , Dijkstra Henk
Published: May 2017

First International Scientific Workshop on GARDEN (Lake Garda Environmental system); Trento, Italy, 2 February 2017
IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression
Authors: Wang Chenhui , Zhang Cun-Jin , Martin Bradley N. , Bulek Katarzyna , Kang Zizhen , Zhao Junjie , Bian Guanglin , Carman Julie A. , Gao Ji , Dongre Ashok , Xue Haibo , Miller Stephen D. , Qian Youcun , Hambardzumyan Dolores , Hamilton Tom , Ransohoff Richard M. , Li Xiaoxia
Published: May 2017

NOTCH1 signalling contributes to defective remyelination by impairing differentiation of oligodendrocyte progenitor cells (OPCs). Here we report that IL-17 stimulation induces NOTCH1 activation in OPCs, contributing to Th17-mediated demyelinating disease. Mechanistically, IL-17R interacts with NOTCH1 via the extracellular domain, which facilitates the cleavage of NOTHC1 intracellular domain (NICD1). IL-17-induced NOTCH1 activation results in the interaction of IL-17R adaptor Act1 with NICD1, followed by the translocation of the Act1–NICD1 complex into the nucleus. Act1–NICD1 are recruited to the promoters of several NOTCH1 target genes (including STEAP4, a metalloreductase important for inflammation and cell proliferation) that are specifically induced in the spinal cord by Th17 cells. A decoy peptide disrupting the IL-17RA–NOTCH1 interaction inhibits IL-17-induced NOTCH1 activation and attenuates Th17-mediated experimental autoimmune encephalitis (EAE). Taken together, these findings demonstrate critical crosstalk between the IL-17 and NOTCH1 pathway, regulating Th17-induced inflammatory and proliferative genes to promote demyelinating disease.
HSPs drive dichotomous T-cell immune responses via DNA methylome remodelling in antigen presenting cells
Authors: Kinner-Bibeau Lauren B. , Sedlacek Abigail L. , Messmer Michelle N. , Watkins Simon C. , Binder Robert J.
Published: May 2017

Immune responses primed by endogenous heat shock proteins, specifically gp96, can be varied, and mechanisms controlling these responses have not been defined. Immunization with low doses of gp96 primes T helper type 1 (Th1) immune responses, whereas high-dose immunization primes responses characterized by regulatory T (Treg) cells and immunosuppression. Here we show gp96 preferentially engages conventional and plasmacytoid dendritic cells (pDCs) under low and high doses, respectively, through CD91. Global DNMT-dependent epigenetic modifications lead to changes in protein expression within these antigen-presenting cells. Specifically, pDCs upregulate neuropilin-1 to enable the long term interactions of pDCs with Treg cells, thereby enhancing suppression of Th1 anti-tumour immunity. Our study defines a CD91-dependent mechanism through which gp96 controls dichotomous immune responses relevant to the therapy of cancer and autoimmunity.
Atomistic Corrective Scheme for Supercell Density Functional Theory Calculations of Charged Defects
Authors: Cao Tengfei , Bongiorno Angelo
Published: May 2017

A new method to correct formation energies of charged defects obtained by supercell density-functional calculations is presented and applied to bulk, surface, and low-dimensional systems. The method relies on atomistic models and a polarizable force field to describe a material system and its dielectric properties. The polarizable force field is based on a minimal set of fitting parameters, it accounts for the dielectric screening arising from ions and electrons separately, and it can be easily implemented in any software for atomistic molecular dynamics simulations. This work illustrates both technical aspects and applications of the new corrective scheme. The method is tested on systems in vacuo to validate the energy scheme. It is applied to charged defects in the bulk and at the surface of realistic materials to achieve comparison with published results obtained by using available corrective schemes based on continuum electrostatics treatments. Moreover, to demonstrate its generality, the method is used to correct the formation energy obtained by DFT of a singly negatively charged S vacancy in monolayer, bilayer, trilayer and bulk MoS2.
Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy
Authors: Zhang Ruiyun , Wu Guangyu , Huang Jiwei , Shi Oumin , Kong Wen , Chen Yonghui , Xu Jianrong , Xue Wei , Zhang Jin , Huang Yiran
Published: May 2017

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.
Tunable Magneto-Optical Kerr Effects of Nanoporous Thin Films
Authors: Zhang Weiwei , Li Jianjun , Ding Xiaokun , Pernod Philippe , Tiercelin Nicolas , Song Yujun
Published: May 2017

