bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial
Authors: Hoy Jennifer F , Grund Birgit , Roediger Mollie , Schwartz Ann V , Shepherd John , Avihingsanon Anchalee , Badal-Faesen Sharlaa , de Wit Stephane , Jacoby Simone , La Rosa Alberto , Pujari Sanjay , Schechter Mauro , White David , Engen Nicole Wyman , Ensrud Kristine , Aagaard Peer D , Carr Andrew ,   for the INSIGHT START Bone Mineral Density Substudy Group
Published: June 2017

ABSTRACT

Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 &gt;500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 &lt;350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (–2.5% versus –1.0%; difference –1.5%, 95% confidence interval [CI] –2.2 to –0.8, p &lt; 0.001) and spine (–1.9% versus –0.4%; difference –1.6%, 95% CI –2.2 to –1.0, p &lt; 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed. Clinical Trials Registration: NCT00867048. © 2017 American Society for Bone and Mineral Research.
The value of N staging with the positive lymph node ratio, and splenectomy, for remnant gastric cancer: A multicenter retrospective study
Authors: Son Sang‐Yong , Kong Seong‐Ho , Ahn Hye Seong , Park Young Suk , Ahn Sang‐Hoon , Suh Yun‐Suhk , Park Do Joong , Lee Hyuk‐Joon , Kim Hyung‐Ho , Yang Han‐Kwang 
Published: June 2017

BackgroundSurgery for remnant gastric cancer (RGC) frequently fails to obtain the >15 lymph nodes necessary for tumor‐node‐metastasis (TNM) staging. We aimed to evaluate the utility of the recently developed tumor‐ratio‐metastasis (TRM) staging system. We also examined the pattern of lymph node metastasis and the role of prophylactic splenectomy in RGC.MethodsBetween May 2003 and December 2012, data from 170 patients who underwent surgery for RGC were retrospectively analyzed.ResultsRGC arising after previous benign disease (n = 46) was associated with retrieval of more lymph nodes (27.3 vs 10.0; P < 0.001), and a lower rate of retrieving ≤15 lymph nodes (15.6% vs 77.4%, P < 0.001), than after previous malignant disease (n = 122). The 5 year survival rate according to TNM staging was 75% in stage I, 77.1% in stage II, and 23.5% in stage III, whereas by TRM staging it was 75%, 81.6%, and 23.2%, respectively. Overall survival was not different between the splenectomy and non‐splenectomy groups at each stage (P = 0.751, 0.723, 0.151, and 0.706 for stage I, II, III, and IV, respectively).ConclusionThe analyses did not identify a survival benefit from prophylactic splenectomy or show an improvement in staging with the TRM system for RGC.
Seasonal variability in phytoplankton stable carbon isotope ratios and bacterial carbon sources in a shallow Dutch lake
Authors: Lammers J. M. , Reichart G. J. , Middelburg J. J. 
Published: June 2017

AbstractEcosystem metabolism of lakes strongly depends on the relative importance of local vs. allochthonous carbon sources and on microbial food‐web functioning and structure. Over the year ecosystem metabolism varies as a result of seasonal changes in environmental parameters such as nutrient levels, light, temperature, and variability in the food web. This is reflected in isotopic compositions of phytoplankton and bacteria. Here, we present the results of a 17‐month study on carbon dynamics in two basins of Lake Naarden, The Netherlands. One basin was restored after anthropogenic eutrophication, whereas the other basin remained eutrophic. We analyzed natural stable carbon isotope abundances (δ13C) of dissolved inorganic carbon, dissolved organic carbon and macrophytes, and combined these data with compound‐specific δ13C analyses of phospholipid‐derived fatty acids, produced by phytoplankton and bacteria. Isotopic fractionation (ε) between phytoplankton biomass and CO2(aq) was similar for diatoms and other eukaryotic phytoplankton, and differences between sampling sites were small. Highest ε values were observed in winter with values of 23.5 ± 0.6‰ for eukaryotic phytoplankton and 13.6 ± 0.3‰ for cyanobacteria. Lowest ε values were observed in summer: 10.5 ± 0.3‰ for eukaryotic phytoplankton and 2.7 ± 0.1‰ for cyanobacteria. The annual range in δ13Cbact was between 6.9‰ and 8.2‰ for the restored and eutrophic basin, respectively, while this range was between 11.6‰ and 13.1‰ for phytoplankton in the restored and eutrophic basin, respectively. Correlations between δ13Cphyto and δ13Cbact were strong at both sites. During summer and fall, bacterial biomass derives mainly from locally produced organic matter, with minor allochthonous contributions. Conversely, during winter, bacterial dependence on allochthonous carbon was 39–77% at the restored site, and 17–46% at the eutrophic site.
Easy as AcHGzrjq: The Quick Letter Name Knowledge Assessment
Authors: Tortorelli Laura S. , Bowles Ryan P. , Skibbe Lori E. 
Published: June 2017

