bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake and utilization of directly acting antiviral medications for hepatitis C infection in U.S. veterans
Authors: Gidwani R. , Barnett P. G. , Goldhaber‐Fiebert J. D. , Asch S. M. , Lo J. , Dally S. K. , Owens D. K. 
Published: November 2014

SummaryNew drugs therapies have revolutionized the treatment of hepatitis C virus (HCV) infection. The objectives of this study were to evaluate uptake and utilization of boceprevir and telaprevir in the Department of Veterans Affairs (VA). We evaluated whether therapies conformed to response‐guided protocols, whether they replaced standard interferon plus ribavirin treatment, and whether IL‐28B was used to guide treatment. We performed an administrative data‐based analysis of all patients receiving pharmacologic treatment for HCV in VA from October 2009 to July 2013. There were 12 737 new HCV prescriptions in VA during this time, with 5564 boceprevir or telaprevir prescriptions (44%) and 7173 prescriptions (56%) written for standard interferon plus ribavirin treatment. Prescriptions for the new treatments heavily favoured boceprevir vs telaprevir (83% vs 17%). Sixty‐two percent (62%) of boceprevir‐treated patients completed their minimum‐specified protocol, while 69.2% of telaprevir‐treated patients completed their minimum‐specified protocol. From October 2010 to July 2012, 4090 patients had an IL‐28B test; less than 16% of these tests guided subsequent HCV prescriptions. Uptake of boceprevir and telaprevir was rapid; the number of patients initiating treatment approximately doubled in the period after their introduction. While new prescriptions favor boceprevir or telaprevir over standard interferon plus ribavirin therapy, there appears to still be a strong role of interferon plus ribavirin in treating HCV patients. This work can inform our understanding of how other new effective HCV therapies will be used, their diffusion, and the timing of their diffusion in actual clinical practice.
Spatial regulation of the spindle assembly checkpoint and anaphase‐promoting complex in Aspergillus nidulans
Authors: Edgerton Heather , Paolillo Vitoria , Oakley Berl R. 
Published: November 2014

SummaryThe spindle assembly checkpoint (SAC) plays a critical role in preventing mitotic errors by inhibiting anaphase until all kinetochores are correctly attached to spindle microtubules. In spite of the economic and medical importance of filamentous fungi, relatively little is known about the behavior of SAC proteins in these organisms. In our efforts to understand the role of γ‐tubulin in cell cycle regulation, we have created functional fluorescent protein fusions of four SAC proteins in Aspergillus nidulans, the homologs of Mad2, Mps1, Bub1/BubR1 and Bub3. Time‐lapse imaging reveals that SAC proteins are in distinct compartments of the cell until early mitosis when they co‐localize at the spindle pole body. SAC activity is, thus, spatially regulated in A. nidulans. Likewise, Cdc20, an activator of the anaphase‐promoting complex/cyclosome, is excluded from interphase nuclei, but enters nuclei at mitotic onset and accumulates to a higher level in mitotic nuclei than in the surrounding nucleoplasm before leaving in anaphase/telophase. The activity of this critical cell cycle regulatory complex is likely regulated by the location of Cdc20. Finally, the γ‐tubulin mutation mipAD159 causes a nuclear‐specific failure of nuclear localization of Mps1 and Bub1/R1 but not of Cdc20, Bub3 or Mad2.
Partner selection in the mycorrhizal mutualism
Authors: Werner Gijsbert D. A. , Kiers E. Toby 
Published: November 2014

SummaryPartner selection in the mycorrhizal symbiosis is thought to be a key factor stabilising the mutualism. Both plant hosts and mycorrhizal fungi have been shown to preferentially allocate resources to higher quality partners. This can help maintain underground cooperation, although it is likely that different plant species vary in the spatial precision with which they can select partners. Partner selection in the mycorrhizal symbiosis is presumably context‐dependent and can be mediated by factors like (relative) resource abundance and resource fluctuations, competition among mycorrhizas, arrival order and cultivation history. Such factors complicate our current understanding of the importance of partner selection and its effectiveness in stimulating mutualistic cooperation.