Magnetoplasmonics, combining magnetic and plasmonic functions, has attracted increasing attention owing to its unique magnetic and optical properties in various nano-architectures. In this work, Ag, CoFeB and ITO layers are fabricated on anodic aluminum oxide (AAO) porous films to form hybrid multi-layered nanoporous thin films by magnetron sputtering deposition process. The designed nanostructure supports localized surface plasmon resonance (LSPR) and tunable magneto-optical (MO) activity, namely, the sign inversion, which can be controlled by AAO porous film geometry (pore diameter and inter-pore spacing) flexibly. The physical mechanism of this special MO phenomena is further analyzed and discussed by the correlation of Kerr rotation and electronic oscillations controlled by the surface plasmon resonance that is related to the nanoporous structure.
Cell fiber-based three-dimensional culture system for highly efficient expansion of human induced pluripotent stem cells
Authors: Ikeda Kazuhiro , Nagata Shogo , Okitsu Teru , Takeuchi Shoji
Published: May 2017

Human pluripotent stem cells are a potentially powerful cellular resource for application in regenerative medicine. Because such applications require large numbers of human pluripotent stem cell-derived cells, a scalable culture system of human pluripotent stem cell needs to be developed. Several suspension culture systems for human pluripotent stem cell expansion exist; however, it is difficult to control the thickness of cell aggregations in these systems, leading to increased cell death likely caused by limited diffusion of gases and nutrients into the aggregations. Here, we describe a scalable culture system using the cell fiber technology for the expansion of human induced pluripotent stem (iPS) cells. The cells were encapsulated and cultured within the core region of core-shell hydrogel microfibers, resulting in the formation of rod-shaped or fiber-shaped cell aggregations with sustained thickness and high viability. By encapsulating the cells with type I collagen, we demonstrated a long-term culture of the cells by serial passaging at a high expansion rate (14-fold in four days) while retaining its pluripotency. Therefore, our culture system could be used for large-scale expansion of human pluripotent stem cells for use in regenerative medicine.
Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
Authors: Shah Fenil , Logsdon Derek , Messmann Richard A. , Fehrenbacher Jill C. , Fishel Melissa L. , Kelley Mark R.
Published: May 2017

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic.
Interlaced zone plate optics for hard X-ray imaging in the 10 nm range
Authors: Mohacsi Istvan , Vartiainen Ismo , Rösner Benedikt , Guizar-Sicairos Manuel , Guzenko Vitaliy A. , McNulty Ian , Winarski Robert , Holt Martin V. , David Christian
Published: May 2017

Multi-keV X-ray microscopy has been particularly successful in bridging the resolution gap between optical and electron microscopy. However, resolutions below 20 nm are still considered challenging, as high throughput direct imaging methods are limited by the availability of suitable optical elements. In order to bridge this gap, we present a new type of Fresnel zone plate lenses aimed at the sub-20 and the sub-10 nm resolution range. By extending the concept of double-sided zone plate stacking, we demonstrate the doubling of the effective line density and thus the resolution and provide large aperture, singlechip optical devices with 15 and 7 nm smallest zone widths. The detailed characterization of these lenses shows excellent optical properties with focal spots down to 7.8 nm. Beyond wave front characterization, the zone plates also excel in typical imaging scenarios, verifying their resolution close to their diffraction limited optical performance.
Transcription regulation mechanism of the syntaxin 1A gene via protein kinase A
Authors: Nakayama Takahiro , Akagawa Kimio
Published: May 2017

Syntaxin 1A (Stx1a) is primarily involved in the docking of synaptic vesicles at active zones in neurons. Its gene is a TATA-less gene, with several transcription initiation sites, which is activated by the binding of Sp1 and acetylated histone H3 (H3) in the core promoter region (CPR) through the derepression of class I histone deacetylase (HDAC). In the present study, to clarify the factor characterizing Stx1a gene expression via the protein kinase A (PKA) pathway inducing the Stx1a mRNA, we investigated whether the epigenetic process is involved in the Stx1a gene transcription induced by PKA signaling. We found that the PKA activator forskolin induced Stx1a expression in non-neuronal cells, FRSK and 3Y1, which do not endogenously express Stx1a, unlike PC12. HDAC8 inhibition by shRNA knockdown and specific inhibitors induced Stx1a expression in FRSK. The PKA inhibitor H89 suppressed HDAC8-Ser39 phosphorylation, H3 acetylation and Stx1a induction by forskolin in FRSK cells. Finally, we also found that forskolin led to the dissociation of HDAC8-CPR interaction and the association of Sp1 and Ac-H3 to CPR in FRSK. The results of the current study suggest that forskolin phosphorylates HDAC8-Ser39 via the PKA pathway and increases histone H3 acetylation in cells expressing HDAC8, resulting in the induction of the Stx1a gene.
Emerging Concepts and Human Trials in Alpha-1-Antitrypsin Deficiency Liver Disease
Authors: Teckman Jeffrey
Published: May 2017

