bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years
Authors: Clifford Katherine M. , Samboju Vishal , Cobigo Yann , Milanini Benedetta , Marx Gabriel A. , Hellmuth Joanna M. , Rosen Howard J. , Kramer Joel H. , Allen Isabel E. , Valcour Victor G. 
Published: June 2017

Background:
Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants.

Methods:
We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24).

Results:
The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status.

Conclusions:
Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.
Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler Ultrasonography
Authors: Li Jia-Wu , Lu Qiang , Luo Yan 
Published: June 2017

Abstract
Hepatic vein stenosis after liver transplantation is a relatively rare complication that could even result in graft loss. However, it is difficult to arrive at a definite diagnosis at the early stage of postoperation, and there are few researches on ultrasonic shear wave elastography in the diagnosis of hepatic vein stenosis. We report the case of an 11-year-old male patient with cirrhosis due to hepatolenticular degeneration who received an auxiliary left hemiliver graft from his uncle. Massive ascites developed in 4 days after the operation. Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness of the graft was revealed by ultrasonic shear wave elastography. The stenosis was confirmed by subsequent digital subtraction angiography. Ascites decreased gradually after the stent implantation. Our case indicates that ultrasonic shear wave elastography combined with Doppler ultrasonography is a promising method for noninvasive diagnosis of hepatic venous outflow stenosis following liver transplantation.
The Volume-outcome Relationship in Deceased Donor Kidney Transplantation and Implications for Regionalization
Authors: Barbas Andrew S. , Dib Martin J. , Rege Aparna S. , Vikraman Deepak S. , Sudan Debra L. , Knechtle Stuart J. , Scarborough John E. 
Published: June 2017

Objective:
The aim of this study was to investigate the volume-outcome relationship in kidney transplantation by examining graft and patient outcomes using standardized risk adjustment (observed-to-expected outcomes). A secondary objective was to examine the geographic proximity of low, medium, and high-volume kidney transplant centers in the United States.

Summary of Background Data:
The significant survival benefit of kidney transplantation in the context of a severe shortage of donor organs mandates strategies to optimize outcomes. Unlike for other solid organ transplants, the relationship between surgical volume and kidney transplant outcomes has not been clearly established.

Methods:
The Scientific Registry of Transplant Recipients was used to examine national outcomes for adults undergoing deceased donor kidney transplantation from January 1, 1999 to December 31, 2013 (15-year study period). Observed-to-expected rates of graft loss and patient death were compared for low, medium, and high-volume centers. The geographic proximity of low-volume centers to higher volume centers was determined to assess the impact of regionalization on patient travel burden.

Results:
A total of 206,179 procedures were analyzed. Compared with low-volume centers, high-volume centers had significantly lower observed-to-expected rates of 1-month graft loss (0.93 vs 1.18, P<0.001), 1-year graft loss (0.97 vs 1.12, P<0.001), 1-month patient death (0.90 vs 1.29, P=0.005), and 1-year patient death (0.95 vs 1.15, P=0.001). Low-volume centers were frequently in close proximity to higher volume centers, with a median distance of 7 miles (interquartile range: 2 to 75).

Conclusions:
A robust volume-outcome relationship was observed for deceased donor kidney transplantation, and low-volume centers are frequently in close proximity to higher volume centers. Increased regionalization could improve outcomes, but should be considered carefully in light of the potential negative impact on transplant volume and access to care.
Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors
Authors: Kayler Liise , Yu Xia , Cortes Carlos , Lubetzky Michelle , Friedmann Patricia 
Published: June 2017

Background
Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear of an additional deleterious effect.

Methods
We performed a retrospective cohort study examining US registry data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys (derived from the same donor transplanted into different recipients) from DCD donors.

Results
On multivariable analysis, death-censored graft survival (DCGS) was comparable between recipients of kidneys with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5 hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer (aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66-1.99; n = 498). There was a higher rate of primary non function in the long CIT groups for delta 1 hour or longer (0.89% vs 1.63%; P = 0.006), 5 hours (1.09% vs 1.67%, P = 0.13); 10 hours (0.53% vs 1.78%; P = 0.03), and 15 hours (0.40% vs 1.61%; P = 0.18), respectively. Between each of the 4 delta CIT levels of shorter and longer CIT, there was a significantly and incrementally higher rate of delayed graft function in the long CIT groups for delta 1 hour or longer (37.3% vs 41.7%; P < 0.001), 5 hours (35.9% vs 42.7%; P < 0.001), 10 hours (29.4% vs 44.2%, P < 0.001), and 15 hours (29.6% vs 46.1%, P < 0.001), respectively. Overall patient survival was comparable with delta CITs of 1 hour or longer (aHR, 0.96; 95% CI, 0.84-1.08), 5 hours (aHR, 1.01; 95% CI, 0.85-1.20), and 15 hours (aHR, 1.27; 95% CI, 0.79-2.06) but not 10 hours (aHR, 1.47; 95% CI, 1.09-1.98).