Contents

Summary
1437

I.
Introduction
1437

II.
Bidirectional partner selection in the arbuscular mycorrhizal symbiosis
1438

III.
Nutrient transport and partner selection
1438

IV.
Mycorrhizal partner selection: an underground biological market?
1438

V.
Potential factors influencing partner selection in the mycorrhizal symbiosis
1440

VI.
Conclusions
1441

Acknowledgements
1441

References
1441
Towards a holistic understanding of the beneficial interactions across the Populus microbiome
Authors: Hacquard Stéphane , Schadt Christopher W. 
Published: November 2014

SummaryInteractions between trees and microorganisms are tremendously complex and the multispecies networks resulting from these associations have consequences for plant growth and productivity. However, a more holistic view is needed to better understand trees as ecosystems and superorganisms, where many interacting species contribute to the overall stability of the system. While much progress has been made on microbial communities associated with individual tree niches and the molecular interactions between model symbiotic partners, there is still a lack of knowledge of the multi‐component interactions necessary for holistic ecosystem‐level understanding. We review recent studies in Populus to emphasize the importance of such holistic efforts across the leaf, stem and rooting zones, and discuss prospects for future research in these important ecosystems.

Contents

Summary
1424

I.
Introduction
1424

II.
The root endosphere and rhizosphere microbiome
1425

III.
The phyllosphere and leaf endosphere microbiome
1426

IV.
The stem and wood microbiome
1427

V.
Toward understanding microbiome functions in a community context
1427

Acknowledgements
1428

References
1428
Large‐scale adaptive differentiation in the alpine perennial herb Arabis alpina
Authors: Toräng Per , Wunder Jörg , Obeso José Ramón , Herzog Michel , Coupland George , Ågren Jon 
Published: November 2014

Summary

Information about the incidence and magnitude of local adaptation can help to predict the response of natural populations to a changing environment, and should be of particular interest in arctic and alpine environments where the effects of climate change are expected to be severe.

To quantify adaptive differentiation in the arctic‐alpine perennial herb Arabis alpina, we conducted reciprocal transplant experiments for 3 yr between Spanish and Scandinavian populations. At the sites of one Spanish and one Scandinavian population, we planted seedlings representing two Spanish and four Scandinavian populations, and recorded survival, flowering propensity and fecundity. The experiment was replicated in two subsequent years.

The results demonstrate strong adaptive differentiation between A. alpina populations from the two regions. At the field site in Spain, survival and fruit production of Spanish populations were higher than those of Scandinavian populations, while the opposite was true at the site in Scandinavia, and these differences were consistent across years. By comparison, fitness varied little among populations from the same region.

The results suggest that the magnitude and geographical scale of local adaptation need to be considered in predictions of the effects of global change on the dynamics of arctic and alpine plant populations.
Ancient horizontal transfer of transaldolase‐like protein gene and its role in plant vascular development
Authors: Yang Zefeng , Zhou Yong , Huang Jinling , Hu Yunyun , Zhang Enying , Xie Zhengwen , Ma Sijia , Gao Yun , Song Song , Xu Chenwu , Liang Guohua 
Published: November 2014

Summary

A major event in land plant evolution is the origin of vascular tissues, which ensure the long‐distance transport of water, nutrients and organic compounds. However, the molecular basis for the origin and evolution of plant vascular tissues remains largely unknown.

Here, we investigate the evolution of the land plant TAL‐type transaldolase (TAL) gene and its potential function in rice (Oryza sativa) based on phylogenetic analyses and transgenic experiments, respectively.

TAL genes are only present in land plants and bacteria. Phylogenetic analyses suggest that land plant TAL genes are derived from Actinobacteria through an ancient horizontal gene transfer (HGT) event. Further evidence reveals that land plant TAL genes have undergone positive selection and gained several introns following its acquisition by the most recent common ancestor of land plants. Transgenic plant experiments show that rice TAL is specifically expressed in vascular tissues and that knockdown of TAL expression leads to changes in both the number and pattern of vascular bundles.

Our findings show that the ancient HGT of TAL from bacteria probably plays an important role in plant vascular development and adaptation to land environments.
The evolution and function of protein tandem repeats in plants
Authors: Schaper Elke , Anisimova Maria 
Published: November 2014

Summary

Sequence tandem repeats (TRs) are abundant in proteomes across all domains of life. For plants, little is known about their distribution or contribution to protein function. We exhaustively annotated TRs and studied the evolution of TR unit variations for all Ensembl plants.

