bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deoxyribonuclease I Activity, Cell-Free DNA, and Risk of Liver Cancer in a Prospective Cohort
Authors: Golonka Rachel M , Yeoh Beng San , Petrick Jessica L , Weinstein Stephanie J , Albanes Demetrius , Gewirtz Andrew T , McGlynn Katherine A , Vijay-Kumar Matam 
Published: January 2019

Abstract

Background
Circulating cell-free DNA (cfDNA) is a proposed latent biomarker for several cancers, including liver cancer. Deoxyribonucleases (DNases) facilitate the timely and efficient degradation of cfDNA, leading us to hypothesize that DNase I and/or II might be a more sensitive early biomarker than cfDNA. To test this hypothesis, a study was conducted in a large, prospective cohort.

Methods
A nested case-control study (224 liver cancer case patients and 224 matched control subjects) was conducted in a cohort of Finnish male smokers, followed from baseline (1985–1988) to 2014. The associations among DNase I activity, cfDNA, and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression.

Results
DNase I activity, whether measured as radius (mm) or as units per milliliter, was statistically significantly associated with increased risk of liver cancer (Ptrend <.01). DNase I activity in the highest quartile was associated with a greater than threefold risk of developing liver cancer (DNase I activity radius >2.7 mm, hazard ratio [HR] = 3.03, 95% confidence interval [CI] = 1.59 to 5.77; DNase I activity >2.72 units/mL, HR = 3.30, 95% CI = 1.64 to 6.65). The strength of this association was not substantially altered by exclusion of cases diagnosed within the first five years of follow-up or those with hepatitis C virus (HCV) infection. In contrast, cfDNA and DNase II was not statistically significantly associated with risk of liver cancer.

Conclusions
DNase I activity was a superior latent biomarker of liver cancer than cfDNA. These findings advance the goal of developing a means to detect liver cancer years well before the development of clinical manifestations.
The origin of galactic metal-rich stellar halo components with highly eccentric orbits
Authors: Fattahi Azadeh , Belokurov Vasily , Deason Alis J , Frenk Carlos S , Gómez Facundo A , Grand Robert J J , Marinacci Federico , Pakmor Rüdiger , Springel Volker 
Published: January 2019

AbstractUsing the astrometry from the ESA’s Gaia mission, previous works have shown that the Milky Way stellar halo is dominated by metal-rich stars on highly eccentric orbits. To shed light on the nature of this prominent halo component, we have analysed 28 Galaxy analogues in the Auriga suite of cosmological hydrodynamics zoom-in simulations. Some three quarters of the Auriga galaxies contain prominent components with high radial velocity anisotropy, β &gt; 0.6. However, only in one third of the hosts do the high-β stars contribute significantly to the accreted stellar halo overall, similar to what is observed in the Milky Way. For this particular subset we reveal the origin of the dominant stellar halo component with high metallicity, [Fe/H] ∼ −1, and high orbital anisotropy, β &gt; 0.8, by tracing their stars back to the epoch of accretion. It appears that, typically, these stars come from a single dwarf galaxy with a stellar mass of the order of $10^9-10^{10}\, {\rm M}_\odot$ that merged around $6-10 \, {\rm Gyr}$ ago, causing a sharp increase in the halo mass. Our study therefore establishes a firm link between the excess of radially anisotropic stellar debris in the halo and an ancient head-on collision between the young Milky Way and a massive dwarf galaxy.
Characterization of patients with chronic refractory gout who do and do not have clinically apparent tophi and their response to pegloticase
Authors: Lawrence Edwards N , Singh Jasvinder A , Troum Orrin , Yeo Anthony E , Lipsky Peter E 
Published: January 2019

Abstract

Objective
To determine the characteristics and response to pegloticase of patients with chronic refractory gout with and without clinically apparent tophi.

Methods
Results from two randomized controlled trials of pegloticase in patients with chronic refractory gout with clinically apparent tophi or without tophi were used to assess baseline and on-treatment between-group differences.

