bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymph Node Response to Neoadjuvant Chemotherapy as an Independent Prognostic Factor in Metastatic Esophageal Cancer
Authors: Urakawa Shinya , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuhiro , Takahashi Tsuyoshi , Kurokawa Yukinori , Motoori Masaki , Kimura Yutaka , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro 
Published: July 2019

Objective:
The aim of this study was to evaluate primary tumor (PT) and lymph node (LN) responses to neoadjuvant chemotherapy (NACT) for predicting long-term survival in patients with metastatic esophageal cancer (EC).

Background:
In evaluating NACT responses in patients with EC, imaging modalities typically target the PT in the esophagus, which is unmeasurable. Targeting measurable organs, like positive LNs, might provide more accurate assessments.

Methods:
We enrolled 251 patients with EC and clinically positive LNs that underwent curative resections, after triplet NACT. The percent reduction of PT area was measured with bidimensional computed tomography. The LN response was defined as the percent reduction of the sum of the short diameters in all positive LNs.

Results:
NACT reduced PTs and LNs by (median, range) 58.0% (38.1–94.9) and 34.5% (46.2–68.2), respectively. Based on the receiver-operating characteristic analyses for predicting a histological response and a 10% stepwise cutoff analyses of recurrence-free survival (RFS), responder/nonresponder cutoff values were ≥60% for PT area reductions and ≥30% for LN size reductions. 39.6% of patients showed discordant PT and LN responses. Compared with PT-responders, LN-responders had significantly less advanced pN (P < 0.0001) and pM (P = 0.015) in addition to less advanced pT (P < 0.0001) and better histological responses (P < 0.0001), and closer correlations to lymphatic, distant metastases and dissemination. A multivariate analysis of RFS identified 2 independent prognostic factors: the LN response [hazard ratio (HR) = 2.51, 95% confidence interval (CI) = 1.63–3.95, P < 0.0001] and the pN (HR = 2.72, 95% CI = 1.44–5.64, P = 0.0016), but not the PT response.

Conclusions:
The LN response to NACT predicted long-term survival more precisely than the PT response in patients with metastatic EC.
Establishing Normal Values for F-Wave Latencies in Diagnosing Peripheral Neuropathies for the Pediatric Population
Authors: Sharma Rishi , Sorenson Eric J. , Ryan Conor S. , Conlee Erin M. , Boon Andrea J. , Laughlin Ruple S. 
Published: July 2019

Purpose:
We present a unique technique applying F-wave latencies to assist in the diagnosis of peripheral neuropathy within the pediatric age group.

Methods:
We calculated an F-wave estimated deviance adjusted for limb length measurements, distal motor conduction velocity, and distal motor latencies. We compared the F-wave estimated deviance from the normal subjects with those with peripheral neuropathy (both axonal and demyelinating) to establish diagnostic accuracy in pediatric patients.

Results:
The normal range for the F-wave estimated deviance in the upper limb was −1 to +6 ms and in the lower limb was −8 to +5 ms. When compared with 82 subjects with peripheral neuropathy, there was a significant difference between the normal subjects and those with neuropathy (P values between 0.002 and 0.0005 for each of the individual nerves tested).

Conclusions:
The F-wave estimated deviance is independent of age and can be accurately applied to the electrodiagnostic testing of pediatric patients with suspected neuropathy.
Individual Variation in Brain Network Topography is Linked to Schizophrenia Symptomatology
Authors: Nawaz Uzma , Lee Ivy , Beermann Adam , Eack Shaun , Keshavan Matcheri , Brady Roscoe 
Published: July 2019

