bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C virus: how to provide the best treatment with what I have
Authors: Nelson David R. , Peter Joy 
Published: January 2016

AbstractThe therapeutic landscape for the treatment of chronic hepatitis C virus infection has been rapidly evolving, and by 2016 there will be six approved, all‐oral regimens for use in patients in the USA and most of Western Europe. However, as many as patient populations will have limited access to new direct acting antiviral regimens, patients and physicians are often faced with the challenge of selecting the best regimen available, as opposed to the optimal treatment. In this paper, the challenges and opportunities in developing a high cure regimen for different patient populations will be discussed and highlighted through case‐based scenarios.
Is the benefit of treating patients with cirrhosis proven?
Authors: Bruno Savino , Boccaccio Vincenzo , Russo Maria Luisa , Maisonneuve Patrick 
Published: January 2016

AbstractHepatitis C virus (HCV)‐related cirrhosis is an extremely heterogeneous pathological condition with a wide spectrum of clinical manifestations, ranging from pre‐clinical to compensated and decompensated stages, each of which is characterized by a different clinical outcome. To measure the benefit of a sustained virological response (SVR) with interferon (IFN)‐based therapy, several studies have been performed in patients with compensated disease, while only a few have been performed in decompensated disease. Nevertheless, these studies have certain methodological weaknesses that may limit the accuracy of results. Access to new, more effective and safe direct acting antivirals (DAAs) has significantly changed these outcomes, with SVR rates that were not seen previously, making antiviral treatment available to patients with end‐stage liver disease. However, the clinical benefit of treating patients with late stage disease is still poorly understood and must be investigated. The existence of a point of no return beyond which a SVR is not beneficial has not yet been determined. All of these issues are discussed in this review.
Hepatitis E, the neglected one
Authors: Blasco‐Perrin Hélène , Abravanel Florence , Blasco‐Baque Vincent , Péron Jean Marie 
Published: January 2016

AbstractHepatitis E virus (HEV) infection is a worldwide disease. It is the first cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 56 000 deaths. In developing countries, hepatitis E is a waterborne infection. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects with a significant mortality rate in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. HEV can cause neurological disorders and in immunocompromised patients, chronic infections. The progression of acute hepatitis E is most often mild and resolves spontaneously. Diagnostic tools include anti‐HEV IgM antibodies in serum and/or viral RNA in the blood or stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China.
The adventure of delta
Authors: Rizzetto Mario 
Published: January 2016

AbstractThe hepatitis D virus (HDV) is unique in animal virology. It has a circular RNA genome that is the smallest of human viruses, requires the HBsAg capsid of the hepatitis B virus to assembly into infectious virions, parasitizes the transcriptional machinery of the host by hijacking cellular RNA polymerases to replicate its RNA genome and is replicated by a rolling circle mechanism unknown to mammalian cells. Hepatitis D is ubiquitous but prevalence varies throughout the world. It is the most severe form of chronic viral liver disorder; carriers of HBsAg superinfected by the HDV are the major victims and the reservoir of the infection. In the last 20 years vaccination against the hepatitis B virus (HBV) has decreased the circulation of HDV in industrialized countries; nevertheless hepatitis D is returning to Western Europe through immigration from HDV endemic areas. Hepatitis D is being rediscovered in the developing world. It has a significant medical impact on areas of Africa, Asia and South America where the partner HBV is not controlled; Pakistan and Mongolia appear to be worldwide the areas with the highest prevalence of the disease. A major obstacle in treatment is that the virus has no replicative function of its own to be targeted by antivirals. Peg‐Interferon remains the mainstay of treatment. New strategies are explored to prevent entry of the virion into hepatocytes by blocking the cellular HBsAg receptor or preventing the prenylation process of the large‐delta antigen necessary for the assembly of the HDV particle.
Iron and the liver
Authors: Pietrangelo Antonello 
Published: January 2016

