bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep Learning-Based Quantification of Pulmonary Hemosiderophages in Cytology Slides
Authors: Marzahl Christian , Aubreville Marc , Bertram Christof A. , Stayt Jason , Jasensky Anne-Katherine , Bartenschlager Florian , Fragoso-Garcia Marco , Barton Ann K. , Elsemann Svenja , Jabari Samir , Krauth Jens , Madhu Prathmesh , Voigt Jörn , Hill Jenny , Klopfleisch Robert , Maier Andreas 
Published: August 2020

AbstractExercise-induced pulmonary hemorrhage (EIPH) is a common condition in sport horses with negative impact on performance. Cytology of bronchoalveolar lavage fluid by use of a scoring system is considered the most sensitive diagnostic method. Macrophages are classified depending on the degree of cytoplasmic hemosiderin content. The current gold standard is manual grading, which is however monotonous and time-consuming. We evaluated state-of-the-art deep learning-based methods for single cell macrophage classification and compared them against the performance of nine cytology experts and evaluated inter- and intra-observer variability. Additionally, we evaluated object detection methods on a novel data set of 17 completely annotated cytology whole slide images (WSI) containing 78,047 hemosiderophages. Our deep learning-based approach reached a concordance of 0.85, partially exceeding human expert concordance (0.68 to 0.86, mean of 0.73, SD of 0.04). Intra-observer variability was high (0.68 to 0.88) and inter-observer concordance was moderate (Fleiss’ kappa = 0.67). Our object detection approach has a mean average precision of 0.66 over the five classes from the whole slide gigapixel image and a computation time of below two minutes. To mitigate the high inter- and intra-rater variability, we propose our automated object detection pipeline, enabling accurate, reproducible and quick EIPH scoring in WSI.
Associations of PRKN–PACRG SNPs and G × G and G × E interactions with the risk of hyperlipidaemia
Authors: Zheng Peng-Fei , Yin Rui-Xing , Wei Bi-Liu , Liu Chun-Xiao , Deng Guo-Xiong , Guan Yao-Zong 
Published: August 2020

AbstractThis research aimed to assess the associations of 7 parkin RBR E3 ubiquitin protein ligase (PRKN) and 4 parkin coregulated gene (PACRG) single-nucleotide polymorphisms (SNPs), their haplotypes, gene–gene (G × G) and gene-environment (G × E) interactions with hyperlipidaemia in the Chinese Maonan minority. The genotypes of the 11 SNPs in 912 normal and 736 hyperlipidaemic subjects were detected with next-generation sequencing technology. The genotypic and allelic frequencies of the rs1105056, rs10755582, rs2155510, rs9365344, rs11966842, rs6904305 and rs11966948 SNPs were different between the normal and hyperlipidaemic groups (P < 0.05–0.001). Correlations between the above 7 SNPs and blood lipid levels were also observed (P < 0.0045–0.001, P < 0.0045 was considered statistically significant after Bonferroni correction). Strong linkage disequilibrium was found among the 11 SNPs (r2 = 0.01–0.64). The most common haplotypes were PRKN C-G-T-G-T-T-C (> 15%) and PACRG A-T-A-T (> 40%). The PRKN C-G-C-A-T-T-C and PRKN–PACRG C-G-T-G-T-T-C-A-T-A-T haplotypes were associated with an increased risk of hyperlipidaemia, whereas the PRKN–PACRG C-G-T-G-C-T-C-A-T-C-T and C-G-T-G-T-T-C-A-T-C-T haplotypes provided a protective effect. Association analysis based on the haplotypes and G × G interaction could improve the power to detect the risk of hyperlipidaemia over the analysis of any one SNP alone. The differences in serum lipid parameters between the hyperlipidaemic and normal groups might partly be due to the effects of the PRKN–PACRG SNPs and their haplotypes.
Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
Authors: Palladino Claudia , Ezeonwumelu Ifeanyi Jude , Mate-Cano Irene , Borrego Pedro , Martínez-Román Paula , Arca-Lafuente Sonia , Resino Salvador , Taveira Nuno , Briz Verónica 
Published: August 2020

AbstractHepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
Correlative study of epigenetic regulation of tumor microenvironment in spindle cell melanomas and cutaneous malignant peripheral nerve sheath tumors
Authors: Vougiouklakis Theodore , Aung Phyu P. , Vasudevaraja Varshini , Prieto Victor G. , Torres-Cabala Carlos A. , Sulman Erik P. , Snuderl Matija , Jour George 
Published: August 2020

AbstractThe tumor microenvironment (TME) plays critical roles in tumor growth and progression, however key regulators of gene expression in the TME of cutaneous malignant peripheral nerve sheath tumor (C-MPNST) and spindle cell melanoma (SCM) have not been well elucidated. Herein, we investigate the epigenetic regulation of promoters and gene bodies and their effect on the TME composition of C-MPNSTs and SCMs. A cohort of 30 patients was analyzed using differential gene expression (DGE) and gene set enrichment analysis (GSEA) using the Nanostring platform. Methylation analysis was carried out utilizing an Infinium Methylation EPIC array targeting 866,562 methylation site (CpG) islands. DGE revealed overexpression of genes related to mast cells in the TME of SCMs, and a predominance of exhausted CD8+ T cells and macrophages in the TME of C-MPNSTs. Interestingly, we further observed promoter hypermethylation in key overexpressed genes and corresponding gene body hypomethylation. Analysis using ENCODE ChIP-sequencing data identified CTCF as the common transcription factor at the site of the hypomethylated probe. These findings support that the TME composition of C-MPNSTs and SCMs is at least partially independent on promoter methylation status, suggesting a possible relationship between gene body enhancers and expression of key TME genes in both entities.
Different luminance- and texture-defined contrast sensitivity profiles for school-aged children
Authors: Silvestre Daphné , Guy Jacalyn , Hanck Julie , Cornish Kim , Bertone Armando 
Published: August 2020

AbstractOur current understanding of how the visual brain develops is based largely on the study of luminance-defined information processing. This approach, however, is somewhat limiting, since everyday scenes are composed of complex images, consisting of information characterized by physical attributes relating to both luminance and texture. Few studies have explored how contrast sensitivity to texture-defined information develops, particularly throughout the school-aged years. The current study investigated how contrast sensitivity to luminance- (luminance-modulated noise) and texture-defined (contrast-modulated noise) static gratings develops in school-aged children. Contrast sensitivity functions identified distinct profiles for luminance- and texture-defined gratings across spatial frequencies (SFs) and age. Sensitivity to luminance-defined gratings reached maturity in childhood by the ages of 9–10 years for all SFs (0.5, 1, 2, 4 and 8 cycles/degree or cpd). Sensitivity to texture-defined gratings reached maturity at 5–6 years for low SFs and 7–8 years for high SFs (i.e., 4 cpd). These results establish that the processing of luminance- and texture-defined information develop differently as a function of SF and age.
A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories
Authors: Abdel-Latif Ghada A. , Elwahab Azza H. Abd , Hasan Rehab A. , ElMongy Noura F. , Ramzy Maggie M. , Louka Manal L. , Schaalan Mona F. 
Published: August 2020

