bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Phylogenies from Shape and Similar Multidimensional Data: Why It Is Not Reliable
Authors: Varón-González Ceferino , Whelan Simon , Klingenberg Christian Peter 
Published: January 2020

AbstractIn recent years, there has been controversy whether multidimensional data such as geometric morphometric data or information on gene expression can be used for estimating phylogenies. This study uses simulations of evolution in multidimensional phenotype spaces to address this question and to identify specific factors that are important for answering it. Most of the simulations use phylogenies with four taxa, so that there are just three possible unrooted trees and the effect of different combinations of branch lengths can be studied systematically. In a comparison of methods, squared-change parsimony performed similarly well as maximum likelihood, and both methods outperformed Wagner and Euclidean parsimony, neighbor-joining and UPGMA. Under an evolutionary model of isotropic Brownian motion, phylogeny can be estimated reliably if dimensionality is high, even with relatively unfavorable combinations of branch lengths. By contrast, if there is phenotypic integration such that most variation is concentrated in one or a few dimensions, the reliability of phylogenetic estimates is severely reduced. Evolutionary models with stabilizing selection also produce highly unreliable estimates, which are little better than picking a phylogenetic tree at random. To examine how these results apply to phylogenies with more than four taxa, we conducted further simulations with up to eight taxa, which indicated that the effects of dimensionality and phenotypic integration extend to more than four taxa, and that convergence among internal nodes may produce additional complications specifically for greater numbers of taxa. Overall, the simulations suggest that multidimensional data, under evolutionary models that are plausible for biological data, do not produce reliable estimates of phylogeny. [Brownian motion; gene expression data; geometric morphometrics; morphological integration; squared-change parsimony; phylogeny; shape; stabilizing selection.]
Persistence of symptoms in dengue patients: a clinical cohort study
Authors: Tiga-Loza Diana Carolina , Martínez-Vega Ruth A , Undurraga Eduardo A , Tschampl Cynthia A , Shepard Donald S , Ramos-Castañeda José 
Published: January 2020

Abstract

Background
Dengue is commonly considered an acute illness and follows three phases: febrile, critical in some cases and recovery. However, a number of studies have described a continuation of dengue symptoms for weeks or months, extending the recovery phase. Here we evaluate this persistence of dengue symptoms during convalescence.

Methods
Our clinical cohort study included patients who sought medical services 48 to 144 h from the onset of fever at seven hospitals or ambulatory centers in Morelos, Mexico. Seventy-nine laboratory-confirmed dengue patients were followed up regularly using clinic and/or home visits and telephone calls for as long as symptoms persisted or up to 6 mo.

Results
In total, 55.7% of patients had dengue-related symptoms 1 mo after the onset of fever; pain and dermatological manifestations were the most common persistent symptoms. Prognostic factors for symptom persistence were: ≥4 d of fever (RR 1.72; 95% CI 1.35 to 2.19), platelet count ≤100 000/mm3 (RR 1.20; 95% CI 1.20 to 2.20), petechiae/bruises (RR 1.97; 95% CI 1.56 to 2.48) and abdominal pain/hepatomegaly (RR 1.79; 95% CI 1.41 to 2.28).

Conclusions
Persistence of dengue symptoms were common in laboratory-confirmed dengue patients. Manifestations related to tissue damage were associated with persistence after 30 d; host characteristics, such as age and health status before infection, were associated with prolonged persistence (&gt;60 d). The burden of dengue may be higher than previously estimated.
Exascale applications: skin in the game
Authors: Alexander Francis , Almgren Ann , Bell John , Bhattacharjee Amitava , Chen Jacqueline , Colella Phil , Daniel David , DeSlippe Jack , Diachin Lori , Draeger Erik , Dubey Anshu , Dunning Thom , Evans Thomas , Foster Ian , Francois Marianne , Germann Tim , Gordon Mark , Habib Salman , Halappanavar Mahantesh , Hamilton Steven , Hart William , (Henry) Huang Zhenyu , Hungerford Aimee , Kasen Daniel , Kent Paul R. C. , Kolev Tzanio , Kothe Douglas B. , Kronfeld Andreas , Luo Ye , Mackenzie Paul , McCallen David , Messer Bronson , Mniszewski Sue , Oehmen Chris , Perazzo Amedeo , Perez Danny , Richards David , Rider William J. , Rieben Rob , Roche Kenneth , Siegel Andrew , Sprague Michael , Steefel Carl , Stevens Rick , Syamlal Madhava , Taylor Mark , Turner John , Vay Jean-Luc , Voter Artur F. , Windus Theresa L. , Yelick Katherine 
Published: January 2020

