bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Cost Effectiveness of Two “New” Lynch Syndrome Case Finding Protocols in Endometrial Cancer Population Contrasted with the IHC-based Protocol
Authors: Gudgeon James M. , Varner Michael W. , Hashibe Mia , Williams Marc S. 
Published: April 2019

AbstractPurposeTo investigate the effectiveness and costs of two Lynch syndrome screening protocols among endometrial cancer (EC) patients and compare to an immunohistochemistry (IHC)–based protocol.MethodsAnalytic models were developed to represent the two protocols: a brief cancer family history questionnaire (bFHQ) and direct-to-sequencing of the germline. Data from reviews of published literature, augmented by local data and expert opinion were used to populate the model representing the number of women diagnosed in the U.S. in 2018. Multiple analyses employing simulation modeling were performed to estimate a variety of clinical and economic outcomes.ResultsUnder conditions considered here to be plausible, the bFHQ is expected to miss 58% (min./max. = 24 to 80%) of LS index cases, a direct-to-sequencing protocol to miss 30% (min./max. = 6% to 53%), and the IHC-based protocol based on previous analysis 58% (min./max. = 33 to 80%). When direct costs of testing and genetic counseling are added to the models, the total screening program costs for the bFHQ protocol are substantially lower at all sequencing price points than the other protocols. For example, at the low end of the sequencing price point (ie, $250), the total cost of screening programs for IHC, bFHQ, and sequencing are $22.9 million, $5.3 million, and $13.8 million, respectively. The best estimate of the break-even price of sequencing, when the cost of the program is equivalent between the IHC and sequencing protocols, is about $635.ConclusionThe bFHQ and direct-to-sequencing LS screening protocols are more effective and cost effective at identifying LS index cases than the standard IHC-based protocol under the conditions represented in our models. These estimates of various outcome metrics of the three LS index case finding protocols may help stakeholders make decisions of the use of limited healthcare dollars.
Hippocampal theta codes for distances in semantic and temporal spaces
Authors: Solomon Ethan A. , Lega Bradley C. , Sperling Michael R. , Kahana Michael J. 
Published: April 2019

ABSTRACTThe medial temporal lobe (MTL) is known to support episodic memory and spatial navigation, raising the possibility that its true function is to form “cognitive maps” of any kind of information. Studies in humans and animals support the idea that the hippocampal theta rhythm (4-8 Hz) is key to this mapping function, as it has been repeatedly observed during spatial navigation tasks. If episodic memory and spatial navigation are two sides of the same coin, we hypothesized that theta oscillations would also reflect relations between explicitly nonspatial items, such as words. We asked 189 neurosurgical patients to perform a verbal free-recall task, of which 96 had indwelling electrodes placed in the MTL. Subjects were instructed to remember short lists of sequentially-presented nouns. We found that hippocampal theta power and connectivity during item retrieval coded for semantic distances between words, as measured using word2vec-derived subspaces. Additionally, hippocampal theta indexed temporal distances between words after filtering lists on recall performance, to ensure adequate dynamic range in time. Theta effects were only noted for semantic subspaces of 1-dimension, indicating a substantial compression of the possible semantic feature space. These results lend further support to our growing confidence that the MTL forms cognitive maps of arbitrary representational spaces, reconciling longstanding differences between the spatial and episodic memory literatures.
The cryptic impacts of invasion: Functional homogenization of tropical ant communities by invasive fire ants
Authors: Wong Mark K. L. , Guénard Benoit , Lewis Owen T. 
Published: April 2019

