bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical heterogeneity under induction with different dosages of cytarabine in core binding factor acute myeloid leukaemia
Authors: Wang Biao , Zhang Jihong , Hua Xiaoying , Li Haiqian , Wang Zhilin , Yang Bin 
Published: January 2020

AbstractRepeated cycles of post-remission high-dose cytarabine (Ara-C) have been suggested to improve survival in core binding factor (CBF) acute myeloid leukaemia (AML). High-dose Ara-C used for induction regimens has also been reported to be associated with increased treatment-related mortality (TRM). Few data are available about intermediate-dose Ara-C serving as induction therapy. The aim of our study was to compare the tolerance and outcomes of standard- and intermediate-dose levels of Ara-C as induction in CBF AML and to analyse the clinical heterogeneity of the two AML entities under these induction settings. We retrospectively investigated the outcomes in adults with CBF AML induced with regimens based on standard-dose Ara-C at 100 to 200 mg/m2 or intermediate-dose Ara-C at 1,000 mg/m2. In total, 152 patients with t(8; 21) and 54 patients with inv(16) AML were administered an induction regimen containing anthracyclines plus either standard- or intermediate-dose Ara-C. After a single course of induction, the complete remission (CR) rate in the inv(16) cohort was 52/52 (100%), higher than the 127/147 (86.4%) in the t(8; 21) cohort (P = 0.005). Intermediate-dose Ara-C (HR = 9.931 [2.135–46.188], P = 0.003) and negative KITmut (HR = 0.304 [0.106–0.874], P = 0.027) independently produced an increased CR rate in the t(8; 21) cohort. Positive CD19 expression (HR = 0.133 [0.045–0.387], P = 0.000) and sex (male) (HR = 0.238 [0.085–0.667], P = 0.006) were associated with superior leukaemia-free survival (LFS) in the t(8; 21) cohort independently of KITmut status or the induction regimen. We conclude that intermediate-dose Ara-C is superior to standard-dose Ara-C for induction of remission in t(8; 21) AML, and CD19 status and sex independently confer prognostic significance for LFS. The KITmut status alone does not have an independent effect on survival in t(8; 21) AML. More intensive induction therapy is unnecessary in inv(16) AML.
Distribution Optimization: An evolutionary algorithm to separate Gaussian mixtures
Authors: Lerch Florian , Ultsch Alfred , Lötsch Jörn 
Published: January 2020

AbstractFinding subgroups in biomedical data is a key task in biomedical research and precision medicine. Already one-dimensional data, such as many different readouts from cell experiments, preclinical or human laboratory experiments or clinical signs, often reveal a more complex distribution than a single mode. Gaussian mixtures play an important role in the multimodal distribution of one-dimensional data. However, although fitting of Gaussian mixture models (GMM) is often aimed at obtaining the separate modes composing the mixture, current technical implementations, often using the Expectation Maximization (EM) algorithm, are not optimized for this task. This occasionally results in poorly separated modes that are unsuitable for determining a distinguishable group structure in the data. Here, we introduce “Distribution Optimization” an evolutionary algorithm to GMM fitting that uses an adjustable error function that is based on chi-square statistics and the probability density. The algorithm can be directly targeted at the separation of the modes of the mixture by employing additional criterion for the degree by which single modes overlap. The obtained GMM fits were comparable with those obtained with classical EM based fits, except for data sets where the EM algorithm produced unsatisfactory results with overlapping Gaussian modes. There, the proposed algorithm successfully separated the modes, providing a basis for meaningful group separation while fitting the data satisfactorily. Through its optimization toward mode separation, the evolutionary algorithm proofed particularly suitable basis for group separation in multimodally distributed data, outperforming alternative EM based methods.
A Protein Interaction Information-based Generative Model for Enhancing Gene Clustering
Authors: Dutta Pratik , Saha Sriparna , Pai Sanket , Kumar Aviral 
Published: January 2020