Using phylogenetic patterns of TR units, we detected conserved TRs with unit number and order preserved during evolution, and those TRs that have diverged via recent TR unit gains/losses. We correlated the mode of evolution of TRs to protein function.

TR number was strongly correlated with proteome size, with about one‐half of all TRs recognized as common protein domains. The majority of TRs have been highly conserved over long evolutionary distances, some since the separation of red algae and green plants c. 1.6 billion yr ago. Conversely, recurrent recent TR unit mutations were rare.

Our results suggest that the first TRs by far predate the first plants, and that TR appearance is an ongoing process with similar rates across the plant kingdom. Interestingly, the few detected highly mutable TRs might provide a source of variation for rapid adaptation. In particular, such TRs are enriched in leucine‐rich repeats (LRRs) commonly found in R genes, where TR unit gain/loss may facilitate resistance to emerging pathogens.
Active ingredients from natural botanicals in the treatment of obesity
Authors: Zhang W.‐L. , Zhu L. , Jiang J.‐G. 
Published: November 2014

SummaryObesity is considered as a chronic disease that can induce a series of comorbidities and complications. Chinese medicine has long clinical experiences in the treatment of obesity. This review summarizes the natural products from traditional Chinese medicine (TCM) that are reported to have anti‐obesity effects in the past two decades. Botanic TCM comprises 90% of total Chinese crude drugs, and generally contains various active ingredients, in which the effective anti‐obesity ingredients identified can be divided into saponins, polysaccharides, alkaloids, polyphenols and others. Astragaloside IV, glycyrrhizin, macrostemonoside A, berberine, betaine, capsaicin, matrine, methyl piperate, piperine, rutaecarpine, asimilobine, epigallocatechingallate, magnolol, resveratrol, soybean‐isoflavone, α‐linolenic acid, emodin, geniposide, phillyrin, salidroside and ursolic acid are specified in this review, and their sources, models, efficacy are described. It is concluded that the mechanisms of these components for the treatment of obesity include: (i) suppression of appetite, increase of satiety, reduction of energy intake; (ii) reduction in the digestion and absorption of exogenous lipid; (iii) attenuation of the synthesis of endogenous lipid; (iv) promotion of the oxidation and expenditure of lipid and (v) improvement of lipid metabolism disorder. Authors believe that the effective compounds from TCM will provide an alternative and hopeful way for the treatment of obesity.
Evaluation of the immune function assay in pediatric living donor liver transplantation
Authors: Fukuda Akinari , Imadome Ken‐Ichi , Sakamoto Seisuke , Shigeta Takanobu , Uchida Hajime , Matsunami Masatoshi , Sasaki Kengo , Kanazawa Hiroyuki , Kawano Fuyuko , Nakazawa Atsuko , Fujiwara Shigeyoshi , Kasahara Mureo 
Published: November 2014

AbstractThe immune function (ImmuKnow) assay is a measure of cell‐mediated immunity based on the peripheral CD4+ T cell ATP activity. The efficacy of ImmuKnow in pediatric LDLT is not well documented. The aim of this study was to assess the correlations between the ImmuKnow and the clinical status in pediatric LDLT recipients. A total of 716 blood samples were obtained from 60 pediatric LDLT recipients (one month to 16 yr of age). The recipient's status was classified as follows: stable, infection, or rejection. The ImmuKnow values in the pediatric LDLT recipients with a clinically stable status had a lower immune response (IQR 85–297 ATP ng/mL) than that previously reported in adults. Meanwhile, the ImmuKnow values of the stable patients were not correlated with age. Furthermore, a significant difference was found in the ImmuKnow values between the bacterial or fungal infection and stable groups, but not between the CMV or EBV infection and stable groups. The ImmuKnow levels in the pediatric LDLT were lower than those observed in the adult LDLT. The proposed reference value is between 85 and 297 ATP ng/mL in pediatric LDLT recipients. We conclude that the ImmuKnow assay could be helpful for monitoring pediatric LDLT recipients with bacterial or fungal infections.
Maternal Cigarette, Alcohol, and Coffee Consumption in Relation to Risk of Clubfoot
Authors: Werler Martha M. , Yazdy Mahsa M. , Kasser James R. , Mahan Susan T. , Meyer Robert E. , Anderka Marlene , Druschel Charlotte M. , Mitchell Allen A. 
Published: November 2014

AbstractBackgroundClubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this association is confined to women who smoke throughout the at‐risk period. Maternal alcohol and coffee drinking have not been well studied in relation to clubfoot.MethodsThe present study used data from a population‐based case–control study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037 controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette smoking, alcohol intake, and coffee drinking.ResultsMore mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of women who smoked when they became pregnant, those who quit in the month after a first missed period had a 40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures. Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable.ConclusionsClubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers, suggested increased risks were only observed in higher levels of intake.
Can ‘Early Programming’ Be Partly Explained by Smoking? Results from a Prospective, Population‐Based Cohort Study
Authors: Kvalvik Liv Grimstvedt , Skjærven Rolv , Klungsøyr Kari , Vollset Stein Emil , Haug Kjell 
Published: November 2014

AbstractBackgroundNumerous studies have focused the association between low birthweight and later disease. Our objective was to study the association between birthweight and later adult smoking and thereby explore a possible mechanism for the association between low birthweight and later adult disease.MethodsWe studied associations between birthweight of women (n = 247 704) born in 1967–1995 and smoking habits at the end of their pregnancy 13–42 years later in a prospective, population‐based cohort study from The Medical Birth Registry of Norway. Similarly, the association between birthweight of men (n = 194 393) and smoking habits of their partners were assessed. Finally, we studied the relation between smoking habits of the participating women and the cause specific death of their mothers (n = 222 808).ResultsTwenty per cent of women with birthweight less than 2000 g were adult daily smokers compared with 11% with birthweight 4000–4499 g [relative risk = 1.8, 95% confidence interval 1.4, 2.2]. Similarly, we found an association between men's birthweight and their partners smoking habits. Mothers of smoking women had doubled risk of dying from lung cancer and from cardiovascular disease compared with mothers of non‐smoking women.ConclusionsBeing born with low birthweight is associated with smoking in adulthood. Associations of adult smoking with partners' birthweight and mothers' smoking‐related causes of death suggest a shared smoking environment, and may account for some of the established association between birthweight and later cardiovascular disease.
Alzheimer's disease patients institutionalized in group homes run by long‐term care insurance exhibit fewer symptoms of behavioural problems as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale
Authors: Kasai Mari , Meguro Kenichi , Akanuma Kyoko , Yamaguchi Satoshi 
Published: November 2014

AbstractBackgroundThe behavioural and psychological symptoms of dementia (BPSD) caused by Alzheimer's disease (AD) can burden caregivers. Group homes (GH), small nursing homes, for the elderly with dementia are institutions commonly run by the public long‐term care insurance system in Japan. The purpose of this study was to compare the prevalence of BPSD of AD, as evaluated by the Behavioural Pathology in Alzheimer's Disease Rating Scale, between GH patients and community residents.MethodsA total of 74 patients with AD were enrolled: 37 were patients institutionalized in GH (Hachinski score < 5) and 37 were demographic‐matched community residents undergoing treatment at the Osaki‐Tajiri SKIP Center. There were no significant differences in mean age (81.4 vs 81.1 years, P = 0.816), mean educational level (7.7 vs 8.0 years, P = 0.497), sex (women/men: 30/7 vs 30/7, P = 1.000) and mean Mini‐Mental State Examination scores (14.1 vs 14.1, P = 0.950) between the two groups. Care level (range: 0.5–5.0, slight to bedridden), activities of daily living care level (range: 1–7, almost normal to severe), and the presence or absence BPSD based on the domains of the Behavioural Pathology in Alzheimer's Disease Rating Scale were compared.ResultsGH patients had a significantly higher care level (P < 0.05) and activities of daily living care level (P < 0.05) but had fewer symptoms of BPSD (P < 0.05) than community residents. When the activities of daily living care level was controlled, GH patients had significantly fewer symptoms than community residents in Aggressiveness (21% vs 50%; χ2 = 4.5, P = 0.035), Affective disturbances (13% vs 42%; χ2 = 5.1, P = 0.023), and Anxieties and phobias (4% vs 46%; χ2 = 11.1, P = 0.001).ConclusionsGH run by the long‐term care insurance system appear to be effective in improving environmental factors for moderate AD patients and reducing Aggressiveness, Affective disturbances, and Anxieties and phobias.
rs10263935 and rs6045676 identified by genome‐wide association study were associated with aortic dissection in a Chinese population
Authors: Qin Chuan , Chen Lin , Xiao Ying‐Bin 
Published: November 2014

