bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer/Testis Antigens Differentially Expressed in Prostate Cancer: Potential New Biomarkers and Targets for Immunotherapies
Authors: Kagohara Luciane T. , Carleton Neil M. , Takahashi Sayuri , Shiraishi Takumi , Mooney Steven M. , Vessella Robert L. , Getzenberg Robert H. , Kulkarni Prakash , Veltri Robert W. 
Published: May 2019

AbstractCurrent clinical tests for prostate cancer (PCa), such as the PSA test, are not fully capable of discerning patients that are highly likely to develop metastatic prostate cancer (MPCa). Hence, more accurate prediction tools are needed to provide treatment strategies that are focused on the different risk groups. Cancer/testis antigens (CTAs) are expressed during embryonic development and present aberrant expression in cancer making them ideal tumor specific biomarkers. Here, the potential use of a panel of CTAs as a biomarker for PCa detection as well as metastasis prediction is explored. We initially identified eight CTAs (CEP55, NUF2, PAGE4, PBK, RQCD1, SPAG4, SSX2andTTK) that are differentially expressed in MPCa when compared to local disease and used this panel to compare the gene and protein expression profiles in paired PCa and normal adjacent prostate tissue. We identified differential expression of all eight CTAs at the protein level when comparing 80 paired samples of PCa and the adjacent non-cancer tissue. Using multiple logistic regression we also show that a panel of these CTAs present high accuracy to discriminate normal from tumor samples. In summary, this study provides evidence that a panel of CTAs, differentially expressed in aggressive PCa, is a potential biomarker for diagnosis and prognosis to be used in combination with the current clinically available tools and is also a potential target for immunotherapy development.
Evaluating FAIR Maturity Through a Scalable, Automated, Community-Governed Framework
Authors: Wilkinson Mark D , Dumontier Michel , Sansone Susanna-Assunta , da Silva Santos Luiz Olavo Bonino , Prieto Mario , Batista Dominique , McQuilton Peter , Kuhn Tobias , Rocca-Serra Philippe , Crosas Mercè , Schultes Erik 
Published: May 2019

AbstractTransparent evaluations of FAIRness are increasingly required by a wide range of stakeholders, from scientists to publishers, funding agencies and policy makers. We propose a scalable, automatable framework to evaluate digital resources that encompasses measurable indicators, open source tools, and participation guidelines, which come together to accommodate domain relevant community-defined FAIR assessments. The components of the framework are: (1) Maturity Indicators - community-authored specifications that delimit a specific automatically-measurable FAIR behavior; (2) Compliance Tests - small Web apps that test digital resources against individual Maturity Indicators; and (3) the Evaluator, a Web application that registers, assembles, and applies community-relevant sets of Compliance Tests against a digital resource, and provides a detailed report about what a machine “sees” when it visits that resource. We discuss the technical and social considerations of FAIR assessments, and how this translates to our community-driven infrastructure. We then illustrate how the output of the Evaluator tool can serve as a roadmap to assist data stewards to incrementally and realistically improve the FAIRness of their resources.
RF heating of deep brain stimulation implants in open-bore vertical MRI systems
Authors: Golestanirad Laleh , Lampman David , Kazemivalipour Ehsan , Habara Hideta , Atalar Ergin , Rosenow Joshua , Pilitsis Julie , Kirsch John 
Published: May 2019

AbstractPurposePatients with deep brain stimulation (DBS) implants highly benefit from MRI, however access to MRI is restricted for these patients due to safety hazards associated with RF heating of the implant. To date, all MRI studies on RF heating of medical implants have been performed in horizontal closed-bore systems. Vertical MRI scanners have a fundamentally different distribution of electric and magnetic fields and are now available at 1.2T, capable of high-resolution structural and functional MRI. This work presents the first simulation study of RF heating of DBS implants in high-field vertical scanners.MethodsWe performed finite element electromagnetic simulations to calculate SAR at tips of DBS leads during MRI in a commercially available 1.2 T vertical coil compared to a 1.5 T horizontal scanner. Both isolated leads and fully implanted systems were included.ResultsWe found 10-30-fold reduction in SAR implication at tips of isolated DBS leads, and up to 19-fold SAR reduction at tips of leads in fully implanted systems in vertical coils compared to horizontal birdcage coils.ConclusionsIf confirmed in larger patient cohorts and verified experimentally, this result can open the door to plethora of structural and functional MRI applications to guide, interpret, and advance DBS therapy.
Detecting Direct Oral Anticoagulants in Trauma Patients using Liquid Chromatography-Mass Spectrometry: a Novel Approach to Medication Reconciliation
Authors: Jayaraman Sudha , DeAntonio Jonathan H. , Leichtle Stefan W. , Han Jinfeng , Liebrecht Loren , Contaifer Daniel , Young Caroline , Chou Christopher , Staschen Julia , Doan David , Kumar Naren Gajenthra , Wolfe Luke , Nguyen Tammy , Chenault Gregory , Anand Rahul J. , Bennett Jonathan D. , Ferrada Paula , Goldberg Stephanie , Procter Levi D. , Rodas Edgar B. , Rossi Alan P. , Whelan James F. , Feeser V. Ramana , Vitto Michael J. , Broering Beth , Hobgood Sarah , Mangino Martin , Aboutanos Michel , Bachmann Lorin , Wijesinghe Dayanjan S 
Published: May 2019