Results
Patients with tophi were significantly older than those without tophi, had a significantly longer duration of disease, higher numbers of tender and swollen joints, higher Patient Global Assessment scores and Health Assessment Questionnaire-Disability Index scores, and lower Arthritis-Specific Health Index scores. Patients with tophaceous gout also had significantly lower scores for physical functioning, role physical, social functioning, and the physical component summary scores of the Short Form 36 vs patients without tophi. In addition, subjects with clinically apparent tophi had a significantly lower mean estimated glomerular filtration rate. Pegloticase treatment of tophaceous patients caused significant reductions in serum urate, flares, Patient Global Assessment, tender joints, swollen joints, Health Assessment Questionnaire-Disability Index, visual analogue scale pain and Short Form 36 Bodily Pain, whereas patients without tophi had significant improvement in serum urate, flares, Patient Global Assessment, tender joints, and Short Form 36 Bodily Pain, but not swollen joints, Health Assessment Questionnaire-Disability Index functional score or pain visual analogue scale. Treatment with pegloticase had no effect on estimated glomerular filtration rate despite significant lowering of the urinary uric acid: creatinine ratio.

Conclusion
Patients with chronic refractory gout and clinically apparent tophi have more severe disease as well as reduced renal function. Both groups experienced significant clinical benefit with pegloticase treatment, although no change in renal function was noted.
Maternal investment, life histories, and the evolution of brain structure in primates
Authors: Powell Lauren E , Street Sally E , Barton Robert A 
Published: January 2019

AbstractLife history is a robust correlate of relative brain size: large-brained mammals and birds have slower life histories and longer lifespans than smaller-brained species. One influential adaptive hypothesis to account for this finding is the Cognitive Buffer Hypothesis (CBH). The CBH proposes that large brains permit greater behavioural flexibility and thereby buffer the animal from unpredictable environmental challenges, allowing reduced mortality and increased lifespan. In contrast, the Developmental Costs Hypothesis (DCH) suggests that life-history correlates of brain size reflect the extension of maturational processes needed to accommodate the evolution of large brains. The hypotheses are not mutually exclusive but do make different predictions. Here we test novel predictions of the hypotheses in primates: examining how the volume of brain components with different developmental trajectories correlate with relevant phases of maternal investment, juvenile period and post-maturational lifespan. Consistent with the DCH, structures with different allocations of growth to pre-natal versus post-natal development exhibit predictably divergent correlations with the associated periods of maternal investment and pre-maturational lifespan. Contrary to the CBH, adult lifespan is uncorrelated with either whole brain size or the size of individual brain components once duration of maternal investment is accounted for. Our results substantiate and elaborate on the role of maternal investment and offspring development in brain evolution, suggest that brain components can evolve partly independently through modifications of distinct developmental mechanisms, and imply that postnatal maturational processes involving interaction with the environment may be particularly crucial for the development of cerebellar function. They also provide an explanation for why apes have relatively extended maturation times, which relate to the relative expansion of the cerebellum in this clade.
Exploring correlations in genetic and cultural variation across language families in Northeast Asia
Authors: Matsumae Hiromi , Ranacher Peter , Savage Patrick E. , Blasi Damián E. , Currie Thomas E. , Kognebuchi Kae , Nishida Nao , Sato Takehiro , Tanabe Hideyuki , Tajima Atsushi , Brown Steven , Stoneking Mark , Shimizu Kentaro K. , Oota Hiroki , Bickel Balthasar 
Published: January 2019

AbstractCulture evolves in ways that are analogous to, but distinct from, genomes. Previous studies examined similarities between cultural variation and genetic variation (population history) at small scales within language families, but few studies empirically investigated such parallels across language families using diverse cultural data. We report an analysis comparing culture and genomes from in and around Northeast Asia spanning 11 language families. We extract and summarize the variation in language (grammar, phonology, lexicon), music (song structure, performance style), and genomes (genome-wide SNPs) and test for correlations. We find that grammatical structure correlates with population history. Recent contact and shared descent fail to explain the signal, suggesting relationships that arose before the formation of current families. Our results suggest that grammar might be a cultural indicator of population history, while also demonstrating differences among cultural and genetic relationships that highlight the complex nature of human history.
rEXPAR: an isothermal amplification scheme that is robust to autocatalytic parasites
Authors: Urtel Georg , Galas Jean-Christophe , Estevez-Torres André 
Published: January 2019

