bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Adverse Birth Outcomes in the PROMISE 1077BF/1077FF Trial
Authors: Sebikari Dorothy , Farhad Mona , Fenton Terry , Owor Maxensia , Stringer Jeffrey S. A. , Qin Min , Chakhtoura Nahida , Chi Benjamin H. , Saidi Friday , Nevrekar Neetal , Violari Avy , Chipato Tsungai , McIntyre James A. , Moodley Dhayendre , Taha Taha E. , Theron Gerhard , Fowler Mary Glenn 
Published: April 2019

Background:
In the multicountry PROMISE 1077BF/1077FF trial, the risk of low birth weight (LBW; <2500 g) and preterm delivery (PTD; <37 weeks) was significantly higher among women initiating a protease inhibitor–based antiretroviral treatment (ART) regimen than those receiving ZDV alone. Among those assigned to a protease inhibitor regimen, tenofovir/emtricitabine was associated with the more severe outcomes of very LBW (<1500 g) and very PTD (<34 weeks) compared with zidovudine/lamivudine.

Methods:
We used multivariate logistic regression to further explore these treatment findings, taking into account demographic baseline clinical and postentry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion.

Results:
Among 3333 women delivering at least 1 live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least 1 previous PTD. Seventeen percent of newborns were LBW, 1% were very LBW, 17% had PTD, and 3% had very PTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included the following: country, gestational age at entry, maternal age, maternal body mass index, previous PTD, history of alcohol use, baseline HIV viral titer, multiple gestation, and several obstetric risk factors.

Conclusions:
ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical, and obstetrical risk factors, which were also associated with these outcomes.
Accurate ethnicity prediction from placental DNA methylation data
Authors: Yuan Victor , Price E Magda , Del Gobbo Giulia F , Mostafavi Sara , Cox Brian , Binder Alexandra M. , Michels Karin B. , Marsit Carmen , Robinson Wendy P. 
Published: April 2019

ABSTRACTBackgroundThe influence of genetics on variation in DNA methylation (DNAme) is well documented. Yet confounding from population stratification is often unaccounted for in DNAme association studies. Existing approaches to address confounding by population stratification using DNAme data may not generalize to populations or tissues outside those in which they were developed. To aid future placental DNAme studies in assessing population stratification, we developed an ethnicity classifier, PlaNET (Placental DNAme Elastic Net Ethnicity Tool), using five cohorts with Infinium Human Methylation 450k BeadChip array (HM450k) data from placental samples that is also compatible with the newer EPIC platform.ResultsData from 509 placental samples was used to develop PlaNET and show that it accurately predicts (accuracy = 0.938, kappa = 0.823) major classes of self-reported ethnicity/race (African: n = 58, Asian: n = 53, Caucasian: n = 389), and produces ethnicity probabilities that are highly correlated with genetic ancestry inferred from genome-wide SNP arrays (>2.5 million SNP) and ancestry informative markers (n = 50 SNPs). PlaNET’s ethnicity classification relies on 1860 HM450K microarray sites, and over half of these were linked to nearby genetic polymorphisms (n = 955). Our placental-optimized method outperforms existing approaches in assessing population stratification in placental samples from individuals of Asian, African, and Caucasian ethnicities.ConclusionPlaNET provides an improved approach to address population stratification in placental DNAme association studies. The method can be applied to predict ethnicity as a discrete or continuous variable and will be especially useful when self-reported ethnicity information is missing and genotyping markers are unavailable. PlaNET is available as an R package at (https://github.com/wvictor14/planet).
Total RNA-sequencing reveals multi-level microbial community changes and functional responses to wood ash application in agricultural and forest soil
Authors: Bang-Andreasen Toke , Anwar Muhammad Zohaib , Lanzén Anders , Kjøller Rasmus , Rønn Regin , Ekelund Flemming , Jacobsen Carsten Suhr 
Published: April 2019