AbstractAortic dissection (AD) is a disease characterized by a tear in the aortic intimal layer and separation of the arterial wall. Some risk factors, such as hypertension and Marfan syndrome, are well known in AD, but the role of genetic factor is largely unknown. In this study, we investigated the relation between two single nucleotide polymorphisms (SNPs) identified by genome‐wide association study and AD. Approximately 177 patients diagnosed with AD through clinical evaluation and imaging techniques and 183 age‐ and sex‐matched control subjects who were suffering from chest pain but without AD were included in the study. Genotyping of rs10263935 and rs6045676 was performed in both patients and control subjects using the TaqMan® method [Life Technologies (AB & Invitrogen), Carlsbad, CA]. The frequency of the AA and AG genotype in rs10263935 was significantly higher in the AD patients (0.085 and 0.435, respectively) than in the control subjects (0.033 and 0.355, respectively). The rs10263935 A allele frequency in the AD patients was higher than that in the control subjects [0.302 vs 0.210, odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.26–2.28, P = 0.005]. Similarly, the frequency of the GG genotype in rs6045676 was significantly higher in the AD patients than in the control subjects (0.107 vs 0.038, P = 0.015). The rs6045676 G allele frequency in the AD patients was higher than that in the control subjects (0.282 vs 0.191, OR = 1.67, 95% CI: 1.18–2.50, P = 0.004). After adjustment of the confounding factors, such as smoking, sex, and age, the differences remain significant in several models (rs10263935: GG vs AA: OR = 3.13, 95% CI: 1.15–8.33, P = 0.025; GG vs AG: OR = 1.57, 95% CI: 1.01–2.44, P = 0.045; rs6045676: GG vs CC: OR = 3.30, 95% CI: 1.32–8.25, P = 0.011). rs10263935 on chromosome 7 and rs6045676 on chromosome 20 are associated with AD. Further studies are warranted to elucidate the functional role of these two variants.
Hybrid Cache Designs for Reliable Hybrid High and Ultra-Low Voltage Operation
Authors: Maric Bojan , Abella Jaume , Cazorla Francisco J. , Valero Mateo 
Published: November 2014

Geometry scaling of semiconductor devices enables the design of ultra-low-cost (e.g., below 1 USD) battery-powered resource-constrained ubiquitous devices for environment, urban life, and body monitoring. These sensor-based devices require high performance to react in front of infrequent particular events as well as extreme energy efficiency in order to extend battery lifetime during most of the time when low performance is required. In addition, they require real-time guarantees. The most suitable technological solution for these devices consists of using hybrid processors able to operate at: (i) high voltage to provide high performance and (ii) near-/subthreshold voltage to provide ultra-low energy consumption. However, the most efficient SRAM memories for each voltage level differ and trading off different SRAM designs is mandatory. This is particularly true for cache memories, which occupy most of the processor's area.
In this article, we propose new, simple, single-Vcc-domain hybrid L1 cache architectures suitable for reliable hybrid high and ultra-low voltage operation. In particular, the cache is designed by combining heterogeneous SRAM cell types: some of the cache ways are optimized to satisfy high-performance requirements during high voltage operation, whereas the rest of the ways provide ultra-low energy consumption and reliability during near-/subthreshold voltage operation. We analyze the performance, energy, and power impact of the proposed cache designs when using them to implement L1 caches in a processor. Experimental results show that our hybrid caches can efficiently and reliably operate across a wide range of voltages, consuming little energy at near-/subthreshold voltage as well as providing high performance at high voltage without decreasing reliability levels to provide strong performance guarantees, as required for our target market.