As noted in Wikipedia,skin in the gamerefers to having ‘incurred risk by being involved in achieving a goal’, where ‘skinis a synecdoche for the person involved, andgameis the metaphor for actions on the field of play under discussion’. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with theskinbeing exascale applications and thegamebeing delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare.This article is part of a discussion meeting issue ‘Numerical algorithms for high-performance computational science’.
Procurement of innovation terminology usage in health care: A scoping review protocol
Authors: Andrews Margaret R. , Ramos Romualdo , Ahlberg Martina , Hazelzet Jan A. , van Raaij Erik M. , Sihag Vikrant , Alessandrello Rossana , Aurín Eva , Bakir Bahar , Carter Desmond , Ikävalko Suzan , Janian Mariet Nouri , Oleari Elettra , Timmermann Maarten M. , Valls-Comamala Victòria , Stamm Tanja A. ,   Platform for Innovation of Procurement and Procurement of Innovation Project
Published: January 2020

AbstractBackgroundAlthough procurement of innovation is an established policy tool used to stimulate collaboration between supply- and demand-side entities during the development of new technologies, there is little scientific literature describing the process as applied in health care settings. Furthermore, what literature exists contains inconsistencies of terms, definitions, and/or concepts related to procurement of innovation. This protocol details our process for a systematic scoping review to describe the current scope of literature and to provide terminology clarification.MethodsA search strategy will be used to search PubMed, EMBASE [OVID], CINAHL [EBSCO], PsycINFO [ProQUEST], ABI/INFORM, ISI Web of Knowledge, EBSCO, JSTOR, the Cochrane Database of Systematic Reviews, and Google Scholar; grey literature, non-scientific reports, policy documents and expert recommendations will also be considered as additional sources for texts. Two researchers will screen titles and abstracts for inclusion/exclusion criteria, followed by full texts. We will extract the following data, if applicable: title, authors, date, author affiliations, country, journal/publication characteristics, setting, aims/purpose, methodology, sample characteristics, assessment/evaluation tools, outcome parameters, key findings, relevance, and terminology usage/definitions. Results will be presented narratively and visually.DiscussionThis paper describes the steps of our proposed systematic scoping review to identify and analyse scientific and non-scientific literature related to procurement of innovation and/or innovation of procurement in health care settings, with a particular focus on digital health technologies. Results are intended to demonstrate the current scope of literature, to provide clarity in language and therefore to serve as a first step for further research in this growing field.
AAV Ablates Neurogenesis in the Adult Murine Hippocampus
Authors: Johnston ST , Parylak SL , Kim S , Mac N , Lim CK , Gallina IS , Bloyd CW , Newberry A , Saavedra CD , Novák O , Gonçalves JT , Gage FH , Shtrahman M 
Published: January 2020

ABSTRACTRecombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hours post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis.In vitroapplication of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentate gyrus (DG)—without ablating adult neurogenesis—can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permitsin vivo2-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system (CNS) should be carefully evaluated.
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
Authors: Cohen Alexander A. , Yang Zhi , Gnanapragasam Priyanthi NP , Ou Susan , Dam Kim-Marie A. , Wang Haoqing , Bjorkman Pamela J. 
Published: January 2020

AbstractCurrent influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that B-cells with receptors that recognize conserved epitopes would be preferentially stimulated through avidity effects by mosaic particles presenting multiple forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like particles (VLPs) and mi3 nanoparticles (NPs), to covalently co-display SpyTagged hemagglutinin (HA) trimers from group 1 and group 2 influenza A strains. Here we show successful homotypic and heterotypic conjugation of up to 8 different HA trimers to both VLPs and NPs. We characterized the HA-VLPs and HA-NPs by cryo-electron tomography to derive the average number of conjugated HAs and their separation distances on particles, and compared immunizations of mosaic and homotypic particles in wild-type mice. Both types of HA particles elicited strong antibody responses, but the mosaic particles did not consistently elicit broader immune responses than mixtures of homotypic particles. We conclude that covalent attachment of HAs from currently-circulating influenza strains represents a viable alternative to current annual influenza vaccine strategies, but in the absence of further modifications, is unlikely to represent a method for making a universal influenza vaccine.
Nuclear Plasticity Increases Susceptibility to Damage During Confined Migration
Authors: Mukherjee Abhishek , Barai Amlan , Singh Ramesh K , Yan Wenyi , Sen Shamik 
Published: January 2020

AbstractLarge nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage.
Potential short-term earthquake forecasting by farm-animal monitoring
Authors: Wikelski Martin , Mueller Uschi , Scocco Paola , Catorci Andrea , Desinov Lev , Belyaev Mikhail , Keim Daniel , Pohlmeier Winfried , Fechteler Gerhard , Mai P. Martin 
Published: January 2020