AbstractA firm foundation in alphabet knowledge is critical for children learning to read. Under new literacy standards, letter name knowledge in preschool and kindergarten can function as a gatekeeper to the rest of the curriculum. Teachers need data about their students’ alphabet knowledge early and often to plan differentiated instruction that moves all students forward in their literacy development. This article describes the Quick Letter Name Knowledge Assessment (Q‐LNK), a rigorous, research‐based letter name knowledge assessment designed for screening and benchmark testing that can be administered in less than a minute per student. The authors discuss the need for alphabet screening and benchmark assessments, the research on how students develop knowledge of letter names, and how the Q‐LNKassessment was developed and tested. The procedure for using the Q‐LNKis illustrated with the description of a teacher administering, scoring, and interpreting results from the assessment in her kindergarten class.
Danish Perioperative Nurses’ Documentation: A Complex, Multifaceted Practice Connected With Unit Culture and Nursing Leadership
Authors: Søndergaard Susanne F. , Lorentzen Vibeke , Sørensen Erik E. , Frederiksen Kirsten 
Published: June 2017

AbstractResearchers have described the documentation practices of perioperative nurses as flawed and characterized by subjectivity and poor quality, which is often related to both the documentation tool and the nurses’ level of commitment. Studies suggest that documentation of nursing care in the OR places special demands on electronic health records (EHRs). The purpose of this study was to explore how the use of an EHR tailored to perioperative practice affects Danish perioperative nurses’ documentation practices. This study was a follow‐up to a baseline study from 2014. For three months in the winter of 2015 to 2016, six participants tested an EHR containing a Danish edition of a selected section of the Perioperative Nursing Data Set. This study relied on realistic evaluation and participant observations to generate data. We found that nursing leadership was essential for improving perioperative nurses’ documentation practices and that a tailored EHR may improve documentation practices.
The Information Regulation of Business Actors
Authors: Parella Kishanthi 
Published: June 2017

A transnational legal order (TLO) is emerging regarding the role of businesses in respecting human rights. This legal order includes multistakeholder initiatives, international organization recommendations and guidelines, NGO certifications, and other voluntary instruments. Many of the norms within this TLO are nonbinding and therefore lack mandatory compliance; what they may possess is persuasive power, particularly when the norms are developed, endorsed, and managed by reputable organizations. It is that reputational, or legitimacy, advantage that matters for encouraging industry associations to comply with the nonbinding norms associated with these organizations. Industry associations and other business actors will gravitate more towards legitimacy enhancing organizations when their own legitimacy is at stake. They pivot towards public organizations such as the United Nations or private NGO initiatives like the Rainforest Alliance, seeking to associate themselves publicly with these organizations that enjoy more perceived legitimacy. These business relationships with legitimizing bodies can take the form of partnerships, certifications, or other arrangements where an industry association adopts and incorporates nonbinding norms when it otherwise might not. In this essay, I discuss three transnational legal processes that encourage industry associations, their members, and other business actors to abide by nonbinding transnational legal norms concerning business and human rights.
On the large-time behaviour of the solution of a stochastic differential equation driven by a Poisson point process
Authors: Nassar Elma , Pardoux Etienne 
Published: June 2017

AbstractWe study a stochastic differential equation driven by a Poisson point process, which models the continuous change in a population's environment, as well as the stochastic fixation of beneficial mutations that might compensate for this change. The fixation probability of a given mutation increases as the phenotypic lagXtbetween the population and the optimum grows larger, and successful mutations are assumed to fix instantaneously (leading to an adaptive jump). Our main result is that the process is transient (i.e. converges to -∞, so that continued adaptation is impossible) if the rate of environmental changevexceeds a parameterm, which can be interpreted as the rate of adaptation in case every beneficial mutation becomes fixed with probability 1. Ifv<m, the process is Harris recurrent and possesses a unique invariant probability measure, while in the limiting casem=v, Harris recurrence with an infinite invariant measure or transience depends upon additional technical conditions. We show how our results can be extended to a class of time varying rates of environmental change.
Asymptotics for the discrete-time average of the geometric Brownian motion and Asian options
Authors: Pirjol Dan , Zhu Lingjiong 
Published: June 2017

Abstract
The time average of geometric Brownian motion plays a crucial role in the pricing of Asian options in mathematical finance. In this paper we consider the asymptotics of the discrete-time average of a geometric Brownian motion sampled on uniformly spaced times in the limit of a very large number of averaging time steps. We derive almost sure limit, fluctuations, large deviations, and also the asymptotics of the moment generating function of the average. Based on these results, we derive the asymptotics for the price of Asian options with discrete-time averaging in the Black–Scholes model, with both fixed and floating strike.
Membrane-binding and activation of LKB1 by phosphatidic acid is essential for development and tumour suppression
Authors: Dogliotti Giada , Kullmann Lars , Dhumale Pratibha , Thiele Christian , Panichkina Olga , Mendl Gudrun , Houben Roland , Haferkamp Sebastian , Püschel Andreas W. , Krahn Michael P. 
Published: June 2017