ABSTRACTIn the absence of DNA, a solution containing the four deoxynucleotidetriphosphates (dNTPs), a DNA polymerase and a nicking enzyme generates a self-replicating mixture of DNA species called parasite. Parasites are problematic in template-based isothermal amplification schemes such as EXPAR, as well as in related molecular programming languages, such as the PEN DNA toolbox. Here we show that the nicking enzyme Nb.BssSI allows to change the sequence design of EXPAR templates in a way that prevents the formation of parasites when dATP is removed from the solution. This method allows to make the EXPAR reaction robust to parasite contamination, a common feature in the laboratory, while keeping it compatible with PEN programs, which we demonstrate by engineering a parasite-proof bistable reaction network.
Network-based hierarchical population structure analysis for large genomic datasets
Authors: Greenbaum Gili , Rubin Amir , Templeton Alan R. , Rosenberg Noah A. 
Published: January 2019

AbstractAnalysis of population structure in natural populations using genetic data is a common practice in ecological and evolutionary studies. With large genomic datasets of populations now appearing more frequently across the taxonomic spectrum, it is becoming increasingly possible to reveal many hierarchical levels of structure, including fine-scale genetic clusters. To analyze these datasets, methods need to be appropriately suited to the challenges of extracting multilevel structure from whole-genome data. Here, we present a network-based approach for constructing population structure representations from genetic data. The use of community detection algorithms from network theory generates a natural hierarchical perspective on the representation that the method produces. The method is computationally efficient, and it requires relatively few assumptions regarding the biological processes that underlie the data. We demonstrate the approach by analyzing population structure in the model plant species Arabidopsis thaliana and in human populations. These examples illustrates how network-based approaches for population structure analysis are well-suited to extracting valuable ecological and evolutionary information in the era of large genomic datasets.
Signatures of replication timing, recombination and sex in the spectrum of rare variants on the human X chromosome and autosomes
Authors: Agarwal Ipsita , Przeworski Molly 
Published: January 2019

AbstractThe sources of human germline mutations are poorly understood. Part of the difficulty is that mutations occur very rarely, and so direct pedigree-based approaches remain limited in the numbers that they can examine. To address this problem, we consider the spectrum of low frequency variants in a dataset (gnomAD) of 13,860 human X chromosomes and autosomes. X-autosome differences are reflective of germline sex differences, and have been used extensively to learn about male versus female mutational processes; what is less appreciated is that they also reflect chromosome-level biochemical features that differ between the X and autosomes. We tease these components apart by comparing the mutation spectrum in multiple genomic compartments on the autosomes and between the X and autosomes. In so doing, we are able to ascribe specific mutation patterns to replication timing and recombination, and to identify differences in the types of mutations that accrue in males and females. In particular, we identify C>G as a mutagenic signature of male meiotic double strand breaks on the X, which may result from late repair. Our results show how biochemical processes of damage and repair in the germline interact with sex-specific life history traits to shape mutation patterns on both the X chromosome and autosomes.
Constitutive Androstane Receptor contributes towards increased drug clearance in cholestasis
Authors: Mathur Bhoomika , Arif Waqar , Patton Megan , Faiyaz Rahiman , Kalsotra Auinash , Wheatley Antony M , Anakk Sayeepriyadarshini 
Published: January 2019

