bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaporation abrupt changes in the Qinghai-Tibet Plateau during the last half-century
Authors: Yao Tianci , Lu Hongwei , Feng Wei , Yu Qing 
Published: December 2019

AbstractPan evaporation (Epan) was regarded as a critical indicator of climate change, especially in the Qinghai-Tibet Plateau (QTP). By using the measured daily Epan data of 274 stations in the QTP from 1970 to 2017, the study detected abrupt changes in annual Epan series in different spatial scales, through integrating the Mann-Kendall abrupt change test, moving t-test and piecewise linear fitting model. Results showed that abrupt changes existed generally in the QTP where mean and trend abrupt changes were detected in 76.6% and 97.8% of 274 stations during the last half-century. Major abrupt change time of mean values and trends was respectively in around 1996, 1989 and 2007. In comparison, early abrupt changes were observed in the south (south of 30°N) and north (north of 35°N) but late ones in the midland (30–35°N). Corresponding to the low frequent behaviors, pan evaporation paradox only existed in the QTP as a whole in 1970–1990 and was not apparent at site scale, with less than 9.5% of 274 stations detected in different periods. The results confirmed prevailing abrupt change of pan evaporation and its distinct spatial pattern in the QTP.
Parallel Reaction Monitoring reveals structure-specific ceramide alterations in the zebrafish
Authors: Zhang Tejia , Trauger Sunia A. , Vidoudez Charles , Doane Kim P. , Pluimer Brock R. , Peterson Randall T. 
Published: December 2019

AbstractExtensive characterisations of the zebrafish genome and proteome have established a foundation for the use of the zebrafish as a model organism; however, characterisation of the zebrafish lipidome has not been as comprehensive. In an effort to expand current knowledge of the zebrafish sphingolipidome, a Parallel Reaction Monitoring (PRM)-based liquid chromatography–mass spectrometry (LC–MS) method was developed to comprehensively quantify zebrafish ceramides. Comparison between zebrafish and a human cell line demonstrated remarkable overlap in ceramide composition, but also revealed a surprising lack of most sphingadiene-containing ceramides in the zebrafish. PRM analysis of zebrafish embryogenesis identified developmental stage-specific ceramide changes based on long chain base (LCB) length. A CRISPR-Cas9-generated zebrafish model of Farber disease exhibited reduced size, early mortality, and severe ceramide accumulation where the amplitude of ceramide change depended on both acyl chain and LCB lengths. Our method adds an additional level of detail to current understanding of the zebrafish lipidome, and could aid in the elucidation of structure-function associations in the context of lipid-related diseases.
Local adaptation of a dominant coastal tree to freshwater availability and solar radiation suggested by genomic and ecophysiological approaches
Authors: Cruz Mariana Vargas , Mori Gustavo Maruyama , Signori-Müller Caroline , da Silva Carla Cristina , Oh Dong-Ha , Dassanayake Maheshi , Zucchi Maria Imaculada , Oliveira Rafael Silva , de Souza Anete Pereira 
Published: December 2019

AbstractLocal adaptation is often a product of environmental variations in geographical space and has implications for biodiversity conservation. We investigated the role of latitudinal heterogeneity in climate on the organization of genetic and phenotypic variation in the dominant coastal tree Avicennia schaueriana. In a common garden experiment, samples from an equatorial region, with pronounced seasonality in precipitation, accumulated less biomass, and showed lower stomatal conductance and transpiration, narrower xylem vessels, smaller leaves and higher reflectance of long wavelengths by the stem epidermis than samples from a subtropical region, with seasonality in temperature and no dry season. Transcriptomic differences identified between trees sampled under field conditions at equatorial and subtropical sites, were enriched in functional categories such as responses to temperature, solar radiation, water deficit, photosynthesis and cell wall biosynthesis. Remarkably, the diversity based on genome-wide SNPs revealed a north-south genetic structure and signatures of selection were identified for loci associated with photosynthesis, anthocyanin accumulation and the responses to osmotic and hypoxia stresses. Our results suggest the existence of divergence in key resource-use characteristics, likely driven by seasonality in water deficit and solar radiation. These findings provide a basis for conservation plans and for predicting coastal plants responses to climate change.
Applied Precision Cancer Medicine in Neuro-Oncology
Authors: Taghizadeh H. , Müllauer L. , Furtner J. , Hainfellner J. A. , Marosi C. , Preusser M. , Prager G. W. 
Published: December 2019