AbstractRecycling of wood ash from energy production may counteract soil acidification and return essential nutrients to soils. However, wood ash amendment affects soil physicochemical parameters that control composition and functional expression of the soil microbial community. Here, we applied Total RNA-sequencing to simultaneously assess the impact of wood ash amendment on the active soil microbial communities and the expression of functional genes from all microbial taxa. Wood ash significantly affected the taxonomic (rRNA) as well as functional (mRNA) profiles of both agricultural and forest soil. Increase in pH, electrical conductivity, dissolved organic carbon and phosphate were the most important physicochemical drivers for the observed changes. Wood ash amendment increased the relative abundance of the copiotrophic groups Chitinonophagaceae (Bacteroidetes) and Rhizobiales (Alphaproteobacteria) and resulted in higher expression of genes involved in metabolism and cell growth. Finally, Total RNA-sequencing allowed us to show that some groups of bacterial feeding protozoa increased concomitantly to the enhanced bacterial growth, which shows their pivotal role in the regulation of bacterial abundance in soil.
Systematic sequencing of chloroplast transcript termini fromArabidopsis thalianareveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures
Authors: Castandet Benoît , Germain Arnaud , Hotto Amber M. , Stern David B. 
Published: April 2019

ABSTRACTChloroplast transcription requires numerous quality control steps to generate the complex but selective mixture of accumulating RNAs. To gain insight into how this RNA diversity is achieved and regulated, we systematically mapped transcript ends by developing a protocol called Terminome-Seq. UsingArabidopsis thalianaas a model, we catalogued >215 primary 5’ ends corresponding to transcription start sites (TSS), as well as 1,628 processed 5’ ends and 1,299 3’ ends. While most termini were found in intergenic regions, numerous abundant termini were also found within coding regions and introns, including several major TSS at unexpected locations. A consistent feature was the clustering of both 5’ and 3’ ends, contrasting with the prevailing description of discrete 5’ termini, suggesting an imprecision of the transcription and/or RNA processing machinery. Numerous termini correlated with the extremities of small RNA footprints or predicted stem-loop structures, in agreement with the model of passive RNA protection. Terminome-Seq was also implemented forpnp1-1, a mutant lacking the processing enzyme polynucleotide phosphorylase. Nearly 2,000 termini were altered inpnp1-1, revealing a dominant role in shaping the transcriptome. In summary, Terminome-Seq permits precise delineation of the roles and regulation of the many factors involved in organellar transcriptome quality control.
psupertime: supervised pseudotime inference for single cell RNA-seq data with sequential labels
Authors: Macnair Will , Claassen Manfred 
Published: April 2019

AbstractSingle cell RNA-seq has been successfully combined with pseudotime inference methods to investigate biological processes which have sequential labels, such as time series studies of development and differentiation. Pseudotime methods developed to date ignore the labels, and where there is substantial variation in the data not associated with the labels (such as cell cycle variation or batch effects), they can fail to find relevant genes. We introducepsupertime, a supervised pseudotime approach which outperforms benchmark pseudotime methods by explicitly using the sequential labels as input.psupertimeuses a simple, regression-based model, which by acknowledging the labels assures that genes relevant to the process, rather than to major drivers of variation, are found.psupertimeis applicable to the wide range of single cell RNA-seq datasets with sequential labels, derived from either experimental design or user-selected cell cluster sequences, and provides a tool for targeted identification of genes regulated along biological processes.
How much do you perceive this? An analysis on perceptions of geometric features, personalities and emotions in virtual humans (Extended Version)
Authors: Araujo Victor , Favaretto Rodolfo Migon , Knob Paulo , Musse Soraia Raupp , Vilanova Felipe , Costa Angelo Brandelli 
Published: April 2019