AbstractThe serine/threonine kinase LKB1 regulates various cellular processes such as cell proliferation, energy homeostasis and cell polarity and is frequently downregulated in various tumours. Many downstream pathways controlled by LKB1 have been described but little is known about the upstream regulatory mechanisms. Here we show that targeting of the kinase to the membrane by a direct binding of LKB1 to phosphatidic acid is essential to fully activate its kinase activity. Consequently, LKB1 mutants that are deficient for membrane binding fail to activate the downstream target AMPK to control mTOR signalling. Furthermore, the in vivo function of LKB1 during development of Drosophila depends on its capacity to associate with membranes. Strikingly, we find LKB1 to be downregulated in malignant melanoma, which exhibit aberrant activation of Akt and overexpress phosphatidic acid generating Phospholipase D. These results provide evidence for a fundamental mechanism of LKB1 activation and its implication in vivo and during carcinogenesis.
Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis
Authors: Zhang Xiaowen , Chiang Huai-Chin , Wang Yao , Zhang Chi , Smith Sabrina , Zhao Xiayan , Nair Sreejith J. , Michalek Joel , Jatoi Ismail , Lautner Meeghan , Oliver Boyce , Wang Howard , Petit Anna , Soler Teresa , Brunet Joan , Mateo Francesca , Angel Pujana Miguel , Poggi Elizabeth , Chaldekas Krysta , Isaacs Claudine , Peshkin Beth N. , Ochoa Oscar , Chedin Frederic , Theoharis Constantine , Sun Lu-Zhe , Curiel Tyler J. , Elledge Richard , Jin Victor X. , Hu Yanfen , Li Rong 
Published: June 2017

AbstractMost BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5′ end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.
Uniform electroactive fibre-like micelle nanowires for organic electronics
Authors: Li Xiaoyu , Wolanin Piotr J. , MacFarlane Liam R. , Harniman Robert L. , Qian Jieshu , Gould Oliver E. C. , Dane Thomas G. , Rudin John , Cryan Martin J. , Schmaltz Thomas , Frauenrath Holger , Winnik Mitchell A. , Faul Charl F. J. , Manners Ian 
Published: June 2017

AbstractMicelles formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention and have uses in a wide variety of fields, whereas applications based on their electronic properties are virtually unexplored. Herein we describe studies of solution-processable, low-dispersity, electroactive fibre-like micelles of controlled length from π-conjugated diblock copolymers containing a crystalline regioregular poly(3-hexylthiophene) core and a solubilizing, amorphous regiosymmetric poly(3-hexylthiophene) or polystyrene corona. Tunnelling atomic force microscopy measurements demonstrate that the individual fibres exhibit appreciable conductivity. The fibres were subsequently incorporated as the active layer in field-effect transistors. The resulting charge carrier mobility strongly depends on both the degree of polymerization of the core-forming block and the fibre length, and is independent of corona composition. The use of uniform, colloidally stable electroactive fibre-like micelles based on common π-conjugated block copolymers highlights their significant potential to provide fundamental insight into charge carrier processes in devices, and to enable future electronic applications.
An L-threonine transaldolase is required for L-threo-β-hydroxy-α-amino acid assembly during obafluorin biosynthesis
Authors: Scott Thomas A. , Heine Daniel , Qin Zhiwei , Wilkinson Barrie 
Published: June 2017

Abstractβ-Lactone natural products occur infrequently in nature but possess a variety of potent and valuable biological activities. They are commonly derived from β-hydroxy-α-amino acids, which are themselves valuable chiral building blocks for chemical synthesis and precursors to numerous important medicines. However, despite a number of excellent synthetic methods for their asymmetric synthesis, few effective enzymatic tools exist for their preparation. Here we report cloning of the biosynthetic gene cluster for the β-lactone antibiotic obafluorin and delineate its biosynthetic pathway. We identify a nonribosomal peptide synthetase with an unusual domain architecture and an L-threonine:4-nitrophenylacetaldehyde transaldolase responsible for (2S,3R)-2-amino-3-hydroxy-4-(4-nitrophenyl)butanoate biosynthesis. Phylogenetic analysis sheds light on the evolutionary origin of this rare enzyme family and identifies further gene clusters encoding L-threonine transaldolases. We also present preliminary data suggesting that L-threonine transaldolases might be useful for the preparation of L-threo-β-hydroxy-α-amino acids.
A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay
Authors: Hu Zhiyuan , Yau Christopher , Ahmed Ahmed Ashour 
Published: June 2017

