bluuebunny/crossref_metadata_2025_split huggingface dataset:
Juvenile northern rock sole (Lepidopsetta polyxystra) spatial distribution and abundance patterns in the eastern Bering Sea: spatially dependent production linked to temperature
Authors: Cooper Daniel W. , Nichol Daniel G. 
Published: February 2016

Abstract
Annual spatial distribution and relative abundance of age-2 and age-3 northern rock sole (Lepidopsetta polyxystra) and summer bottom temperatures were analysed using data from eastern Bering Sea summer trawl surveys from 1982 through 2012. Previously observed differences in age-0 northern rock sole distribution persisted until age-2 and age-3. Latitudinal distributions of age-2 and age-3 fish were correlated most strongly with summer bottom temperatures 2 and 3 years prior to the survey year, during the time that the fish would have been age-0. Thus, temperature during the age-0 year may affect spatial distribution for the first few years of life. Distribution of age-2 and age-3 fish shifted northwards 2 years after the beginning of a warming trend from 1999 to 2003, and shifted southwards 2 years after a cooling trend from 2004 through 2010. Northerly distributions were correlated with high abundances. Density dependence was ruled out as a reason for northward shifts in distribution given a lack of correlation between latitudinal distributions and the annual abundances within the southern part of the distribution. We propose that the large northern nursery area produces large cohorts of northern rock sole, and that bottom temperatures in the age-0 year affect use of the northern nursery area.
START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection
Authors: Siedner Mark J. 
Published: February 2016

Abstract
The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed.
Lamina Cribrosa Depth is Associated With the Cup-to-Disc Ratio in Eyes With Large Optic Disc Cupping and Cup-to-Disc Ratio Asymmetry
Authors: Jung Kyoung In , Jeon Sooji , Park Chan Kee 
Published: February 2016

Purpose:
To investigate the lamina cribrosa (LC) depth and its relationship with the cup-to-disc ratio (CDR) in the eyes with generalized increased optic disc cupping and CDR asymmetry.

Methods:
Glaucoma suspect subjects with a CDR≥0.7, CDR asymmetry ≥0.2 in the absence of visual field (VF) loss, and normal control subjects were enrolled. The optic nerve head was imaged using the enhanced depth imaging modes of Spectralis optical coherence tomography. The LC depth was determined at the mid-horizontal, and the superior and inferior mid-peripheral regions of the optic nerve head.

Results:
Disc area and CDRs were larger in the glaucoma suspect group compared with the control group (P<0.001). The mean LC depth was significantly greater in the disc area–matched glaucoma suspect group compared with the normal control group (P<0.001). The mean LC depth was positively correlated with the average and vertical CDRs (r=0.755 and 0.664, respectively; both P<0.001), which was maintained after controlling for the disc area (r=0.756 and 0.645, respectively; both P<0.001). In eyes with CDR asymmetry, the LC was located more posteriorly in eyes with a higher CDR compared with fellow eyes with a lower CDR (P<0.001).

Conclusions:
The LC depth was greater in eyes with generalized increased cupping, as well as in eyes with a higher CDR than fellow eyes, and was significantly related to the CDR. These results suggest that the clinical appearance of cup enlargement or cupping has LC displacement components.
Accuracy of Measurements With the iCare HOME Rebound Tonometer
Authors: Termühlen Julia , Mihailovic Natasa , Alnawaiseh Maged , Dietlein Thomas S. , Rosentreter André 
Published: February 2016

Purpose:
To evaluate the accuracy of intraocular pressure (IOP) measurements obtained with the newly available iCare HOME (RTHOME) rebound tonometer compared with the iCare ONE (RTONE) tonometer and Goldmann applanation tonometry (GAT), and possible correlation with central corneal thickness (CCT).

Materials and Methods:
IOP measurements were obtained from 154 patients by an ophthalmologist (doc) using each of the above-mentioned tonometers. In addition, patients (pat) measured their own IOP with the RTHOME and RTONE. The means and SD of results obtained with the different tonometers were compared. Agreement between the tonometers was calculated using the Bland-Altman method.