Conclusions
These results suggest that in the setting of a prior ischemic donor event, prolonged CIT has limited bearing on long-term outcomes.
Informatics for Cancer Immunotherapy
Authors: Hammerbacher J. , Snyder A. 
Published: June 2017

AbstractThe rapid development of immunomodulatory cancer therapies has led to a concurrent increase in the application of informatics techniques to the analysis of tumors, the tumor microenvironment, and measures of systemic immunity. In this review, the use of tumors to gather genetic and expression data will first be explored. Next, techniques to assess tumor immunity are reviewed, including HLA status, predicted neoantigens, immune microenvironment deconvolution and T-cell receptor (TCR) sequencing. Attempts to integrate these data are in early stages of development and are discussed next. Finally, we review the application of these informatics strategies to therapy development, with a focus on vaccines, adoptive cell transfer, and checkpoint blockade therapies.
Resting-State fMRI Dynamics and Null Models: Perspectives, Sampling Variability, and Simulations
Authors: Miller Robyn , Abrol Anees , Adali Tulay , Levin-Schwarz Yuri , Calhoun Vince 
Published: June 2017

AbstractStudies of resting state functional MRI (rs-fRMI) are increasingly focused on “dynamics”, or on those properties of brain activation that manifest and vary on timescales shorter than the scan’s full duration. This shift in focus has led to a flurry of interest in developing hypothesis testing frameworks and null models applicable to the dynamical setting. Thus far however, these efforts have been weakened by a number of crucial shortcomings that are outlined and discussed in this short paper. We focus here on aspects of recently proposed null models that, we argue, are poorly formulated relative to the hypotheses they are designed to test, i.e. their potential role in separating functionally relevant BOLD signal dynamics from noise or intermittent background and maintenance type processes is limited by factors that are fundamental rather than merely quantitative or parametric. In this short position paper, we emphasize that (1) serious care must be exercised in building null models for rs-fMRI dynamics from distributionally stationary univariate or multivariate timeseries, i.e. timeseries whose values are each independently drawn from one pre-specified probability distribution; and (2) measures such as kurtosis that quantify over-concentration of observed values in the far tails of some reference distribution may not be particularly suitable for capturing signal features most plausibly contributing to functionally relevant brain dynamics. Other metrics targeted, for example, at capturing the epochal temporal variation that contributes heavily to dynamic functional connectivity estimates and is and often taken as a signature of brain responsiveness to stimuli or experimental tasks, could play a more scientifically clarifying role. As we learn more about the phenomenon of functionally relevant brain dynamics and its imaging correlates, scientifically meaningful null hypotheses and well-tuned null models will naturally emerge. We also revisit the important concept of distributional stationarity, discuss how it manifests within realizations versus across multiple realizations, and provide guidance on the benefits and limitations of employing this type of stationarity in modeling the absence or functionally relevant temporal dynamics in resting state fMRI. We hope that the discussions herein are useful, and promote thoughtful consideration of these important issues.
Variable precision in visual perception
Authors: Shen Shan , Ma Wei Ji 
Published: June 2017

