bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience
Authors: Victor David W. , Monsour Howard P. , Boktour Maha , Lunsford Keri , Balogh Julius , Graviss Edward A. , Nguyen Duc T. , McFadden Robert , Divatia Mukul K. , Heyne Kirk , Ankoma-Sey Victor , Egwim Chukwuma , Galati Joseph , Duchini Andrea , Saharia Ashish , Mobley Constance , Gaber A. Osama , Ghobrial R. Mark 
Published: June 2019

Background.
Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. Currently, liver transplantation may be the optimal treatment for HCC in cirrhotic patients. Patient selection is currently based on tumor size. We developed a program to offer liver transplantation to selected patients with HCC outside of traditional criteria.

Methods.
Retrospective review for patients transplanted with HCC between April 2008 and June 2017. Patients were grouped by tumor size according to Milan, University of California San Francisco (UCSF), and outside UCSF criteria. Patient demographics, laboratory values, and outcomes were compared. Patients radiographically outside Milan criteria were selected based on tumor control with locoregional therapy (LRT) and 9 months of stability from LRT. α-fetoprotein values were not exclusionary.

Results.
Two hundred twenty HCC patients were transplanted, 138 inside Milan, 23 inside UCSF, and 59 beyond UCSF criteria. Patient survival was equivalent at 1, 3, or 5 years despite pathologic tumor size. Waiting time to transplantation was not significantly different at an average of 344 days. In patients outside UCSF, tumor recurrence was equivalent to Milan and UCSF criteria recipients who waited >9 months from LRT. Although tumor recurrence was more likely in outside of UCSF patients (3% versus 9% versus 15%; P = 0.02), recurrence-free survival only trended toward significance among the groups (P = 0.053).

Conclusions.
Selective patients outside of traditional size criteria can be effectively transplanted with equivalent survival to patients with smaller tumors, even when pathologic tumor burden is considered. Tumor stability over time can be used to help select patients for transplantation.
Development and Validation of Phenotype Classifiers across Multiple Sites in the Observational Health Sciences and Informatics (OHDSI) Network
Authors: Kashyap Mehr , Seneviratne Martin , Banda Juan M , Falconer Thomas , Ryu Borim , Yoo Sooyoung , Hripcsak George , Shah Nigam H 
Published: June 2019

ABSTRACTObjectiveAccurate electronic phenotyping is essential to support collaborative observational research. Supervised machine learning methods can be used to train phenotype classifiers in a high-throughput manner using imperfectly labeled data. We developed ten phenotype classifiers using this approach and evaluated performance across multiple sites within the Observational Health Sciences and Informatics (OHDSI) network.Materials and MethodsWe constructed classifiers using the Automated PHenotype Routine for Observational Definition, Identification, Training and Evaluation (APHRODITE) R-package, an open-source framework for learning phenotype classifiers using datasets in the OMOP CDM. We labeled training data based on the presence of multiple mentions of disease-specific codes. Performance was evaluated on cohorts derived using rule-based definitions and real-world disease prevalence. Classifiers were developed and evaluated across three medical centers, including one international site.ResultsCompared to the multiple mentions labeling heuristic, classifiers showed a mean recall boost of 0.43 with a mean precision loss of 0.17. Performance decreased slightly when classifiers were shared across medical centers, with mean recall and precision decreasing by 0.08 and 0.01, respectively, at a site within the USA, and by 0.18 and 0.10, respectively, at an international site.Discussion and ConclusionWe demonstrate a high-throughput pipeline for constructing and sharing phenotype classifiers across multiple sites within the OHDSI network using APHRODITE. Classifiers exhibit good portability between sites within the USA, however limited portability internationally, indicating that classifier generalizability may have geographic limitations, and consequently, sharing the classifier-building recipe, rather than the pre-trained classifiers, may be more useful for facilitating collaborative observational research.
Glycan size and attachment site location affect electron transfer dissociation (ETD) fragmentation and automated glycopeptide identification
Authors: Alagesan Kathirvel , Hinneburg Hannes , Seeberger Peter H , Varón Silva Daniel , Kolarich Daniel 
Published: June 2019