AbstractThis work aims to evaluate people’s perception regarding geometric features, personalities and emotions characteristics in virtual humans. For this, we use as a basis, a dataset containing the tracking files of pedestrians captured from spontaneous videos and visualized them as identical virtual humans. The goal is to focus on their behavior and not being distracted by other features. In addition to tracking files containing their positions, the dataset also contains pedestrian emotions and personalities detected using Computer Vision and Pattern Recognition techniques. We proceed with our analysis in order to answer the question if subjects can perceive geometric features as distances/speeds as well as emotions and personalities in video sequences when pedestrians are represented by virtual humans. Regarding the participants, an amount of 73 people volunteered for the experiment. The analysis was divided in two parts: i) evaluation on perception of geometric characteristics, such as density, angular variation, distances and speeds, and ii) evaluation on personality and emotion perceptions. Results indicate that, even without explaining to the participants the concepts of each personality or emotion and how they were calculated (considering geometric characteristics), in most of the cases, participants perceived the personality and emotion expressed by the virtual agents, in accordance with the available ground truth.
Formation of multinucleated variant endothelial cells with altered mitochondrial function in cultured coronary endothelium under simulated diabetes
Authors: De la Herrán Hilda Carolina Delgado , Donis-Maturano Luis , Álvarez-Delgado Carolina , Villarreal Francisco , Moreno-Ulloa Aldo 
Published: April 2019

AbstractCoronary endothelial dysfunction is associated with atherosclerosis and myocardial infarction in subjects with type 2 diabetes mellitus (T2DM). Vascular endothelial cells are referred to as small and polygonal mononuclear cells. However, multi-nucleated and large endothelial cells (named as multinucleated variant endothelial cells [MVECs]) have been reported in the aorta, wherein their abundance correlates with atherosclerosis severity. The role of MVECs in coronary endothelium remains obscure. We hypothesized that simulated diabetic conditions increase the number of MVECs and affect their mitochondrial structure/function in cultured coronary endothelium. The in vitro model of diabetes consisted in the treatment of bovine coronary artery endothelial cells (BCAECs) with high-insulin (100 nmol/L, HI) for three days followed by high-glucose (20 mmol/L, HG) and HI for nine additional days. Simulated diabetic conditions increased the abundance of MVECs compared to normal glucose (NG, 5.5 mM). MVECs had a higher nucleic acid content (7.2-Fold), cell diameter (2.2-Fold), and cell area (11.4-Fold) than mononuclear cells. Immunodetection of von-Willebrand factor (endothelial cell marker) in MVECs was positive. The mitochondrial mass was reduced, and mitochondrial membrane potential increased in mononuclear cells cultured in HG+HI compared to mononuclear cells grown in NG. However, the opposite mitochondrial findings were noted in MVECs compared to mononuclear cells. Mass spectrometry-based quantitative proteomic and gene ontology analysis suggested augmented mitochondrial autophagy, apoptosis, and inflammation suppression in cells cultured under HG+HI compared to NG conditions. These findings show that simulated diabetes increases the abundance of MVECs, and that mitochondrial structure and function are differentially affected between MVECs and mononuclear cells.
Myosin motor domains carrying mutations implicated in early or late onset Hypertrophic Cardiomyopathy have similar properties
Authors: Vera Carlos D. , Johnson Chloe A. , Walklate Jonathan , Adhikari Arjun , Svicevic Marina , Mijailovich Srboljub M. , Combs Ariana C. , Langer Stephen J. , Ruppel Kathleen M. , Spudich James A. , Geeves Michael A. , Leinwand Leslie A. 
Published: April 2019

AbstractHypertrophic Cardiomyopathy (HCM) is a common genetic disorder that typically involves left ventricular hypertrophy and cardiac hypercontractility. Mutations in β cardiac myosin heavy chain (β-MyHC) are a major cause of HCM, but the specific mechanistic changes to myosin function that lead to the disease remain incompletely understood. Predicting the severity of any single β-MyHC mutation is hindered by a lack of detailed evaluation at the molecular level. In addition, since the cardiomyopathy can take 20 or more years to develop, the severity of the mutations must be somewhat subtle. We hypothesized that mutations which result in early onset disease may show more severe molecular changes in function compared to later onset mutations. In this work, we performed steady-state and transient kinetic analyses of myosins carrying 1 of 7 missense mutations in the motor domain. Of these 7, 4 have been identified in early onset cardiomyopathy screens. The derived parameters were used to model the ATP driven cross-bridge cycle. Contrary to our hypothesis, the results show no clear differences between early and late onset HCM mutations. Despite the lack of distinction between early and late onset HCM, the predicted occupancy of the force-holding actin.myosin.ADP complex at [Actin] = 3 Kapp along with the closely related Duty Ratio (DR; fraction of myosin in strongly attached force-holding states) and the measured ATPases all change in parallel (in both sign and degree of change) compared to wild type (WT) values. Six of the 7 HCM mutations are clearly distinct from a set of DCM mutations previously characterized.
Parasitic worm-derived ES-62 promotes health- and life-span in high calorie diet-fed mice
Authors: Crowe Jenny , Lumb Felicity E. , Doonan James , Broussard Margaux , Tarafdar Anuradha , Pineda Miguel A. , Landabaso Carmen , Mulvey Lorna , Hoskisson Paul A. , Babayan Simon A. , Selman Colin , Harnett William , Harnett Margaret M. 
Published: April 2019

AbstractThe recent extension of human lifespan has not been matched by equivalent improvements in late-life health due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, ageing-associated conditions exacerbated by widespread adoption of the high calorie Western diet (HCD). As a novel therapeutic strategy, we have investigated the potential of ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, to improve healthspan by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We found that ES-62 improves a range of inflammatory but also pathophysiological, metabolic and microbiome parameters, when administered subcutaneously at only 1 µg/week throughout the lifespan of HCD-fed mice. Strikingly, ES-62 induced sex-specific healthspan signatures and indeed, it substantially increased the median survival of male, but not female, HCD-mice. Modelling of 113 responses contributing to these differential signatures by machine learning approaches now signposts candidate parameters key to promoting both healthspan and lifespan.
Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences
Authors: Rives Alexander , Meier Joshua , Sercu Tom , Goyal Siddharth , Lin Zeming , Liu Jason , Guo Demi , Ott Myle , Zitnick C. Lawrence , Ma Jerry , Fergus Rob 
Published: April 2019

AbstractIn the field of artificial intelligence, a combination of scale in data and model capacity enabled by un-supervised learning has led to major advances in representation learning and statistical generation. In the life sciences, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Protein language modeling at the scale of evolution is a logical step toward predictive and generative artificial intelligence for biology. To this end we use unsupervised learning to train a deep contextual language model on 86 billion amino acids across 250 million protein sequences spanning evolutionary diversity. The resulting model contains information about biological properties in its representations. The representations are learned from sequence data alone. The learned representation space has a multi-scale organization reflecting structure from the level of biochemical properties of amino acids to remote homology of proteins. Information about secondary and tertiary structure is encoded in the representations and can be identified by linear projections. Representation learning produces features that generalize across a range of applications, enabling state-of-the-art supervised prediction of mutational effect and secondary structure, and improving state-of-the-art features for long-range contact prediction.
Distentangling the systems contributing to changes in learning during adolescence
Authors: Master Sarah L. , Eckstein Maria K. , Gotlieb Neta , Dahl Ronald , Wilbrecht Linda , Collins Anne G.E. 
Published: April 2019