AbstractNonsense-mediated decay (NMD) eliminates transcripts with premature termination codons. Although NMD-induced loss-of-function has been shown to contribute to the genesis of particular cancers, its global functional consequence in tumours has not been characterized. Here we develop an algorithm to predict NMD and apply it on somatic mutations reported in The Cancer Genome Atlas. We identify more than 73 K mutations that are predicted to elicit NMD (NMD-elicit). NMD-elicit mutations in tumour suppressor genes (TSGs) are associated with significant reduction in gene expression. We discover cancer-specific NMD-elicit signatures in TSGs and cancer-associated genes. Our analysis reveals a previously unrecognized dependence of hypermutated tumours on hypofunction of genes that are involved in chromatin remodelling and translation. Half of hypermutated stomach adenocarcinomas are associated with NMD-elicit mutations of the translation initiators LARP4B and EIF5B. Our results unravel strong therapeutic opportunities by targeting tumour dependencies on NMD-elicit mutations.
Iron-mediated soil carbon response to water-table decline in an alpine wetland
Authors: Wang Yiyun , Wang Hao , He Jin-Sheng , Feng Xiaojuan 
Published: June 2017

AbstractThe tremendous reservoir of soil organic carbon (SOC) in wetlands is being threatened by water-table decline (WTD) globally. However, the SOC response to WTD remains highly uncertain. Here we examine the under-investigated role of iron (Fe) in mediating soil enzyme activity and lignin stabilization in a mesocosm WTD experiment in an alpine wetland. In contrast to the classic ‘enzyme latch’ theory, phenol oxidative activity is mainly controlled by ferrous iron [Fe(II)] and declines with WTD, leading to an accumulation of dissolvable aromatics and a reduced activity of hydrolytic enzyme. Furthermore, using dithionite to remove Fe oxides, we observe a significant increase of Fe-protected lignin phenols in the air-exposed soils. Fe oxidation hence acts as an ‘iron gate’ against the ‘enzyme latch’ in regulating wetland SOC dynamics under oxygen exposure. This newly recognized mechanism may be key to predicting wetland soil carbon storage with intensified WTD in a changing climate.
Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors
Authors: Tao Liang , Peng Lisheng , Berntsson Ronnie P.-A. , Liu Sai Man , Park SunHyun , Yu Feifan , Boone Christopher , Palan Shilpa , Beard Matthew , Chabrier Pierre-Etienne , Stenmark Pål , Krupp Johannes , Dong Min 
Published: June 2017

AbstractBotulinum neurotoxin B is a Food and Drug Administration-approved therapeutic toxin. However, it has lower binding affinity toward the human version of its major receptor, synaptotagmin II (h-Syt II), compared to mouse Syt II, because of a residue difference. Increasing the binding affinity to h-Syt II may improve botulinum neurotoxin B’s therapeutic efficacy and reduce adverse effects. Here we utilized the bacterial adenylate cyclase two-hybrid method and carried out a saturation mutagenesis screen in the Syt II-binding pocket of botulinum neurotoxin B. The screen identifies E1191 as a key residue: replacing it with M/C/V/Q enhances botulinum neurotoxin B binding to human synaptotagmin II. Adding S1199Y/W or W1178Q as a secondary mutation further increases binding affinity. Mutant botulinum neurotoxin B containing E1191M/S1199Y exhibits ~11-fold higher efficacy in blocking neurotransmission than wild-type botulinum neurotoxin B in neurons expressing human synaptotagmin II, demonstrating that enhancing receptor binding increases the overall efficacy at functional levels. The engineered botulinum neurotoxin B provides a platform to develop therapeutic toxins with improved efficacy.
Observation of reflectionless absorption due to spatial Kramers–Kronig profile
Authors: Ye Dexin , Cao Cheng , Zhou Tianyi , Huangfu Jiangtao , Zheng Guoan , Ran Lixin 
Published: June 2017

AbstractAs a fundamental phenomenon in electromagnetics and optics, material absorption has been extensively investigated for centuries. However, omnidirectional, reflectionless absorption in inhomogeneous media has yet to be observed. Previous research on transformation optics indicated that such absorption cannot easily be implemented without involving gain media. A recent theory on wave propagation, however, implies the feasibility to implement such absorption requiring no gain, provided that the permittivity profile of this medium can satisfy the spatial Kramers–Kronig relations. In this work, we implement such a profile over a broad frequency band based on a novel idea of space–frequency Lorentz dispersion. A wideband, omnidirectionally reflectionless absorption is then experimentally observed in the gigahertz range, and is in good agreement with theoretical analysis and full-wave simulations. The proposed method based on the space–frequency dispersion implies the practicability to construct gain-free omnidirectionally non-reflecting absorbers.