bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Extra-anatomical Hepatic Artery Reconstruction During Living Donor Liver Transplantation on Biliary Complications and Graft and Patient Survival
Authors: Rhu Jinsoo , Kim Jong Man , Choi Gyu-Seong , David Kwon Choon Hyuck , Joh Jae-Won 
Published: February 2019

Background.
This study was designed to analyze the feasibility of extra-anatomical hepatic artery (HA) reconstruction in living donor liver transplantation (LT).

Methods.
Patients who underwent their first living donor LT at our center between January 2008 and December 2017 were reviewed. HA reconstruction was classified as anatomical or extra-anatomical reconstruction (EAR). We compared the background characteristics and posttransplantation outcomes, including complications, biliary complications, graft survival, and overall survival. The potential risk factors for bile leakage were analyzed using multivariable logistic regression, while risk factors for biliary stricture-free survival, graft survival, and overall survival were analyzed using multivariable Cox regression.

Results.
Among 800 patients, 35 (4.4%) underwent EAR, of whom 7 (7/35, 20.0%) experienced HA complications after the initial anatomical reconstruction and required EAR during reoperation. Patients who underwent EAR (n = 2/35, 5.7%) had a similar rate of HA complications compared with those who underwent anatomical reconstruction (n = 46/772, 5.9%, P = 0.699). EAR was a significant risk factor for bile leakage (odds ratio [OR], 4.167; 95% confidence interval [CI], 1.928-9.006; P < 0.001) along with multiple bile ducts (OR, 1.606; 95% CI, 1.022-2.526; P = 0.040) and hepaticojejunostomy (OR, 4.108; 95% CI, 2.190-7.707; P < 0.001). However, EAR had no statistical relationship to biliary stricture-free survival (hazard ratio [HR], 1.602; 95% CI, 0.982-2.613; P = 0.059), graft survival (HR, 1.745; 95% CI, 0.741-4.109; P = 0.203), or overall survival (HR, 1.405; 95% CI, 0.786-2.513; P = 0.251). HA complications were associated with poor biliary stricture-free survival (HR, 2.060; 95% CI, 1.329-3.193; P = 0.001), graft survival (HR, 5.549; 95% CI, 2.883-10.681; P < 0.001), and overall survival (HR, 1.958; 95% CI, 1.195-3.206; P = 0.008).

Conclusion.
Extra-anatomical HA reconstruction during living donor LT was not a risk factor for biliary stricture, graft failure, or overall survival.
FL/GCSF/AMD3100-mobilized Hematopoietic Stem Cells Induce Mixed Chimerism With Nonmyeloablative Conditioning and Transplantation Tolerance
Authors: Xu Hong , Zhu Ziqiang , Huang Yiming , Ildstad Suzanne T. 
Published: February 2019

Background.
Mobilization of hematopoietic stem cells (HSCs) has become the preferred approach for HSC transplantation. AMD3100, a competitive inhibitor of C-X-C motif chemokine receptor-4, has been found to be a rapid mobilizing agent. The present study evaluated approaches to optimize the product collected.

Methods.
Mobilized peripheral blood mononuclear cells (mPBMCs) from B6 mice were transplanted to recipient BALB/c mice conditioned with ablative or nonmyeloablative approaches.

Results.
The optimal dose of AMD3100 was found to be 5.0 mg/kg. Optimal HSC mobilization was observed when AMD3100 (day 10) was coadministered with Flt3 ligand (FL) (days 1–10) and granulocyte colony-stimulating factor (GCSF) (days 4–10). There was a 228.8-fold increase of HSC with FL/GCSF/AMD3100 compared with AMD3100 treatment alone. When unmodified mPBMCs were transplanted into ablated allogeneic recipients, all recipients expired by day 40 from severe acute graft versus host disease (GVHD). When T cells were depleted from mPBMC, long-term survival and engraftment were achieved in majority of the recipients. When PBMC mobilized by FL/GCSF/AMD3100 were transplanted into recipients conditioned nonmyeloablatively with anti-CD154/rapamycin plus 100, 200, and 300 cGy of total body irradiation, 42.9%, 85.7%, and 100% of mice engrafted, respectively. Donor chimerism was durable, multilineage, and stable. Lymphocytes from mixed chimeras showed no response to host or donor antigens, suggesting functional bidirection T-cell tolerance in vitro. Most importantly, none of the engrafted mice exhibited clinical features of GVHD.