AbstractBackgroundAccurate medication reconciliation in trauma patients is essential but difficult. Currently there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS) based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival.MethodsPlasma samples were collected from 356 patients who provided informed consent including-10 healthy controls, 19 known positive or negative controls and 327 trauma patients over 65 years of age who were evaluated at our large, urban Level 1 Trauma Center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage was compared with LCMS results to determine overall accuracy, sensitivity, specificity and positive and negative predictive values (PPV, NPV) of the assay.ResultsOf 356 patients, 39 were on DOACs (10.96%): 21 were on Apixaban, 14 on rivaroxaban and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.06%, (PPV 92.50% and NPV 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.11% (PPV 86.36% and NPV 99.40%). There were three false positive results and two false negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity.ConclusionsThis LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients.Study type: diagnostic testBasic Science paper: therefore does not require a level of evidence.
Classification of unlabeled observations in Species Distribution Modelling using Point Process Models
Authors: Guilbault Emy , Renner Ian , Mahony Michael , Beh Eric 
Published: May 2019

1AbstractSpecies distribution modelling, which allows users to predict the spatial distribution of species with the use of environmental covariates, has become increasingly popular, with many software platforms providing tools to fit species distribution models. However, the species observations used in species distribution models can have varying levels of quality and can have incomplete information, such as uncertain species identity.In this paper, we develop two algorithms to reclassify observations with unknown species identities which simultaneously predict different species distributions using spatial point processes. We compare the performance of the different algorithms using different initializations and parameters with models fitted using only the observations with known species identity through simulations.We show that performance varies with differences in correlation among species distributions, species abundance, and the proportion of observations with unknown species identities. Additionally, some of the methods developed here outperformed the models that didn’t use the misspecified data.These models represent an helpful and promising tool for opportunistic surveys where misidentification happens or for the distribution of species newly separated in their taxonomy.
Modification of oxygen consumption and blood flow in mouse somatosensory cortex by cell-type-specific neuronal activity
Authors: Dahlqvist Matilda , Thomsen Kirsten , Postnov Dmitry , Lauritzen Martin 
Published: May 2019

AbstractGamma activity arises from the interplay between pyramidal neurons and fast-spiking parvalbumin (PV) interneurons, is an integral part of higher cognitive functions and is assumed to contribute importantly to brain metabolic responses. Cerebral metabolic rate of oxygen (CMRO2) responses were evoked by optogenetic stimulation of cortical PV interneurons and pyramidal neurons. We found that CMRO2 responses depended on neuronal activation, but not on the power of gamma activity induced by optogenetic stimulation. This implies that evoked gamma activity per se is not energy demanding. Optogenetic stimulation of PV interneurons during somatosensory stimulation reduced excitatory neuronal activity but did not potentiate O2 consumption as previously hypothesized. In conclusion, our data suggest that activity-driven CMRO2 responses depend on neuronal excitation rather than the cerebral rhythmic activity they induce. Excitation of both excitatory and inhibitory neurons requires energy, but inhibition of cortical excitatory neurons by interneurons does not potentiate activity-driven energy consumption.
Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis
Authors: Alahmad Ayham , Paffrath Vanessa , Clima Rosanna , Busch Jonas Felix , Rabien Anja , Kilic Ergin , Villegas Sonia , Timmermann Bernd , Attimonelli Marcella , Jung Klaus , Meierhofer David 
Published: May 2019

AbstractPapillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increasedde novosynthesis rate of GSH, based on glutamine consumption. Furthermore, rewiring of the main pathways involved in ATP and glucose synthesis was observed at the protein level. In contrast, transcripts encoding for the respiratory chain were not regulated, which prompts for non-genetic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.SIGNIFICANCE STATEMENTWe applied proteome- and metabolome profiling to elucidate molecular features in malign papillary renal cell carcinomas. By this characterization, a reprogramming of the main metabolic pathways, such as gluconeogenesis and fatty acid- and amino acid metabolism were identified. The proteins involved in the respiratory chain and the corresponding enzymatic activities were strongly reduced in pRCC, showing an anti-correlation compared with the transcriptome. Similar to renal oncocytomas, the ROS scavenger glutathione was identified as a hallmark in pRCC. Our results suggest that impaired metabolism and dysfunctional mitochondria determine the fate of pRCC. Furthermore, we propose that the specific regulation of the mitochondrial respiratory chain can differentiate highly similar malignant pRCCs from benign renal oncocytomas.
Microbiomes from feces vs. gut in aquatic vertebrates: distinct community compositions between substrates and preservation methods
Authors: Anslan Sten , Li Huan , Künzel Sven , Vences Miguel 
Published: May 2019

AbstractSample type and preservation methods are likely to influence microbiome analysis results. Relatively few studies have explored the differences between feces and gut as well as ethanol-stored and frozen samples. Here, we sampled the same individuals of three aquatic vertebrates from the Qinghai-Tibetan Plateau non-invasively for feces, and subsequently for hindgut through dissection. Our study species, two fishes (Gymnocypris cf. namensis and Triplophysa sp.) and one amphibian (tadpoles of Nanorana parkeri), were all collected at the same time and site. Gut and fecal samples were stored in ethanol, and additionally, part of the gut samples were frozen, but temporarily thawed during transport as it often happens under difficult field conditions. Our results showed that both substrate (gut content vs. feces) as well as preservation method can influence the analysis of intestinal microbiomes. Frozen gut samples strongly differed from ethanol-stored samples, and especially in Nanorana most frozen samples were dominated (in relative abundance) by a set of Proteobacteria OTUs that were completely absent from the ethanol-stored samples. This blooming of contaminant bacteria occurred after less than 12 h of thawing, thus caution should be taken when constancy of cold temperatures cannot be maintained in the field for sample preservation purposes. Among ethanol-stored samples, bacterial communities from feces differed from those recovered from guts, but in part recovered similar patterns, such as a higher bacterial richness in the more herbivorous Nanorana tadpoles. Although our results argue against combining gut and fecal samples in analyses of host-specific microbiome differences, they also confirm that non-invasive sampling of feces can provide useful information of gut microbiomes in aquatic vertebrates, which may be important especially when working with endangered species.
PastView: a user-friendly interface to explore evolutionary scenarios
Authors: Chevenet François , Castel Guillaume , Jousselin Emmanuelle , Gascuel Olivier 
Published: May 2019

AbstractBackgroundAncestral character states computed from the combination of phylogenetic trees with extrinsic traits are used to decipher evolutionary scenarios in various research fields such as phylogeography, epidemiology, and ecology. Despite the existence of powerful methods and software in ancestral character state inference, difficulties may arise when interpreting the outputs of such inferences. The growing complexity of data (trees, annotations), the diversity of optimization criteria for computing trees and ancestral character states, the combinatorial explosion of potential evolutionary scenarios if some ancestral characters states do not stand out clearly from others, requires the design of new methods that operate on tree topologies and extrinsic traits associations to ease the identification of evolutionary scenarios.ResultWe developed a tool, PastView, a user-friendly interface that includes numerical and graphical features to help users to import and/or compute ancestral character states and extract evolutionary scenario as a set of successive transitions of ancestral character states from the tree root to its leaves. PastView offers synthetic views such as transition maps and integrates comparative analysis methods to highlight agreements or discrepancies between methods of ancestral annotations inference.ConclusionThe main contribution of PastView is to assemble known numerical and graphical methods into a multi-maps graphical user interface dedicated to the computing, searching and viewing of evolutionary scenarios based on phylogenetic trees and ancestral character states. PastView is available publicly as a standalone software on www.pastview.org.
A deep learning-based approach for high-throughput hypocotyl phenotyping
Authors: Dobos Orsolya , Horvath Peter , Nagy Ferenc , Danka Tivadar , Viczián András 
Published: May 2019