AbstractBackgroundResting state fMRI (rsfMRI) demonstrates that the brain is organized into distributed networks. Numerous studies have examined links between psychiatric symptomatology and network functional connectivity. Traditional rsfMRI analyses assume that the spatial organization of networks is invariant between individuals. This dogma has recently been overturned by the demonstration that networks show significant variation between individuals. We tested the hypothesis that previously observed relationships between schizophrenia negative symptom severity and network connectivity are actually due to individual differences in network spatial organization.Methods44 participants diagnosed with schizophrenia underwent rsfMRI scans and clinical assessments. A multivariate pattern analysis determined how whole brain functional connectivity correlates with negative symptom severity at the individual voxel level.ResultsBrain connectivity to a region of the right dorso-lateral pre-frontal cortex correlates with negative symptom severity. This finding results from individual differences in the topographic distribution of two networks: the default mode network (DMN) and the task positive network (TPN). Both networks demonstrate strong (r∼0.49) and significant (p<0.001) relationships between topography and symptom severity. For individuals with low symptom severity, this critical region is part of the DMN. In highly symptomatic individuals, this region is part of the TPN.ConclusionPreviously overlooked individual variation in brain organization is tightly linked to differences in schizophrenia symptom severity. Recognizing critical links between network topography and pathological symptomology may identify key circuits that underlie cognitive and behavioral phenotypes. Individual variation in network topography likely guides different responses to clinical interventions that rely on anatomical targeting (e.g. TMS).
Taxonomic Uncertainty and the Anomaly Zone: Phylogenomics Disentangle a Rapid Radiation to Resolve Contentious Species (Gila robusta complex) in the Colorado River
Authors: Chafin Tyler K. , Douglas Marlis R. , Bangs Max R. , Martin Bradley T. , Mussmann Steven M. , Douglas Michael E. 
Published: July 2019

AbstractSpecies is an indisputable unit for biodiversity conservation, yet their delimitation is fraught with both conceptual and methodological difficulties. A classic example is the taxonomic controversy surrounding the Gila robusta complex in the lower Colorado River of southwestern North America. Nominal species designations were originally defined according to weakly diagnostic morphological differences that conflicted with traditional genetic analyses. Consequently, the complex was re-defined as a single polytypic unit, with the proposed ‘threatened’ status of two being withdrawn at the federal level. Here, we utilized dense spatial and genomic sampling (N=387 and >22k loci) to re-evaluate the status of the complex, based on SNP-based coalescent and polymorphism-aware phylogenetic models. In doing so, all three species were supported as evolutionarily independent lineages, despite widespread phylogenetic discordance. To understand this discrepancy with past studies, we categorized evolutionary mechanisms driving discordance. We tested (and subsequently rejected) prior hypotheses suggesting that phylogenetic discord in the complex was hybridization-driven. Instead, we found the G. robusta complex to have diverged within the ‘anomaly zone’ of tree space and, as such, have accumulated inconsistent patterns of diversity which have confounded prior studies. After extending these analyses with phylogeographic modeling, we propose that this is reflective of a rapid radiation promoted by Plio-Pleistocene tectonism. Our results not only support resurrection of the three species as distinct entities, but also offer an empirical example of how phylogenetic discordance can be categorized in other recalcitrant taxa where variation is primarily partitioned at the species-level.
Effects of distraction on taste-related neural processing
Authors: Duif I. , Wegman J. , Mars M. , de Graaf C. , Smeets P.A.M. , Aarts E. 
Published: July 2019

SummaryDistracted eating is associated with increased food intake and overweight. However, the underlying neurocognitive mechanisms are unknown. To elucidate these mechanisms, 41 healthy normal-weight participants received sips of high- and low-sweet isocaloric chocolate milk, while performing a high- or low-distracting detection task during fMRI on two test days. Subsequently, we measured ad libitum food intake. As expected, a region in the primary taste cortex – located in the insula – responded more to the sweeter drink. Distraction did not affect this right insula sweetness response across the group, but did weaken sweetness-related connectivity of this region to a secondary taste region in the right orbitofrontal cortex. Moreover, distraction-related attenuation of taste processing in the insula predicted increased subsequent ad libitum food intake after distraction between subjects. These results reveal a previously unknown mechanism explaining how distraction during consumption attenuates neural taste processing and increases food intake. The study was preregistered at https://osf.io/vxdhg/register/5771ca429ad5a1020de2872e?view_only=e3207cd6567f41f0a1505e343a64b5aa.
Assessment of Phenotype Microarray plates for rapid and high-throughput analysis of collateral sensitivity networks
Authors: Dunkley Elsie J. , Chalmers James D. , Cho Stephanie , Finn Thomas J. , Patrick Wayne M. 
Published: July 2019