In α-1-antitrypsin (AAT) deficiency, individuals homozygous for the AAT mutant Z gene synthesize large quantities of mutant Z protein in the liver, which folds improperly during biogenesis and is retained within the hepatocytes rather than appropriated secreted. This accumulation of mutant Z protein triggers an intracellular injury cascade causing cell death in the population of hepatocytes with the largest accumulations of Z protein. Hepatocellular proliferation, hepatic fibrosis, and hepatocellular cancer in some individuals can be the result. New insights from basic science studies have now allowed the application of new biotechnologies to this previously untreatable disease. Specifically, drugs designed to accelerate the intracellular removal of the mutant Z protein (autophagy enhancers) and siRNA strategies designed to shut down synthesis of the toxic, mutant Z protein, are now in human trials. Other approaches, such as gene correction, cell therapy, and antifibrotic drugs are in preclinical development.
Immunotolerance in Liver Transplantation
Authors: Mastoridis Sotiris , Martinez-Llordella Marc , Sanchez-Fueyo Alberto
Published: May 2017

The burden of life-long immunosuppressive medication must be overcome if progress is to be made in long-term outcomes following transplantation. The liver exhibits intrinsic tolerogenic properties that contribute to a unique propensity toward spontaneous acceptance when transplanted. Hence, a proportion of liver transplant recipients develop a state of immunotolerance and display persistently normal allograft function despite the discontinuation of immunosuppression. However, this phenomenon remains elusive for the majority of recipients. Investigations performed in experimental models of spontaneous liver allograft tolerance and in clinical cases of immunosuppression-free liver transplant acceptance have yielded mechanistic insights at the heart of recent strategies toward tolerance prediction and promotion. Results from recent clinical trials signal a shift in how liver allograft tolerance is viewed—not an elusive rarity of academic interest, but a potentially relevant clinical opportunity, which can be safely pursued if appropriately targeted.
Disorders in Hepatic Copper Secretion: Wilson's Disease and Pleomorphic Syndromes
Authors: Lalioti Vasiliki , Tsubota Akihito , Sandoval Ignacio
Published: May 2017

Wilson's disease (WD) is a rare disease the prevalence of which is higher than previously thought. Caused by genetic variations that target the copper (Cu) transporting P-ATPase Atp7b and disrupt the elimination of Cu by the liver, Atp7b truncations are associated with early severe liver disease and missense mutations with the late presentation of neurologic disorders. The asymptomatic initiation and false unimportance of initial symptoms often delays the crucial early diagnosis and a treatment that is lifesaving. The occasional acute liver failure persistently threatens the life of patients with WD. The gravity and progression of the disease are strongly dependent on the genetic background that organizes the response to the oxidative damage produced by the raised levels of free Cu. In this review, the authors focus on the prevalence, genetics, pathogenesis, clinical presentation, and treatment options in WD. They also discuss the new association of cuprotoxicosis with pleomorphic syndromes, of which MEDNIK is the first example, produced by genetic variations that disrupt the universal mechanisms of protein transport and thus perturb the traffic of Atp7b linked to Cu excretion.
Development and Evaluation of a Blog about Cleft Lip and Cleft Palate and Hearing
Authors: Maximino Luciana , Zambonato Ticiana , Picolini-Pereira Mirela , Castro Corrêa Camila , Feniman Mariza , Blasca Wanderléia
Published: May 2017

Introduction Cleft lip and cleft palate can result in impairments in communication, specifically in hearing, making the use of technological resources such as blogs a fundamental guideline for health professionals.

Objective The aim of this study was to prepare and analyze the access to a blog about cleft lip and cleft palate and hearing as a pedagogical tool for health professionals.

Methods The first stage for the development of the blog was the selection of the content that would be addressed and the respective illustrations. The second stage was making the blog available through the WordPress platform, and the third stage included the evaluation of the blog, of the access to the WordPress statistical features, and of the quality of the blog through the Emory questionnaire, which was answered by 75 professionals.

