bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between outflow resistance and trabecular meshwork stiffness in mice
Authors: Wang Ke , Li Guorong , Read A. Thomas , Navarro Iris , Mitra Ashim K. , Stamer W. Daniel , Sulchek Todd , Ethier C. Ross 
Published: April 2018

AbstractIt has been suggested that common mechanisms may underlie the pathogenesis of primary open-angle glaucoma (POAG) and steroid-induced glaucoma (SIG). The biomechanical properties (stiffness) of the trabecular meshwork (TM) have been shown to differ between POAG patients and unaffected individuals. While features such as ocular hypertension and increased outflow resistance in POAG and SIG have been replicated in mouse models, whether changes of TM stiffness contributes to altered IOP homeostasis remains unknown. We found that outer TM was stiffer than the inner TM and, there was a significant positive correlation between outflow resistance and TM stiffness in mice where conditions are well controlled. This suggests that TM stiffness is intimately involved in establishing outflow resistance, motivating further studies to investigate factors underlying TM biomechanical property regulation. Such factors may play a role in the pathophysiology of ocular hypertension. Additionally, this finding may imply that manipulating TM may be a promising approach to restore normal outflow dynamics in glaucoma. Further, novel technologies are being developed to measure ocular tissue stiffness in situ. Thus, the changes of TM stiffness might be a surrogate marker to help in diagnosing altered conventional outflow pathway function if those technologies could be adapted to TM.
IL23 and TGF-ß diminish macrophage associated metastasis in pancreatic carcinoma
Authors: Hussain S. Mazher , Reed Leighton F. , Krasnick Bradley A. , Miranda-Carboni Gustavo , Fields Ryan C. , Bi Ye , Elahi Abul , Ajidahun Abidemi , Dickson Paxton V. , Deneve Jeremiah L. , Hawkins William G. , Shibata David , Glazer Evan S. 
Published: April 2018

AbstractThe precise role of tumor associated macrophages remains unclear in pancreatic ductal adenocarcinoma (PDAC) while TGF-ß has an unclear role in metastases formation. In order to understand the role of IL23, an interleukin associated with macrophage polarization, we investigated IL23 in the context of TGF-ß expression in PDAC. We hypothesized that IL23 expression is associated with metastatic development and survival in PDAC. We investigated IL23 and TGF-ß protein expression on resected PDAC patient tumor sections who were divided into short-term (<12 months) survivors and long-term (>30 months) survivors. Panc-1 cells treated with IL23, TGF-ß, macrophages, or combinations thereof, were orthotopically implanted into NSG mice. Patients in the long-term survivor group had higher IL23 protein expression (P = 0.01). IL23 expression was linearly correlated with TGF-ß expression in patients in the short-term survivor group (P = 0.038). Macrophages induce a higher rate of PDAC metastasis in the mouse model (P = 0.02), which is abrogated by IL23 and TGF-ß treatment (P < 0.001). Macrophages serve a critical role in PDAC tumor growth and metastasis. TGF-ß contributes to a less tumorigenic TME through regulation of macrophages. Macrophages increases PDAC primary tumor growth and metastases formation while combined IL23 and TGF-ß pre-treatment diminishes these processes.
Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR
Authors: Manzella Christopher , Singhal Megha , Alrefai Waddah A. , Saksena Seema , Dudeja Pradeep K. , Gill Ravinder K. 
Published: April 2018