AbstractHumans have evolved to retain iron in the body and are exposed to a high risk of iron overload and iron‐related toxicity. Excess iron in the blood, in the absence of increased erythropoietic needs, can saturate the buffering capacity of serum transferrin and result in non‐transferrin‐bound highly reactive forms of iron that can cause damage, as well as promote fibrogenesis and carcinogenesis in the parenchymatous organs. A number of hereditary or acquired diseases are associated with systemic or local iron deposition or iron misdistribution in organs or cells. Two of these, the HFE‐ and non‐HFE hemochromatosis syndromes represent the paradigms of genetic iron overload. They share common clinical features and the same pathogenic basis, in particular, a lack of synthesis or activity of hepcidin, the iron hormone. Before hepcidin was discovered, the liver was simply regarded as the main site of iron storage and, as such, the main target of iron toxicity. Now, as the main source of hepcidin, it appears that the loss of the hepcidin‐producing liver mass or genetic and acquired factors that repress hepcidin synthesis in the liver may also lead to iron overload. Usually, there is low‐grade excess iron which, through oxidative stress, is sufficient to worsen the course of the underlying liver disease or other chronic diseases that are apparently unrelated to iron, such as chronic metabolic and cardiovascular diseases. In the future, modulation of hepcidin synthesis and activity or hepcidin hormone‐replacing strategies may become therapeutic options to cure iron‐related disorders.
HCV‐HIV co‐infected patients: no longer a ‘special’ population?
Authors: Sulkowski Mark S. 
Published: January 2016

AbstractPrior to the advent of safe and highly effective hepatitis C virus (HCV) treatment, patients with human immunodeficiency virus (HIV)/HCV co‐infection were referred to as a ‘special’ population. This definition was based on more rapid HCV disease progression in the presence of HIV co‐infection, limited effectiveness of interferon‐based HCV treatment and potential drug interactions between medications used to treat HIV and those to treat HCV infection. Although the availability of interferon‐free, oral direct‐acting antivirals (DAAs) has dramatically increased the effectiveness of HCV treatment in patients with HIV co‐infection, this population still warrants special consideration. Specific issues for the treatment of patients with HIV/HCV co‐infection in the era of oral DAAs include a high HCV disease burden with ongoing HCV infection and re‐infection following successful treatment, frequent drug interactions that must be carefully evaluated and unanswered questions on the role of shorter HCV treatment durations.
Resource limitation underlying multiple masting models makes mast seeding sensitive to future climate change
Authors: Monks Adrian , Monks Joanne M. , Tanentzap Andrew J. 
Published: January 2016

Summary

Mechanistic models can help resolve controversy over the responses of mast seeding plants to future environmental change.

We evaluate drivers of mast seeding by: developing and validating a new mechanistic resource‐based model of mast seeding using four 40‐yr Chionochloa (snow tussock) datasets; and comparing the performance of competing empirically‐based statistical models, that aim to approximate the mechanisms underlying mast seeding, in explaining simulated and observed data.

Our mechanistic model explained 90–99% of the variation in Chionochloa flowering, with higher rates of stored resource mobilisation and lower probability of climatic induction of flowering occurring at lower fertility sites. Inter‐annual variation in floral induction and the degree to which seeding is resource‐limited explained shifts in the relative performance of different empirical models fitted to data simulated from the mechanistic model. Empirical models explicitly capturing the interaction between the floral induction cue and internal resource state underlying the resource‐limited induction mechanism had > 8.7× the statistical support of alternatives when fitted to Chionochloa datasets.

We find support for resource‐limited floral induction with multiple empirical models consistent with this same mechanism. As both resource acquisition and flowering cues are climate sensitive, we expect climate change to impact upon patterns of mast seeding.
TNL‐mediated immunity in Arabidopsis requires complex regulation of the redundant ADR1 gene family
Authors: Dong Oliver Xiaoou , Tong Meixuezi , Bonardi Vera , El Kasmi Farid , Woloshen Virginia , Wünsch Lisa K. , Dangl Jeffery L. , Li Xin 
Published: January 2016

Summary

Nucleotide‐binding leucine‐rich repeat proteins (NLRs) serve as intracellular immune receptors in animals and plants. Sensor NLRs perceive pathogen‐derived effector molecules and trigger robust host defense. Recent studies revealed the role of three coiled‐coil‐type NLRs (CNLs) of the ADR1 family – ADR1, ADR1‐L1 and ADR1‐L2 – as redundant helper NLRs, whose function is required for defense mediated by multiple sensor NLRs.