AbstractInvasive insects represent major threats to ecosystems worldwide. Yet their effects on the functional dimension of biodiversity, measured as the diversity and distribution of traits, are overlooked. Such measures often determine the resilience of ecological communities and the ecosystem processes they modulate. The fire ant Solenopsis invicta is a highly problematic invasive species occurring on five continents. Its impacts on the taxonomic diversity of native ant communities have been studied but its impacts on their functional diversity are unknown. Comparing invaded and uninvaded plots in tropical grasslands of Hong Kong, we investigated how the presence of S. invicta affects the diversity and distribution of ant species and traits within and across communities, the functional identities of communities, and functionally unique species. We calculated the functional diversity of individual species, including the trait variation from intraspecific polymorphisms, and scaled up these values to calculate functional diversity at the community level. Invasion had only limited effects on species richness and functional richness, which were 13% and 8.5% lower in invaded communities respectively. In contrast, invasion had pronounced effects on taxonomic and functional composition due to turnover in species and trait values. Furthermore, invaded communities were functionally more homogeneous, displaying 23% less turnover and 56% more redundancy than uninvaded communities, as well as greater clustering and lower divergence in trait values. Invaded communities had fewer functionally-unique individuals and were characterized by ant species with narrower heads and bodies and shorter mandibles. Our results suggest that studies based only on taxonomic measures of diversity or indices describing trait variety risk underestimating the full ramifications of invasions. Investigating the diversity and distributions of traits at species, community and landscape levels can reveal the cryptic impacts of alien species which, despite causing little taxonomic change, may substantially modify the structure and functioning of ecological communities.
CNCC: An analysis tool to determine genome-wide DNA break end structure at single-nucleotide resolution
Authors: Szlachta Karol , Raimer Heather M , Comeau Laurey D. , Wang Yuh-Hwa 
Published: April 2019

AbstractDNA double-stranded breaks (DSBs) are potentially deleterious events in a cell. The end structures (blunt, 3’- and 5’-overhangs) at sites of double-stranded breaks contribute to the fate of their repair and provide critical information for consequences of the damage. Here, we describe the use of a coverage-normalized cross correlation analysis (CNCC) to process high-precision genome-wide break mapping data, and determine genome-wide break end structure distributions at single-nucleotide resolution. For the first time, on a genome-wide scale, our analysis revealed the increase in the 5’ to 3’ end resection following etoposide treatment, and the global progression of the resection due to the removal of DNA topoisomerase II cleavage complexes. Further, our method distinguished the change in the pattern of DSB end structure with increasing doses of the drug. The ability of this method to determine DNA break end structures withouta prioriknowledge of break sequences or genomic position should have broad applications in understanding genome instability.
The Positive End of the Polygenic Score Distribution for ADHD: A Low Risk or a Protective Factor?
Authors: Li James J. 
Published: April 2019

AbstractBackgroundPolygenic scores (PGS) are widely used to characterize genetic liability for heritable mental disorders, including attention-deficit/hyperactivity disorder (ADHD). However, little is known about the effects of a low burden of genetic liability for ADHD, including whether this functions as a low risk or protective factor for ADHD and related functional outcomes in later life. The current study examines the association of low ADHD PGS and functional outcomes in adulthood.MethodsParticipants were from Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health) (N=7,088; mean age=29, s.d.=1.74). ADHD PGS was computed from an existing genome-wide association study, and adult functional outcomes, including cognition, educational attainment, mental health and physical health were assessed during in-home interviews.ResultsIndividuals at the lowest end of the ADHD PGS distribution (i.e., lowest 20th percentile) had the lowest probabilities of ADHD, exhibiting a 17-19% reduction in risk for ADHD relative to the observed 8.3% prevalence rate of ADHD in Add Health. Furthermore, individuals with low ADHD PGS had higher cognitive performance, greater levels of educational attainment, and lower BMI relative to individuals representing the rest of the ADHD PGS distribution, including those who were in the medium and high PGS groups.ConclusionsFindings indicate that psychiatric PGS likely capture far more than just the risk and the absence of risk for a psychiatric outcome; where one lies along the PGS distribution may predict diverging functional consequences, for better and for worse.
Comparing and Validating Automated Tools for Individualized Electric Field Simulations in the Human Head
Authors: Puonti Oula , Saturnino Guilherme B. , Madsen Kristoffer H. , Thielscher Axel 
Published: April 2019