AbstractAryl hydrocarbon receptor (AhR) is a nuclear receptor that controls xenobiotic detoxification via induction of cytochrome P450 1A1 (CYP1A1) and regulates immune responses in the intestine. Metabolites of L-tryptophan activate AhR, which confers protection against intestinal inflammation. We tested the hypothesis that serotonin (5-HT) is an endogenous activator of AhR in intestinal epithelial cells. Treatment of Caco-2 monolayers with 5-HT induced CYP1A1 mRNA in a time- and concentration-dependent manner and also stimulated CYP1A1 activity. CYP1A1 induction by 5-HT was dependent upon uptake via serotonin transporter (SERT). Antagonism of AhR and knockdown of AhR and its binding partner aryl hydrocarbon receptor nuclear translocator (ARNT) attenuated CYP1A1 induction by 5-HT. Activation of AhR was evident by its nuclear translocation after 5-HT treatment and by induction of an AhR-responsive luciferase reporter. In vivo studies showed a dramatic decrease in CYP1A1 expression and other AhR target genes in SERT KO ileal mucosa by microarray analysis. These results suggest that intracellular accumulation of 5-HT via SERT induces CYP1A1 expression via AhR in intestinal epithelial cells, and SERT deficiency in vivo impairs activation of AhR. Our studies provide a novel link between the serotonergic and AhR pathways which has implications in xenobiotic metabolism and intestinal inflammation.
Proteomic analysis at the sites of clinical infection with invasive Streptococcus pyogenes
Authors: Edwards Robert J. , Pyzio Marta , Gierula Magdalena , Turner Claire E. , Abdul-Salam Vahitha B. , Sriskandan Shiranee 
Published: April 2018

AbstractInvasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive S. pyogenes infection (empyema, septic arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were found in a single pleural fluid sample including streptococcal inhibitor of complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human proteins were detected in patient fluids, 177 (38%) of which could be identified as neutrophil proteins, including alpha enolase and lactotransferrin which, together, were found in all 17 samples. Our data suggest that streptococcal proteins are difficult to detect in infected fluid samples. A vast array of human proteins associated with leukocyte activity are, however, present in samples that deserve further evaluation as potential biomarkers of infection.
Deformation behavior of dragonfly-inspired nodus structured wing in gliding flight through experimental visualization approach
Authors: Zhang Sheng , Sunami Yuta , Hashimoto Hiromu 
Published: April 2018

AbstractDragonfly has excellent flight performance and maneuverability due to the complex vein structure of wing. In this research, nodus as an important structural element of the dragonfly wing is investigated through an experimental visualization approach. Three vein structures were fabricated as, open-nodus structure, closed-nodus structure (with a flex-limiter) and rigid wing. The samples were conducted in a wind tunnel with a high speed camera to visualize the deformation of wing structure in order to study the function of nodus structured wing in gliding flight. According to the experimental results, nodus has a great influence on the flexibility of the wing structure. Moreover, the closed-nodus wing (with a flex-limiter) enables the vein structure to be flexible without losing the strength and rigidity of the joint. These findings enhance the knowledge of insect-inspired nodus structured wing and facilitate the application of Micro Air Vehicle (MAV) in gliding flight.
Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever
Authors: Boisen Matthew L. , Hartnett Jessica N. , Shaffer Jeffrey G. , Goba Augustine , Momoh Mambu , Sandi John Demby , Fullah Mohamed , Nelson Diana K. S. , Bush Duane J. , Rowland Megan M. , Heinrich Megan L. , Koval Anatoliy P. , Cross Robert W. , Barnes Kayla G. , Lachenauer Anna E. , Lin Aaron E. , Nekoui Mahan , Kotliar Dylan , Winnicki Sarah M. , Siddle Katherine J. , Gbakie Michael , Fonnie Mbalu , Koroma Veronica J. , Kanneh Lansana , Kulakosky Peter C. , Hastie Kathryn M. , Wilson Russell B. , Andersen Kristian G. , Folarin Onikepe O. , Happi Christian T. , Sabeti Pardis C. , Geisbert Thomas W. , Saphire Erica Ollmann , Khan S. Humarr , Grant Donald S. , Schieffelin John S. , Branco Luis M. , Garry Robert F. 
Published: April 2018

AbstractLassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient’s clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100% specificity. ReLASV immunoassays performed better than the most robust qPCR currently available, which had 82% sensitivity and 95% specificity. The performance characteristics of recombinant antigen-based Lassa virus immunoassays indicate that they can aid in the diagnosis of LASV Infection and inform the clinical management of Lassa fever patients.
Meta-scale mountain grassland observatories uncover commonalities as well as specific interactions among plant and non-rhizosphere soil bacterial communities
Authors: Yashiro Erika , Pinto-Figueroa Eric , Buri Aline , Spangenberg Jorge E. , Adatte Thierry , Niculita-Hirzel Helene , Guisan Antoine , van der Meer Jan Roelof 
Published: April 2018

AbstractInteractions between plants and bacteria in the non-rhizosphere soil are rarely assessed, because they are less direct and easily masked by confounding environmental factors. By studying plant vegetation alliances and soil bacterial community co-patterning in grassland soils in 100 sites across a heterogeneous mountain landscape in the western Swiss Alps, we obtained sufficient statistical power to disentangle common co-occurrences and weaker specific interactions. Plant alliances and soil bacterial communities tended to be synchronized in community turnover across the landscape, largely driven by common underlying environmental factors, such as soil pH or elevation. Certain alliances occurring in distinct, local, environmental conditions were characterized by co-occurring specialist plant and bacterial species, such as theNardus strictaand Thermogemmatisporaceae. In contrast, some generalist taxa, likeAnthoxanthum odoratumand 19 Acidobacteria species, spanned across multiple vegetation alliances. Meta-scale analyses of soil bacterial community composition and vegetation surveys, complemented with local edaphic measurements, can thus prove useful to identify the various types of plant-bacteria interactions and the environments in which they occur.
The Effects of Sampling Location and Predictor Point Estimate Certainty on Posterior Support in Bayesian Phylogeographic Generalized Linear Models
Authors: Magee Daniel , Taylor Jesse E. , Scotch Matthew 
Published: April 2018

AbstractThe use of generalized linear models in Bayesian phylogeography has enabled researchers to simultaneously reconstruct the spatiotemporal history of a virus and quantify the contribution of predictor variables to that process. However, little is known about the sensitivity of this method to the choice of the discrete state partition. Here we investigate this question by analyzing a data set containing 299 sequences of the West Nile virus envelope gene sampled in the United States and fifteen predictors aggregated at four spatial levels. We demonstrate that although the topology of the viral phylogenies was consistent across analyses, support for the predictors depended on the level of aggregation. In particular, we found that the variance of the predictor support metrics was minimized at the most precise level for several predictors and maximized at more sparse levels of aggregation. These results suggest that caution should be taken when partitioning a region into discrete locations to ensure that interpretable, reproducible posterior estimates are obtained. These results also demonstrate why researchers should use the most precise discrete states possible to minimize the posterior variance in such estimates and reveal what truly drives the diffusion of viruses.
Affective and cognitive rather than somatic symptoms of depression predict 3-year mortality in patients on chronic hemodialysis
Authors: Cheng Hui-Teng , Ho Miao-Chun , Hung Kuan-Yu 
Published: April 2018

AbstractDepression is more common in many medical conditions than among the general population and is associated with an increased risk of mortality. We aimed to determine whether somatic symptoms of depression were more predictive of mortality than affective and cognitive symptoms in hemodialysis patients. We conducted a prospective cohort study in which the survival outcomes of 151 subjects were followed for more than 3 years. Depression was assessed with the Taiwanese Depression Questionnaire (TDQ). Subjects with TDQ scores 19–54 (correlated with clinically significant depressive symptoms) and those with scores 15–18 had higher 3-year mortality rates than the two groups with lower scores (40.0%, 46.7%, 16.0% and 19.6%, p = 0.021, ANOVA). Affective and cognitive symptoms, including sadness, tenseness, indecisiveness and low self-confidence, and one somatic item (bodily discomfort) were associated with mortality. Affective and cognitive symptoms affected quality of life more than somatic symptoms. The somatic subscale was associated with female gender, low income and education, dialysis vintage, and low serum creatinine and albumin levels, whereas the affective and cognitive subscale was associated with less education and a low serum albumin level. In conclusion, affective and cognitive symptoms of depression may better predict long-term mortality in patients undergoing chronic hemodialysis than somatic symptoms.
Projected effectiveness and added value of HIV vaccination campaigns in South Africa: A modeling study
Authors: de Montigny Simon , Adamson Blythe J. S. , Mâsse Benoît R. , Garrison Louis P. , Kublin James G. , Gilbert Peter B. , Dimitrov Dobromir T. 
Published: April 2018