AbstractBrain tumours that are refractory to treatment have a poor prognosis and constitute a major challenge in offering effective treatment strategies. By targeting molecular alterations, precision cancer medicine may be a viable option for the treatment of brain tumours. In this retrospective analysis of our PCM platform, we describe the molecular profiling of primary brain tumours from 50 patients. Tumour samples of the patients were examined by a 161-gene next-generation sequencing panel, immunohistochemistry, and fluorescencein situhybridization (FISH). We identified 103 molecular aberrations in 36 (72%) of the 50 patients. The predominant mutations wereTP53(14.6%),IDH1(9.7%) andPIK3CA(6.8%). No mutations were detected in 14 (28%) of the 50 patients. IHC demonstrated frequent overexpression of EGFR and mTOR, in 38 (76%) and 35 (70%) patients, respectively. Overexpression of PDGFRa and PDGFRb were less common and detected in 16 and four patients, respectively. For 35 patients a targeted therapy was recommended. In our database, the majority of patients displayed mutations, against which targeted therapy could be offered. Based on our observations, PCM may be a feasible novel treatment approach in neuro-oncology.
High MAST2 mRNA expression and its role in diagnosis and prognosis of liver cancer
Authors: Jiao Yan , Li Yanqing , Jiang Peiqiang , Fu Zhuo , Liu Yahui 
Published: December 2019

AbstractLiver cancer is a high morbidity and low survival disease all over the world. Chromosomal instability is hallmark of liver cancer. Microtubule-associated serine and threonine kinase 2 (MAST2), as a microtubule associated protein, may involve in tumorous chromosomal instability and plays important roles in cell proliferation and survival. The role of MAST2 in liver cancer has not been well elucidated, which is the aim of our study. In this study, The Cancer Genome Atlas database was used to study the MAST2 mRNA expression in liver cancer, and Chi-squared tests were performed to test the correlation between clinical features and MAST2 expression. ROC curve was performed to examined the diagnostic capacity. The prognostic value of MAST2 in liver cancer was assessed through Kaplan–Meier curves as well as Cox analysis. Our results showed MAST2 was upregulated in liver cancer, and the area under the curve (AUC) was 0.925 and indicated powerful diagnostic capability. High MAST2 expression was associated with advanced clinical status such as histological type (p = 0.0059), histologic grade (p = 0.0142), stage (p = 0.0008), T classification (p = 0.0028), N classification (p = 0.0107), survival status (p = 0.0062), and poor prognosis of patients. Importantly, MAST2 was an independent risk factor for patients’ prognosis after adjusting for other risk factors including stage, T classification, and residual tumor. In total, MAST2 is a potential diagnostic and prognostic biomarker of liver cancer.
Efficacy and Safety of Nivestim Versus Neupogen for Mobilization of Peripheral Blood Stem Cells for Autologous Stem Cell Transplantation
Authors: Chew Cindy , Ng Hong Yen 
Published: December 2019

Abstract A retrospective cohort study was conducted in Singapore General Hospital to study the safety and efficacy of biosimilar granulocyte-colony stimulating factor (G-CSF) Nivestim for chemo-mobilization of stem cells for autologous stem cell transplant (autoSCT). All patients who underwent an autoSCT between January 2011 and December 2016 were screened for eligibility. A total of 194 patients were screened, and 131 were included. Nivestim was used in 65 patients and the originator G-CSF (Neupogen) in 66. Patient characteristics were similar between both arms except for chemo-mobilization regimen used (p < 0.0001). Mobilization success rates were found to be comparable, at 96.9% (Nivestim) and 97% (Neupogen). Adverse events rates were also similar. Median duration of G-CSF use and hospitalization were both found to be shorter in the Nivestim arm. Median drug acquisition cost per mobilization cycle was significantly lower in the Nivestim arm at $533.40 (range $213.40–$1280.20) as compared to $1261.90 (range $574–$2755.20) in the Neupogen arm (p < 0.0001). No difference was observed for neutrophil and platelet engraftment after autoSCT. Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length of hospitalization.
Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo
Authors: Janjic Marija M. , Prévide Rafael M. , Fletcher Patrick A. , Sherman Arthur , Smiljanic Kosara , Abebe Daniel , Bjelobaba Ivana , Stojilkovic Stanko S. 
Published: December 2019