AbstractMultiple neurocognitive systems contribute simultaneously to learning. For example, dopamine and basal ganglia (BG) systems are thought to support reinforcement learning (RL) by incrementally updating the value of choices, while the prefrontal cortex (PFC) contributes different computations, such as actively maintaining precise information in working memory (WM). It is commonly thought that WM and PFC show more protracted development than RL and BG systems, yet their contributions are rarely assessed in tandem. Here, we used a simple learning task to test how RL and WM contribute to changes in learning across adolescence. We tested 187 subjects ages 8 to 17 and 53 adults (25-30). Participants learned stimulus-action associations from feedback; the learning load was varied to be within or exceed WM capacity. Participants age 8-12 learned slower than participants age 13-17, and were more sensitive to load. We used computational modeling to estimate subjects’ use of WM and RL processes. Surprisingly, we found more robust changes in RL than WM during development. RL learning rate increased significantly with age across adolescence and WM parameters showed more subtle changes, many of them early in adolescence. These results underscore the importance of changes in RL processes for the developmental science of learning.Highlights- Subjects combine reinforcement learning (RL) and working memory (WM) to learn- Computational modeling shows RL learning rates grew with age during adolescence- When load was beyond WM capacity, weaker RL compensated less in younger adolescents- WM parameters showed subtler and more puberty-related changes- WM reliance, maintenance, and capacity had separable developmental trajectories- Underscores importance of RL processes in developmental changes in learning
Does a strong reduction of colony workforce affect the foraging strategy of a social pollinator?
Authors: Biella Paolo , Tommasi Nicola , Akter Asma , Guzzetti Lorenzo , Klecka Jan , Sandionigi Anna , Labra Massimo , Galimberti Andrea 
Published: April 2019

AbstractThe way pollinators gather resources may play a key role for buffering their population declines. Social pollinators like bumblebees could adjust their foraging after significant workforce reductions to keep provisions to the colony optimal, especially in terms of pollen quality, diversity, and quantity. To test what effects a workforce reduction causes on the foraging for pollen, colonies of the bumblebee Bombus terrestris were experimentally manipulated in field by removing half the number of workers. The pollen pellets of the workers were taxonomically identified with DNA metabarcoding, a ROC approach was used to filter out underrepresented OTUs, and video cameras and network analyses were employed to investigate foraging strategies and behaviour. The results suggested that the plant diversity in the pollen pellets was high but plant identity and pollen quantity traits were influenced mainly by plant phenology. During the experiment, although the treated colonies increased foraging effort in relation to control nests, only minor changes in the diet breadth and in the other node-level and network-level indices were observed after workforce removal. Therefore, a consistency in the bumblebees’ feeding strategies emerges despite the lowered workforce, which questions the ability of social pollinators to adjust their foraging in the field.
Electrical Impedance Spectroscopy to easily assess structural changes in dominant versus auxiliary upper arms due to pathophysiological events
Authors: Dell’Osa A. H. , Fois A. , Mela Q. , Loviselli A. , Capone A. , Marongiu G. , Tocco Filippo , Concu A. , Velluzzi F. 
Published: April 2019

AbstractThe resistive component of the bioimpedance was non invasively assessed in both right and left forearms of 11 healthy female and 9 males (28.4 ± 1.4 years; 63.8 ± 11.8 kg; 167.4 ± 7.5 cm) all of which were right-handed. A homemade electrical impedance spectroscopy device which implemented the AD 5933 electronic board from Analog Devices Inc., USA, was utilized, and the bipolar modality of bioimpedance assessment was chosen using two disposable ECG surface electrodes placed in each end of the biceps brachial muscles while subject were comfortably sitting. Forearms resistance was acquired at sweeping frequencies steps of 15, 30, 45, 60 and 75 KHz. Results showed a significantly lower man value of resistance in right versus left forearms (- 27.4 Ω, P<0.05), or about -4%, at the frequency of 15 KHz. Even though there was a progressive reduction, this right versus left forearm resistance difference persisted as statistically significant up to the frequency of 45 KHz. It was concluded that the risk of some mistakes do exists when lymphedema may occur in one arm and electrical impedance spectroscopy was utilized to monitoring in that arm the water volume trend in comparison with the other side arm since these results underline in the main forearm a largely low value of the resistance than in the auxiliary one, even in healthy subjects. So, care must be taken when the electrical impedance spectroscopy was adopted in these clinical assessments.