AbstractPromising multi-dose HIV vaccine regimens are being tested in trials in South Africa. We estimated the potential epidemiological and economic impact of HIV vaccine campaigns compared to continuous vaccination, assuming that vaccine efficacy is transient and dependent on immune response. We used a dynamic economic mathematical model of HIV transmission calibrated to 2012 epidemiological data to simulate vaccination with anticipated antiretroviral treatment scale-up in South Africa. We estimate that biennial vaccination with a 70% efficacious vaccine reaching 20% of the sexually active population could prevent 480,000–650,000 HIV infections (13.8–15.3% of all infections) over 10 years. Assuming a launch price of $15 per dose, vaccination was found to be cost-effective, with an incremental cost-effectiveness ratio of $13,746 per quality-adjusted life-year as compared to no vaccination. Increasing vaccination coverage to 50% will prevent more infections but is less likely to achieve cost-effectiveness. Campaign vaccination is consistently more effective and costs less than continuous vaccination across scenarios. Results suggest that a partially effective HIV vaccine will have substantial impact on the HIV epidemic in South Africa and offer good value if priced less than $105 for a five-dose series. Vaccination campaigns every two years may offer greater value for money than continuous vaccination reaching the same coverage level.
Management of glycemic variation in diabetic patients receiving parenteral nutrition by continuous subcutaneous insulin infusion (CSII) therapy
Authors: Li Feng-fei , Zhang Wen-li , Liu Bing-li , Zhang Dan-feng , Chen Wei , Yuan Li , Chen Mao-yuan , Zhai Xiao-fang , Wu Jin-dan , Su Xiao-fei , Ye Lei , Cao Hong-yong , Ma Jian-hua 
Published: April 2018

AbstractTo compare the continuous subcutaneous insulin infusion (CSII) or insulin glargine based multiple injections (MDI) therapy on glycemic variations in diabetic patients receiving PN outside of intensive care settings. This was a single-center, randomized, open-label trial. Patients with type 2 diabetes (T2D) who were receiving parenteral nutrition (PN) were recruited. After baseline data were collected, recruited patients were then randomized 1:1 to a CSII group or a MDI group. All patients were subjected to a 4-day retrospective Continuous Glucose Monitoring (CGM). The primary endpoint was the differences of the 24-hrs mean amplitude of glycemic excursion (MAGE) in patients receiving the PN therapy between the two groups. A total of 102 patients with T2D receiving PN were recruited. Patients in the CSII group had a significantly decreased mean glucose level (MBG), the standard deviation of MG (SDBG), MAGE, and the coefficient of variation (CV%) compared to those in MDI group (all P < 0.01). Furthermore, we found that the patients who received a bolus insulin dose required maintaining euglycemic control was gradually decreased during the PN period in both groups at the endpoint. The administration of insulin via CSII led to a significant decrease in glycemic variations in patients receiving PN.
A Firefly Luciferase Dual Color Bioluminescence Reporter Assay Using Two Substrates To Simultaneously Monitor Two Gene Expression Events
Authors: Branchini Bruce R. , Southworth Tara L. , Fontaine Danielle M. , Kohrt Dawn , Florentine Catherine M. , Grossel Martha J. 
Published: April 2018