AbstractWe used a small synthetic glycopeptide library to systematically evaluate the effect of glycosylation site location and glycan size on the efficiency of ETD MS/MS fragmentation and subsequent automated identification. Understanding how the physico-chemical properties of glycopeptides influence glycopeptide fragmentation allows for optimizing fragmentation conditions and software assisted data analyses, which rely on informative fragmentation spectra for subsequent data processing to identify glycopeptides. Often, mis-assignment of glycopeptides occurs due to uncertainties such as failure to produce sufficient peptide backbone fragment ions. Our synthetic glycopeptide library contained glycopeptides differing in glycosylation site position within the peptide as well as glycan size (from the pentasaccharide N-glycan core to fully sialylated, biantennary N-glycans). Different software solutions such as SEQUEST and Amanda were compared for ETD glycopeptide identification. We found that all, glycan size, glycosylation site position within a glycopeptide and individual precursor m/z significantly impacted the number and quality of assignable glycopeptide backbone fragments, and thus the likelihood to be correctly identified in software assisted data analyses.
genesorteR: Feature Ranking in Clustered Single Cell Data
Authors: Ibrahim Mahmoud M , Kramann Rafael 
Published: June 2019

ABSTRACTMarker genes identified in single cell experiments are expected to be highly specific to a certain cell type and highly expressed in that cell type. Detecting a gene by differential expression analysis does not necessarily satisfy those two conditions and is typically computationally expensive for large cell numbers.Here we present genesorteR, an R package that ranks features in single cell data in a manner consistent with the expected definition of marker genes in experimental biology research. We benchmark genesorteR using various data sets and show that it is distinctly more accurate in large single cell data sets compared to other methods. genesorteR is orders of magnitude faster than current implementations of differential expression analysis methods, can operate on data containing millions of cells and is applicable to both single cell RNA-Seq and single cell ATAC-Seq data.genesorteR is available at https://github.com/mahmoudibrahim/genesorteR.
Genome-wide characterization of satellite DNA arrays in a complex plant genome using nanopore reads
Authors: Vondrak Tihana , Robledillo Laura Ávila , Novák Petr , Koblížková Andrea , Neumann Pavel , Macas Jiří 
Published: June 2019

AbstractBackgroundAmplification of monomer sequences into long contiguous arrays is the main feature distinguishing satellite DNA from other tandem repeats, yet it is also the main obstacle in its investigation because these arrays are in principle difficult to assemble. Here we explore an alternative, assembly-free approach that utilizes ultra-long Oxford Nanopore reads to infer the length distribution of satellite repeat arrays, their association with other repeats and the prevailing sequence periodicities.ResultsWe have developed a computational workflow for similarity-based detection and downstream analysis of satellite repeats in individual nanopore reads that led to genome-wide characterization of their properties. Using the satellite DNA-rich legume plantLathyrus sativusas a model, we demonstrated this approach by analyzing eleven major satellite repeats using a set of nanopore reads ranging from 30 to over 200 kb in length and representing 0.73x genome coverage. We found surprising differences between the analyzed repeats because only two of them were predominantly organized in long arrays typical for satellite DNA. The remaining nine satellites were found to be derived from short tandem arrays located within LTR-retrotransposons that occasionally expanded in length. While the corresponding LTR-retrotransposons were dispersed across the genome, this array expansion occurred mainly in the primary constrictions of theL. sativuschromosomes, which suggests that these genome regions are favorable for satellite DNA accumulation.ConclusionsThe presented approach proved to be efficient in revealing differences in long-range organization of satellite repeats that can be used to investigate their origin and evolution in the genome.
Discovering candidate imprinted genes and Imprinting Control Regions in the human genome
Authors: Bina Minou 
Published: June 2019