AbstractCyclophosphamide (CP) is a chemotherapeutic agent that induces oxidative stress causing multiple organ damage. Sacubitril/valsartan, is a combined formulation of neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (valsartan), that induces the protective effect of brain natriuretic peptide. The aim of the current study is to investigate the prophylactic impacts of sacubitril/valsartan versus valsartan against CP-induced lung toxicity in rats. Rats were assigned randomly into 6 groups; control; received corn oil (2 ml/kg/day; p.o. for 6 days), sacubitril/valsartan (30 mg/kg; p.o. for 6 days), valsartan (15 mg/kg; p.o. for 6 days), CP (200 mg/kg; i.p. on day 5), sacubitril/valsartan + CP (30 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively), valsartan + CP (15 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively). Both sacubitril/valsartan and valsartan produced a significant decrease in the inflammation and fibrosis markers in the BALF, in comparison with the CP group. Both sacubitril/valsartan and valsartan produced an apparent decrease in the relative genes expression of miR-150-3p and NF-κB, as well as a significant decrease in the relative expression of P38 and ERK1/2 MAPKs and an increase in the relative gene expression of Nrf-2, compared to CP group. Intriguingly, sacubitril/valsartan , showed subtle superiority in almost all investigated parameters, compared to valsartan. In conclusion, sacubitril/valsartan effectively abrogated the CP induced lung inflammation and fibrosis, providing a potential promising protection that could be linked to their ability to inhibit miR-150-3p via inhibition of NF-κB and MAPK signaling pathways.
The diversification and lineage-specific expansion of nitric oxide signaling in Placozoa: insights in the evolution of gaseous transmission
Authors: Moroz Leonid L. , Romanova Daria Y. , Nikitin Mikhail A. , Sohn Dosung , Kohn Andrea B. , Neveu Emilie , Varoqueaux Frederique , Fasshauer Dirk 
Published: August 2020

AbstractNitric oxide (NO) is a ubiquitous gaseous messenger, but we know little about its early evolution. Here, we analyzed NO synthases (NOS) in four different species of placozoans—one of the early-branching animal lineages. In contrast to other invertebrates studied, Trichoplax and Hoilungia have three distinct NOS genes, including PDZ domain-containing NOS. Using ultra-sensitive capillary electrophoresis assays, we quantified nitrites (products of NO oxidation) and l-citrulline (co-product of NO synthesis from l-arginine), which were affected by NOS inhibitors confirming the presence of functional enzymes in Trichoplax. Using fluorescent single-molecule in situ hybridization, we showed that distinct NOSs are expressed in different subpopulations of cells, with a noticeable distribution close to the edge regions of Trichoplax. These data suggest both the compartmentalized release of NO and a greater diversity of cell types in placozoans than anticipated. NO receptor machinery includes both canonical and novel NIT-domain containing soluble guanylate cyclases as putative NO/nitrite/nitrate sensors. Thus, although Trichoplax and Hoilungia exemplify the morphologically simplest free-living animals, the complexity of NO-cGMP-mediated signaling in Placozoa is greater to those in vertebrates. This situation illuminates multiple lineage-specific diversifications of NOSs and NO/nitrite/nitrate sensors from the common ancestor of Metazoa and the preservation of conservative NOS architecture from prokaryotic ancestors.
A model for the geomagnetic field reversal rate and constraints on the heat flux variations at the core-mantle boundary
Authors: Carbone Vincenzo , Alberti Tommaso , Lepreti Fabio , Vecchio Antonio 
Published: August 2020

AbstractA striking feature of many natural magnetic fields generated by dynamo action is the occurrence of polarity reversals. Paleomagnetic measurements revealed that the Earth’s magnetic field has been characterised by few hundred stochastic polarity switches during its history. The rate of reversals changes in time, maybe obeying some underlying regular pattern. While chaotic dynamical systems can describe the short-term behaviour of the switches of the Earth’s magnetic polarity, modelling the long-term variations of the reversal rate is somewhat problematic, as they occur on timescales of tens to hundreds of millions of years, of the order of mantle convection timescales. By investigating data of geomagnetic reversal rates, we find the presence of cycles with variable frequency and show that the transition towards periods where reversals do not occur for tens of million years (superchrons) can be described by a second-order phase transition that we interpret to be driven by variations of the heat flux at the core-mantle boundary (CMB). The model allows us to extract from the reversal sequence quantitative information on the susceptibility of the reversal rate caused by changes in the CMB heat flux amplitude, thus providing direct information on the deep inner layers of the Earth.
Age negatively impacts reproduction in high-ranking male rhesus macaques on Cayo Santiago, Puerto Rico
Authors: Milich Krista M. , Ruiz-Lambides Angelina , Maldonado Elizabeth , Maestripieri Dario 
Published: August 2020