ABSTRACTThe crisis of antimicrobial resistance is driving research into the phenomenon of collateral sensitivity. Sometimes, when a bacterium evolves resistance to one antimicrobial, it becomes sensitive to others. In this study, we have investigated the utility of Phenotype Microarray (PM) plates for identifying collateral sensitivities with unprecedented throughput. We assessed the relative resistance/sensitivity phenotypes of nine strains ofStaphylococcus aureus(two laboratory strains and seven clinical isolates) towards the 72 antimicrobials contained in three PM plates. In general, the PM plates reported on resistance and sensitivity with a high degree of reproducibility. However, a rigorous comparison of PM growth phenotypes with minimum inhibitory concentration (MIC) measurements revealed a trade-off between throughput and accuracy. Small differences in PM growth phenotype did not necessarily correlate with changes in MIC. Thus, we conclude that PM plates are useful for the rapid and high-throughput assessment of large changes in collateral sensitivity phenotypes during the evolution of antimicrobial resistance, but more subtle examples of cross-resistance or collateral sensitivity cannot be reliably identified using this approach.
Evaluation of waste paper for cultivation of oyster mushroom (Pleurotus ostreatus) with some added supplementary materials
Authors: Tesfay Teklemichael , Godifey Tesfay , Mesfin Roman , Kalayu Girmay 
Published: July 2019

AbstractMushroom cultivation is an economically feasible bio-technological process for conversion of various lignocellulosic wastes. This study was conducted at Aksum University with the aim of evaluating the suitability of waste paper supplemented with corn stalk and wheat bran for Oyster mushroom cultivation. Spawn were prepared in Microbiology laboratory and inoculated into the prepared substrates. Waste paper supplemented with corn stalk and wheat bran with 0%, 25% and 50% were tested for their productivity and biological efficiency (BE) for cultivation ofP.ostreatusmushroom. Data were analyzed using SPSS version 20. Higher (26.20± 19.36) mean weight, pileus diameter (7.90 ±2.66cm), total yield (646.4 ±273.1gm) and BE (64.64± 273 % were obtained from waste paper (50%) +cornstalk (25%) +wheat bran (25%). However, Lower (17.92±81.95%) BE were obtained from waste paper (100%). Moreover, the highest (3.88 ±0.32 cm) mean stalk length were obtained from waste paper (50%) + cornstalk (50). This study revealed that waste paper supplemented with corn stalk and wheat bran results in high BE and total yield. Thus, appears to be a promising alternative for the cultivation of oyster mushroom. Yet, waste paper without supplement poorly supports the growth ofP.ostreatusmushroom.
A restriction enzyme reduced representation sequencing approach for low-cost, high-throughput metagenome profiling
Authors: Hess Melanie K. , Rowe Suzanne J. , Van Stijn Tracey C. , Henry Hannah M. , Hickey Sharon M. , Brauning Rudiger , McCulloch Alan F. , Hess Andrew S. , Kirk Michelle R. , Kittelmann Sandra , Wood Graham R. , Janssen Peter H. , McEwan John C. 
Published: July 2019

