bluuebunny/crossref_metadata_2025 huggingface dataset:
Elastic scattering of electrons by Sr atom: a study of critical minima and spin polarization
Authors: Kumar Ashok , Abdullah M N A , Haque A K F , Singh Indu , Uddin M Alfaz
Published: May 2019

Within the framework of the complex optical potential, the critical minima (CM) in the differential cross sections and the spin polarization in the elastic scattering of electrons by the Sr atom are studied in the energy range E

i
 = 1–1000 eV using the Dirac and Schrödinger partial wave methods. The two methods are, respectively, termed as the optical potential method of Dirac (OPMD) and optical potential method of Schrödinger (OPMS). The differential cross sections (DCSs), total cross sections (TCSs), momentum transfer cross sections (MTCSs), integral elastic cross sections (IECSs), viscosity cross sections (VCSs) and inelastic cross sections (INCSs) for e–Sr scattering are also calculated for the same energy range. In OPMD, the complex optical potential is composed of the static, exchange, polarization and absorption potentials. The OPMS potential, on the other hand, comprises the static, local exchange, polarization, spin-orbit, and absorption components. The number of CM points has been found to be respectively 7 and 5 with OPMD and OPMS methods in the DCSs of e–Sr scattering. The number of maximum spin polarization points observed is 13 and 10 for the OPMD and OPMS respectively. The energy dependence of TCS, MTCS, IECS, VCS, and INCS, studied in this work, show a non-monotonous pattern for energies beyond about 50 eV. So far as we are concerned, this is the first work for the study of CM in the DCSs of the e–Sr scattering as there are neither experimental nor theoretical studies published in the literature for the same.
Foreign Geographical Indications, Consumer Preferences, and the Domestic Market for Cheese
Authors: Slade Peter , Michler Jeffrey D. , Josephson Anna
Published: May 2019

The protection of geographical indications (GIs) is an important feature of modern trade agreements. In the Canada‐European Union Comprehensive Economic and Trade Agreement (CETA), Canada agreed to stronger protections for GIs of European cheeses and other food products. Under this agreement, new Canadian producers can no longer label cheese as “feta” but instead must refer to it as “imitation feta,” “feta style,” or “feta type.” We use a choice experiment to determine the effect of this agreement on Canadian cheese producers. We find that the effect of GI recognition varies depending on the terms used to label Canadian cheese and the information given to consumers. The results imply that policies that give greater latitude to food marketers will weaken the impact of GI recognition.
Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma
Authors: Vaziri Fard Elmira , Ali Yasir , Wang Xiaohong I , Saluja Karan , H Covinsky Michael , Wang Lei , Zhang Songlin
Published: May 2019

Objectives

Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer.

Methods

We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups.

Results

TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance.

Conclusions

Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.
Evidence of local adaptation and stabilizing selection on quantitative traits in populations of the multipurpose American species Acacia aroma (Fabaceae)
Authors: Pometti Carolina L , Bessega Cecilia F , Cialdella Ana M , Ewens Mauricio , Saidman Beatriz O , Vilardi Juan C
Published: May 2019

Economically and ecologically important quantitative traits of Acacia aroma are related to life history and the size and shape of fruits and leaves. Substantial variation is observed for these traits in natural populations, suggesting a possible genetic basis that could be useful for selection programmes. Our objective was to detect signals of selection on 12 phenotypic traits in 170 individuals belonging to seven populations of A. aroma in the Chaco Region of Argentina. Phenotypic traits were compared with molecular markers assessed in the same populations. Here, we search for signatures of natural selection by comparing quantitative trait variation to neutral genetic variation through the PST–FST test. We further test for differences among populations for the 12 phenotypic traits, an association of phenotypic variation with environmental variables and geographical distance, and we compare the power of discrimination between the phenotypic and AFLP datasets. The PST–FST test suggested directional selection for tree height and stabilizing selection for the remaining traits. Analyses of variance showed significant differentiation for eight phenotypic traits. These results suggest selecting among provenances as a management strategy to improve tree height (which showed divergent selection), whereas significant genetic gain for the other traits might be obtained by selection within provenances.
Institutional barriers and enablers to implementing and complying with internationally accepted quality standards in the local pharmaceutical industry of Pakistan: a qualitative study
Authors: Tauqeer Fatima , Myhr Kirsten , Gopinathan Unni
Published: May 2019