AbstractBased on sexual selection theory, the reproductive potential of male primates is expected to be limited by access to fertile females. Alpha males, the highest ranking males in a social group, are predicted to have better access to mates and produce more offspring until they are no longer dominant, which usually corresponds with age. Little is known about male reproductive senescence independent of rank changes in nonhuman primates. Here, we examine variation in the reproductive success of high-ranking male rhesus macaques on Cayo Santiago. We recorded behavioral data for 21 adult males across 9 social groups during the 2013 mating season. Additionally, we used paternity data from the long-term database to determine the number of offspring each subject sired over his lifetime and during the study period. Older high-ranking males in stable groups had fewer offspring than younger high-ranking males in stable groups in 2013. The low reproductive output for the older males was not a result of lower mating effort, and reproductive output in 2013 was not predicted by total prior reproductive success. Our results provide novel evidence of post-copulatory reproductive senescence in high-ranking male nonhuman primates.
Rapid microbial diversification of dissolved organic matter in oceanic surface waters leads to carbon sequestration
Authors: Hach Philipp F. , Marchant Hannah K. , Krupke Andreas , Riedel Thomas , Meier Dimitri V. , Lavik Gaute , Holtappels Moritz , Dittmar Thorsten , Kuypers Marcel M. M. 
Published: August 2020

AbstractThe pool of dissolved organic matter (DOM) in the deep ocean represents one of the largest carbon sinks on the planet. In recent years, studies have shown that most of this pool is recalcitrant, because individual compounds are present at low concentrations and because certain compounds seem resistant to microbial degradation. The formation of the diverse and recalcitrant deep ocean DOM pool has been attributed to repeated and successive processing of DOM by microorganisms over time scales of weeks to years. Little is known however, about the transformation and cycling that labile DOM undergoes in the first hours upon its release from phytoplankton. Here we provide direct experimental evidence showing that within hours of labile DOM release, its breakdown and recombination with ambient DOM leads to the formation of a diverse array of new molecules in oligotrophic North Atlantic surface waters. Furthermore, our results reveal a preferential breakdown of N and P containing molecules versus those containing only carbon. Hence, we show the preferential breakdown and molecular diversification are the crucial first steps in the eventual formation of carbon rich DOM that is resistant to microbial remineralization.
Global transcriptome analysis of subterranean pod and seed in peanut (Arachis hypogaea L.) unravels the complexity of fruit development under dark condition
Authors: Liu Hao , Liang Xuanqiang , Lu Qing , Li Haifen , Liu Haiyan , Li Shaoxiong , Varshney Rajeev , Hong Yanbin , Chen Xiaoping 
Published: August 2020

AbstractPeanut pods develop underground, which is the most salient characteristic in peanut. However, its developmental transcriptome remains largely unknown. In the present study, we sequenced over one billion transcripts to explore the developmental transcriptome of peanut pod using Illumina sequencing. Moreover, we identified and quantified the abundances of 165,689 transcripts in seed and shell tissues along with a pod developmental gradient. The dynamic changes of differentially expressed transcripts (DETs) were described in seed and shell. Additionally, we found that photosynthetic genes were not only pronouncedly enriched in aerial pod, but also played roles in developing pod under dark condition. Genes functioning in photomorphogenesis showed distinct expression profiles along subterranean pod development. Clustering analysis unraveled a dynamic transcriptome, in which transcripts for DNA synthesis and cell division during pod expansion were transitioning to transcripts for cell expansion and storage activity during seed filling. Collectively, our study formed a transcriptional baseline for peanut fruit development under dark condition.
Immune outcomes of Zika virus infection in nonhuman primates
Authors: Schouest Blake , Fahlberg Marissa , Scheef Elizabeth A. , Ward Matthew J. , Headrick Kyra , Szeltner Dawn M. , Blair Robert V. , Gilbert Margaret H. , Doyle-Meyers Lara A. , Danner Victoria W. , Bonaldo Myrna C. , Wesson Dawn M. , Panganiban Antonito T. , Maness Nicholas J. 
Published: August 2020