ABSTRACTComparing electric field simulations from individualized head models against in-vivo recordings is important for direct validation of computational field modeling for transcranial brain stimulation and brain mapping techniques such as electro- and magnetoencephalography. This also helps to improve simulation accuracy by pinning down the factors having the largest influence on the simulations. Here we compare field simulations from four different automated pipelines, against intracranial voltage recordings in an existing dataset of 14 epilepsy patients. We show that ignoring uncertainty in the simulations leads to a strong bias in the estimated linear relationship between simulated and measured fields. In addition, even though the simulations between the pipelines differ notably, this is not reflected in the correlation with the measurements. We discuss potential reasons for this apparent mismatch and propose a new Bayesian regression analysis of the data that yields unbiased estimates enabling robust conclusions to be reached.
Production of high cellulase yields from polypore fungi in solid-state fermentation using green tea waste
Authors: Nguyen KA , Penkhrue W , Lumyong S 
Published: April 2019

AbstractPolypores are diverse macrofungi that have been extensively studied for their enzyme production capabilities. Presently, these enzymes are being used for many industrial purposes. However, the high-cost associated with their production is the main barrier to their broader application. This work aimed to study the optimal medium and conditions by using solid state fermentation. Seven polypore strains were used for cellulase activity screening. The fermentation experiments were carried out in 250 mL Erlenmeyer flasks with green tea waste as a substrate. Notably, Microporus sp. KA038 showed the best level of activity of 81.8 IU/gds. Various parameters such as temperature on growth, moisture content, nitrogen source, initial pH value, inoculum size and incubation time were considered to determine the optimal conditions for cellulase production. The optimal medium consisted of green tea leaves as a carbon source, beef extract as an organic nitrogen source, and NH4H2PO4 as an inorganic nitrogen source, while pH 7.0 and an incubation temperature of 30°C for 4 days resulted in a high enzyme yield with Microporus sp. KA038.
Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver
Authors: Liu Bingdong , Pan Xiaohan , Yao Liheng , Chen Shujie , Liu Zhihong , Han Mulan , Yin Yulong , Xu Guohuan , Wan Dan , Dai Xiaoshuang , Sun Jia , Pan Jiyang , Zhang Huabing , Wang Wei , Liu Li , Xie Liwei 
Published: April 2019

AbstractIron is an essential trace mineral for the growth, systemic metabolism, and immune response. Imbalance of tissue iron absorption and storage leads to various diseases. The excessive iron accumulation is associated with inflammation and cancer while iron deficiency leads to growth retardation. Studies investigated in Kenyan infants and school children suggests that both low and high iron intake result in dysbiosis of gut microbiota. This would lead to the disruption of microbial diversity, an increase of pathogen abundance and the induction of intestinal inflammation. Despite this progress, in-depth studies investigating the relationship between iron availability and gut microbiota is not completely explored. In the current study, we established a murine model to study the connection between iron and microbiota by feeding mice with either iron-deprived or -fortified diet. To identify key microbiota related to iron levels, we combined the 16S rRNA amplicon sequencing with the innovated bioinformatic algorithms, such as RDA, co-occurrence, and machine learning to identify key microbiota. Manipulation of iron levels in the diet leads to systemic iron dysregulation and dysbiosis of gut microbiota. The bioinformatic algorithms used here detect five key bacteria that correlate with systemic iron levels. Leveraging on these key microbiotas, we also established a prediction model which could precisely distinguish the individual under either iron-deprived or iron-fortified physiological condition to further prove the link between microbiota and systemic iron homeostasis. This innovated and non-invasive approach could be potentially used for the early diagnosis and therapy of iron-dysregulation related diseases, e.g. anemia, inflammatory disease, fibrosis, and cancers.
Genomic profiling ofNitrospiraspecies reveals ecological success of comammoxNitrospira
Authors: Palomo Alejandro , Dechesne Arnaud , Smets Barth F. 
Published: April 2019