AbstractMicrobial community profiles have been associated with a variety of traits, including methane emissions in livestock, however, these profiles can be difficult and expensive to obtain for thousands of samples. The objective of this work was to develop a low-cost, high-throughput approach to capture the diversity of the rumen microbiome. Restriction enzyme reduced representation sequencing (RE-RRS) using ApeKI or PstI, and two bioinformatic pipelines (reference-based and reference-free) were compared to 16S rRNA gene sequencing using repeated samples collected two weeks apart from 118 sheep that were phenotypically extreme (60 high and 58 low) for methane emitted per kg dry matter intake (n=236). DNA was extracted from freeze-dried rumen samples using a phenol chloroform and bead-beating protocol prior to sequencing. The resulting sequences were used to investigate the repeatability of the rumen microbial community profiles, the effect of host genetics, laboratory and analytical method, and the genetic and phenotypic correlations with methane production. The results suggested that the best method was PstI RE-RRS analyzed with the reference-free approach via a correspondence analysis, with estimates for repeatability of 0.62±0.06, heritability 0.31±0.29, and genetic and phenotypic correlation with methane emissions of 0.88±0.25 and 0.64±0.05 respectively for the first component of correspondence analysis. The reference-free approach assigned 62.0±5.7% of reads to common 65 bp tags, much higher than the reference-based approach of 6.8±1.8% of reads assigned. Sensitivity studies suggested approximately 2000 samples could be sequenced in a single lane on an Illumina HiSeq 2500, therefore the current work of 118 samples/lane and future proposed 384 samples/lane are well within that threshold. Our approach is now being used to investigate host factors affecting the rumen and its association with a variety of production and environmental traits. With minor adaptations, our approach could be used to obtain microbial profiles from other metagenomic samples.
Macropinocytosis and Clathrin-Dependent Endocytosis Play Pivotal Roles for the Infectious Entry of Puumala Virus
Authors: Bauherr Sandy , Larsberg Filip , Petrich Annett , Sperber Hannah Sabeth , Klose Victoria , Azab Walid , Schade Matthias , Luckner Madlen , Höfer Chris Tina , Lehmann Maik Joerg , Witkowski Peter T. , Krüger Detlev H. , Herrmann Andreas , Schwarzer Roland 
Published: July 2019

AbstractViruses from the taxonomic familyHantaviridaeare encountered as emerging pathogens causing two life-threatening human zoonoses: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) with case fatalities of up to 50%. Here we comprehensively investigated entry of the Old-World Hantavirus, Puumala virus (PUUV), into mammalian cells, showing that upon treatment with pharmacological inhibitors of macropinocytosis and clathrin-mediated endocytosis, PUUV infections are significantly reduced. We demonstrated that the inhibitors did not interfere with viral replication and that RNA interference, targeting cellular mediators of macropinocytosis, is able to decrease PUUV infection levels significantly. Moreover, we established lipophilic tracer staining of PUUV virus particles and showed co-localization of stained virions and markers of macropinocytic uptake. Cells treated with lysosomotrophic agents were shown to exhibit an increased resistance to infection, confirming previous data suggesting that a low pH-dependent step is involved in PUUV infection. Finally, we observed a significant increase in the fluid-phase uptake of cell infected with PUUV, indicative of a virus-triggered promotion of macropinocytosis.Author SummaryTheHantaviridaefamily comprises a very diverse group of virus species and is considered an emerging global public health threat. Human pathogenic hantaviruses are primarily rodent-borne. Zoonosis is common with more than 150,000 annually registered cases and a case fatality index of up to 50%. Individual hantavirus species differ significantly in terms of their pathogenicity, but also their cell biology and host-pathogen interactions. In this study, we focused on the most prevalent pathogenic hantavirus in Europe, Puumala virus (PUUV), and investigated the entry and internalization of PUUV virions into mammalian cells. We showed that both, clathrin-mediated endocytosis and macropinocytosis, are cellular pathways exploited by the virus to establish productive infections and demonstrated that pharmacological inhibition of macropinocytosis or its targeted knockdown using RNA interference significantly reduced viral infections. We also found indications for an increase of macropinocytic uptake upon PUUV infections, suggesting that the virus triggers specific cellular mechanisms in order to promote its own internalization and facilitate infections.
m6A-binding YTHDF proteins promote stress granule formation by modulating phase separation of stress granule proteins
Authors: Fu Ye , Zhuang Xiaowei 
Published: July 2019

AbstractDiverse RNAs and RNA-binding proteins form phase-separated, membraneless granules in cells under stress conditions. However, the role of the prevalent mRNA methylation, m6A, and its binding proteins in stress granule (SG) assembly remain unclear. Here, we show that m6A-modified mRNAs are enriched in SGs, and that m6A-binding YTHDF proteins are critical for SG formation. Depletion of YTHDF1/3 inhibits SG formation and recruitment of m6A-modified mRNAs to SGs. Both the N-terminal intrinsically disordered region and the C-terminal m6A-binding YTH domain of YTHDF proteins are crucial for SG formation. Super-resolution imaging further reveals that YTHDF proteins are in a super-saturated state, forming clusters that reside in the periphery of and at the junctions between SG core clusters, and promote SG phase separation by reducing the activation energy barrier and critical size for condensate formation. Our results reveal a new function and mechanistic insights of the m6A-binding YTHDF proteins in regulating phase separation.
Benchmarking predictions of MHC class I restricted T cell epitopes
Authors: Paul Sinu , Croft Nathan P. , Purcell Anthony W. , Tscharke David C. , Sette Alessandro , Nielsen Morten , Peters Bjoern 
Published: July 2019