AbstractIn the field of computational bioinformatics, identifying a set of genes which are responsible for a particular cellular mechanism, is very much essential for tasks such as medical diagnosis or disease gene identification. Accurately grouping (clustering) the genes is one of the important tasks in understanding the functionalities of the disease genes. In this regard, ensemble clustering becomes a promising approach to combine different clustering solutions to generate almost accurate gene partitioning. Recently, researchers have used generative model as a smart ensemble method to produce the right consensus solution. In the current paper, we develop a protein-protein interaction-based generative model that can efficiently perform a gene clustering. Utilizing protein interaction information as the generative model’s latent variable enables enhance the generative model’s efficiency in inferring final probabilistic labels. The proposed generative model utilizes different weak supervision sources rather utilizing any ground truth information. For weak supervision sources, we use a multi-objective optimization based clustering technique together with the world’s largest gene ontology based knowledge-base named Gene Ontology Consortium(GOC). These weakly supervised labels are supplied to a generative model that eventually assigns all genes to probabilistic labels. The comparative study with respect to silhouette score, Biological Homogeneity Index (BHI) and Biological Stability Index (BSI) proves that the proposed generative model outperforms than other state-of-the-art techniques.
Natural drivers of multidecadal Arctic sea ice variability over the last millennium
Authors: Halloran Paul R. , Hall Ian R. , Menary Matthew , Reynolds David J. , Scourse James D. , Screen James A. , Bozzo Alessio , Dunstone Nick , Phipps Steven , Schurer Andrew P. , Sueyoshi Tetsuo , Zhou Tianjun , Garry Freya 
Published: January 2020

AbstractThe climate varies due to human activity, natural climate cycles, and natural events external to the climate system. Understanding the different roles played by these drivers of variability is fundamental to predicting near-term climate change and changing extremes, and to attributing observed change to anthropogenic or natural factors. Natural drivers such as large explosive volcanic eruptions or multidecadal cycles in ocean circulation occur infrequently and are therefore poorly represented within the observational record. Here we turn to the first high-latitude annually-resolved and absolutely dated marine record spanning the last millennium, and the Paleoclimate Modelling Intercomparison Project (PMIP) Phase 3 Last Millennium climate model ensemble spanning the same time period, to examine the influence of natural climate drivers on Arctic sea ice. We show that bivalve oxygen isotope data are recording multidecadal Arctic sea ice variability and through the climate model ensemble demonstrate that external natural drivers explain up to third of this variability. Natural external forcing causes changes in sea-ice mediated export of freshwater into areas of active deep convection, affecting the strength of the Atlantic Meridional Overturning Circulation (AMOC) and thereby northward heat transport to the Arctic. This in turn leads to sustained anomalies in sea ice extent. The models capture these positive feedbacks, giving us improved confidence in their ability to simulate future sea ice in in a rapidly evolving Arctic.
Plasmonic ternary hybrid photocatalyst based on polymeric g-C3N4 towards visible light hydrogen generation
Authors: Che Yuping , Liu Qingqing , Lu Bingxin , Zhai Jin , Wang Kefeng , Liu Zhaoyue 
Published: January 2020

AbstractSurface plasmon resonance (SPR) effect of noble metal nanoparticles (NPs) for photocatalysis has a significant enhancement. In this system, a plasmonic ternary hybrid photocatalyst of Ag/AgBr/g-C3N4was synthetized and used in water splitting to generation H2under visible light irradiation. 18%Ag/AgBr/g-C3N4showed the highest photoactivity, with the efficiency of hydrogen generation as high as 27-fold to that of pristine g-C3N4. Compared to simple mixture of Ag/AgBr and g-C3N4, hetero-composite Ag/AgBr/g-C3N4showed a higher photoactivity, even though they contained same content of Ag/AgBr. We find that significant factors for enhancing properties were the synergistic effect between Ag/AgBr and g-C3N4, and the light absorption enhancing by SPR effect of Ag NPs. Ag/AgBr NPs firmly anchored on the surface of g-C3N4and their high dispersion were also responsible for the improved activity and long-term recycling ability. The structure of Ag/AgBr/g-C3N4hybrid materials and their enhancement to photocatalytic activity were discussed. Meanwhile, the possible reaction mechanism of this system was proposed.
Manatee: detection and quantification of small non-coding RNAs from next-generation sequencing data
Authors: Handzlik Joanna E. , Tastsoglou Spyros , Vlachos Ioannis S. , Hatzigeorgiou Artemis G. 
Published: January 2020