Conclusions.
FL/GCSF/AMD3100 is an efficient treatment to maximally mobilize HSC. Durable engraftment and donor-specific tolerance can be achieved with mPBMC in nonmyeloablative conditioning without GVHD.
CYP1A2 Genetic Polymorphism Is Associated With Treatment Remission to Antidepressant Venlafaxine in Han Chinese Population
Authors: Zhu Yuhao , Zhang Naixing , Ren Decheng , Bi Yan , Xu Fei , Niu Weibo , Sun Qianqian , Guo Zhenming , Yuan Ruixue , Yuan Fan , Wu Xi , Cao Yanfei , Yang Fengping , Wang Lu , Du Li , Li Weidong , Xu Yifeng , Li Xingwang , Zhu Liping , He Lin , Shi Lei , He Guang , Yu Tao 
Published: February 2019

AbstractMajor depressive disorder (MDD) is a common mental disorder. Venlafaxine (VEN) is used to treat patients with MDD as an antidepressant of serotonin-norepinephrine reuptake inhibitor. In addition, current reports reveal that CYP enzymes mediate its metabolism, thereby affecting the treatment efficacy. The aim of this study was to test whether the genetic polymorphisms ofCYP1A2are associated with remission after VEN treatment for MDD. A total of 175 Han Chinese depressed patients have been recruited to accept a 6-week treatment with VEN. Three single-nucleotide polymorphisms ofCYP1A2were selected from dbSNP and previous literature to compare the allele and genotype frequencies between remitters and nonremitters. The A 17-item Hamilton Depression Scale was used to access the improvement of patients' depressive symptoms from the baseline to endpoint. A logistic regression analysis for remission was conducted. Between remitters and nonremitters, the allele and genotype frequencies of single-nucleotide polymorphism rs2470890 demonstrated significant differences. They still had significant differences between remitters and nonremitters after controlling baseline Hamilton Depression Scale scores, sex, and age in logistic regression. Our results suggest that the single-nucleotide polymorphism rs2470890 ofCYP1A2gene might be associated with treatment remission after VEN treatment in patients with MDD.
A general framework for predicting the transcriptomic consequences of non-coding variation
Authors: Abdalla Moustafa , Abdalla Mohamed , McCarthy Mark I. , Holmes Chris C. 
Published: February 2019

ABSTRACTGenome wide association studies (GWASs) for complex traits have implicated thousands of genetic loci. Most GWAS-nominated variants lie in noncoding regions, complicating the systematic translation of these findings into functional understanding. Here, we leverage convolutional neural networks to assist in this challenge. Our computational framework, peaBrain, models the transcriptional machinery of a tissue as a two-stage process: first, predicting the mean tissue specific abundance of all genes and second, incorporating the transcriptomic consequences of genotype variation to predict individual abundance on a subject-by-subject basis. We demonstrate that peaBrain accounts for the majority (>50%) of variance observed in mean transcript abundance across most tissues and outperforms regularized linear models in predicting the consequences of individual genotype variation. We highlight the validity of the peaBrain model by calculating non-coding impact scores that correlate with nucleotide evolutionary constraint that are also predictive of disease-associated variation and allele-specific transcription factor binding. We further show how these tissue-specific peaBrain scores can be leveraged to pinpoint functional tissues underlying complex traits, outperforming methods that depend on colocalization of eQTL and GWAS signals. We subsequently derive continuous dense embeddings of genes for downstream applications, and identify putatively functional eQTLs that are missed by high-throughput experimental approaches.
A framework for evaluating correspondence between brain images using anatomical fiducials
Authors: Lau Jonathan C. , Parrent Andrew G. , Demarco John , Gupta Geetika , Kai Jason , Stanley Olivia W. , Kuehn Tristan , Park Patrick J. , Ferko Kayla , Khan Ali R. , Peters Terry M. 
Published: February 2019

AbstractAccurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point-based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.
Multi-phosphorylation reaction and clustering tune Pom1 gradient mid-cell levels according to cell size
Authors: Gerganova Veneta , Floderer Charlotte , Archetti Anna , Michon Laetitia , Carlini Lina , Reichler Thaïs , Manley Suliana , Martin Sophie G 
Published: February 2019

AbstractProtein concentration gradients convey information at a distance from the source to both pattern developing organisms and organize single cells. In the rod-shaped cells of Schizosaccharomyces pombe, the DYRK-family kinase Pom1 forms concentration gradients with maxima at the cell poles. Pom1 controls the timing of mitotic entry by inhibiting the SAD-family kinase Cdr2, which forms stable membrane-associated nodes at mid-cell. Pom1 gradients rely on membrane association regulated by a phosphorylation-dephosphorylation cycle and lateral diffusion modulated by clustering. Whether the graded pattern directly alters Pom1 medial levels has been controversial. Here, using a combination of quantitative imaging approaches, including single particle tracking PALM and TIRF microscopy, we find that individual Pom1 molecules do not bind the membrane long enough to diffuse from cell pole to cell middle. Instead we propose they exchange within longer-lived clusters that form the functional gradient units. By creating an allelic series progressively blocking auto-phosphorylation, we show that multi-phosphorylation shapes and buffers the gradient to control the cortical mid-cell Pom1 levels, which represent the critical pool regulating Cdr2. Specific imaging of this cortical pool by TIRF microscopy demonstrates that more Pom1 overlaps with Cdr2 nodes in short than long cells, consistent with Pom1 inhibition of Cdr2 decreasing with cell growth. We conclude that Pom1 gradients modulate Pom1 mid-cell levels according to cell size.
Comparative genomics reveals the origin of fungal hyphae and multicellularity
Authors: Kiss Enikő , Hegedüs Botond , Varga Torda , Merényi Zsolt , Kószó Tamás , Bálint Balázs , Prasanna Arun N. , Krizsán Krisztina , Riquelme Meritxell , Takeshita Norio , Nagy László G. 
Published: February 2019

AbstractHyphae represent a hallmark structure of multicellular fungi with immense importance in their life cycle, including foraging for nutrients, reproduction, or virulence. Hypha morphogenesis has been the subject to intense interest, yet, the origins and genetic underpinning of the evolution of hyphae are hardly known. Using comparative genomics, we here show that the emergence of hyphae correlates with multiple types of genetic changes, including alterations of gene structure, gene family diversification as well as co-option and exaptation of ancient eukaryotic genes (e.g. phagocytosis-related genes). Half of the gene families involved in hypha morphogenesis have homologs in unicellular fungi and non-fungal eukaryotes and show little or no duplications coincident with the origin of multicellular hyphae. Considerable gene family diversification was observed only in transcriptional regulators and genes related to cell wall synthesis and modification. Despite losing 35-46% of their genes, yeasts retained significantly more multicellularity-related genes than expected by chance. We identified 414 gene families that evolved in a correlated fashion with hyphal multicellularity and may have contributed to its evolution. Contrary to most multicellular lineages, the origin of hyphae did not correlate with the expansion of gene families encoding kinases, receptors or adhesive proteins. Our analyses suggest that fungi took a unique route to multicellularity that involved limited gene family diversification and extensive co-option of ancient eukaryotic genes.
CONSENT: Scalable long read self-correction and assembly polishing with multiple sequence alignment
Authors: Morisse Pierre , Marchet Camille , Limasset Antoine , Lecroq Thierry , Lefebvre Arnaud 
Published: February 2019