From a mutant snc1‐enhancing (MUSE) forward genetic screen in Arabidopsis targeted to identify negative regulators of snc1 that encodes a TIR‐type NLR (TNL), we isolated two alleles of muse15, both carrying mutations in ADR1‐L1. Interestingly, loss of ADR1‐L1 also enhances immunity‐related phenotypes in other autoimmune mutants including cpr1, bal and lsd1. This immunity‐enhancing effect is not mediated by increased SNC1 protein stability, nor is it fully dependent on the accumulation of the defense hormone salicylic acid (SA).

Transcriptional analysis revealed an upregulation of ADR1 and ADR1‐L2 in the adr1‐L1 background, which may overcompensate the loss of ADR1‐L1, resulting in enhanced immunity. Interestingly, autoimmunity of snc1 and chs2, which encode typical TNLs, is fully suppressed by the adr1 triple mutant, suggesting that the ADRs are required for TNL downstream signaling.

This study extends our knowledge on the interplay among ADRs and reveals their complexity in defense regulation.
Structurally distinct Arabidopsis thaliana NLR immune receptors recognize tandem WY domains of an oomycete effector
Authors: Goritschnig Sandra , Steinbrenner Adam D. , Grunwald Derrick J. , Staskawicz Brian J. 
Published: January 2016

Summary

Nucleotide‐binding leucine‐rich repeat (NB‐LRR, or NLR) receptors mediate pathogen recognition. The Arabidopsis thaliana NLR RPP1 recognizes the tandem WY‐domain effector ATR1 from the oomycete Hyaloperonospora arabidopsidis through direct association with C‐terminal LRRs.

We isolated and characterized homologous NLR genes RPP1‐EstA and RPP1‐ZdrA from two Arabidopsis ecotypes, Estland (Est‐1) and Zdarec (Zdr‐1), responsible for recognizing a novel spectrum of ATR1 alleles.

RPP1‐EstA and ‐ZdrA encode nearly identical NLRs that are phylogenetically distinct from known immunity‐activating RPP1 homologs and possess greatly expanded LRR domains. Site‐directed mutagenesis and truncation analysis of ATR1 suggests that these homologs recognize a novel surface of the 2nd WY domain of ATR1, partially specified by a C‐terminal region of the LRR domain. Synteny comparison with RPP1 loci involved in hybrid incompatibility suggests that these functions evolved independently.

Closely related RPP1 homologs have diversified their recognition spectra through LRR expansion and sequence variation, allowing them to detect multiple surfaces of the same pathogen effector. Engineering NLR receptor specificity may require a similar combination of repeat expansion and tailored amino acid variation.
The effectiveness of nasal mask vs face mask ventilation in anesthetized, apneic pediatric subjects over 2 years of age: a randomized controlled trial
Authors: Itagaki Taiga , Gubin Tatyana A. , Sayal Puneet , Jiang Yandong , Kacmarek Robert M. , Anderson Thomas Anthony 
Published: January 2016