AbstractSmall non-coding RNAs (sncRNAs) play important roles in health and disease. Next Generation Sequencing (NGS) technologies are considered as the most powerful and versatile methodologies to explore small RNA (sRNA) transcriptomes in diverse experimental and clinical studies. Small RNA-Seq (sRNA-Seq) data analysis proved to be challenging due to non-unique genomic origin, short length, and abundant post-transcriptional modifications of sRNA species. Here, we present Manatee, an algorithm for the quantification of sRNA classes and the detection of novel expressed non-coding loci. Manatee combines prior annotation of sRNAs with reliable alignment density information and extensive rescue of usually neglected multimapped reads to provide accurate transcriptome-wide sRNA expression quantification. Comparison of Manatee against state-of-the-art implementations using real and simulated data demonstrates its high accuracy across diverse sRNA classes. Manatee also goes beyond common pipelines by identifying and quantifying expression from unannotated loci and microRNA isoforms (isomiRs). It is user-friendly, can be easily incorporated in pipelines, and provides a simplified output suitable for direct usage in downstream analyses and functional studies.
Rice pyramided line IRBB67 (Xa4/Xa7) homeostasis under combined stress of high temperature and bacterial blight
Authors: Dossa Gerbert Sylvestre , Quibod Ian , Atienza-Grande Genelou , Oliva Ricardo , Maiss Edgar , Vera Cruz Casiana , Wydra Kerstin 
Published: January 2020

AbstractRice bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) implies substantial yield loss to rice. In times of climate change, increasing temperatures are observed and further acceleration is expected worldwide. Increasing temperature often turns into inhibition of host plant defense to pathogens. Recently, a reduced resistance in rice IRBB4 carrying Xa4, but an increase in resistance in IRBB7 carrying Xa7 resistance by increasing temperature has been reported. Influence of high temperature on both R genes (Xa4+Xa7) combined in IRBB67 was analyzed under growth chamber conditions and transcriptomic analysis performed. The pyramided line IRBB67 showed no differences in lesion length between both temperature regimes, demonstrating that non-effectiveness of Xa4 at high temperature did not affect IRBB67 resistance. Moreover, Xa4 complements Xa7 resistance with no Xoo spread in planta beyond the symptomatic area under both temperature regimes in IRBB67. Time course transcriptomic analysis revealed that temperature enhanced IRBB67 resistance to combined heat and Xoo. Our findings highlight altered cellular compartments and point at a role of the cell wall involved in Xoo resistance and heat stress tolerance in both susceptible (IR24) and the resistant (IRBB67) NILs. Interestingly, up-regulation of trehalose-6-phosphatase gene and low affinity cation transporter in IRBB67 suggest that IRBB67 maintained a certain homeostasis under high temperature which may have enhanced its resistance. The interplay of both heat stress and Xoo responses as determined by up-regulated and down-regulated genes demonstrates how resistant plants cope with combined biotic and abiotic stresses.
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity
Authors: Wilk Anna , Hayat Faisal , Cunningham Richard , Li Jianfeng , Garavaglia Silvia , Zamani Leila , Ferraris Davide M. , Sykora Peter , Andrews Joel , Clark Jennifer , Davis Amanda , Chaloin Laurent , Rizzi Menico , Migaud Marie , Sobol Robert W. 
Published: January 2020

AbstractChanges in nicotinamide adenine dinucleotide (NAD+) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD+ levels also affect DNA repair capacity as NAD+ is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5′-nucleotidase CD73, an ectoenzyme highly expressed in cancer, is suggested to regulate intracellular NAD+ levels by processing NAD+ and its bio-precursor, nicotinamide mononucleotide (NMN), from tumor microenvironments, thereby enhancing tumor DNA repair capacity and chemotherapy resistance. We therefore investigated whether expression of CD73 impacts intracellular NAD+ content and NAD+-dependent DNA repair capacity. Reduced intracellular NAD+ levels suppressed recruitment of the DNA repair protein XRCC1 to sites of genomic DNA damage and impacted the amount of accumulated DNA damage. Further, decreased NAD+ reduced the capacity to repair DNA damage induced by DNA alkylating agents. Overall, reversal of these outcomes through NAD+ or NMN supplementation was independent of CD73. In opposition to its proposed role in extracellular NAD+ bioprocessing, we found that recombinant human CD73 only poorly processes NMN but not NAD+. A positive correlation between CD73 expression and intracellular NAD+ content could not be made as CD73 knockout human cells were efficient in generating intracellular NAD+ when supplemented with NAD+ or NMN.
Analysis of O-glycoforms of the IgA1 hinge region by sequential deglycosylation
Authors: Ohyama Yukako , Yamaguchi Hisateru , Nakajima Kazuki , Mizuno Tomohiro , Fukamachi Yukihiro , Yokoi Yasuto , Tsuboi Naotake , Inaguma Daijo , Hasegawa Midori , Renfrow Matthew B. , Novak Jan , Yuzawa Yukio , Takahashi Kazuo 
Published: January 2020