MotivationThird-generation sequencing technologies Pacific Biosciences and Oxford Nanopore allow the sequencing of long reads of tens of kbp, that are expected to solve various problems, such as contig and haplotype assembly, scaffolding, and structural variant calling. However, they also display high error rates that can reach 10 to 30%, for basic ONT and non-CCS PacBio reads. As a result, error correction is often the first step of projects dealing with long reads. As first long reads sequencing experiments produced reads displaying error rates higher than 15% on average, most methods relied on the complementary use of short reads data to perform correction, in a hybrid approach. However, these sequencing technologies evolve fast, and the error rate of the long reads now reaches 10 to 12%. As a result, self-correction is now frequently used as the first step of third-generation sequencing data analysis projects. As of today, efficient tools allowing to perform self-correction of the long reads are available, and recent observations suggest that avoiding the use of second-generation sequencing reads could bypass their inherent bias.ResultsWe introduce CONSENT, a new method for the self-correction of long reads that combines different strategies from the state-of-the-art. More precisely, we combine a multiple sequence alignment strategy with the use of local de Bruijn graphs. Moreover, the multiple sequence alignment benefits from an efficient segmentation strategy based on k-mer chaining, which allows a considerable speed improvement. Our experiments show that CONSENT compares well to the latest state-of-the-art self-correction methods, and even outperforms them on real Oxford Nanopore datasets. In particular, they show that CONSENT is the only method able to efficiently scale to the correction of Oxford Nanopore ultra-long reads, and is able to process a full human dataset, containing reads reaching lengths up to 1.5 Mbp, in 15 days. Additionally, CONSENT also implements an assembly polishing feature, and is thus able to correct errors directly from raw long read assemblies. Our experiments show that CONSENT outperforms state-of-the-art polishing tools in terms of resource consumption, and provides comparable results. Moreover, we also show that, for a full human dataset, assembling the raw data and polishing the assembly afterwards is less time consuming than assembling the corrected reads, while providing better quality results.Availability and implementationCONSENT is implemented in C++, supported on Linux platforms and freely available at https://github.com/morispi/CONSENT.Contactpierre.morisse2@univ-rouen.fr
The Human Nickel Microbiome and its relationship to Allergy and Overweight in Women
Authors: Lusi E.A. , Santino I. , Petrucca A. , Zollo V. , Magri F. , O’Shea D , Tammaro A. 
Published: February 2019

AbstractIntroductionNickel exposure usually presents as Allergic Contact Dermatitis. However, Nickel not only causes dermatitis, but an excess of dietary Nickel is reported to be responsible for overweight, metabolic disorders and imbalance of gut microflora.ObjectiveThe aim of study is to expand a preliminary reported evidence of the presence of Nickel-resistant bacteria isolated in human microbiome and further evaluate their association with nickel allergy and overweight in females, the gender mostly affected by Nickel exposure.Materials and MethodsWe collected stool samples from 11 lean female with a nickel allergy (BMI <25) and 17 overweight nickel allergic subjects (BMI >25). 11 subjects not allergic to nickel served as control group. Stool cultures were supplemented with increasing concentrations of nickel sulphate (NiSO4⋅6H2O) from 0.1mM up to 50 mM, in both aerobic and anaerobic conditions(culturomics-approach Lusi, 2017). Stool cultures not supplemented with nickel were used as controls. Identification of Nickel resistant bacteria was made by MALDI-TOF technology.ResultsIn control subjects, 5 mM NiSO4 was the cut off for microbial growth. Conversely, gut bacteria continued to grow at concentration higher than 5 mM in allergic subjects. In particular, Nickel resistant bacteria able to tolerate 32 mM of NiSO4 was detected in 10% of lean allergic and 29% of overweight allergic females. Gut microbes able to grow in at extremely high NiSO4 concentration (50mM) could only be detected in overweight patients with a severe nickel allergy. At increasing NiSO4 concentration, allergic females, especially those with increased BMI, showed a progressive decrease ofEnterobacteriaceaealong with an increased presence ofLactobacillaceae,BacillaceaeandClostridiaceaecompared to control subjects. Major changes in microbial composition were noted at 50 mM of NiSO4 in overweight allergic females.ConclusionOverweight females with a nickel allergy harbor gut microbes highly resistant to nickel and the role of these bacterial strains must be further elucidated.
Accelerating Dissociative Events in Molecular Dynamics Simulations by Selective Potential Scaling
Authors: Deb Indrajit , Frank Aaron T. 
Published: February 2019