Results The blog, titled “Fissure and Hearing”, was developed with the architecture of a digital information environment containing a system of organization, navigation, labeling and search (first stage). The address hosting the blog was: http://fissuraeaudicao.wordpress.com (second stage). The result of the third stage included 56,269 views of the blog from different countries, and Brazil was the country with the highest viewing. Regarding the assessment by the Emory questionnaire, we found that for most of the major issues, the percentages obtained were or equal to 90%, while the analysis of the scales, navigation and structure presented the lowest scores.

Conclusion The blog was developed and enabled greater access to information available on the web about cleft lip and cleft palate and hearing.
Aktuelle Aspekte bei der Diagnostik und Therapie des Plasmazellmyeloms
Authors: Bärtsch Marc- , Goldschmidt Hartmut
Published: May 2017

Was ist neu?

Definition, Inzidenz und klinisches Bild Die mediane Überlebenszeit mit Multiplem Myelom (MM) hat sich in den letzten 15 Jahren verdoppelt.

Diagnostik Die Diagnosekriterien des therapiepflichtigen MM wurden 2014 um Biomarker erweitert.

Erstlinientherapie Fitte, junge Patienten sind mit einer Dreierkombination zu behandeln. Die Hochdosistherapie ist weiterhin ein wesentliches Element der Initialtherapie junger MM-Patienten.

Rezidivtherapie In den letzten 2 Jahren wurden 5 neue Substanzen zur Behandlung des rezidivierten MM zugelassen.

Ausblick Remissionstiefe und Immunonkologie gewinnen zunehmend an Bedeutung in der Therapie des MM.
Sarkoidose – was ist neu?
Authors: Prasse Antje
Published: May 2017

Was ist neu?

Epidemiologie Die Sarkoidose ist eine multifaktorielle Erkrankung. Die in den letzten Jahrzehnten stattfindenden Änderungen des Lebensalltages führen zu Fluktuationen in der Manifestation.

Definition und Pathogenese Nach wie vor ist die Sarkoidose eine Ausschlussdiagnose. Frühere Ansichten, die Sarkoidose sei monokausal verursacht sind heute nicht mehr gültig. Viele verschiedene Faktoren können bei entsprechender genetischer Veranlagung die Erkrankung auslösen.

Diagnostik Mittels der neuen Technik der ultraschallgesteuerten Lymphknotenpunktion und der bereits etablierten Standardverfahren transbronchiale Biopsie und bronchoalveoläre Lavage (BAL), gelingt es heute bei Lungenbefall fast immer die Diagnose zu stellen. MRT und PET verbessern die Abklärung von Organmanifestationen deutlich.

Monitoring Der Funktionsdiagnostik von Organmanifestationen kommt eine elementare Bedeutung zu. Diese ändert sich stetig durch den technischen Fortschritt.

Therapie Die Prednison-Monotherapie wird unverändert als Erstlinientherapie bei drohendem Organfunktionsschaden eingesetzt; allerdings werden im Vergleich zu früher eher geringere Dosierungen eingesetzt und individuelle Besonderheiten berücksichtigt. Infliximab hat sich weltweit zur Behandlung therapierefraktärer Verläufe etabliert.
Direct peroral cholangioscopy for diagnosis of bile duct lesions using an I-SCAN ultraslim endoscope: a pilot study
Authors: Lee Yun , Moon Jong , Choi Hyun , Lee Tae , Choi Moon , Cha Sang-Woo , Cho Young , Park Sang-Heum
Published: May 2017

Background and study aims I-SCAN is a computed virtual chromoendoscopy (CVC) system designed to enhance surface and vascular patterns. In this study, we evaluated the usefulness of direct peroral cholangioscopy (POC) using I-SCAN compared with a conventional white-light image (WLI) to diagnose bile duct lesions.

Patients and methods Patients with mucosal lesions in the bile duct detected during direct POC were enrolled prospectively. The quality of endoscopic visualization and the visual diagnosis were assessed using I-SCAN and WLI modes, respectively, during direct POC.

Results A total of 20 patients (9 malignant and 11 benign lesions) underwent I-SCAN to evaluate lesions in the bile duct using direct POC. The quality of endoscopic visualization using direct POC with I-SCAN was significantly higher than that of WLI for surface structure (P = 0.04), surface microvascular architecture (P = 0.01), and margins (P = 0.02). Overall diagnostic accuracy of the visual diagnosis was not different between I-SCAN and WLI (90.0 % vs. 75.0 %; P = 0.20).

Conclusion Direct POC using CVC by I-SCAN seems to be helpful for evaluating mucosal lesions of the bile duct, without the interference from bile.

Clinical trial registration: UMIN000021009