ABSTRACTGenomic imprinting is a process thereby a subset of genes is expressed in a parent-of-origin specific manner. This evolutionary novelty is restricted to mammals and controlled by genomic DNA segments known as Imprinting Control Regions (ICRs). The known imprinted genes function in many important developmental and postnatal processes including organogenesis, neurogenesis, and fertility. Furthermore, defects in imprinted genes could cause severe diseases and abnormalities. Because of the importance of the ICRs to the regulation of parent-of-origin specific gene expression, I developed a genome-wide strategy for their localization. This strategy located clusters of the ZFBS-Morph overlaps along the entire human genome. Previously, I showed that in the mouse genome, clusters of 2 or more of these overlaps correctly located ∼ 90% of the fully characterized ICRs and germline Differentially Methylated Regions (gDMRs). The ZFBS-Morph overlaps are composite-DNA-elements comprised of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. My strategy consists of creating plots to display the density of ZFBS-Morph overlaps along genomic DNA. Peaks in these plots pinpointed several of the known ICRs/gDMRs within relatively long genomic DNA sections and even along entire chromosomal DNA. Therefore, peaks in the density-plots are likely to reflect the positions of known or candidate ICRs. I also found that by locating the genes in the vicinity of candidate ICRs, I could discover potential and novel human imprinting genes. Additionally, my exploratory assessments revealed a connection between several of the potential imprinted genes and human developmental anomalies including syndromes.
Temperature-Dependent Regulation of Upstream Open Reading Frame Translation inS. Cerevisiae
Authors: Kulkarni Shardul D. , Zhou Fujun , Sen Neelam Dabas , Zhang Hongen , Hinnebusch Alan G. , Lorsch Jon R. 
Published: June 2019

AbstractBackgroundTranslation of an mRNA in eukaryotes starts at AUG in most cases. Near-cognate codons (NCCs) such as UUG, ACG and AUU are also used as start sites at low levels inS. cerevisiae. Initiation from NCCs or AUGs in the 5’-untranslated regions (UTRs) of mRNAs can lead to translation of upstream open reading frames (uORFs) that might regulate expression of the main ORF (mORF). Although there is some circumstantial evidence that the translation of uORFs can be affected by environmental conditions, little is known about how it is affected by changes in growth temperature.ResultsUsing reporter assays, we found that changes in growth temperature can affect translation from NCC start sites in yeast cells, suggesting the possibility that gene expression could be regulated by temperature by altering use of different uORF start codons. Using ribosome profiling, we provide evidence that growth temperature regulates the efficiency of translation of nearly 200 uORFs inS. cerevisiae. Of these uORFs, most that start with an AUG codon have increased translational efficiency at 37 °C relative to 30 °C and decreased efficiency at 20 °C. For translationally regulated uORFs starting with NCCs, we did not observe a general trend for the direction of regulation as a function of temperature, suggesting mRNA-specific features can determine the mode of temperature-dependent regulation. Consistent with this conclusion, the position of the uORFs in the 5’-leader relative to the 5’-cap and the start codon of the main ORF correlates with the direction of temperature-dependent regulation of uORF translation. We have identified several novel cases in which changes in uORF translation are inversely correlated with changes in the translational efficiency of the downstream main ORF. Our data suggest that translation of these mRNAs is subject to temperature-dependent, uORF-mediated regulation.ConclusionsOverall, our data suggest that alterations in the translation of specific uORFs by temperature can regulate gene expression inS. cerevisiae.
Vascular Progenitors Generated from Tankyrase Inhibitor-Regulated Naïve Diabetic Human iPSC Potentiate Efficient Revascularization of Ischemic Retina
Authors: Park Tea Soon , Zimmerlin Ludovic , Evans-Moses Rebecca , Thomas Justin , Huo Jeffrey S. , Kanherkar Riya , He Alice , Ruzgar Nensi , Grebe Rhonda , Bhutto Imran , Lutty Gerard , Zambidis Elias T. 
Published: June 2019