Results:
Mean IOPs for the right eyes only were 15.9±6.4 mm Hg (RTONEdoc), 15.8±6.4 mm Hg (RTONEpat), 15.0±5.9 mm Hg (RTHOMEdoc), 14.9±6.3 mm Hg (RTHOMEpat), and 15.8±4.4 mm Hg (GAT). Bland-Altman analysis revealed mean differences (bias) between RTONEdoc and RTHOMEdoc, between RTHOMEdoc and RTHOMEpat, and between RTHOMEdoc and GAT of 0.8, 0.1, and −0.8 mm Hg, respectively, with 95% limits of agreement of −3.5 to 5.2, −4.9 to 5.1, and −7.2 to 5.6 mm Hg, respectively. Linear regression of the comparisons revealed a proportional error over the range of pressures examined in the case of RTHOMEdoc versus GAT (slope=0.32, P<0.001). Considering the data from all eyes, the difference between RTHOMEdoc and GAT correlated significantly with the CCT (P=0.01).

Conclusion:
RTHOME readings correlate well with the GAT results although some limitations such as dependency of readings on CCT and increasing differences at lower and higher IOP levels need to be taken into account.
Dopamine regulates termite soldier differentiation through trophallactic behaviours
Authors: Yaguchi Hajime , Inoue Takaya , Sasaki Ken , Maekawa Kiyoto 
Published: February 2016

Caste polyphenism in social insects is regulated by social interactions among colony members. Trophallaxis is one of the most frequently observed interactions, but no studies have been conducted identifying the intrinsic factors involved in this behaviour and caste differentiation. Dopamine (DA) has multiple roles in the modulation of behaviours and physiology, and it produces species-specific behaviours in animals. Here, to verify the role of DA in termite soldier differentiation, we focused on the first soldier in an incipient colony ofZootermopsis nevadensis, which always differentiates from the oldest 3rd instar (No. 1 larva) via a presoldier. First, brain DA levels of the No. 1 larva at day 3 after its appearance were significantly higher than day 0. Second, DA synthesis gene expression levels were extraordinarily high in the No. 1 larva at day 0–1 after appearance. Finally, injection of a DA receptor antagonist into the No. 1 larva resulted in the inhibition of presoldier differentiation. Behavioural observations of the antagonist or control-injected larvae suggested that brain DA and signalling activity regulate the frequencies of trophallaxis from reproductives and presoldier differentiation. Because trophallaxis is a social behaviour frequently observed in natural conditions, the role of DA should be investigated in other social insects with frequent trophallactic and allogrooming behaviour.
Deep genome sequencing and variation analysis of 13 inbred mouse strains defines candidate phenotypic alleles, private variation, and homozygous truncating mutations
Authors: Doran Anthony G. , Wong Kim , Flint Jonathan , Adams David J. , Hunter Kent W. , Keane Thomas M. 
Published: February 2016

AbstractBackgroundThe Mouse Genomes Project is an ongoing collaborative effort to sequence the genomes of the common laboratory mouse strains. In 2011, the initial analysis of sequence variation across 17 strains found 56.7M unique SNPs and 8.8M indels. We carry out deep sequencing of 13 additional inbred strains (BUB/BnJ, C57BL/10J, C57BR/cdJ, C58/J, DBA/1J, I/LnJ, KK/HiJ, MOLF/EiJ, NZB/B1NJ, NZW/LacJ, RF/J, SEA/GnJ and ST/bJ), cataloging molecular variation within and across the strains. These strains include important models for immune response, leukemia, age-related hearing loss and rheumatoid arthritis. We now have several examples of fully sequenced closely related strains that are divergent for several disease phenotypes.ResultsApproximately, 27.4M unique SNPs and 5M indels are identified across these strains compared to the C57BL/6J reference genome (GRCm38). The amount of variation found in the inbred laboratory mouse genome has increased to 71M SNPs and 12M indels. We investigate the genetic basis of highly penetrant cancer susceptibility in RF/J finding private novel missense mutations in DNA damage repair and highly cancer associated genes. We use two highly related strains (DBA/1J and DBA/2J) to investigate the genetic basis of collagen induced arthritis susceptibility.ConclusionThis paper significantly expands the catalog of fully sequenced laboratory mouse strains and now contains several examples of highly genetically similar strains with divergent phenotypes. We show how studying private missense mutations can lead to insights into the genetic mechanism for a highly penetrant phenotype.
AAV-mediated CRISPR/Cas gene editing of retinal cellsin vivo
Authors: Hung Sandy SC , Chrysostomou Vicki , Li Fan , Lim Jeremiah KH , Wang Jiang-Hui , Powell Joseph E , Tu Leilei , Daniszewski Maciej , Lo Camden , Wong Raymond C , Crowston Jonathan G , Pébay Alice , King Anna E , Bui Bang V , Liu Guei-Sheung , Hewitt Alex W 
Published: February 2016