AbstractA common renal disease, immunoglobulin A (IgA) nephropathy (IgAN), is associated with glomerular deposition of IgA1-containing immune complexes. IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine with β1,3-linked galactose and variable sialylation. IgA1 glycoforms with some galactose-deficient (Gd) HR O-glycans play a key role in IgAN pathogenesis. The clustered and variable O-glycans make the IgA1 glycomic analysis challenging and better approaches are needed. Here, we report a comprehensive analytical workflow for IgA1 HR O-glycoform analysis. We combined an automated quantitative analysis of the HR O-glycopeptide profiles with sequential deglycosylation to remove all but Gd O-glycans from the HR. The workflow was tested using serum IgA1 from healthy subjects. Twelve variants of glycopeptides corresponding to the HR with three to six O-glycans were detected; nine glycopeptides carried up to three Gd O-glycans. Sites with Gd O-glycans were unambiguously identified by electron-transfer/higher-energy collision dissociation tandem mass spectrometry. Extracted ion chromatograms of isomeric glycoforms enabled quantitative assignment of Gd sites. The most frequent Gd site was T236, followed by S230, T233, T228, and S232. The new workflow for quantitative profiling of IgA1 HR O-glycoforms with site-specific resolution will enable identification of pathogenic IgA1 HR O-glycoforms in IgAN.
Effects of the Van der Waals Force on the Vibration of Typical Multi-layered Two-dimensional Nanostructures
Authors: Zhang Yiqing , Wang Lifeng 
Published: January 2020

AbstractRecently, two-dimensional nanostructures have caught much attention because of their magnificent physical characteristics. The vibrational behavior of typical multi-layered two-dimensional nanostructures (TMLTNs) is extraordinary significant to TMLTN-based nanoresonantors. In this investigation, the vibrational behavior of TMLTNs, taking black phosphorus (BP), graphene and BN as examples, is studied adopting molecular dynamics (MD) simulations and the sandwich plate model (SPM). The MD results show that the fundamental resonant frequency of multi-layered BP (MLBP) and multi-layered BN (MLBN) increase obviously with the number of layers. However, the fundamental resonant frequency of a multi-layered graphene sheet (MLGS) rise slightly when the number of layers increases. This phenomenon is caused by the shear modulus in the xz-plane and yz-plane resulted by the vdW force. Hence, an SPM considering the shear modulus in the xz-plane and yz-plane caused by the vdW force is used to investigate the vibration of the TMLTN. Compared with the MD results, it is shown that the SPM can better predict the vibration of the TMLTN.
Exploring ion-ion preferences through structure-property correlations: amino acid-derived, bis(guanidinium) disiloxane salts
Authors: Tabisz Łukasz , Rozwadowski Zbigniew , Katrusiak Andrzej , Łęska Bogusława 
Published: January 2020

AbstractIn a more synthetical approach to the study of ion-specific phenomena, four dipodal bis(guanidinium) siloxanes have been synthesized starting from glycine, β-alanine, γ-aminobutanoic acid, L-proline and 1,3-bis(3-aminopropyl)tetramethyldisiloxane. Together with their non-amide progenitor they were comparatively studied in regards to their interactions with nine different anions: sulphate, chromate, molybdate, benzoate, chloride, azide, nitrite, nitrate and thiocyanate. Their aqueous solubilities, form, 1H NMR and FT-IR spectra were examined while searching for anion-specific interactions falling in- or outside of the Hofmeister series. We show that although the “chao-” and “kosmotropic” ions affect the properties of solutions in a predictable way, more selective cation-anion pairing is responsible for phase separation and crystallinity. As a prominent example, crystal structure of one of the benzoate salts was successfully obtained and reveals a synergy of hydrophobic packing, ionic and hydrogen bonding. Immobilized but still flexible siloxane bridges give rise to crystals described by P 42/n space group and neatly segregated into hydro- and lipophilic sections.
Autogenous Healing in Cementitious Materials with Superabsorbent Polymers Quantified by Means of NMR
Authors: Snoeck D. , Pel L. , De Belie N. 
Published: January 2020