AbstractNitrification was long thought to consist in the stepwise oxidation of ammonia to nitrite and of nitrite to nitrate by ammonia oxidizing and nitrite oxidizing microorganisms, respectively. Recently, single microorganisms capable of complete ammonia to nitrate oxidation (comammox) were identified in theNitrospiragenus. This genus, previously considered to only contain canonical nitrite oxidizers is diverse and has a broad environmental distribution. Yet, a global insight into the abundance, niche preference, and genomic diversity ofNitrospirais missing. Here, we established the largestNitrospiragenome database to date, revealing 68 putative species, most without cultivated representatives. We performed a global survey through read recruitment of metagenomic data from various environments against this database that identified that environmental filtering structures species distribution, without large scale biogeographical signal. The ecological success of comammoxNitrospirais evident as they outnumber and are more diverse than canonicalNitrospirain communities from all environments but wastewater treatment plants. We detect a phylogenetic signal inNitrospiraspecies habitat preference, that is strongest for canonicalNitrospiraspecies. ComammoxNitrospiraeco-evolutionary history is more complex with subclades achieving rapid niche divergence via horizontal transfer of genes, including that encoding the hydroxylamine oxidoreductase, one of the key enzymes involved in nitrification.
A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
Authors: Fazal Asif , Thankachan Divya , Harris Ellie , Seipke Ryan F. 
Published: April 2019

AbstractCloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign BGCs by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.
Pharmacological manipulations of judgement bias: a systematic review and meta-analysis
Authors: Neville Vikki , Nakagawa Shinichi , Zidar Josefina , Paul Elizabeth S. , Lagisz Malgorzata , Bateson Melissa , Løvlie Hanne , Mendl Michael 
Published: April 2019

AbstractValidated measures of animal affect are crucial to research spanning a number of disciplines including neuroscience, psychopharmacology, and animal welfare science. Judgement bias, which assesses decision-making under ambiguity, is a promising measure of animal affect. One way of validating this measure is to induce affective states using pharmacological manipulations and determine whether the predicted judgement biases are observed. Here, we conducted a systematic review and meta-analysis using data from 19 published research articles that use this approach from which 440 effect sizes were extracted. The results of the meta-analysis suggest that pharmacological manipulations overall altered judgement bias as predicted. However, there were several moderating factors including the neurobiological target of the drug, whether the drug was hypothesised to induce a relatively positive or negative affective state, dosage, and the presented cue. This may partially reflect interference from adverse effects of the drug, such as sedation. Thus, while judgement bias can be used to measure pharmacologically-induced affective states, potential adverse effects of the drug should be considered when interpreting results.
Endogenous RNAi pathway evolutionarily shapes the destiny of the antisense lncRNAs transcriptome
Authors: Szachnowski Ugo , Andus Sara , Foretek Dominika , Morillon Antonin , Wery Maxime 
Published: April 2019

ABSTRACTAntisense (as)lncRNAs are extensively degraded by the nuclear exosome and the cytoplasmic exoribonuclease Xrn1 in the budding yeast Saccharomyces cerevisiae, lacking RNA interference (RNAi). Whether the ribonuclease III Dicer affects aslncRNAs in close RNAi-capable relatives remains unknown. Using genome-wide RNA profiling, here we show that aslncRNAs are primarily targeted by the exosome and Xrn1 in the RNAi-capable budding yeast Naumovozyma castellii, Dicer only affecting Xrn1-sensitive lncRNAs (XUTs) levels in Xrn1-deficient cells. The dcr1 and xrn1 mutants display synergic growth defects, indicating that Dicer becomes critical in the absence of Xrn1. Small RNA sequencing showed that Dicer processes aslncRNAs into small RNAs, with a preference for asXUTs. Consistently, Dicer localizes into the cytoplasm. Finally, we observed an expansion of the exosome-sensitive antisense transcriptome in N. castellii compared to S. cerevisiae, suggesting that the presence of cytoplasmic RNAi has reinforced the nuclear RNA surveillance machinery to temper aslncRNAs expression. Our data provide fundamental insights into aslncRNAs metabolism and open perspectives into the possible evolutionary contribution of RNAi in shaping the aslncRNAs transcriptome.
Telomeric small RNAs in the genus Caenorhabditis
Authors: Frenk Stephen , Lister-Shimauchi Evan H. , Ahmed Shawn 
Published: April 2019