ABSTRACTPURPOSECRISPR/Cas has recently been adapted to enable efficient editing of the mammalian genome, opening novel avenues for therapeutic intervention of inherited diseases. In seeking to disrupt Yellow Fluorescent Protein (YFP) in a Thy1-YFP transgenic mouse, we assessed the feasibility of utilising the adeno-associated virus 2 (AAV2) to deliver CRISPR/Cas for gene modification of retinal cellsin vivo.METHODSsgRNA plasmids were designed to targetYFPand afterin vitrovalidation, selected guides were cloned into a dual AAV system. One AAV2 construct was used to deliver SpCas9 and the other delivered sgRNA againstYFPorLacZ(control) in the presence of mCherry. Five weeks after intravitreal injection, retinal function was determined using electroretinography and CRISPR/Casmediated gene modifications were quantified in retinal flat mounts.RESULTSAAV2-mediatedin vivodelivery of SpCas9 with sgRNA targetingYFP, significantly reduced the number of YFP fluorescent cells of the inner retina of our transgenic mouse model. Overall, we found an 84.0% (95% CI: 81.8-86.9) reduction of YFP-positive cells inYFP-sgRNA infected retinal cells compared to eyes treated withLacZ-sgRNA. Electroretinography profiling found no significant alteration in retinal function following AAV2-mediated delivery of CRISPR/Cas components compared to contralateral untreated eyes.CONCLUSIONSThy1-YFP transgenic mice were used as a rapid quantifiable means to assess the efficacy of CRISPR/Cas-based retinal gene modificationin vivo. We demonstrate that genomic modification of cells in the adult retina can be readily achieved by viral mediated delivery of CRISPR/Cas.
Predicting symptom severity in autism spectrum disorder based on cortical thickness measures in agglomerative data
Authors: Moradi Elaheh , Khundrakpam Budhachandra , Lewis John D. , Evans Alan C. , Tohka Jussi 
Published: February 2016

AbstractMachine learning approaches have been widely used for the identification of neuropathology from neuroimaging data. However, these approaches require large samples and suffer from the challenges associated with multi-site, multi-protocol data. We propose a novel approach to address these challenges, and demonstrate its usefulness with the Autism Brain Imaging Data Exchange (ABIDE) database. We predict symptom severity based on cortical thickness measurements from 156 individuals with autism spectrum disorder (ASD) from four different sites. The proposed approach consists of two main stages: a domain adaptation stage using partial least squares regression to maximize the consistency of imaging data across sites; and a learning stage combining support vector regression for regional prediction of severity with elastic-net penalized linear regression for integrating regional predictions into a whole-brain severity prediction. The proposed method performed markedly better than simpler alternatives, better with multi-site than single-site data, and resulted in a considerably higher cross-validated correlation score than has previously been reported in the literature for multi-site data. This demonstration of the utility of the proposed approach for detecting structural brain abnormalities in ASD from the multi-site, multi-protocol ABIDE dataset indicates the potential of designing machine learning methods to meet the challenges of agglomerative data.
Prioritizing variants in complete Hereditary Breast and Ovarian Cancer (HBOC) genes in patients lacking knownBRCAmutations
Authors: Caminsky Natasha G. , Mucaki Eliseos J. , Perri Ami M. , Lu Ruipeng , Knoll Joan H. M. , Rogan Peter K. 
Published: February 2016

AbstractBRCA1andBRCA2testing for HBOC does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N=287), including non-coding and flanking sequences ofATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, andXRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (4 natural, 6 cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure, and 17 for pseudoexon activation. Additionally, 4 frameshift, 2 in-frame deletions, and 5 stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis.
Next-generation sequencing in neuropathological diagnosis of infections of the nervous system
Authors: Salzberg Steven L. , Breitwieser Florian P. , Kumar Anupama , Hao Haiping , Burger Peter , Rodriguez Fausto J. , Lim Michael , Quiñones-Hinojosa Alfredo , Gallia Gary L. , Tornheim Jeffrey A. , Melia Michael T. , Sears Cynthia L. , Pardo Carlos A. 
Published: February 2016

AbstractObjectiveTo determine the feasibility of next-generation sequencing (NGS) microbiome approaches in the diagnosis of infectious disorders in brain or spinal cord biopsies in patients with suspected central nervous system (CNS) infections.MethodsIn a prospective-pilot study, we applied NGS in combination with a new computational analysis pipeline to detect the presence of pathogenic microbes in brain or spinal cord biopsies from ten patients with neurological problems indicating possible infection but for whom conventional clinical and microbiology studies yielded negative or inconclusive results.ResultsDirect DNA and RNA sequencing of brain tissue biopsies generated 8.3 million to 29.1 million sequence reads per sample, which successfully identified with high confidence the infectious agent in three patients, identified possible pathogens in two more, and helped to understand neuropathological processes in three others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Validation techniques confirmed the pathogens identified by NGS in each of the three positive cases. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in eight of ten cases, and were non-contributory in the remaining two.ConclusionsNGS-guided metagenomic studies of brain, spinal cord or meningeal biopsies offer the possibility for dramatic improvements in our ability to detect (or rule out) a wide range of CNS pathogens, with potential benefits in speed, sensitivity, and cost. NGS-based microbiome approaches present a major new opportunity to investigate the potential role of infectious pathogens in the pathogenesis of neuroinflammatory disorders.
Multi-dimensional structure function relationships in human β-cardiac myosin from population scale genetic variation
Authors: Homburger Julian R. , Green Eric M. , Caleshu Colleen , Sunitha Margaret , Taylor Rebecca , Ruppel Kathleen M. , Metpally Raghu ,   SHaRe Investigators, Colan Steven D. , Michels Michelle , Day Sharlene , Olivotto Iacopo , Bustamante Carlos D. , Dewey Frederick , Ho Carolyn Y. , Spudich James A. , Ashley Euan A. 
Published: February 2016

AbstractMyosin motors are the fundamental force-generating element of muscle contraction. Variation in the human β-cardiac myosin gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 HCM patients to elucidate novel structure-function relationships within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein three-dimensional space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified another region enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as a myosin mesa. This surface is prominent in the pre-stroke model, but substantially reduced in size following the power stroke. Notably, HCM patients with variants in the enriched regions have earlier presentation and worse outcome than those with variants in other regions. In summary, this study provides a model for the combination of protein structure, large-scale genetic sequencing and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease.
Auditor switch decisions under forced auditor change: evidence from China
Authors: Kuo Li-Chun , Lin Chan-Jane , Lin Hsiao-Lun 
Published: February 2016

Purpose– From 2000 to 2007, 14 Chinese accounting firms had their audit licenses terminated or suspended for different reasons, forcing clients of these accounting firms to select new auditors within a short period of time. The purpose of this paper is to examine the auditor switching patterns and audit partner following decision of these clients and the effect of both client and (terminated or suspended) auditor characteristics on the auditor change decisions.Design/methodology/approach– By using 245 (191) clients of terminated or suspended audit firms, the authors apply logistic regressions to investigate clients’ switching decision (following decision).Findings– The empirical results indicate that state-owned enterprises tend not to switch to Big 4 audit firms; clients with dual shares tend to choose from the Big 4 for their succeeding audit firms. Moreover, companies whose preceding auditors received severe regulatory sanctions are less likely to switch to auditors of higher quality; companies who hired local auditors are more likely to follow their preceding audit partners as a result of forced auditor change.Originality/value– This study enriches forced auditor change literature by discussing both clients’ and preceding auditor’s attributes on clients’ switching and following decisions.
Ownership concentration, family control, and auditor choice
Authors: Darmadi Salim 
Published: February 2016

Purpose– The purpose of this paper is to extend the existing, yet limited, literature on the influence of ownership concentration and family control on the demands for high-quality audits. This study focusses on an emerging market, namely, Indonesia, where ownership concentration and family control are relatively higher than those in developed markets.Design/methodology/approach– The sample consists of 787 firm-year observations of public firms listed on the Indonesia Stock Exchange. Following prior studies, a firm is considered using a higher quality audit when its external auditor is one of the Big 4 audit firms. Logistic regressions are employed to test research hypotheses.Findings– Empirical evidence obtained reveals that firms with higher ownership concentration are more likely to hire a Big 4 auditor. Hence, in such firms, high-quality audits are employed to mitigate agency issues. However, when the controlling shareholder is a family, the association between ownership concentration and the demands for high-quality auditors turns negative, implying that family-controlled firms tend to sustain opaqueness gains by hiring lower quality auditors.Originality/value– Previous empirical studies examining the influence of ownership concentration and family control on auditor choice are relatively limited in the literature and are heavily focussed on developed economies. In addition, the present study is one of the first to investigate the association between family control and auditor choice in the context of a developing economy.