AbstractEffective methods for monitoring eukaryotic gene expression and regulation based on bioluminescence - the emission of light by living organisms - are well established. Typically, the expression of a gene of interest is reported on with high sensitivity and over a wide dynamic range by the emission of light from a variety of engineered luciferase genes from beetles and marine organisms. The luciferase reporter genes are expressed downstream of the target gene or promoter and detected after exogenous addition of luciferin substrates. We describe a novel bioluminescence reporter method for the simultaneous monitoring of two genes expressing engineered firefly luciferase variants that emit readily distinguishable green and red light signals. The key feature is the selectivity of the enzymes for two luciferin substrates that determine each emission color. To validate our method, we performed a complex promoter transactivation experiment side-by-side with the Dual-Luciferase Reporter protocol and obtained essentially identical results. Additional comparative experiments demonstrated that our assay system provided improvements in background, cell normalization, and detectability compared to representative available methods. With access to a luminometer equipped with two optical filters, this method is an excellent choice for genetic reporter assays that can be performed with a single reagent solution.
NIPS, a 3D network-integrated predictor of deleterious protein SAPs, and its application in cancer prognosis
Authors: Wang Bo , Li Jing , Cheng Xi , Zhou Qiao , Yang Jingxu , Zhang Menghuan , Chen Haifeng , Li Jing 
Published: April 2018

AbstractIdentifying deleterious mutations remains a challenge in cancer genome sequencing projects, reflecting the vast number of candidate mutations per tumour and the existence of interpatient heterogeneity. Based on a 3D protein interaction network profiled via large-scale cross-linking mass spectrometry, we propose a weighted average formula involving the combination of three types of information into a ‘meta-score’. We assume that a single amino acid polymorphism (SAP) may have a deleterious effect if the mutation rarely occurs naturally during evolution, if it inhibits binding between a pair of interacting proteins when located at their interface, or if it plays an important role in a protein interaction (PPI) network. Cross-validation indicated that this new method presents an AUC value of 0.93 and outperforms other widely used tools. The application of this method to the CPTAC colorectal cancer dataset enabled the accurate identification of validated deleterious mutations and yielded insights into their potential pathogenesis. Survival analysis showed that the accumulation of deleterious SAPs is significantly associated with a poor prognosis. The new method provides an alternative method to identifying and ranking deleterious cancer SAPs based on a 3D PPI network and will contribute to the understanding of pathogenesis and the discovery of prognostic biomarkers.
Accurate identification of RNA editing sites from primitive sequence with deep neural networks
Authors: Ouyang Zhangyi , Liu Feng , Zhao Chenghui , Ren Chao , An Gaole , Mei Chuan , Bo Xiaochen , Shu Wenjie 
Published: April 2018

AbstractRNA editing is a post-transcriptional RNA sequence alteration. Current methods have identified editing sites and facilitated research but require sufficient genomic annotations and prior-knowledge-based filtering steps, resulting in a cumbersome, time-consuming identification process. Moreover, these methods have limited generalizability and applicability in species with insufficient genomic annotations or in conditions of limited prior knowledge. We developed DeepRed, a deep learning-based method that identifies RNA editing from primitive RNA sequences without prior-knowledge-based filtering steps or genomic annotations. DeepRed achieved 98.1% and 97.9% area under the curve (AUC) in training and test sets, respectively. We further validated DeepRed using experimentally verified U87 cell RNA-seq data, achieving 97.9% positive predictive value (PPV). We demonstrated that DeepRed offers better prediction accuracy and computational efficiency than current methods with large-scale, mass RNA-seq data. We used DeepRed to assess the impact of multiple factors on editing identification with RNA-seq data from the Association of Biomolecular Resource Facilities and Sequencing Quality Control projects. We explored developmental RNA editing pattern changes during human early embryogenesis and evolutionary patterns in Drosophila species and the primate lineage using DeepRed. Our work illustrates DeepRed’s state-of-the-art performance; it may decipher the hidden principles behind RNA editing, making editing detection convenient and effective.