AbstractTelomeric DNA is composed of simple tandem repeat sequences and has a G-rich strand that runs 5’ to 3’ towards the chromosome terminus. Small RNAs with homology to telomeres have been observed in several organisms and could originate from telomeres or from interstitial telomere sequences (ITSs), which are composites of degenerate and perfect telomere repeat sequences found on chromosome arms. We identified C. elegans small RNAs composed of the Caenorhabditis telomere sequence (TTAGGC)n with up to three mismatches, which might interact with telomeres. We rigorously defined ITSs for genomes of C. elegans and for two closely related nematodes, C. briggsae and C. remanei. We found that most telomeric small RNAs with mismatches originated from ITSs, which were depleted from mRNAs and but were enriched in introns whose genes often displayed hallmarks of genomic silencing. C. elegans small RNAs composed of perfect telomere repeats were very rare but were increased by several orders of magnitude in C. briggsae and C. remanei. Major small RNA species in C. elegans begin with a 5’ guanine nucleotide, which was strongly depleted from perfect telomeric small RNAs of all three Caenorhabditis species. Perfect telomeric small RNAs corresponding to the G-rich strand of the telomere commonly began with 5’ UAGGCU and 5’UUAGGC, whereas C-rich strand RNAs commonly begin with 5’CUAAGC. In contrast, telomeric small RNAs with mismatches had a mixture of all four 5’ nucleotides. Together, our results imply that perfect telomeric small RNAs have a mechanism of biogenesis that is distinct from known classes of small RNAs and that a dramatic change in their regulation occurred during recent Caenorhabditis evolution.
Exploring and analysing immune single cell multi-omics data with VDJView
Authors: Samir Jerome , Rizzetto Simone , Gupta Money , Luciani Fabio 
Published: April 2019

AbstractBackgroundSingle cell RNA sequencing provides unprecedented opportunity to simultaneously explore the transcriptomic and immune receptor diversity of T and B cells. However, there are limited tools available that simultaneously analyse large multi-omics datasets integrated with metadata such as patient and clinical information.ResultsWe developed VDJView, which permits the simultaneous or independent analysis and visualisation of gene expression, immune receptors, and clinical metadata of both T and B cells. This tool is implemented as an easy-to-use R shiny web-application, which integrates numerous gene expression and TCR analysis tools, and accepts data from plate-based sorted or high-throughput single cell platforms. We utilised VDJView to analyse several 10X scRNA-seq datasets, including a recent dataset of 150,000 CD8+ T cells with available gene expression, TCR sequences, quantification of 15 surface proteins, and 44 antigen specificities (across viruses, cancer, and self-antigens). We performed quality control, filtering of tetramer non-specific cells, clustering, random sampling and hypothesis testing to discover antigen specific gene signatures which were associated with immune cell differentiation states and clonal expansion across the pathogen specific T cells. We also analysed 563 single cells (plate-based sorted) obtained from 11 subjects, revealing clonally expanded T and B cells across primary cancer tissues and metastatic lymph-node. These immune cells clustered with distinct gene signatures according to the breast cancer molecular subtype. VDJView has been tested in lab meetings and peer-to-peer discussions, showing effective data generation and discussion without the need to consult bioinformaticians.ConclusionsVDJView enables researchers without profound bioinformatics skills to analyse immune scRNA-seq data, integrating and visualising this with clonality and metadata profiles, thus accelerating the process of hypothesis testing, data interpretation and discovery of cellular heterogeneity. VDJView is freely available at https://bitbucket.org/kirbyvisp/vdjview.