AbstractUnderstanding the alterations in drug metabolism in different liver diseases is crucial for appropriate therapeutic intervention. We performed high-throughput RNA sequencing on various liver injury models, including cholestasis, diet-induced steatosis, and regeneration. Comparative liver transcriptome analysis revealed overlapping and distinct gene profiles among different liver diseases. Particularly, cholestatic livers displayed robust induction of drug metabolizing genes. This upregulation is not a generic hepatic stress response, as it was suppressed or unchanged in other models of liver diseases. Consistently, drug metabolic gene profiles were induced in a subset of biliary atresia patients, but not in individuals with hepatitis B or C viral infection, and alcoholic hepatitis. Further analysis revealed this induction was specific to genes regulated by nuclear receptor CAR (Constitutive Androstane Receptor). To test this, we challenged cholestatic mice with a paralytic agent, zoxazolamine. Compared to controls, these mice displayed significantly reduced paralysis time, reflecting increased drug metabolism, and this effect was lost upon inhibition of CAR. Thus, CAR activation can alter therapeutic efficacy of certain drugs in a subset of cholestatic individuals.
Meiotic viral attenuation through an ancestral apoptotic pathway
Authors: Gao Jie , Chau Sabrina , Chowdhury Fuad , Zhou Tina , Hossain Saif , Angus McQuibban G. , Meneghini Marc D. 
Published: January 2019

AbstractThe programmed release of apoptogenic proteins from mitochondria is a core event of apoptosis, though ancestral roles of this phenomenon are not known. In mammals, one such apoptogenic protein is Endonuclease G (EndoG), a conserved nuclease that fragments the DNA of dying cells. In this work, we show that budding yeast executes meiotically programmed mitochondrial release of an EndoG homologue, Nuc1, during sporulation. In contrast to EndoG’s ostensible pro-death function during apoptosis, Nuc1 mitochondrial release attenuates the cytosolic dsRNA mycovirus, Killer, protecting spores from a lethal accumulation of its encoded toxin. Our identification of cell-protective viral attenuation as a target of this rudimentary apoptotic pathway illuminates a primordial role for mitochondrial release of EndoG.One Sentence SummaryYeast sporulation induces release of mitochondrial endonuclease G to accomplish viral attenuation.
A demographic model for estimating the inter-division lifespans of stem cells and the subsequent transit amplifying stages
Authors: Gadre Purna , Chatterjee Shambhabi , Varshney Bhavna , Mazumdar Debasmita , Gupta Samir , Nitsure Nitin , Ray Krishanu 
Published: January 2019

AbstractThe division rates of stem cells and their progeny shape the growth and maintenance of tissues. Here, we present a mathematical model that could estimate the stage-wise lifespans of germline stem cells (GSCs) and subsequent transit amplifying (TA) cells from their steady-state distribution inDrosophilatestis. Analysis of the wild-type data using this model indicated that the inter-division lifespans of the first two TA cycles remain similar to that of the GSCs, and then reduce by nearly 2-folds for the third and fourth cycles. Also, loss of Cyclin E and Cdk1 functions in the early germline cells, which decreased the rates of GSC divisions, is suggested to extend the lifespans of GSCs and the TA stages without affecting subsequent differentiation. Similar perturbations at the 4 and 8-cell stages, however, arrested the mitoses at the 8-cell stage, and only the Cyclin E-deficient cells continued with premature meiosis. Together, these results suggest that regulation of the G1-S and G2-M transitions in the GSCs and the rapidly dividing TA stages differentially impacts the amplification of the germline pool and subsequent differentiation. The model also helped to quantify distinct influences of these cell cycle regulatory molecules in determining the lifespans at different TA stages.HighlightsA model for calculating the lifespans of transit amplifying stages from demography. Transit-amplifying divisions accelerate by nearly 2-folds after the second mitosis. Cyclin E and Cdk1 regulate the lifespans of GSCs and transit amplifying cells. The premature arrest of the final transit amplifying division induces meiosis.
Understanding and responding to new forms of competition
Authors: Keller Kevin Lane 
Published: January 2019

Purpose
The purpose of this note is to provide some brand strategy perspectives to Sheth and Koschmann’s Do brands compete or coexist? How persistence of brand loyalty segments the market.

Design/methodology/approach
This paper is a comment piece written in response to Sheth and Koschmann’s “Do brands compete or coexist? How persistence of brand loyalty segments the market”.

Findings
In their article, Jagdish Sheth and Anthony Koschmann provide a very useful empirically grounded example of how categories can evolve to be dominated by two or three key players and some of the implications which result from that. In doing so, they offer a number of useful insights. At the same time, however, it should be recognized that a number of competitive forces have emerged in recent years that have disrupted long-established equilibria and threatened long-term leadership in numerous categories. This note describes the nature of those forces and outlines three strategic approaches to improve the odds of long-term brand leadership and success.

Originality/value
This response to Sheth and Koschmann’s paper provides a scholarly dialogue centered upon the premise of brand loyalty within the context of market competition.
How TV sponsorship can help television spot advertising
Authors: Bellman Steven , Murphy Jamie , Arismendez Shruthi Vale , Varan Duane 
Published: January 2019

Purpose
This paper aims to test TV sponsorship bumper effects, for the same brand, on 30-s TV spot advertising.

Design/methodology/approach
An experimental study tests sponsorship bumpers and 30-s TV spot ads for eight brands, four familiar and four unfamiliar, using realistic stimuli and a sample representative of the US population.

Findings
Sponsorship boosts ad effectiveness and is measured by ad awareness and ad liking. Both effects were stronger for unfamiliar brands.

Research limitations/implications
The results show that combining sponsorship with spot advertising has an additive effect. The study design did not allow tests for potential synergy (multiplicative) effects.

Practical implications
Advertisers can use the results to evaluate investing in sponsorship and advertising packages, which can help unfamiliar brands achieve familiar brand awareness.

Originality/value
To the authors’ knowledge, this is the first study to compare the effectiveness of sponsorship-boosted ads with sponsorship bumpers alone and with TV spot ads.
Lean, Six Sigma and its influence on potential and realized absorptive capacity
Authors: Muraliraj J. , Kuppusamy S. , Zailani Suhaiza , Santha C. 
Published: January 2019

PurposeThe purpose of this paper is to explore how Lean and Six Sigma’s distinctive practices relate to potential absorptive capacity (PACAP) and realized absorptive capacity (RACAP). The paper seeks to understand which of the practices in Lean Six Sigma are needed to manage absorptive capacity systematically.Design/methodology/approachPartial least square based structural equation modeling (PLS-SEM) was used to test the theoretical model drawing on a sample of 125 manufacturing organizations in Malaysia. In addition to examining direct effects, the study also examines indirect effects using bootstrapping method to identify possible mediation effects proposed in the model.FindingsThe results explain that Lean’s social practices (LSP), Six Sigma’s roles structure (RS) and structured improvement procedure (SIP) positively influence potential absorptive capacity (PACAP). Meanwhile LSP, RS and focus on metrics (FOM) positively influence realized absorptive capacity (RACAP). SIP was found to influence RACAP through PACAP. The analysis reveals the combination of Lean Six Sigma practices that are required in managing PACAP and RACAP differentially.Research limitations/implicationsThe study is only confined to manufacturing industries in Peninsular Malaysia. Data collected were cross-sectional in nature. The application of Lean Six Sigma and how it influences absorptive capacity may get sturdier across time, and this may change the effect toward sustainability of firm’s competitive advantage. A longitudinal study may be useful in that context. The study also makes specific recommendations for future research.Practical implicationsThe results of this study can be used by Lean Six Sigma practitioners to prioritize the implementation of Lean Six Sigma practices to develop absorptive capacity of the organization through PACAP and RACAP, which needs to be managed differentially as they exert differential outcomes. This would enable organizations to tactfully navigate and balance between PACAP and RACAP in accordance to business strategies and market conditions.Originality/valueAbsorptive capacity in Lean and Six Sigma context has largely been studied as a unidimensional construct or used as a grounding theoretical support. Therefore, understanding the multidimensionality through PACAP and RACAP provide insights on how to enhance and maneuver absorptive capacity through Lean Six Sigma systematically. The findings may pave the way for future research in enhancing the current knowledge threshold in Lean Six Sigma.