AbstractAlthough the Zika virus (ZIKV) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. Nonhuman primate (NHP) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. Here, we infected a small group of male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques with a minimally passaged Brazilian ZIKV isolate and used multicolor flow cytometry and transcriptional profiling to describe early immune patterns following infection. We found evidence of strong innate antiviral responses together with induction of neutralizing antibodies and T cell responses. We also assessed the relative importance of CD8 T cells in controlling infection by carrying out CD8 T cell depletion in an additional two animals of each species. CD8 depletion appeared to dysregulate early antiviral responses and possibly increase viral persistence, but the absence of CD8 T cells ultimately did not impair control of the virus. Together, these data describe immunological trends in two NHP species during acute ZIKV infection, providing an account of early responses that may be important in controlling infection.
Direct and quantitative analysis of altered metabolic flux distributions and cellular ATP production pathway in fumarate hydratase-diminished cells
Authors: Noguchi Shingo , Ishikawa Hirokazu , Wakita Kenichi , Matsuda Fumio , Shimizu Hiroshi 
Published: August 2020

AbstractFumarate hydratase (FH) is an enzyme in the tricarboxylic acid (TCA) cycle, biallelic loss-of-function mutations of which are associated with hereditary leiomyomatosis and renal cell cancer. However, how FH defect modulates intracellular metabolic fluxes in human cells has remained unclear. This study aimed to reveal metabolic flux alterations induced by reduced FH activity. We applied 13C metabolic flux analysis (13C-MFA) to an established cell line with diminished FH activity (FHdim) and parental HEK293 cells. FHdim cells showed reduced pyruvate import flux into mitochondria and subsequent TCA cycle fluxes. Interestingly, the diminished FH activity decreased FH flux only by about 20%, suggesting a very low need for FH to maintain the oxidative TCA cycle. Cellular ATP production from the TCA cycle was dominantly suppressed compared with that from glycolysis in FHdim cells. Consistently, FHdim cells exhibited higher glucose dependence for ATP production and higher resistance to an ATP synthase inhibitor. In summary, using FHdim cells we demonstrated that FH defect led to suppressed pyruvate import into mitochondria, followed by downregulated TCA cycle activity and altered ATP production pathway balance from the TCA cycle to glycolysis. We confirmed that 13C-MFA can provide direct and quantitative information on metabolic alterations induced by FH defect.
Diatoms constrain forensic burial timelines: case study with DB Cooper money
Authors: Kaye Thomas G. , Meltzer Mark 
Published: August 2020

AbstractDiatoms are found universally in waters around the world. Some diatom species such as Asterionella formosa have a broad variation in seasonal abundance leading to the possibility that diatoms could constrain the time of year when an object was immersed in water. Here we apply this technique to the cold case of DB Cooper’s money. Nine years after the crime, six thousand dollars in three bundles were found on the shore of the Columbia River near Portland, Oregon. This burial site was ~30 km from his reported jump location which gave no apparent reason for the money to end up there. This study found diatoms on a recovered bill which indicates that the money was immersed before burial. The species mix found on the bills was compared to a test bill submerged in the Columbia River in November which was the timeframe for the crime. The Cooper bill contained diatoms from summer bloom species suggesting that the money was not directly buried dry and the immersion happened months after the late November hijacking. This finding rules out of a majority of current theories related to the crime and proposes diatoms as a feasible methodology to constrain seasonal timelines in forensics.