ABSTRACTGiven the same sensory stimuli in the same task, human observers do not always make the same response. Well-known sources of behavioral variability are sensory noise and guessing. Visual short-term memory studies have suggested that the precision of the sensory noise is itself variable. However, it is unknown whether precision is also variable in perceptual tasks without a memory component. We searched for evidence for variable precision in 11 visual perception tasks with a single relevant feature, orientation. We specifically examined the effect of distractor stimuli: distractors were absent, homogeneous and fixed across trials, homogeneous and variable, or heterogeneous and variable. We first considered four models: with and without guessing, and with and without variability in precision. We quantified the importance of both factors using six metrics: factor knock-in difference, factor knock-out difference, and log factor posterior ratio, each based on AIC or BIC. According to all six metrics, we found strong evidence for variable precision in five experiments. Next, we extended our model space to include potential confounding factors: the oblique effect and decision noise. This left strong evidence for variable precision in only one experiment, in which distractors were homogeneous but variable. Finally, when we considered suboptimal decision rules, the evidence also disappeared in this experiment. Our results provide little evidence for variable precision overall and only a hint when distractors are variable. Methodologically, the results underline the importance of including multiple factors in factorial model comparison: testing for only two factors would have yielded an incorrect conclusion.
CD-HIT-OTU-MiSeq, an Improved Approach for Clustering and Analyzing Paired End MiSeq 16S rRNA Sequences
Authors: Li Weizhong , Chang Yuanyuan 
Published: June 2017

AbstractIn recent years, Illumina MiSeq sequencers replaced pyrosequencing platforms and became dominant in 16S rRNA sequencing. One unique feature of MiSeq technology, compared with Pyrosequencing, is the Paired End (PE) reads, with each read can be sequenced to 250-300 bases to cover multiple variable regions on the 16S rRNA gene. However, the PE reads need to be assembled into a single contig at the beginning of the analysis. Although there are many methods capable of assembling PE reads into contigs, a big portion of PE reads can not be accurately assembled because the poor quality at the 3’ ends of both PE reads in the overlapping region. This causes that many sequences are discarded in the analysis. In this study, we developed a novel approach for clustering and annotation MiSeq-based 16S sequence data, CD-HIT-OTU-MiSeq. This new approach has four distinct novel features. (1) The package can clustering PE reads without joining them into contigs. (2) Users can choose a high quality portion of the PE reads for analysis (e.g. first 200 / 150 bases from forward / reverse reads), according to base quality profile. (3) We implemented a tool that can splice out the target region (e.g. V3-V4) from a full-length 16S reference database into the PE sequences. CD-HIT-OTU-MiSeq can cluster the spliced PE reference database together with samples, so we can derive Operational Taxonomic Units (OTUs) and annotate these OTUs concurrently. (4) Chimeric sequences are effectively identified throughde novoapproach. The package offers high speed and high accuracy. The software package is freely available as open source package and is distributed along with CD-HIT fromhttp://cd-hit.org. Within the CD-HIT package, CD-HIT-OTU-MiSeq is within the usecase folder.
Distinct gut microbiome patterns associate with consensus molecular subtypes of colorectal cancer
Authors: Purcell Rachel V , Visnovska Martina , Biggs Patrick J , Schmeier Sebastian , Frizelle Frank A 
Published: June 2017

AbstractColorectal cancer (CRC) is a heterogeneous disease and recent advances in subtype classification have successfully stratified the disease using molecular profiling. The contribution of bacterial species to CRC development is increasingly acknowledged, and here, we sought to analyse CRC microbiomes and relate them to tumour consensus molecular subtypes (CMS), in order to better understand the relationship between bacterial species and the molecular mechanisms associated with CRC subtypes. We classified 34 tumours into CRC subtypes using RNA-sequencing derived gene expression and determined relative abundances of bacterial taxonomic groups using 16S rRNA amplicon metabarcoding. 16S rRNA analysis showed enrichment of Fusobacteria and Bacteroidetes, and decreased levels of Firmicutes and Proteobacteria in CMS1. A more detailed analysis of bacterial taxa using non-human RNA-sequencing reads uncovered distinct bacterial communities associated with each molecular subtype. The most highly enriched species associated with CMS1 includedFusobacterium hwasookiiandPorphyromonas gingivalis. CMS2 was enriched forSelenomasandPrevotellaspecies, while CMS3 had few significant associations. Targeted quantitative PCR validated these findings and also showed an enrichment ofFusobacterium nucleatum, Parvimonas micraandPeptostreptococcus stomatisin CMS1. In this study, we have successfully associated individual bacterial species to CRC subtypes for the first time.
Variants at the ADAMTS13, BGALT5, SSBP2 and TKT Loci are associated with Post-term birth
Authors: Schierding William , Antony Jisha , Karhunen Ville , Vääräsmäki Marja , Franks Steve , Elliott Paul , Kajantie Eero , Sebert Sylvain , Blakemore Alex , Horsfield Julia A. , Järvelin Marjo-Riitta , O’Sullivan Justin M. , Cutfield Wayne S. 
Published: June 2017

AbstractGestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born pre and post-term,i.e.having short and long gestational ages, are heritable and influenced by the pre- and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood. Here we identify one globally significant intronic genetic variant within theADAMTS13gene that is associated with prolonged gestation in 9,141 white European individuals from the 1966 and 1986 Northern Finland birth cohorts. Additional variants that reached suggestive levels of significance were identified within introns at theTKT,andARGHAP42genes, and in the upstream (5’) intergenic regions of theB3GALT5andSSBP2genes. The variants near theADAMTS13, B3GALT5, SSBP2andTKTloci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for theBGALT5andTKTloci. Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation.
zUMIs - A fast and flexible pipeline to process RNA sequencing data with UMIs
Authors: Parekh Swati , Ziegenhain Christoph , Vieth Beate , Enard Wolfgang , Hellmann Ines 
Published: June 2017

AbstractSingle cell RNA-seq (scRNA-seq) experiments typically analyze hundreds or thousands of cells after amplification of the cDNA. The high throughput is made possible by the early introduction of sample-specific barcodes (BCs) and the amplification bias is alleviated by unique molecular identifiers (UMIs). Thus the ideal analysis pipeline for scRNA-seq data needs to efficiently tabulate reads according to both BC and UMI.zUMIsis such a pipeline, it can handle both known and random BCs and also efficiently collapses UMIs, either just for Exon mapping reads or for both Exon and Intron mapping reads. Another unique feature ofzUMIsis the adaptive downsampling function, that facilitates dealing with hugely varying library sizes, but also allows to evaluate whether the library has been sequenced to saturation.zUMIsflexibility allows to accommodate data generated with any of the major scRNA-seq protocols that use BCs and UMIs. To illustrate the utility ofzUMIs, we analysed a single-nucleus RNA-seq dataset and show that more than 35% of all reads map to Introns. We furthermore show that these intronic reads are informative about expression levels, significantly increasing the number of detected genes and improving the cluster resolution.Availability:https://github.com/sdparekh/zUMIs
Drug treatment efficiency depends on the initial state of activation in nonlinear pathways
Authors: Doldán-Martelli Victoria , Míguez David G. 
Published: June 2017

ABSTRACTAn accurate prediction of the outcome of a given drug treatment requires quantitative values for all parameters and concentrations involved as well as a detailed characterization of the network of interactions where the target molecule is embedded. Here, we present a high-throughputin silicoscreening of all potential networks of three interacting nodes to study the effect of the initial conditions of the network in the efficiency of drug inhibition. Our study shows that most network topologies can induce multiple dose-response curves, where the treatment has an enhanced, reduced or even no effect depending on the initial conditions. The type of dual response observed depends on how the potential bistable regimes interplay with the inhibition of one of the nodes inside a nonlinear pathway architecture. We propose that this dependence of the strength of the drug on the initial state of activation of the pathway may be affecting the outcome and the reproducibility of drug studies and clinical trials.
Ectopic activation of the Spindle Assembly Checkpoint reveals its biochemical design and physiological operation
Authors: Chen Chu , Whitney Ian P. , Banerjee Anand , Sekhri Palak , Kern David M. , Fontan Adrienne , Tyson John J. , Cheeseman Iain M. , Joglekar Ajit P. 
Published: June 2017

SummarySwitch-like activation of the Spindle Assembly Checkpoint (SAC) is critical for accurate chromosome segregation during cell division. To determine the mechanisms that implement it, we engineered an ectopic, kinetochore-independent SAC activator, the “eSAC”. The eSAC stimulates the SAC signaling cascade by artificially dimerizing the Mps1 kinase domain and a cytosolic KNL1 phosphodomain, the signaling scaffold in the kinetochore. Quantitative analyses and mathematical modeling of the eSAC reveal that the recruitment of multiple SAC proteins by the KNL1 phosphodomain stimulates synergistic signaling, which enables a small number of KNL1 molecules produce a disproportionately strong anaphase-inhibitory signal. However, when multiple KNL1 molecules signal concurrently, they compete for a limited cellular pool of SAC proteins. This frustrates synergistic signaling and modulates signal output. Together, these mechanisms institute automatic gain control – inverse, non-linear scaling between the signal output per kinetochore and the unattached kinetochore number, and thus enact the SAC switch.