AbstractContinuous, as opposed to pulsatile, delivery of hypothalamic gonadotropin-releasing hormone (GnRH) leads to a marked decrease in secretion of pituitary gonadotropins LH and FSH and impairment of reproductive function. Here we studied the expression profile of gonadotropin subunit and GnRH receptor genes in rat pituitary in vitro and in vivo to clarify their expression profiles in the absence and continuous presence of GnRH. Culturing of pituitary cells in GnRH-free conditions downregulated Fshb, Cga, and Gnrhr expression, whereas continuous treatment with GnRH agonists upregulated Cga expression progressively and Gnrhr and Fshb expression transiently, accompanied by a prolonged blockade of Fshb but not Gnrhr expression. In contrast, Lhb expression was relatively insensitive to loss of endogenous GnRH and continuous treatment with GnRH, probably reflecting the status of Egr1 and Nr5a1 expression. Similar patterns of responses were observed in vivo after administration of a GnRH agonist. However, continuous treatment with GnRH stimulated LH secretion in vitro and in vivo, leading to decrease in LH cell content despite high basal Lhb expression. These data suggest that blockade of Fshb expression and depletion of the LH secretory pool are two major factors accounting for weakening of the gonadotroph secretory function during continuous GnRH treatment.
TDP-43 aggregation inside micronuclei reveals a potential mechanism for protein inclusion formation in ALS
Authors: Droppelmann Cristian A. , Campos-Melo Danae , Moszczynski Alexander J. , Amzil Hind , Strong Michael J. 
Published: December 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease with no known etiology. The formation of pathological protein inclusions, including RNA-binding proteins such as TDP-43 and rho guanine nucleotide exchange factor (RGNEF) are a hallmark of ALS. Despite intensive research, the mechanisms behind protein aggregate formation in ALS remains unclear. We have investigated the role of metabolic stress in protein aggregate formation analyzing how it is relevant to the co-aggregation observed between RGNEF and TDP-43 in motor neurons of ALS patients. Metabolic stress was able to induce formation of micronuclei, small nuclear fragments, in cultured cells. Notably, we observed the formation TDP-43 protein inclusions within micronuclei that co-aggregate with RGNEF and can be released to the cytoplasm. We observed that the leucine-rich domain of RGNEF is critical for its interaction with TDP-43 and localization in micronuclei. Finally, we described that micronuclei-like structures can be found in brain and spinal cord of ALS patients. This work is the first description of protein inclusion formation within micronuclei which also is linked with a neurodegenerative disease. The formation of TDP-43 inclusions within micronuclei induced by metabolic stress is a novel mechanism of protein aggregate formation which may have broad relevance for ALS and other neurodegenerative diseases.
Increase in bone metabolic markers and circulating osteoblast-lineage cells after orthognathic surgery
Authors: Abe Yoko , Chiba Mirei , Yaklai Sanicha , Pechayco Roan Solis , Suzuki Hikari , Takahashi Tetsu 
Published: December 2019

AbstractIncreased mineralisation rate and bone formation after surgery or fracture is the regional acceleratory phenomenon (RAP), and its systemic impact is the systemic acceleratory phenomenon (SAP). The proportion of circulating osteoblast lineage cells, including osteocalcin-positive (OCN+) cells, in the peripheral blood is markedly higher during pubertal growth and in patients with bone fractures. This study aimed to elucidate the dynamic changes in bone metabolic activity after orthognathic surgery by longitudinal prospective observation. Peripheral venous blood samples were collected from patients who had undergone orthognathic surgery, and serum bone metabolic markers and the proportion of OCN+ cells were measured. Orthognathic surgery induces systemic dynamic changes in bone metabolic activity by targeting steps in the bone healing process and related proteins, such as surgical stress/inflammation (C-reactive protein), bone resorption (type I collagen C-telopeptide), and bone formation (alkaline phosphatase and bone-specific alkaline phosphatase). During the early post-operative period, the population of OCN+ cells significantly increased. Confocal microscopy revealed that OCN proteins were localised in the cytoplasm in Triton X-100-treated OCN+ cells. Furthermore, OCN, ALP, and COL1A1 gene expression was detected in OCN+ cells, suggesting the contribution of the local maturation of bone marrow-derived OCN+ cells at the site of bone healing.
Statistical Analysis of Dual-task Gait Characteristics for Cognitive Score Estimation
Authors: Matsuura Taku , Sakashita Kazuhiro , Grushnikov Andrey , Okura Fumio , Mitsugami Ikuhisa , Yagi Yasushi 
Published: December 2019