SummaryBackgroundWe hypothesized that anesthetized, apneic children could be ventilated equivalently or more efficiently by nasal mask ventilation (NMV) than face mask ventilation (FMV). The aim of this randomized controlled study was to test this hypothesis by comparing the expiratory tidal volume (Vte) between NMV and FMV.MethodsAfter the induction of anesthesia, 41 subjects, 3–17 years of age without anticipated difficult mask ventilation, were randomly assigned to receive either NMV or FMV with neck extension. Both groups were ventilated with pressure control ventilation (PCV) at 20 cmH2O of peak inspiratory pressure (PIP) with positive end‐expiratory pressure (PEEP) levels of 0, 5, and 10 cmH2O. An additional mouth closing maneuver (MCM) was applied for the NMV group.ResultsThe Vte was higher in the FMV group compared with the NMV group (median difference [95% CI]: 8.4 [5.5–11.6] ml·kg−1; P < 0.001) when MCM was not applied. NMV achieved less PEEP than FMV (median difference [95% CI]: 5.0 [4.3–5.3] cmH2O at 10 cmH2O; P < 0.001) though both groups achieved the set PIP level. In the NMV group, MCM markedly increased Vte (median increase [95% CI]: 5.9 [2.5–9.0] ml·kg−1; P < 0.005) and PEEP (median increase [95% CI]: 5.0 [0.6–8.6] cmH2O at 10 cmH2O; P < 0.005); however, PEEP was highly variable and lower than that of FMV (median difference [95% CI]: 2.5 [0.8–8.5] cmH2O at 10 cmH2O; P < 0.05).ConclusionsIn anesthetized, apneic children greater than 2 years of age ventilated with an anesthesia ventilator and neck extension, FMV established a greater Vte than NMV regardless of mouth status. NMV could not maintain the set PEEP level due to an air leak from the mouth. The MCM increased the Vte and PEEP.
A novel null HLA‐B allele, B*15:375N, due to a seven base pair deletion within exon 3
Authors: Planelles D. , Balas A. , Muñoz C. , Puig N. , Vicario J. L. 
Published: January 2016

AbstractCharacterization of a novel HLA‐B null allele, B*15:375N, with a seven base pair deletion in exon 3.
Becoming Physically Literate for Life: Embracing the Functions, Forms, Feelings and Flows of Alternative and Mainstream Physical Activity
Authors: Lloyd Rebecca J. 
Published: January 2016

Purpose:To explore a conceptual shift from mechanism, the dominant ‘body-as-machine’ (Tinning, 2010) paradigm, to vitalism, the philosophical phenomenological tenets of physical literacy (Whitehead, 2010) upon which the curriculum of physical education in Canada is based, within the context of an alternative physical education program.Method:A motion-sensitive phenomenological approach (Lloyd & Smith, 2006b; 2015), conceptually framed by the Function2Flow (F2F) model, was conducted with a sample of N = 153 students from seven different schools in Ottawa (Canada) who booked the JungleSport climbing program of their own accord. Sources of information included phenomenological observations, small group interviews, and journal entries. Exemplars of two in depth student experiences are featured in this article.Results & Discussion:The phenomenological analysis of the climbing experiences, in addition to the F2F curriculum support tools that were developed, provide practical and philosophical pathways for understanding how we may broaden assessments of learning in physical education.
Translating Science into Survival: Report on the Inaugural International Cancer Immunotherapy Conference
Authors: Hubbard-Lucey Vanessa M. , Tontonoz Matthew J. 
Published: January 2016

Abstract
The inaugural International Cancer Immunotherapy Conference, cohosted by the Cancer Research Institute (CRI), the American Association for Cancer Research (AACR), the Association for Cancer Immunotherapy (CIMT), and the European Academy of Tumor Immunology (EATI), was held in New York City on September 16–19, 2015. The conference brought together nearly 1,400 scientists, clinicians, regulators, patient advocates, and other stakeholders to discuss the latest scientific developments in cancer immunology and immunotherapy, as well as the regulatory hurdles facing new drug development. This conference report summarizes the main themes that emerged during the 4-day meeting. Cancer Immunol Res; 4(1); 3–11. ©2016 AACR.
Seasonal-to-Interannual Prediction Skills of Near-Surface Air Temperature in the CMIP5 Decadal Hindcast Experiments
Authors: Choi Jung , Son Seok-Woo , Ham Yoo-Geun , Lee June-Yi , Kim Hye-Mi 
Published: January 2016