AbstractHypocotyl length determination is a widely used method to phenotype young seedlings. The measurement itself has been developed from using rulers and millimeter papers to the assessment of digitized images, yet it remained a labour-intensive, monotonous and time consuming procedure. To make high-throughput plant phenotyping possible, we developed a deep learning-based approach to simplify and accelerate this method. Our pipeline does not require a specialized imaging system but works well with low quality images, produced with a simple flatbed scanner or a smartphone camera. Moreover, it is easily adaptable for a diverse range of datasets, not restricted toArabidopsis thaliana. Furthermore, we show that the accuracy of the method reaches human performance. We not only provide the full code athttps://github.com/biomag-lab/hypocotyl-UNet, but also give detailed instructions on how the algorithm can be trained with custom data, tailoring it for the requirements and imaging setup of the user.One-sentence summaryA deep learning-based algorithm, providing an adaptable tool for determining hypocotyl or coleoptile length of different plant species.
Genetic analysis and ecological niche modeling delimit species boundary of the Przewalski’s scorpion (Scorpiones: Buthidae) in arid Asian inland
Authors: Zhang Xue-Shu , Liu Gao-Ming , Feng Yu , Zhang De-Xing , Shi Cheng-Min 
Published: May 2019

AbstractReliable delimitation of venomous scorpions is not only consequential to toxicological studies but also instructive to conservation and exploration of these important medical resources. In the present study, we delimited species boundary for the the Przewalski’s scorpion from arid northwest China through a combined approach employing phylogenetic analysis, ecological niche modeling and morphological comparison. Our results indicate that the the Przewalski’s scorpion represent an independent taxonomic unit and should be recognized as full species rank,Mesobuthus przewalsiistat. n.. This species and the Chinese scorpionM. martensiirepresent the eastern members of theM. caucasicusspecies group which manifests a trans-Central Asia distribution across the Tianshan Mountains range. We also discussed the likely geographic barrier and climatic boundary that demarcate distributional range of the the Przewalski’s scorpion.
Mitigating biomass composition uncertainties in flux balance analysis using ensemble representations
Authors: Choi Yoon-Mi , Choi Dong-Hyuk , Lee Yi Qing , Koduru Lokanand , Lewis Nathan E. , Lakshmanan Meiyappan , Lee Dong-Yup 
Published: May 2019

AbstractThe biomass equation is a critical component in genome-scale metabolic models (GEMs): it is used as the de facto objective function in flux balance analysis (FBA). This equation accounts for the quantities of all known biomass precursors that are required for cell growth based on the macromolecular and monomer compositions measured at certain conditions. However, it is often reported that the macromolecular composition of cells could change across different environmental conditions; the use of the same single biomass equation in FBA, under multiple conditions, is questionable. Thus, we first investigated the qualitative and quantitative variations of macromolecular compositions of three representative host organisms, Escherichia coli, Saccharomyces cerevisiae and Cricetulus griseus, across different environmental/genetic variations. While macromolecular building blocks such as DNA, RNA, protein, and lipid composition vary notably, variations in fundamental biomass monomer units such as nucleotides and amino acids are not appreciable. We further observed that while macromolecular compositions are similar across taxonomically closer species, certain monomers, especially fatty acids, vary substantially. Based on the analysis results, we subsequently propose a new extension to FBA, named “Flux Balance Analysis with Ensemble Biomass (FBAwEB)”, to embrace the natural variation in selected components of the biomass equation. The current study clearly highlights that certain components of the biomass equation are very sensitive to different conditions, and the ensemble representation of biomass equation in the FBA framework enables us to account for such natural variations accurately during GEM-guided in silico simulations.
Thermostability improvement ofAspergillus awamoriglucoamylase via directed evolution of its gene located on episomal expression vector inPichia pastoris
Authors: Schmidt Alexander , Shvetsov Alexey , Soboleva Elena , Kil Yury , Sergeev Vladimir , Surzhik Marina 
Published: May 2019

AbstractNovel thermostable forms of glucoamylase (GA) from filamentous fungusAspergillus awamoriX100 were constructed using the directed evolution approach based on random mutagenesis by error-prone PCR of the catalytic domain region of glucoamylase gene with its localization on a new episomal expression vector pPEHα inPichia pastoriscells. Of 3000 yeast transformants screened, six new thermostable GA mutants with amino acid substitutions Val301Asp, Thr390Ala, Thr390Ala/Ser436Pro, Leu7Met/His391Tyr, Asp9His/Ile82Phe, Ser8Arg/Gln338Leu were identified and studied. To estimate the effect of every single substitution in the double mutants, we have constructed an appropriate single mutants of GA by site-directed mutagenesis and analyzed their thermal properties. Results of the analysis showed that only Ile82Phe and Ser8Arg mutations caused an increased thermostability. While Leu7Met and Asp9His mutations decreased the thermal stability of GA, and Gln338Leu had little effect, the synergistic effect of double mutant forms Leu7Met/His391Tyr, Asp9His/Ile82Phe and Ser8Arg/Gln338Leu revealed the significant thermostability improvement as compared to wild type GA.