AbstractTraditional approaches for the screening of cognitive function are often based on paper tests, such as Mini-Mental State Examination (MMSE), that evaluate the degree of cognitive impairment and provide a score of patient’s mental ability. Procedures for conducting paper tests require time investment involving a questioner and not suitable to be carried out frequently. Previous studies showed that dementia impaired patients are not capable of multi-tasking efficiently. Based on this observation an automated system utilizing Kinect device for collecting primarily patient’s gait data who carry out locomotion and calculus tasks individually (i.e., single-tasks) and then simultaneously (i.e., dual-task) was introduced. We installed this system in three elderly facilities and collected 10,833 behavior data from 90 subjects. We conducted analyses of the acquired information extracting 12 features of single- and dual-task performance developed a method for automatic dementia score estimation to investigate determined which characteristics are the most important. In result, a machine learning algorithm using single and dual-task performance classified subjects with an MMSE score of 23 or lower with a recall 0.753 and a specificity 0.799. We found the gait characteristics were important features in the score estimation, and referring to both single and dual-task features was effective.
Diversity of SpaP in genetic and salivary agglutinin mediated adherence among Streptococcus mutans strains
Authors: Yang Jingmei , Deng Dongmei , Brandt Bernd W. , Nazmi Kamran , Wu Yafei , Crielaard Wim , Ligtenberg Antoon J. M. 
Published: December 2019

AbstractStreptococcus mutans SpaP mediates the binding of this cariogenic bacteria to tooth surfaces. It was reported that the SpaP of S. mutans clinical isolates could be classified to 2 genotypes, type A and B. Our aims are to examine spaP genotypes in often-used S. mutans laboratory strains as well as clinical isolates and to explore the relationship between the genotypes of S. mutans strains and their adherence to salivary-agglutinin (SAG). The sequences of SpaP of 11 S. mutans strains were analyzed with alignment tools. Out of these strains, 9 strains were examined for their adherence to SAG-coated surfaces. The SpaP expression on the cell surfaces and in the spent media of 9 strains were examined by a dot-blot assay. Based on the alignment of the variable V region of SpaP, 9 strains were classified as previously-defined type-A and 3 strains type-B. Among type-B strains, the SpaPs of GS5 and HG723 contain a premature stop codon which resulted in loss of adherence and absence of SpaP expression on the cell surfaces. However, clear SpaP expression was observed in the spent media of both strains. The type-B strain UA159 demonstrated low SpaP expression on the cell surface, but it showed similar adherence ability as the type-A strains. In conclusion, the presence of SpaP on the cell surface determines the adherence of S. mutans to SAG. No difference in SAG-mediated adherence could be seen between type A and B strains, probably due to the limited number of type B strain tested.
A multiple coefficient of determination-based method for parsing SNPs that correlate with mRNA expression
Authors: Song Fan , Tao Yu , Sun Yue , Saffen David 
Published: December 2019

AbstractIn this study, we present a novel, multiple coefficient of determination (R2M)-based method for parsing SNPs located within the chromosomal neighborhood of a gene into semi-independent families, each of which corresponds to one or more functional variants that regulate transcription of the gene. Specifically, our method utilizes a matrix equation framework to calculate R2M values for SNPs within a chromosome region of interest (ROI) based upon the choices of 1-4 “index” SNPs (iSNPs) that serve as proxies for underlying regulatory variants. Exhaustive testing of sets of 1–4 candidate iSNPs identifies iSNP models that best account for estimated R2 values derived from single-variable linear regression analysis of correlations between mRNA expression and genotypes of individual SNPs. Subsequent genotype-based estimation of pairwise r2 linkage disequilibrium (LD) coefficients between each iSNP and the other ROI SNPs allows the SNPs to be parsed into semi-independent families. Analysis of mRNA expression and genotypes data downloaded from Gene Expression Omnibus (GEO) and database for Genotypes and Phenotypes (dbGAP) demonstrates the usefulness of this method for parsing SNPs based on experimental data. We believe that this method will be widely applicable for the analysis of the genetic basis of mRNA expression and visualizing the contributions of multiple genetic variants to the regulation of individual genes.
Optical decomposition of DNA gel and modification of object mobility on micrometre scale
Authors: Shimomura Suguru , Nishimura Takahiro , Ogura Yusuke , Tanida Jun 
Published: December 2019