Abstract
This study explores the seasonal-to-interannual near-surface air temperature (TAS) prediction skills of state-of-the-art climate models that were involved in phase 5 of the Coupled Model Intercomparison Project (CMIP5) decadal hindcast/forecast experiments. The experiments are initialized in either November or January of each year and integrated for up to 10 years, providing a good opportunity for filling the gap between seasonal and decadal climate predictions. The long-lead multimodel ensemble (MME) prediction is evaluated for 1981–2007 in terms of the anomaly correlation coefficient (ACC) and mean-squared skill score (MSSS), which combines ACC and conditional bias, with respect to observations and reanalysis data, paying particular attention to the seasonal dependency of the global-mean and equatorial Pacific TAS predictions. The MME shows statistically significant ACCs and MSSSs for the annual global-mean TAS for up to two years, mainly because of long-term global warming trends. When the long-term trends are removed, the prediction skill is reduced. The prediction skills are generally lower in boreal winters than in other seasons regardless of lead times. This lack of winter prediction skill is attributed to the failure of capturing the long-term trend and interannual variability of TAS over high-latitude continents in the Northern Hemisphere. In contrast to global-mean TAS, regional TAS over the equatorial Pacific is predicted well in winter. This is mainly due to a successful prediction of the El Niño–Southern Oscillation (ENSO). In most models, the wintertime ENSO index is reasonably well predicted for at least one year in advance. The sensitivity of the prediction skill to the initialized month and method is also discussed.
Simulating Human Water Regulation: The Development of an Optimal Complexity, Climate-Adaptive Reservoir Management Model for an LSM
Authors: Solander Kurt C. , Reager John T. , Thomas Brian F. , David Cédric H. , Famiglietti James S. 
Published: January 2016

Abstract
The widespread influence of reservoirs on global rivers makes representations of reservoir outflow and storage essential components of large-scale hydrology and climate simulations across the land surface and atmosphere. Yet, reservoirs have yet to be commonly integrated into earth system models. This deficiency influences model processes such as evaporation and runoff, which are critical for accurate simulations of the coupled climate system. This study describes the development of a generalized reservoir model capable of reproducing realistic reservoir behavior for future integration in a global land surface model (LSM). Equations of increasing complexity relating reservoir inflow, outflow, and storage were tested for 14 California reservoirs that span a range of spatial and climate regimes. Temperature was employed in model equations to modulate seasonal changes in reservoir management behavior and to allow for the evolution of management seasonality as future climate varies. Optimized parameter values for the best-performing model were generalized based on the ratio of winter inflow to storage capacity so a future LSM user can generate reservoirs in any grid location by specifying the given storage capacity. Model performance statistics show good agreement between observed and simulated reservoir storage and outflow for both calibration (mean normalized RMSE = 0.48; mean coefficient of determination = 0.53) and validation reservoirs (mean normalized RMSE = 0.15; mean coefficient of determination = 0.67). The low complexity of model equations that include climate-adaptive operation features combined with robust model performance show promise for simulations of reservoir impacts on hydrology and climate within an LSM.
Roles of an Atmospheric River and a Cutoff Low in the Extreme Precipitation Event in Hiroshima on 19 August 2014
Authors: Hirota Nagio , Takayabu Yukari N. , Kato Masaya , Arakane Sho 
Published: January 2016

Abstract
Precipitation in excess of 100 mm h−1 in Hiroshima, Japan, on 19 August 2014, caused a flash flood that resulted in 75 deaths and destroyed 330 houses. This study examined the meteorological background of this fatal flood. During this event, considerable filamentary transport of water vapor from the Indochina Peninsula to the Japanese islands occurred, forming a so-called atmospheric river (AR). This AR had a deep structure with an amount of free tropospheric moisture comparable with that of the boundary layer. Furthermore, a cutoff low (COL), detached from the subtropical jet over the central Pacific, moved northwestward to the Japanese islands. Instability associated with the cold core of the COL and dynamical ascent induced in front of it, interacted with the free tropospheric moisture of the AR, which caused the considerable precipitation in Hiroshima. Moreover, the mountains of the Japanese islands played a role in localizing the precipitation in Hiroshima. These roles were separately evaluated on the basis of sensitivity experiments with a cloud-resolving model.