ABSTRACTVascular regenerative therapies with conventional human induced pluripotent stem cells (hiPSC) currently remain limited by high interline variability of differentiation and poor efficiency for generating functionally transplantable vascular progenitors (VP). Here, we report the advantage of tankyrase inhibitor-regulated naïve hiPSC (N-hiPSC) for significantly improving vascular cell therapies. Conventional hiPSC reprogrammed from type-1 diabetic donor fibroblasts (DhiPSC) were stably reverted to naïve epiblast-like state with high functional pluripotency with a cocktail of LIF and three small molecules inhibiting the tankyrase, MEK, and GSK3β signaling pathways (LIF-3i). Naïve diabetic VP (N-DVP) differentiated from naïve DhiPSC (N-DhiPSC) expanded more efficiently, possessed higher proliferation, possessed more stable genomic integrity and displayed higher in vitro vascular functionality than primed diabetic VP (DVP) generated from isogenic conventional DhiPSC. Moreover, N-DVP survived, migrated, and engrafted in vivo into the deep vasculature of the neural retinal layers with significantly higher efficiencies than isogenic primed DVP in a murine model of ischemic retinopathy. Epigenetic analyses of CpG DNA methylation and histone configurations at developmental promoters of N-hiPSC revealed tight regulation of lineage-specific gene expression and a de-repressed naïve epiblast-like epigenetic state that was highly poised for multi-lineage transcriptional activation. We propose that reprogramming of patient donor cells to a tankyrase inhibitor-regulated N-hiPSC may more effectively erase epigenetic aberrations sustained from chronic diseases such as diabetes for subsequent regenerative therapies. More broadly, tankyrase inhibitor-regulated N-hiPSC represent a new class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.
A Universal Phase Transition in Plankton Trait Dynamics
Authors: Held Jenny , Lorimer Tom , Stoop Ruedi , Pomati Francesco , Albert Carlo 
Published: June 2019

AbstractKey ecological traits, like cell size, often follow scale-free or self-similar distributions. This indicates that these systems might operate near a critical (i.e. second-order) phase transition where macroscopic system behaviour is largely decoupled from microscopic system details, allowing an extremely simple, yet accurate and robust mathematical system characterisation. However, how trait-distribution scaling results from a critical transition has not yet been explicitly demonstrated. Here, we demonstrate that a generic class of cell growth and division models exhibits a critical transition from a growth-dominated to a division-dominated phase. We find experimental evidence for this transition, both in the population dynamics and in the moment scaling of chlorophyll distributions, for prokaryotic and eukaryotic phytoplankton growth under different light intensities. Our approach offers testable predictions of the response of unicellular trait-distributions to perturbations.
The mouse lung early cellular innate immune response is not sufficient to control fungal infection with Cryptococcus neoformans
Authors: Rudman Jacob , Marriott Helen Maria , Carlin Leo M. , Johnston Simon Andrew 
Published: June 2019

AbstractCryptococcus neoformanscauses life-threatening infection in the immunocompromised. This and other opportunistic pathogens are an increasing threat as immunosuppression increases globally. To counter antibiotic resistance, there is precedent for developing immune enhancing therapy. However, our understanding of how immunocompetent patients resolve these infections is poor as opportunistic infections typically resolve subclinically. Because this has led to a lack of clinical data, we rely on animal models. Currentin vivoinfection models either lack mammalian immunity or are not compatible with long term high content imaging required to model the complexities of human host-pathogen interactions. Therefore, we have developed anex vivomurine precision cut lung slice (PCLS) model to understand innate immunity in cryptococcosis. C57BL/6 mice were sacrificed 0 or 24 hours post infection withKN99αcryptococci. Lungs were inflated with 37°C agarose, 300μm thick PCLS were prepared on a vibratome and imaged by confocal or wide-field fluorescence microscopy. Using PCLS and immunofluorescence, we demonstrate cryptococcal replication and clearance rates are balanced over the first 24 hours of infection. Cell-mediated immunity is alveolar macrophage centric, although alveolar macrophages demonstrate limited phagocytosis of cryptococci and enable intracellular cryptococcal replication.Cryptococcus neoformansresponded to the lung environment by forming enlarged cells, although these were not large enough to be titan cells. To further understand cryptococcal proliferationin vivo, we also infected animals withplb1mutantCryptococcus neoformansthat has been shown to exhibit proliferation defectsin vivo. We found no difference in fungal burden withplb1infected animals 24 hours post infection, but observed significantly larger fungal cells and no incidences of phagocytosis. Thus, the PCLS model can be used to assess the lung immune response early in cryptococcal infection, demonstrating that resident lung macrophages cannot control cryptococcal infection and offer an intracellular niche forCryptococcus neoformansgrowth.
Phytochemical Constituency Profiling and Antimicrobial Activity Screening of Seaweeds Extracts Collected from the Bay of Bengal Sea Coasts
Authors: Hasan Mahmudul , Imran Md. Abdus Shukur , Bhuiyan Farhana Rumzum , Ahmed Sheikh Rashel , Shanzana Parsha , Moli Mahmuda Akter , Foysal Shakhawat Hossain , Dabi Suma Bala 
Published: June 2019