AbstractDNA gels can be engineered to exhibit specific properties through the choice of DNA sequences and modification with dye molecules, and can therefore be useful in biomedical applications such as the detection of biomolecules. State transitions of DNA gels on the micrometre scale can generate a viscosity gradient, which can be used to modify the mobility of micrometre-sized objects. In this paper, we propose a method for changing the viscosity of DNA gels using optical decomposition. The use of light allows for decomposition on the micrometre scale, which can be used to achieve patterned viscosity changes within DNA gels. Decomposition was induced by thermal energy released through non-radiative relaxation of excited quenchers. We demonstrated the decomposition of DNA gels in response to irradiation patterns on the micrometre scale. In addition, as a result of changes in DNA gel viscosity due to decomposition, the mobility of polystyrene beads was shown to increase. This technique could provide a new optical approach for controlling the mobility of micrometre-sized objects.
Potential of electrospun cationic BSA fibers to guide osteogenic MSC differentiation via surface charge and fibrous topography
Authors: Raic Annamarija , Friedrich Frank , Kratzer Domenic , Bieback Karen , Lahann Joerg , Lee-Thedieck Cornelia 
Published: December 2019

AbstractLarge or complex bone fractures often need clinical treatments for sufficient bone repair. New treatment strategies have pursued the idea of using mesenchymal stromal cells (MSCs) in combination with osteoinductive materials to guide differentiation of MSCs into bone cells ensuring complete bone regeneration. To overcome the challenge of developing such materials, fundamental studies are needed to analyze and understand the MSC behavior on modified surfaces of applicable materials for bone healing. For this purpose, we developed a fibrous scaffold resembling the bone/bone marrow extracellular matrix (ECM) based on protein without addition of synthetic polymers. With this biomimetic in vitro model we identified the fibrous structure as well as the charge of the material to be responsible for its effects on MSC differentiation. Positive charge was introduced via cationization that additionally supported the stability of the scaffold in cell culture, and acted as nucleation point for mineralization during osteogenesis. Furthermore, we revealed enhanced focal adhesion formation and osteogenic differentiation of MSCs cultured on positively charged protein fibers. This pure protein-based and chemically modifiable, fibrous ECM model allows the investigation of MSC behavior on biomimetic materials to unfold new vistas how to direct cells’ differentiation for the development of new bone regenerating strategies.
Deep sequencing and automated histochemistry of human tissue slice cultures improve their usability as preclinical model for cancer research
Authors: Haehnel Susann , Reiche Kristin , Loeffler Dennis , Horn Andreas , Blumert Conny , Puppel Sven-Holger , Kaiser Nicole , Rapp Felicitas , Rade Michael , Horn Friedemann , Meixensberger Juergen , Bechmann Ingo , Gaunitz Frank , Winter Karsten 
Published: December 2019

AbstractCancer research requires models closely resembling the tumor in the patient. Human tissue cultures can overcome interspecies limitations of animal models or the loss of tissue architecture inin vitromodels. However, analysis of tissue slices is often limited to histology. Here, we demonstrate that slices are also suitable for whole transcriptome sequencing and present a method for automated histochemistry of whole slices. Tumor and peritumoral tissue from a patient with glioblastoma was processed to slice cultures, which were treated with standard therapy including temozolomide and X-irradiation. Then, RNA sequencing and automated histochemistry were performed. RNA sequencing was successfully accomplished with a sequencing depth of 243 to 368 x 106reads per sample. Comparing tumor and peritumoral tissue, we identified 1888 genes significantly downregulated and 2382 genes upregulated in tumor. Treatment significantly downregulated 2017 genes, whereas 1399 genes were upregulated. Pathway analysis revealed changes in the expression profile of treated glioblastoma tissue pointing towards downregulated proliferation. This was confirmed by automated analysis of whole tissue slices stained for Ki67. In conclusion, we demonstrate that RNA sequencing of tissue slices is possible and that histochemical analysis of whole tissue slices can be automated which increases the usability of this preclinical model.