Complying with good manufacturing practices (GMP) and ensuring a quality system is integral to production and supply of quality medicines and achieving universal health coverage. This study focus on the local production of medicines in Pakistan, a lower middle-income country that has observed considerable growth in the number of pharmaceutical companies over the past two decades. Against this background, we investigated: (1) How is quality assurance (QA) and GMP compliance understood and acted upon by local pharmaceutical manufacturers?; (2) What are the institutional barriers and enablers for QA and GMP compliance in the local pharmaceutical sector from the perspective of key stakeholders?; and (3) What are the institutional barriers and enablers for strengthening local regulatory capacity to improve QA in the industry in the long term? We used a qualitative study design involving 22 interviews of the drug regulatory bodies (n = 9), academia (n = 3) and local manufacturers (n = 10), identifying key themes in data by thematic analysis. Document analysis was used to collect additional information and supplement the interview data. We identified that manufacturing facilities operated under different GMP standards and interpretations, pointing towards an absence of harmonization in quality standards across the industry. Views diverged about the status of GMP compliance, with interviewees from academia presenting a more critical view compared with regulators who promoted a more positive story. Among the barriers explaining why companies struggled with quality standards, the lack of a mindset promoting quality and safety among profit-oriented manufacturers was prominent. At the federal level, DRAP’s establishment represented an institutional improvement aiming to promote QA through inspections and guidance. While some positive measures to promote quality have been observed, the need for DRAP to strengthen its technical and regulatory capacity, enhance its engagement in international collaboration and learning, and improve transparency and accountability were highlighted. Overall, since the challenges in Pakistan are shared with other low- and middle-income countries with local production, there is a need to commit to international collaborative mechanisms, such as those lead by WHO, on this issue.
Not As Clear As It May Appear: Challenges Associated with Transparent Camouflage in the Ocean
Authors: Bagge Laura E
Published: May 2019

The “superpower” of invisibility is a reality and a necessity for many animals that live in featureless environments like the open ocean, where there is nowhere to hide. How do animals achieve invisibility? Many animals match their color patterns to their background, but this strategy is limited when the background scene is dynamic. Transparency allows organisms to match any background all the time. However, it is challenging for an organism to maintain transparency across its entire body volume. To be transparent, tissues must minimize light scattering, both at the surface and within. Until recently, it has been unclear how clear animals with complex bodies (such as many crustaceans with hard cuticles, thick muscles, and other internal organs) minimize such light scattering. This is especially challenging in an environment where light can come from many directions: reflections from downwelling sunlight and bioluminescent searchlights from predators. This review summarizes several recent discoveries of multiple unique adaptations for minimizing light scattering both on the exterior cuticle surface and throughout the body volume of transparent crustaceans, as well as the potential tradeoffs and challenges associated with transparent camouflage.
Words Matter: How WTO Rulings Handle Controversy
Authors: Busch Marc L , Pelc Krzysztof J
Published: May 2019

The rulings of internationals courts are often reduced to “who won?,” but much more is at stake. Like other institutions, the World Trade Organization (WTO) offers rulings that balance legal discipline against political constraints. We argue that one way in which the WTO handles politically sensitive issues is by increasing the amount of affect in their rulings. In doing so, judges provide national governments with discursive resources to persuade their domestic audiences of the legitimacy of compliance. To test our expectations, we conduct a text analysis of all rulings rendered by the institution since 1995. Specifically, we find that more politically charged decisions, such as the ones concerning nonfiscal rather than fiscal aspects of national treatment claims, are explained in qualitatively different terms. We also find that, as an issue gets ruled on repeatedly, the amount of affect deployed progressively decreases. In sum, the WTO chooses its words strategically to persuade litigants, and their domestic audiences, of the legitimacy of compliance in politically fraught disputes.
Identifying current and emerging resources and tools utilized for detection, prediction, and visualization of viral zoonotic disease clusters: a Delphi study
Authors: Beard Rachel , Scotch Matthew
Published: May 2019

Zoonotic disease surveillance presents a substantial problem in the management of public health. Globally, zoonoses have the potential to spread and negatively impact population health economic growth, and security. This research was conducted to investigate the current data sources, analytical methods, and limitations for cluster detection and prediction with particular interest in emerging bioinformatics tools and resources to inform the development of zoonotic surveillance spatial decision support systems. We recruited 10 local health personnel to participate in a Delphi study. Participants agreed cluster detection is a priority, though mathematical modeling methods and bioinformatics resources are not commonly used toward this endeavor. However, participants indicated a desire to utilize preventative measures. We identified many limitations for identifying clusters including software availability, appropriateness, training, and usage of emerging genetic data. Future decision support system development should focus on state health personnel priorities and tasks to better utilize emerging developments and available data.
Substituting corn silage with reconstituted forage or nonforage fiber sources in the starter diets of Holstein calves: effects on performance, ruminal fermentation, and blood metabolites
Authors: Kargar Shahryar , Kanani Meysam , Albenzio Marzia , Caroprese Mariangela
Published: May 2019

We examined the effects of replacing corn silage (CS) with reconstituted alfalfa hay (AH) or beet pulp (BP) in the starter diet on the nutrient intake and digestibility, growth performance, rumen fermentation characteristics, selected blood metabolites, and health status in Holstein dairy calves. Newborn female calves (n = 54; 3 d of age; 39.8 ± 1.36 kg BW) were assigned randomly to 3 groups receiving starter diets containing CS [10% dry matter (DM) basis; CS diet) and reconstituted AH (10% DM, RAH diet) or BP (10% DM; RBP diet). The starter diets had the same nutrient composition and DM content. The calves were weaned on day 50 and the study continued until day 70. Nutrient intake, body weight (at weaning and at the end of the study), daily weight gain, feed efficiency, and body measurements (including heart girth, withers height, body length, body barrel, hip height, and hip width) were not affected by the diet (P > 0.05). Health-related variables including rectal temperature, fecal score, and general appearance score were not influenced by the diets (P > 0.05). During the postweaning period, apparent total tract digestibility of DM, organic matter, and crude protein were higher for RBP (P = 0.001); however, digestibility of neutral detergent fiber was lower in RAH compared with CS or RBP (P = 0.001). Daily amount of nutrient digestibility did not change across the diets (P > 0.05). Rumen fluid pH and total volatile fatty acid concentration and profile were not different across the diets after weaning (P > 0.05). Calves fed RAH or RBP had higher blood concentration of β-hydroxy butyric acid compared with CS only before weaning (P = 0.03). Blood albumin concentration was higher for RBP compared with CS or RAH during the preweaning (P = 0.006) and overall (P = 0.005) periods; however, it was lower for CS compared with RBP after weaning (P = 0.03). Concentration of other blood variables including glucose, blood urea N, total protein, and globulin did not change across the diets (P > 0.05). Calves, in general, were healthy, and replacing CS with RAH or RBP in the starter diet had no beneficial effect on their feed intake or growth performance indicating that CS and reconstituted AH or BP can be used interchangeably in dairy calf starter diets until 70 d of age, allowing dairy producers more choices in selecting the feed ingredients.
Lipid peroxidation impairs growth and viability of nursery pigs reared under commercial conditions1
Authors: Chang Petra L , Boyd R Dean , Zier-Rush Cate , Rosero David S , van Heugten Eric
Published: May 2019

The objective of this study was to investigate the impact of lipid peroxidation in a dose-dependent manner on growth, health, and oxidative stress status of nursery pigs. A total of 2,200 weaned pigs (5.95 ± 0.20 kg BW) were housed in 100 pens (22 pigs per pen) in a randomized complete block design based on initial BW and sex. Pigs were randomly assigned within blocks to 5 dietary treatments, consisting of a corn–soybean meal-based diet supplemented with 5% of either control corn oil (iodine value = 118, FFA = 0.06%, anisidine value = 3, peroxide value = 3 mEq/kg oil) or peroxidized corn oil (iodine value = 120, FFA = 0.35%, anisidine value = 30, peroxide value = 163 mEq/kg oil). These 2 diets were blended to obtain 5 levels of peroxidation with final treatments designated as 0 (diet with 5% control oil), 25%, 50%, 75%, and 100% (diet with peroxidized corn oil) peroxidation. Diets were fed ad libitum for 43 d. Blood samples were collected on d 33 from 20 pigs per treatment to determine serum oxidative stress markers and vitamin E concentrations and again on d 43 (14 d after vaccination) to determine immune response to porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae (Mhyo). Gain:feed ratio decreased linearly (P = 0.023) with increasing peroxidation, but pen ADG and ADFI were not affected. Number of pigs removed for medical treatment, total number medically treated, pigs culled for low end weight, and mortality increased, and full-value pigs linearly decreased (P < 0.04) with increasing peroxidation. Consequently, total pen gain (weight of viable pigs that remained in test pens at the end of the study minus weight of pigs placed) decreased linearly (P < 0.01) with increasing peroxidation. Antibody titers to Mhyo and PCV2 increased postvaccination (P < 0.001), but did not differ due to dietary treatment. Serum concentrations of malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and protein carbonyl were not affected by peroxidation. Total antioxidant capacity and serum vitamin E concentrations decreased (P = 0.01) linearly with increasing peroxidation. Data show a dose-dependent negative impact of lipid peroxidation on pig productivity when determined under field population conditions, being primarily manifested by increased mortality, number of pigs medically treated, and number of culled pigs (≤13.6 kg BW). Results underscore the importance of proper assessment of lipid peroxidation as part of quality control to prevent oxidative stress and performance losses in weaned pigs.
Compositional Hierarchical Structure Evolves through Cultural Transmission: An Experimental Study
Authors: Saldana Carmen , Kirby Simon , Truswell Robert , Smith Kenny
Published: May 2019

Compositional hierarchical structure is a prerequisite for productive languages; it allows language learners to express and understand an infinity of meanings from finite sources (i.e., a lexicon and a grammar). Understanding how such structure evolved is central to evolutionary linguistics. Previous work combining artificial language learning and iterated learning techniques has shown how basic compositional structure can evolve from the trade-off between learnability and expressivity pressures at play in language transmission. In the present study we show, across two experiments, how the same mechanisms involved in the evolution of basic compositionality can also lead to the evolution of compositional hierarchical structure. We thus provide experimental evidence showing that cultural transmission allows advantages of compositional hierarchical structure in language learning and use to permeate language as a system of behaviour.
Long-Term Outcomes of Refractive Surgery Performed During the Military
Authors: Godiwalla Roxana Y , Magone M Teresa , Kaupp Sandor B , Jung Hoon , Cason John B
Published: May 2019

Introduction

To evaluate the long-term refractive results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) performed by the military in a veteran population.

Materials and Methods

Three Department of Veterans Affairs (VA) hospital sites (Puget Sound, Buffalo, and Washington D.C.) obtained IRB approval for this multi-center study. Comprehensive ophthalmologic assessment including refraction and keratometry were obtained at the time of the long-term VA examination and compared to the patients’ postoperative military records.

Results

Eighty patients (160 eyes) enrolled in this study. At the time of treatment, patients were 21–52 years of age. Long-term post-operative data was available from 4 to 17 years post-operatively. Fifteen percent of the treatment types were LASIK and 85% PRK. At the time of their military post-operative exam (range 3–14 months, mean 4 months), 82% of patients had uncorrected visual acuity (UCVA) of 20/20 or better, and their average manifest refraction was −0.08 D (SD ± 0.48 D). At the time of the long-term ophthalmological exam at the VA medical centers (range 4–11 years, mean of 8.2 years), 49% of patients had an UCVA of 20/20 or better and an average manifest refraction was −0.64 D (SD ± 0.69 D).

Conclusion

This is the first long-term study evaluating refractive surgery outcomes up to 17 years in a military population. Our study demonstrates safety after refractive surgery in the military with less than 0.1D increase in myopia per year and strong keratometric stability. Other changes in the eye may be the likely cause for this observed mild refractive shift.
A new RASS galaxy cluster catalogue with low contamination extending to z ∼ 1 in the DES overlap region
Authors: Klein M , Grandis S , Mohr J J , Paulus M , Abbott T M C , Annis J , Avila S , Bertin E , Brooks D , Buckley-Geer E , Rosell A Carnero , Kind M Carrasco , Carretero J , Castander F J , Cunha C E , D’Andrea C B , da Costa L N , De Vicente J , Desai S , Diehl H T , Dietrich J P , Doel P , Evrard A E , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Giles P A , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hollowood D L , Honscheid K , Hoyle B , James D J , Jeltema T , Kuehn K , Kuropatkin N , Lima M , Maia M A G , March M , Marshall J L , Menanteau F , Miquel R , Ogando R L C , Plazas A A , Romer A K , Roodman A , Sanchez E , Scarpine V , Schindler R , Serrano S , Sevilla-Noarbe I , Smith M , Smith R C , Soares-Santos M , Sobreira F , Suchyta E , Swanson M E C , Tarle G , Thomas D , Vikram V ,   the DES Collaboration
Published: May 2019

We present the MARD-Y3 catalogue of between 1086 and 2171 galaxy clusters (52 per cent and 65 per cent new) produced using multicomponent matched filter (MCMF) follow-up in 5000 deg2 of DES-Y3 optical data of the ∼20 000 overlapping ROSAT All-Sky Survey source catalogue (2RXS) X-ray sources. Optical counterparts are identified as peaks in galaxy richness as a function of redshift along the line of sight towards each 2RXS source within a search region informed by an X-ray prior. All peaks are assigned a probability fcont of being a random superposition. The clusters lie at 0.02 < z < 1.1 with more than 100 clusters at z > 0.5. Residual contamination is 2.6 per cent and 9.6 per cent for the cuts adopted here. For each cluster we present the optical centre, redshift, rest frame X-ray luminosity, M500 mass, coincidence with NWAY infrared sources, and estimators of dynamical state. About 2 per cent of MARD-Y3 clusters have multiple possible counterparts, the photo-z’s are high quality with σΔz/(1 + z) = 0.0046, and ∼1 per cent of clusters exhibit evidence of X-ray luminosity boosting from emission by cluster active galactic nuclei. Comparison with other catalogues (MCXC, RM, SPT-SZ, Planck) is performed to test consistency of richness, luminosity, and mass estimates. We measure the MARD-Y3 X-ray luminosity function and compare it to the expectation from a fiducial cosmology and externally calibrated luminosity- and richness–mass relations. Agreement is good, providing evidence that MARD-Y3 has low contamination and can be understood as a simple two step selection – X-ray and then optical – of an underlying cluster population described by the halo mass function.
Highly efficient silencing of microRNA by heteroduplex oligonucleotides
Authors: Yoshioka Kotaro , Kunieda Taiki , Asami Yutaro , Guo Huijia , Miyata Haruka , Yoshida-Tanaka Kie , Sujino Yumiko , Piao Wenying , Kuwahara Hiroya , Nishina Kazutaka , Hara Rintaro Iwata , Nagata Tetsuya , Wada Takeshi , Obika Satoshi , Yokota Takanori
Published: May 2019

AntimiR is an antisense oligonucleotide that has been developed to silence microRNA (miRNA) for the treatment of intractable diseases. Enhancement of its in vivo efficacy and improvement of its toxicity are highly desirable but remain challenging. We here design heteroduplex oligonucleotide (HDO)-antimiR as a new technology comprising an antimiR and its complementary RNA. HDO-antimiR binds targeted miRNA in vivo more efficiently by 12-fold than the parent single-stranded antimiR. HDO-antimiR also produced enhanced phenotypic effects in mice with upregulated expression of miRNA-targeting messenger RNAs. In addition, we demonstrated that the enhanced potency of HDO-antimiR was not explained by its bio-stability or delivery to the targeted cell, but reflected an improved intracellular potency. Our findings provide new insights into biology of miRNA silencing by double-stranded oligonucleotides and support the in vivo potential of this technology based on a new class of for the treatment of miRNA-related diseases.
To randomize, or not to randomize, that is the question: using data from prior clinical trials to guide future designs
Authors: Vanderbeek Alyssa M , Ventz Steffen , Rahman Rifaquat , Fell Geoffrey , Cloughesy Timothy F , Wen Patrick Y , Trippa Lorenzo , Alexander Brian M
Published: May 2019

Background

Understanding the value of randomization is critical in designing clinical trials. Here, we introduce a simple and interpretable quantitative method to compare randomized designs versus single-arm designs using indication-specific parameters derived from the literature. We demonstrate the approach through application to phase II trials in newly diagnosed glioblastoma (ndGBM).

Methods

We abstracted data from prior ndGBM trials and derived relevant parameters to compare phase II randomized controlled trials (RCTs) and single-arm designs within a quantitative framework. Parameters included in our model were (i) the variability of the primary endpoint distributions across studies, (ii) potential for incorrectly specifying the single-arm trial’s benchmark, and (iii) the hypothesized effect size. Strengths and weaknesses of RCT and single-arm designs were quantified by various metrics, including power and false positive error rates.

Results

We applied our method to show that RCTs should be preferred to single-arm trials for evaluating overall survival in ndGBM patients based on parameters estimated from prior trials. More generally, for a given effect size, the utility of randomization compared with single-arm designs is highly dependent on (i) interstudy variability of the outcome distributions and (ii) potential errors in selecting standard of care efficacy estimates for single-arm studies.

Conclusions

A quantitative framework using historical data is useful in understanding the utility of randomization in designing prospective trials. For typical phase II ndGBM trials using overall survival as the primary endpoint, randomization should be preferred over single-arm designs.
A Comparative Transcriptomic and Proteomic Analysis of Hexaploid Wheat’s Responses to Colonization by Bacillus velezensis and Gaeumannomyces graminis, Both Separately and Combined
Authors: Kang Xingxing , Wang Lanhua , Guo Yu , ul Arifeen Muhammad Zain , Cai Xunchao , Xue Yarong , Bu Yuanqin , Wang Gang , Liu Changhong
Published: May 2019

Tritrophic interactions involving a biocontrol agent, a pathogen, and a plant have been analyzed predominantly from the perspective of the biocontrol agent. To explore the adaptive strategies of wheat in response to beneficial, pathogenic, and combined microorganisms, we performed the first comprehensive transcriptomic, proteomic, and biochemical analysis in wheat roots after exposure to Bacillus velezensis CC09, Gaeumannomyces graminis var. tritici, and their combined colonization, respectively. The transcriptional or translational programming of wheat roots inoculated with beneficial B. velezensis showed mild alterations compared with that of pathogenic G. graminis var. tritici. However, the combination of B. velezensis and G. graminis var. tritici activated a larger transcriptional or translational program than for each single microorganism, although the gene expression pattern was similar to that of individual infection by G. graminis var. tritici, suggesting a prioritization of defense against G. graminis var. tritici infection. Surprisingly, pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity made wheat pretreated with B. velezensis more sensitive to subsequent G. graminis var. tritici infection. Additionally, B. velezensis triggered a salicylic acid (SA)-dependent mode of induced systemic resistance that resembles pathogen-induced systemic acquired resistance. Wheat plants mainly depend on SA-mediated resistance, and not that mediated by jasmonic acid (JA), against the necrotrophic pathogen G. graminis var. tritici. Moreover, SA–JA interactions resulted in antagonistic effects regardless of the type of microorganisms in wheat. Further enhancement of SA-dependent defense responses such as lignification to the combined infection was shown to reduce the level of induced JA-dependent defense against subsequent infection with G. graminis var. tritici. Altogether, our results demonstrate how the hexaploid monocot wheat responds to beneficial or pathogenic microorganisms and prolongs the onset of take-all disease through modulation of cell reprogramming and signaling events.
RNASeqR: an R package for automated two-group RNA-Seq analysis workflow
Authors: Chao Kuan-Hao , Hsiao Yi-Wen , Lee Yi-Fang , Lee Chien-Yueh , Lai Liang-Chuan , Tsai Mong-Hsun , Lu Tzu-Pin , Chuang Eric Y.
Published: May 2019

RNA-Seq analysis has revolutionized researchers' understanding of the transcriptome in biological research. Assessing the differences in transcriptomic profiles between tissue samples or patient groups enables researchers to explore the underlying biological impact of transcription. RNA-Seq analysis requires multiple processing steps and huge computational capabilities. There are many well-developed R packages for individual steps; however, there are few R/Bioconductor packages that integrate existing software tools into a comprehensive RNA-Seq analysis and provide fundamental end-to-end results in pure R environment so that researchers can quickly and easily get fundamental information in big sequencing data. To address this need, we have developed the open source R/Bioconductor package, RNASeqR. It allows users to run an automated RNA-Seq analysis with only six steps, producing essential tabular and graphical results for further biological interpretation. The features of RNASeqR include: six-step analysis, comprehensive visualization, background execution version, and the integration of both R and command-line software. RNASeqR provides fast, light-weight, and easy-to-run RNA-Seq analysis pipeline in pure R environment. It allows users to efficiently utilize popular software tools, including both R/Bioconductor and command-line tools, without predefining the resources or environments. RNASeqR is freely available for Linux and macOS operating systems from Bioconductor (https://bioconductor.org/packages/release/bioc/html/RNASeqR.html).
Pseudo-chromosome length genome assembly of a double haploid ‘Bartlett’ pear (Pyrus communis L.)
Authors: Linsmith Gareth , Rombauts Stephane , Montanari Sara , Deng Cecilia H. , Celton Jean-Marc , Guérif Philippe , Liu Chang , Lohaus Rolf , Zurn Jason D. , Cestaro Alessandro , Bassil Nahla V. , Bakker Linda V. , Schijlen Elio , Gardiner Susan E. , Lespinasse Yves , Durel Charles-Eric , Velasco Riccardo , Neale David , Chagné David , Van de Peer Yves , Troggio Michela , Bianco Luca
Published: May 2019

We report an improved assembly and scaffolding of the European pear (Pyrus communis L.) genome (referred to as BartlettDHv2.0), obtained using a combination of Pacific Biosciences RSII Long read sequencing (PacBio), Bionano optical mapping, chromatin interaction capture (Hi-C), and genetic mapping. A total of 496.9 million bases (Mb) corresponding to 97% of the estimated genome size were assembled into 494 scaffolds. Hi-C data and a high-density genetic map allowed us to anchor and orient 87% of the sequence on the 17 chromosomes of the pear genome. About 50% (247 Mb) of the genome consists of repetitive sequences. Comparison with previous assemblies of Pyrus communis and Pyrus x bretschneideri confirmed the presence of 37,445 protein-coding genes, which is 13% fewer than previously predicted.
Cancer/Testis Antigens Differentially Expressed in Prostate Cancer: Potential New Biomarkers and Targets for Immunotherapies
Authors: Kagohara Luciane T. , Carleton Neil M. , Takahashi Sayuri , Shiraishi Takumi , Mooney Steven M. , Vessella Robert L. , Getzenberg Robert H. , Kulkarni Prakash , Veltri Robert W.
Published: May 2019

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

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

Purpose

Patients with deep brain stimulation (DBS) implants highly benefit from MRI, however access to MRI is restricted for these patients due to safety hazards associated with RF heating of the implant. To date, all MRI studies on RF heating of medical implants have been performed in horizontal closed-bore systems. Vertical MRI scanners have a fundamentally different distribution of electric and magnetic fields and are now available at 1.2T, capable of high-resolution structural and functional MRI. This work presents the first simulation study of RF heating of DBS implants in high-field vertical scanners.

Methods

We performed finite element electromagnetic simulations to calculate SAR at tips of DBS leads during MRI in a commercially available 1.2 T vertical coil compared to a 1.5 T horizontal scanner. Both isolated leads and fully implanted systems were included.

Results

We found 10-30-fold reduction in SAR implication at tips of isolated DBS leads, and up to 19-fold SAR reduction at tips of leads in fully implanted systems in vertical coils compared to horizontal birdcage coils.

Conclusions

If confirmed in larger patient cohorts and verified experimentally, this result can open the door to plethora of structural and functional MRI applications to guide, interpret, and advance DBS therapy.
Detecting Direct Oral Anticoagulants in Trauma Patients using Liquid Chromatography-Mass Spectrometry: a Novel Approach to Medication Reconciliation
Authors: Jayaraman Sudha , DeAntonio Jonathan H. , Leichtle Stefan W. , Han Jinfeng , Liebrecht Loren , Contaifer Daniel , Young Caroline , Chou Christopher , Staschen Julia , Doan David , Kumar Naren Gajenthra , Wolfe Luke , Nguyen Tammy , Chenault Gregory , Anand Rahul J. , Bennett Jonathan D. , Ferrada Paula , Goldberg Stephanie , Procter Levi D. , Rodas Edgar B. , Rossi Alan P. , Whelan James F. , Feeser V. Ramana , Vitto Michael J. , Broering Beth , Hobgood Sarah , Mangino Martin , Aboutanos Michel , Bachmann Lorin , Wijesinghe Dayanjan S
Published: May 2019

Background

Accurate medication reconciliation in trauma patients is essential but difficult. Currently there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS) based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival.

Methods

Plasma samples were collected from 356 patients who provided informed consent including-10 healthy controls, 19 known positive or negative controls and 327 trauma patients over 65 years of age who were evaluated at our large, urban Level 1 Trauma Center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage was compared with LCMS results to determine overall accuracy, sensitivity, specificity and positive and negative predictive values (PPV, NPV) of the assay.

Results

Of 356 patients, 39 were on DOACs (10.96%): 21 were on Apixaban, 14 on rivaroxaban and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.06%, (PPV 92.50% and NPV 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.11% (PPV 86.36% and NPV 99.40%). There were three false positive results and two false negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity.

Conclusions

This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients.

Study type: diagnostic test

Basic Science paper: therefore does not require a level of evidence.
Classification of unlabeled observations in Species Distribution Modelling using Point Process Models
Authors: Guilbault Emy , Renner Ian , Mahony Michael , Beh Eric
Published: May 2019

1

Species distribution modelling, which allows users to predict the spatial distribution of species with the use of environmental covariates, has become increasingly popular, with many software platforms providing tools to fit species distribution models. However, the species observations used in species distribution models can have varying levels of quality and can have incomplete information, such as uncertain species identity.

In this paper, we develop two algorithms to reclassify observations with unknown species identities which simultaneously predict different species distributions using spatial point processes. We compare the performance of the different algorithms using different initializations and parameters with models fitted using only the observations with known species identity through simulations.

We show that performance varies with differences in correlation among species distributions, species abundance, and the proportion of observations with unknown species identities. Additionally, some of the methods developed here outperformed the models that didn’t use the misspecified data.

These models represent an helpful and promising tool for opportunistic surveys where misidentification happens or for the distribution of species newly separated in their taxonomy.
Modification of oxygen consumption and blood flow in mouse somatosensory cortex by cell-type-specific neuronal activity
Authors: Dahlqvist Matilda , Thomsen Kirsten , Postnov Dmitry , Lauritzen Martin
Published: May 2019

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

Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy. Isotope tracing of pRCC derived cell lines revealed an increasedde novosynthesis rate of GSH, based on glutamine consumption. Furthermore, rewiring of the main pathways involved in ATP and glucose synthesis was observed at the protein level. In contrast, transcripts encoding for the respiratory chain were not regulated, which prompts for non-genetic profiling. The molecular characteristics of pRCC are increased GSH synthesis to cope with ROS stress, deficient anabolic glucose synthesis, and compromised oxidative phosphorylation, which could potentially be exploited in innovative anti-cancer strategies.

SIGNIFICANCE STATEMENT

We applied proteome- and metabolome profiling to elucidate molecular features in malign papillary renal cell carcinomas. By this characterization, a reprogramming of the main metabolic pathways, such as gluconeogenesis and fatty acid- and amino acid metabolism were identified. The proteins involved in the respiratory chain and the corresponding enzymatic activities were strongly reduced in pRCC, showing an anti-correlation compared with the transcriptome. Similar to renal oncocytomas, the ROS scavenger glutathione was identified as a hallmark in pRCC. Our results suggest that impaired metabolism and dysfunctional mitochondria determine the fate of pRCC. Furthermore, we propose that the specific regulation of the mitochondrial respiratory chain can differentiate highly similar malignant pRCCs from benign renal oncocytomas.
Microbiomes from feces vs. gut in aquatic vertebrates: distinct community compositions between substrates and preservation methods
Authors: Anslan Sten , Li Huan , Künzel Sven , Vences Miguel
Published: May 2019

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

The epithelial-mesenchymal transition (EMT) often plays a critical role in cancer metastasis and chemoresistance, and decoding its dynamics is crucial to design effective therapeutics. EMT is regulated at multiple levels transcriptional, translational, protein stability, and epigenetics; the mechanisms by which epigenetic regulation can alter the dynamics of EMT remain elusive. Here, to identify the possible effects of epigenetic regulation in EMT, we incorporate a feedback term in our previously proposed model of EMT regulation of the miR 200/ZEB/miR 34/SNAIL circuit. This epigenetic feedback that stabilizes long-term transcriptional activity can alter the relative stability and distribution of states in a given cell population, particularly when incorporated in the inhibitory effect on miR 200 from ZEB. This feedback can stabilize the mesenchymal state, thus making transitions out of that state difficult. Conversely, epigenetic regulation of the self activation of ZEB has only minor effects. Our model predicts that this effect could be seen in experiments, when epithelial cells are treated with an external EMT inducing signal for a sufficiently long period of time and then allowed to recover. Our preliminary experimental data indeed shows that a prolonged TGF beta; exposure gives rise to increasing difficult reversion back to the epithelial state. Thus, this integrated theoretical experimental approach yields insights into how an epigenetic feedback may alter the dynamics of EMT.