AbstractA recent advance in construction technology is the use of self-healing cementitious materials containing synthetic microfibers and superabsorbent polymers. By stimulating autogenous healing by means of superabsorbent polymers, cracks are closed and this will cause an increase in durability and service life. However, this improved healing capacity has not been quantified yet in terms of increased further hydration and volume of healing products. This is needed to model the material and to stimulate the practical application in constructions. This paper provides quantitative data, obtained by an NMR study. Addition of 1 m% of selected superabsorbent polymer versus cement to a cementitious material, stimulated further hydration with nearly 40% in comparison with a traditional cementitious material, if 1 h water contact per day was allowed. At 90% relative humidity, no healing was observed in reference samples. While the further hydration around a crack in specimens with superabsorbent polymers was still 68% of that of a reference system with cyclic water contact, due to the uptake of moisture by the superabsorbent polymers. As such, NMR results quantify the positive influence of superabsorbent polymers in terms of stimulated autogenous healing and substantiate their benefits for application in the construction area.
Molecular phylogeny of one extinct and two critically endangered Central Asian sturgeon species (genus Pseudoscaphirhynchus) based on their mitochondrial genomes
Authors: Nedoluzhko Artem V. , Sharko Fedor S. , Tsygankova Svetlana V. , Boulygina Eugenia S. , Barmintseva Anna E. , Krasivskaya Anna A. , Ibragimova Amina S. , Gruzdeva Natalia M. , Rastorguev Sergey M. , Mugue Nikolai S. 
Published: January 2020

AbstractThe enigmatic and poorly studied sturgeon genus Pseudoscaphirhynchus (Scaphirhynchinae: Acipenseridae) comprises three species: the Amu Darya shovelnose sturgeon (Pseudoscaphirhynchus kaufmanni (Bogdanow)), dwarf Amu Darya shovelnose sturgeon P. hermanni (Kessler), and Syr Darya shovelnose sturgeon (P. fedtschenkoi (Bogdanow). Two species – P. hermanni and P. kaufmanni – are critically endangered due to the Aral Sea area ecological disaster, caused by massive water use for irrigation to support cotton agriculture, subsequent pesticide pollution and habitat degradation. For another species – P. fedtschenkoi – no sightings have been reported since 1960-s and it is believed to be extinct, both in nature and in captivity. In this study, complete mitochondrial (mt) genomes of these three species of Pseudoscaphirhynchus were characterized using Illumina and Sanger sequencing platforms. Phylogenetic analyses showed the significant divergence between Amu Darya and Syr Darya freshwater sturgeons and supported the monophyletic origin of the Pseudoscaphirhynchus species. We confirmed that two sympatric Amu Darya species P. kaufmanni and P. hermanni form a single genetic cluster, which may require further morphological and genetic study to assess possible hybridization, intraspecific variation and taxonomic status and to develop conservation measures to protect these unique fishes.
Ventral striatum supports Methylphenidate therapeutic effects on impulsive choices expressed in temporal discounting task
Authors: Martinez Eva , Pasquereau Benjamin , Drui Guillaume , Saga Yosuke , Météreau Élise , Tremblay Léon 
Published: January 2020

AbstractMethylphenidate (MPH) is a dopamine transporter (DAT) inhibitor used to treat attention-deficit/hyperactivity-disorder (ADHD). ADHD patients make impulsive choices in delay discounting tasks (DDT) and MPH reduces such impulsivity, but its therapeutic site of action remains unknown. Based on the high density of DAT in the striatum, we hypothesized that the striatum, especially the ventral striatum (VS) and caudate nucleus which both encode temporal discounting, can be preferential MPH action sites. To determine whether one of these striatal territories is predominantly involved in the effect of MPH, we trained monkeys to make choices during DDT. First, consistent with clinical observations, we found an overall reduction of impulsive choices with a low dose of MPH administered via intramuscular injections, whereas we reported sedative-like effects with a higher dose. Then, using PET-imaging, we found that the therapeutic reduction of impulsive choices was associated with selective DAT occupancy of MPH in the VS. Finally, we confirmed the selective involvement of the VS in the effect of MPH by testing the animals’ impulsivity with microinjections of the drug in distinct striatal territories. Together, these results show that the therapeutic effect of MPH on impulsive decisions is mainly restricted to its action in the VS.