AbstractSeaweeds are able to produce a great variety of secondary metabolites that are characterized by a broad spectrum of biological activities. Two seaweeds species, namelyHypnea musciformisandEnteromorpha intestinalis werestudied to evaluate the phytochemical constituency and antimicrobial activities. First of all, crude extracts of both sea weeds were prepared by two different extraction methods (soaking and water bath) using different solvents. Phytochemicals profiling results revealed the presence of bioactive compounds (flavonoids, alkaloids, tannin, saponin and phenols) in both seaweed extracts. Quantification results for ethanolic extracts ofH. musciformis and E. intestinalisestimated 51 mg and 43 mg tannins in per gram of dried samples and flavonoids contents were found 67 mg and 57 mg/g mg QE/g respectively. Total phenolic contents were determined in terms of gallic acid equivalent (GAE).H. musciformisexhibited higher amount of phenolics (59 ± 0.0002 mg GAE/g) thanE. intestinalisextracts (41 ± 0.0002 mg GAE/g). In antimicrobial activity test, ethanol extractsof H. musciformisandE. intestinaliswere found 10 mm of inhibition diameter against all of the bacterial strains. Besides, methanol extracts ofE. intestinaliswere more susceptible toStaphylococcus aureus and Pseudomonaswhich was close to the inhibition diameter (>15 mm) of the mainstream antibiotic; Gentamicin. Moreover,Klebsiella sp. was found more susceptible to ethanol and methanol extracts of Hypnea musciformisas it showed inhibition zone greater than 15 mm. Both Seaweed extracts possessed higher amount of phytochemicals and showed promising antimicrobial activities when compared with the standards.
A phylogenomic analysis ofNepenthes(Nepenthaceae)
Authors: Murphy Bruce , Forest Félix , Barraclough Timothy , Rosindell James , Bellot Sidonie , Cowan Robyn , Golos Michal , Jebb Matthew , Cheek Martin 
Published: June 2019

AbstractNepenthaceae is one of the largest carnivorous plant families and features ecological and morphological adaptations indicating an impressive adaptive radiation. However, investigation of evolutionary and taxonomic questions is hindered by poor phylogenetic understanding, with previous molecular studies based on limited loci and taxa. We use high-throughput sequencing with a target-capture methodology based on a 353-loci, probe set to recover sequences for 197 samples, representing 151 described or putativeNepenthesspecies. Phylogenetic analyses were performed using supermatrix and maximum quartet species tree approaches. Our analyses confirm five Western outlier taxa, followed byN. danseri, as successively sister to the remainder of the group. We also find mostly consistent recovery of two major Southeast Asian clades. The first contains common or widespread lowland species plus a Wallacean–New Guinean clade. Within the second clade, sects.InsignesandTentaculataeare well supported, while geographically defined clades representing Sumatra, Indochina, Peninsular Malaysia, Palawan, Mindanao and Borneo are also consistently recovered. However, we find considerable conflicting signal at the site and locus level, and often unstable backbone relationships. A handful of Bornean taxa are inconsistently placed and require further investigation. We make further suggestions for a modified infra-generic classification of genusNepenthes.