ABSTRACTMolecular dynamics (or MD) simulations can be a powerful tool for modeling complex dissociative processes such as ligand unbinding. However, many biologically relevant dissociative processes occur on timescales that far exceed the timescales of typical MD simulations. Here, we implement and apply an enhanced sampling method in which specific energy terms in the potential energy function are selectively “scaled” to accelerate dissociative events during simulations. Using ligand unbinding as an example of a complex dissociative process, we selectively scaled-up ligand-water interactions in an attempt to increase the rate of ligand unbinding. By applying our selectively scaled MD (or ssMD) approach to three cyclin-dependent kinase 2 (CDK2)-inhibitor complexes, we were able to significantly accelerate ligand unbinding thereby allowing, in some cases, unbinding events to occur within as little as 2 ns. Moreover, we found that we could make realistic estimates of the unbinding as well as the binding free energies (∆Gsim) of the three inhibitors from our ssMD simulation data. To accomplish this, we employed a previously described Kramers’-based rate extrapolation (KRE) method and a newly described free energy extrapolation (FEE) method. Because our ssMD approach is general, it should find utility as an easy-to-deploy, enhanced sampling method for modeling other dissociative processes.
Real-time computation of the TMS-induced electric field in a realistic head model
Authors: Stenroos Matti , Koponen Lari 
Published: February 2019

AbstractBackgroundTranscranial magnetic stimulation (TMS) is often targeted using a model of TMS-induced electric field (E). In such navigated TMS, the E-field models have been based on spherical approximation of the head. Such models omit the effects of cerebrospinal fluid (CSF) on the E-field, leading to potentially large errors in the computed field. So far, realistic models have been too slow for interactive TMS navigation.ObjectiveWe present computational methods that enable real-time solving of the E-field in a realistic head model that contains the CSF.MethodsUsing reciprocity and Geselowitz integral equation, we separate the computations to coil-dependent and -independent parts. For the coil-dependent part of Geselowitz integrals, we present a fast numerical quadrature. Further, we present a moment-matching approach for optimizing dipole-based coil models. We verify the new methods using simulations in a realistic head model that contains the brain, CSF, skull, and scalp.ResultsThe new quadrature introduces a relative error of 1.1%. The total error of the quadrature and coil model was 1.43% and 1.15% for coils with 38 and 76 dipoles, respectively. The difference between our head model and a simpler realistic model that omits the CSF was 29%. Using a standard PC and a 38-dipole coil, our solver computed the E-field in 84 coil positions per second in 20000 points on the cortex.ConclusionThe presented methods enable real-time solving of the TMS-induced E-field in a realistic head model that contains the CSF. The new methodology allows more accurate targeting and precise adjustment of intensity during experimental or clinical TMS mapping.
Machine Learning Methods to Identify Genetic Correlates of Radiation-Associated Contralateral Breast Cancer in the WECARE Study
Authors: Lee Sangkyu , Liang Xiaolin , Woods Meghan , Reiner Anne S. , Thomas Duncan , Concannon Patrick , Bernstein Leslie , Lynch Charles F. , Boice John D. , Deasy Joseph O. , Bernstein Jonine L. , Oh Jung Hun 
Published: February 2019

AbstractThe purpose of this study is to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve of 0.62 (p=0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC.