bluuebunny/crossref_metadata_2025_split huggingface dataset:
A two‐phase Bayesian methodology for the analysis of binary phenotypes in genome‐wide association studies
Authors: Joyner Chase , McMahan Christopher , Baurley James , Pardamean Bens 
Published: September 2019

AbstractRecent advances in sequencing and genotyping technologies are contributing to a data revolution in genome‐wide association studies that is characterized by the challenging large p small n problem in statistics. That is, given these advances, many such studies now consider evaluating an extremely large number of genetic markers (p) genotyped on a small number of subjects (n). Given the dimension of the data, a joint analysis of the markers is often fraught with many challenges, while a marginal analysis is not sufficient. To overcome these obstacles, herein, we propose a Bayesian two‐phase methodology that can be used to jointly relate genetic markers to binary traits while controlling for confounding. The first phase of our approach makes use of a marginal scan to identify a reduced set of candidate markers that are then evaluated jointly via a hierarchical model in the second phase. Final marker selection is accomplished through identifying a sparse estimator via a novel and computationally efficient maximum a posteriori estimation technique. We evaluate the performance of the proposed approach through extensive numerical studies, and consider a genome‐wide application involving colorectal cancer.
Test–retest reproducibility of a multi‐atlas automated segmentation tool on multimodality brain MRI
Authors: Rezende Thiago J. R. , Campos Brunno M. , Hsu Johnny , Li Yue , Ceritoglu Can , Kutten Kwame , França Junior Marcondes C. , Mori Susumu , Miller Michael I. , Faria Andreia V. 
Published: September 2019

AbstractIntroductionThe increasing use of large sample sizes for population and personalized medicine requires high‐throughput tools for imaging processing that can handle large amounts of data with diverse image modalities, perform a biologically meaningful information reduction, and result in comprehensive quantification. Exploring the reproducibility of these tools reveals the specific strengths and weaknesses that heavily influence the interpretation of results, contributing to transparence in science.MethodsWe tested–retested the reproducibility of MRICloud, a free automated method for whole‐brain, multimodal MRI segmentation and quantification, on two public, independent datasets of healthy adults.ResultsThe reproducibility was extremely high for T1‐volumetric analysis, high for diffusion tensor images (DTI) (however, regionally variable), and low for resting‐state fMRI.ConclusionIn general, the reproducibility of the different modalities was slightly superior to that of widely used software. This analysis serves as a normative reference for planning samples and for the interpretation of structure‐based MRI studies.
Crowdfunding as a tool to support sustainability‐oriented initiatives: Preliminary insights into the role of product/service attributes
Authors: Testa Stefania , Roma Paolo , Vasi Maria , Cincotti Silvano 
Published: September 2019

AbstractA common goal of current research seems to uncover whether crowdfunding (CF) could be considered an effective way to support sustainability‐oriented initiatives in securing funding, due to diverging results emerging from literature. We claim that the objective of proving whether CF may benefit sustainability‐oriented initiatives could be misplaced; rather, we deem more fruitful to understand how critical are some attributes of products/services pursued within CF campaigns to benefiting sustainability‐oriented initiatives and increasing their odds of success in CF. We focus on food‐related projects as in this sector, sustainability issues apply more than to any other human activities and construct a unique sample of food CF campaigns launched and ended in the European Economic Area countries on the world's most popular reward‐based CF platform, that is, Kickstarter. We identify campaigns with a sustainability orientation and perform an in‐depth qualitative analysis, which allows us to classify them into meaningful clusters and subclusters. Our research suggests that the emphasis on egoistic/self‐centered product attributes, rather than on altruistic/society‐centered attributes, is generally more crucial to facilitate CF support to sustainability‐oriented projects. However, the emphasis on altruistic/society‐centered attributes emerges to be more beneficial for initiatives specifically supporting local products. Our results also suggest that reward‐based CF is not suitable for sustainability‐oriented projects targeting disadvantaged individuals/groups. These results offer both theoretical and empirical contributions to the literature as well as practical implications.
The Biosynthetic Gene Cluster of Pyrazomycin—A C‐Nucleoside Antibiotic with a Rare Pyrazole Moiety
Authors: Zhao Guiyun , Yao Shunyu , Rothchild Kristina W. , Liu Tengfei , Liu Yu , Lian Jiazhang , He Hai‐Yan , Ryan Katherine S. , Du Yi‐Ling 
Published: September 2019

AbstractPyrazomycin is a rare C‐nucleoside antibiotic containing a naturally occurring pyrazole ring, the biosynthetic origin of which has remained obscure for decades. In this study we report the identification of the gene cluster responsible for pyrazomycin biosynthesis in Streptomyces candidus NRRL 3601, revealing that the StrR‐family regulator PyrR is the cluster‐situated transcriptional activator governing pyrazomycin biosynthesis. Furthermore, our results from in vivo reconstitution and stable‐isotope feeding experiments provide support for the hypothesis that PyrN is a new nitrogen–nitrogen bond‐forming enzyme that catalyzes the linkage of the ϵ‐NH2 nitrogen atom of l‐N6‐OH‐lysine and the α‐NH2 nitrogen atom of l‐glutamic acid. This study lays the foundation for further genetic and biochemical characterization of pyrazomycin pathway enzymes involved in constructing the characteristic pyrazole ring.
Exogenous hydrogen sulfide protects fatty liver against ischemia–reperfusion injury by regulating endoplasmic reticulum stress‐induced autophagy in macrophage through mediating the class A scavenger receptor pathway in rats
Authors: Ruan Zhiyan , Liang Minhua , Deng Xiangliang , Lai Manxiang , Shang Ling , Su Xinguo 
Published: September 2019

AbstractFatty liver disease is a disease manifested with excessive alcohol intake and obese. Importantly, hydrogen sulfide (H2S) has been revealed to participate in the progression of fatty liver; however, the underlying mechanism has not been clearly elucidated yet. In this study, we aimed to investigate the effects of exogenous H2S on fatty liver ischemia–reperfusion injury (IRI) through mediating class A scavenger receptor (SRA) pathway in rats. By determining endoplasmic reticulum stress (ERS)‐related factors, autophagy markers and apoptosis‐related factors in liver tissue and liver function, levels of oxidative stress, inflammatory factors, and hepatocyte apoptosis, the effects of H2S on IRI‐induced autophagy, oxidative stress, and inflammation were all examined in rat model of fatty liver IRI. Results from obtained data showed that H2S decreased the expression of SRA, Grp78, PERK, CHOP, and Caspase‐3, and increased that of LC3‐II/LC3‐I, in addition to alleviating the pathological changes of liver and reducing the levels of ALT, AST, LDH TBARS, and MDA. Moreover, H2S decreased the levels of oxidative stress, the expression of pro‐inflammatory factors including tumor necrosis factor α, interleukin 1, and interleukin 6, and the apoptosis of hepatocytes. Our findings suggested exogenous H2S could reduce ERS by mediating the SRA pathway and protect liver function by inducing autophagy, and protect against IRI by reducing oxidative stress and inflammation.
Initial report of safety and procedure duration of robotic‐assisted chronic total occlusion coronary intervention
Authors: Hirai Taishi , Kearney Kathleen , Kataruka Akash , Gosch Kensey L. , Brandt Hunter , Nicholson William J. , Lombardi William L. , Grantham J. Aaron , Salisbury Adam C. 
Published: September 2019

AbstractBackgroundNo previous reports have examined the impact of robotic‐assisted (RA) chronic total occlusion (CTO) PCI on procedural duration or safety compared to totally manual CTO PCI.MethodsAmong 95 patients who underwent successful PCI of a single CTO lesion at two centers, 49 (52%) were performed RA and were performed 46 (48%) totally manually. Cockpit time was the time the primary operator entered to robotic cockpit until the procedure was complete. “Theoretical” cockpit time in the control group was time the primary operator would have entered the cockpit after lesion crossing until the procedure was complete. Major adverse events (MAEs) were the composite of death, myocardial infarction, clinical perforation, significant vessel dissection, arrhythmia, acute thrombosis, and stroke.ResultsThe lesion characteristics, procedural time, and contrast dose were similar. All procedures except for one (2%) selected for robotic completion after lesion crossing were completed successfully. The frequency of MAE was similar between groups and there were no in‐hospital deaths. The cockpit time was 8 min longer in RA CTO PCI than the theoretical cockpit time in totally manual CTO PCI (40.6 ± 12.7 vs. 32.1 ± 17.8, p < .01).ConclusionRA CTO PCI was not associated with excess adverse events compared with totally manual CTO PCI and resulted in an average 41 min cockpit time equaling to 48% of procedure time without radiation exposure or requirement for the primary operator to wear a lead apron. Understanding the relationship between cockpit time and reductions in radiation exposure and lead apron‐related orthopedic complications for operators requires future study.
Projections to the putamen from neurons located in the white matter and the claustrum in the macaque
Authors: Borra Elena , Luppino Giuseppe , Gerbella Marzio , Rozzi Stefano , Rockland Kathleen S. 
Published: September 2019

AbstractContinuing investigations of corticostriatal connections in rodents emphasize an intricate architecture where striatal projections originate from different combinations of cortical layers, include an inhibitory component, and form terminal arborizations which are cell‐type dependent, extensive, or compact. Here, we report that in macaque monkeys, deep and superficial cortical white matter neurons (WMNs), peri‐claustral WMNs, and the claustrum proper project to the putamen. WMNs retrogradely labeled by injections in the putamen (four injections in three macaques) were widely distributed, up to 10 mm antero‐posterior from the injection site, mainly dorsal to the putamen in the external capsule, and below the premotor cortex. Striatally projecting labeled WMNs (WMNsST) were heterogeneous in size and shape, including a small GABAergic component. We compared the number of WMNsST with labeled claustral and cortical neurons and also estimated their proportion in relation to total WMNs. Since some WMNsST were located adjoining the claustrum, we wanted to compare results for density and distribution of striatally projecting claustral neurons (ClaST). ClaST neurons were morphologically heterogeneous and mainly located in the dorsal and anterior claustrum, in regions known to project to frontal, motor, and cingulate cortical areas. The ratio of ClaST to WMNsST was about 4:1 averaged across the four injections. These results provide new specifics on the connectional networks of WMNs in nonhuman primates, and delineate additional loops in the corticostriatal architecture, consisting of interconnections across cortex, claustralstriatal and striatally projecting WMNs.
Protocols for the Analysis of microRNA Expression, Biogenesis, and Function in Immune Cells
Authors: Zhang Nannan , Hu Guowu , Myers Timothy G. , Williamson Peter R. 
Published: September 2019

AbstractMicroRNAs (miRNAs) are short (19‐ to 25‐nucleotide) noncoding RNA molecules that target mRNAs to repress gene expression and that play important roles in regulating many fundamental biological functions including cell differentiation, development, growth, and metabolism. They are well conserved in eukaryotic cells and are considered essential ancient elements of gene regulation. miRNA genes are transcribed by RNA polymerase II to generate primary miRNAs (pri‐miRNAs), which are cleaved by microprocessor complex in the nucleus to generate stem‐loop structures known as pre‐miRNAs. Pre‐miRNAs are translocated to the cytoplasm and cleaved by Dicer to form the mature miRNAs, which mediate mRNA degradation through their loading to the RNA‐induced silencing complex (RISC) and binding to complementary sequences within target mRNAs to repress their translation by mRNA degradation and/or translation inhibition. Because ∼1900 miRNA genes are reported in the human genome, many associated with disease, appropriate methods to study miRNA expression and regulation under physiological and pathological conditions have become increasingly important to the study of many aspects of human biology, including immune regulation. As with small interfering RNA (siRNA), the mechanism of miRNA‐mediated targeting has been used to develop miRNA‐based therapeutics. For a complete and systematic analysis, it is critical to utilize a variety of different tools to analyze the expression of pri‐mRNAs, pre‐miRNAs, and mature miRNAs and characterize their targets both in vitro and in vivo. Such studies will facilitate future novel drug design and development. This unit provides six basic protocols for miRNA analysis, covering next‐generation sequencing, quantitative real‐time PCR (qRT‐PCR), and digoxigenin‐based expression analysis of pri‐mRNAs, pre‐miRNAs, and mature miRNAs; mapping of pri‐miRNA and their cleavage sites by rapid amplification of cDNA ends (RACE); electrophoretic mobility shift assays (EMSAs) or biotin‐based nonradioactive detection of miRNA‐protein complexes (miRNPs); and functional analysis of miRNAs using miRNA mimics and inhibitors. © 2019 by John Wiley & Sons, Inc.
Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains
Authors: Fields Francisco R. , Freed Stefan D. , Carothers Katelyn E. , Hamid Md Nafiz , Hammers Daniel E. , Ross Jessica N. , Kalwajtys Veronica R. , Gonzalez Alejandro J. , Hildreth Andrew D. , Friedberg Iddo , Lee Shaun W. 
Published: September 2019

AbstractBacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives. However, bacteriocins display diverse mechanisms of action, a narrow spectrum of activity, and inherent challenges in natural product isolation making in vitro verification of putative bacteriocins difficult. A subset of bacteriocins exert their antimicrobial effects through favorable biophysical interactions with the bacterial membrane mediated by the charge, hydrophobicity, and conformation of the peptide. We have developed a pipeline for bacteriocin‐derived compound design and testing that combines sequence‐free prediction of bacteriocins using machine learning and a simple biophysical trait filter to generate 20 amino acid peptides that can be synthesized and evaluated for activity. We generated 28,895 total 20‐mer candidate peptides and scored them for charge, α‐helicity, and hydrophobic moment. Of those, we selected 16 sequences for synthesis and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. Peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Our combined method incorporates machine learning and biophysical‐based minimal region determination to create an original approach to swiftly discover bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.
Long‐term evolutionary conflict, Sisyphean arms races, and power in Fisher's geometric model
Authors: Scott Trey J. , Queller David C. 
Published: September 2019

AbstractEvolutionary conflict and arms races are important drivers of evolution in nature. During arms races, new abilities in one party select for counterabilities in the second party. This process can repeat and lead to successive fixations of novel mutations, without a long‐term increase in fitness. Models of co‐evolution rarely address successive fixations, and one of the main models that use successive fixations—Fisher's geometric model—does not address co‐evolution. We address this gap by expanding Fisher's geometric model to the evolution of joint phenotypes that are affected by two parties, such as probability of infection of a host by a pathogen. The model confirms important intuitions and offers some new insights. Conflict can lead to long‐term Sisyphean arms races, where parties continue to climb toward their fitness peaks, but are dragged back down by their opponents. This results in far more adaptive evolution compared to the standard geometric model. It also results in fixation of mutations of larger effect, with the important implication that the common modeling assumption of small mutations will apply less often under conflict. Even in comparison with random abiotic change of the same magnitude, evolution under conflict results in greater distances from the optimum, lower fitness, and more fixations, but surprisingly, not larger fixed mutations. We also show how asymmetries in selection strength, mutation size, and mutation input allow one party to win over another. However, winning abilities come with diminishing returns, helping to keep weaker parties in the game.
Effects of soil microbes on plant competition: a perspective from modern coexistence theory
Authors: Ke Po‐Ju , Wan Joe 
Published: September 2019

AbstractGrowing evidence shows that soil microbes affect plant coexistence in a variety of systems. However, since these systems vary in the impacts microbes have on plants and in the ways plants compete with each other, it is challenging to integrate results into a general predictive theory. To this end, we suggest that the concepts of niche and fitness difference from modern coexistence theory should be used to contextualize how soil microbes contribute to plant coexistence. Synthesizing a range of mechanisms under a general plant–soil microbe interaction model, we show that, depending on host specificity, both pathogens and mutualists can affect the niche difference between competing plants. However, we emphasize the need to also consider the effect of soil microbes on plant fitness differences, a role often overlooked when examining their role in plant coexistence. Additionally, since our framework predicts that soil microbes modify the importance of plant–plant competition relative to other factors for determining the outcome of competition, we suggest that experimental work should simultaneously quantify microbial effects and plant competition. Thus, we propose experimental designs that efficiently measure both processes and show how our framework can be applied to identify the underlying drivers of coexistence. Using an empirical case study, we demonstrate that the processes driving coexistence can be counterintuitive, and that our general predictive framework provides a better way to identify the true processes through which soil microbes affect coexistence.
Impact of tussock grasses removal on soil water content dynamics of a tropical mountain hillslope
Authors: Montenegro‐Díaz Paola , Ochoa‐Sánchez Ana , Célleri Rolando 
Published: September 2019

AbstractLand use impacts on soil water content (SWC) are scarcely studied in mountain humid ecosystems, such as the Andean páramos, despite its influence on ecohydrological processes. Our objective was to analyze the impacts of extensive grazing on SWC of an Andean páramo hillslope with native tussock grasses. Along two parallel transects in a hillslope, we monitored SWC through pairs of SWC sensors placed at different soil depths (Ah horizon= 10 –35 cm; C horizon= 65 – 75 cm). The tussock grasses were cutout from one transect (Experimental) as an emulation of extensive grazing (without soil destruction), whereas the second transect (Control) remained intact. Both transects were hourly monitored for 10 months (post‐intervention period). Post‐intervention period was compared with a pre‐intervention period of similar precipitation characteristics to minimize the influence of precipitation in the interpretation of the results. We analyzed both periods through differences in SWC between the pairs of sensors (Experimental minus Control) and differences in SWC dynamic of the pairs of sensors through linear regressions (slope and intercept values). Results suggest that the emulation did not change the mean SWC, but caused a reduction of SWC dynamic. Causes of SWC attenuation were a lower interception and transpiration, a higher amount of effective rainfall infiltrated, and similar evaporation from the soil than under unchanged conditions. These observations were done at all the soil depths. Probably, extensive grazing does not negatively affect the hydrological functioning of páramo ecosystems, particularly its water yield, as long as the soil remains undisturbed.
Impact of environmental factors on heart failure decompensations
Authors: Escolar Vanessa , Lozano Ainara , Larburu Nekane , Kerexeta Jon , Álvarez Roberto , Juez Benjamín , Echebarria Amaia , Azcona Alberto , Artola Garazi 
Published: September 2019

AbstractAimsHeart failure (HF) is a clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. This disease often causes decompensations, which may lead to hospital admissions, deteriorating patients' quality of life and causing an increment on the healthcare cost. Environmental exposure is an important but underappreciated risk factor contributing to the development and severity of cardiovascular diseases, such as HF.Methods and resultsWe used two different sets of data (January 2012 to August 2017): one related to the number of hospital admissions and the other one related to the environmental factors (weather and air quality). Admissions related data were grouped in weeks, and then two different studies were performed: (i) a univariate regression to determine whether the admissions may influence future hospitalizations prediction and (ii) a multivariate regression to determine the impact of environmental factors on admission rates. A total number of 8338 hospitalizations of 5343 different patients are available in this dataset, with a mean of 4.02 admissions per day. In European warm period (from June to October), there are significant less admissions than that in the cold period (from December to March), with a clear seasonality of admissions, because there is a similar pattern every year. Air temperature is the most significant environmental factor (r = −0.3794, P < 0.001) related to HF hospital admissions, showing an inversed correlation. Some other attributes, such as precipitation (r = 0.0795, P = 0.05), along with SO2 (precursor of acid rain) (r = 0.2692, P < 0.001) and NOX air (major air pollutant formed by combustion systems and motor vehicles) (r = 0.2196, P < 0.001) quality parameters, are also relevant. Humidity and PM10 parameters do not have significant correlations in this study (r = 0.0469 and r = −0.0485 respectively), neither relevant P‐values (P = 0.238 and P = 0.324, respectively).ConclusionsSeveral environmental factors, such as weather temperature and precipitation, and major air pollutants, such as SO2 and NOX air, have an impact on the HF‐related hospital admissions rate and, hence, on HF decompensations and patient's quality of life.