AbstractT cell epitope candidates are commonly identified using computational prediction tools in order to enable applications such as vaccine design, cancer neoantigen identification, development of diagnostics and removal of unwanted immune responses against protein therapeutics. Most T cell epitope prediction tools are based on machine learning algorithms trained on MHC binding or naturally processed MHC ligand elution data. The ability of currently available tools to predict T cell epitopes has not been comprehensively evaluated. In this study, we used a recently published dataset that systematically defined T cell epitopes recognized in vaccinia virus (VACV) infected mice, considering both peptides predicted to bind MHC or experimentally eluted from infected cells, making this the most comprehensive dataset of T cell epitopes mapped in a complex pathogen. We evaluated the performance of all currently publicly available computational T cell epitope prediction tools to identify these major epitopes from all peptides encoded in the VACV proteome. We found that all methods were able to improve epitope identification above random, with the best performance achieved by neural network-based predictions trained on both MHC binding and MHC ligand elution data (NetMHCPan-4.0 and MHCFlurry). Impressively, these methods were able to capture more than half of the major epitopes in the top 0.04% (N = 277) of peptides in the VACV proteome (N = 767,788). These performance metrics provide guidance for immunologists as to which prediction methods to use. In addition, this benchmark was implemented in an open and easy to reproduce format, providing developers with a framework for future comparisons against new tools.Author summaryComputational prediction tools are used to screen peptides to identify potential T cell epitope candidates. These tools, developed using machine learning methods, save time and resources in many immunological studies including vaccine discovery and cancer neoantigen identification. In addition to the already existing methods several epitope prediction tools are being developed these days but they lack a comprehensive and uniform evaluation to see which method performs best. In this study we did a comprehensive evaluation of publicly accessible MHC I restricted T cell epitope prediction tools using a recently published dataset of Vaccinia virus epitopes. We found that methods based on artificial neural network architecture and trained on both MHC binding and ligand elution data showed very high performance (NetMHCPan-4.0 and MHCFlurry). This benchmark analysis will help immunologists to choose the right prediction method for their desired work and will also serve as a framework for tool developers to evaluate new prediction methods.
Bifrost – Highly parallel construction and indexing of colored and compacted de Bruijn graphs
Authors: Holley Guillaume , Melsted Páll 
Published: July 2019

AbstractMotivationDe Bruijn graphs are the core data structure for a wide range of assemblers and genome analysis software processing High Throughput Sequencing datasets. For population genomic analysis, the colored de Bruijn graph is often used in order to take advantage of the massive sets of sequenced genomes available for each species. However, memory consumption of tools based on the de Bruijn graph is often prohibitive, due to the high number of vertices, edges or colors in the graph. In order to process large and complex genomes, most short-read assemblers based on the de Bruijn graph paradigm reduce the assembly complexity and memory usage by compacting first all maximal non-branching paths of the graph into single vertices. Yet, de Bruijn graph compaction is challenging as it requires the uncompacted de Bruijn graph to be available in memory.ResultsWe present a new parallel and memory efficient algorithm enabling the direct construction of the compacted de Bruijn graph without producing the intermediate uncompacted de Bruijn graph. Bifrost features a broad range of functions such as sequence querying, storage of user data alongside vertices and graph editing that automatically preserve the compaction property. Bifrost makes full use of the dynamic index efficiency and proposes a graph coloring method efficiently mapping eachk-mer of the graph to the set of genomes in which it occurs. Experimental results show that our algorithm is competitive with state-of-the-art de Bruijn graph compaction and coloring tools. Bifrost was able to build the colored and compacted de Bruijn graph of about 118,000 Salmonella genomes on a mid-class server in about 4 days using 103 GB of main memory.Availabilityhttps://github.com/pmelsted/bifrostavailable with a BSD-2 licenseContactguillaumeholley@gmail.com