AbstractWhether changes in animal behavior allow for short-term earthquake predictions has been debated for a long time. During the 2016/2017 earthquake sequence in Italy, we instrumentally observed the activity of farm animals (cows, dogs, sheep) close to the epicenter of the devastating magnitude M6.6 Norcia earthquake (Oct-Nov 2016) and over a subsequent longer observation period (Jan-Apr 2017). Relating 5304 (in 2016) and 12948 (in 2017) earthquakes with a wide magnitude range (0.4 ≤ M ≤ 6.6) to continuously measured animal activity, we detected how the animals collectively reacted to earthquakes. We also found consistent anticipatory activity prior to earthquakes during times when the animals were in a stable, but not during their time on a pasture. We detect these anticipatory patterns not only in periods with high, but also in periods of low seismic activity. Earthquake anticipation times (1-20hrs) are negatively correlated with the distance between the farm and earthquake hypocenters. Our study suggests that continuous instrumental monitoring of animal collectives has the potential to provide statistically reliable patterns of pre-seismic activity that could allow for short-term earthquake forecasting.One Sentence SummaryA collective of domestic animals repeatedly showed unusually high activity levels before earthquakes, with anticipation times (1-20h) negatively related to distance from epicenters (5-28km).
Three major dimensions of human brain cortical ageing in relation to cognitive decline across the 8thdecade of life
Authors: Cox SR , Harris MA , Ritchie SJ , Buchanan CR , Valdés Hernández MC , Corley J , Taylor AM , Madole JW , Harris SE , Whalley HC , McIntosh AM , Russ TC , Bastin ME , Wardlaw JM , Deary IJ , Tucker-Drob EM 
Published: January 2020

AbstractDifferent brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflates information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the 8thdecade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1,376 MRI scans. Volumetricchangesamong cortical regions of interest (ROIs) were more strongly correlated (averager= 0.805, SD = 0.252) than werecross-sectionalvolumes of the same ROIs (averager= 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions, that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r= 0.431,p< 0.001) and in the domains of visuospatial ability (r= 0.415,p= 0.002), processing speed (r= 0.383,p< 0.001) and memory (r= 0.372,p< 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.
The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells
Authors: De Cecco Elena , Celauro Luigi , Vanni Silvia , Grandolfo Micaela , Aguzzi Adriano , Legname Giuseppe 
Published: January 2020

AbstractTauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell-to-cell transfer of tau protein amyloids, yet the spreading mechanisms are unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, we found that tau amyloids bind to PrPC; internalization of tau fibrils was reduced in isogenic cells devoid of the gene encoding PrPC. Antibodies against N-proximal epitopes of PrPCimpaired the binding of tau amyloids and decreased their uptake. Surprisingly, exposure of chronically prion-infected cells to tau amyloids reduced the accumulation of aggregated prion protein; this effect lasted for more than 72 hours after amyloid removal. These results point to bidirectional interactions between the two proteins: whilst PrPCmediates the entrance of tau fibrils in cells, PrPScbuildup is greatly reduced in their presence, possibly because of an impairment in the prion conversion process.
Diagnostic of begomoviruses in complex infections –a case study
Authors: Jovel Juan 
Published: January 2020

AbstractComplexes of viruses inducing a syndrome in plants strongly hinder the identification of the causal agent of a disease. TheSida micranthamosaic disease is associated with a complex of begomoviruses. For more than twenty years, two DNAs A (DNA A2 and DNA A3) belonging to this complex could neither be detected nor isolated fromSida micranthaSchr. plants, although one of them (DNA A2) now appears to be the major component of the complex. A random unintendedBemisia tabaci-mediated transmission of begomoviruses from several Sida species – includingS. micrantha– to experimentalMalva parvifloraplants resulted in the serendipitous finding of these new DNAs A. Simultaneously, a number of other begomoviruses infecting Sida plants from several Latin American countries were transmitted toM. parvifloraplants and the convergence of them resulted in natural pseudorecombinants. Pseudorecombination, however, took place exclusively between heterologous genomic components that shared identical binding sites for the replication-associated protein AC1. This case study constitutes an exceptional opportunity for the analysis of plant–virus– vector interactions in a quasi-natural environment. In addition to that, the methodology described here may be used to isolate and characterize different begomoviruses inducing a syndrome during mix infections.
Connecting secretome to hematopoietic stem cell phenotype shifts in an engineered bone marrow niche
Authors: Gilchrist Aidan E. , Harley Brendan A.C. 
Published: January 2020

AbstractHematopoietic stem cells (HSCs) primarily reside in the bone marrow, where they receive external cues from their local microenvironment. The complex milieu of biophysical cues, cellular components, and cell-secreted factors regulates the process by which HSC produce the blood and immune system. We previously showed direct co-culture of primary murine hematopoietic stem and progenitor cells with a population of marrow-derived mesenchymal stromal and progenitor cells (MSPCs) in a methacrylamide-functionalized gelatin (GelMA) hydrogel improves hematopoietic progenitor maintenance. However, the mechanism by which MSPCs influenced HSC fate decisions remained unknown. Herein, we report the use of proteomic analysis to correlate HSC phenotype to a broad candidate pool of 200 soluble factors produced by combined mesenchymal and hematopoietic progeny. Partial Least Squares Regression (PLSR), along with an iterative filter method, identified TGFβ-1, MMP-3, c-RP, and TROY as positively correlated with HSC maintenance. Experimentally, we then observe exogenous stimulation of HSC monocultures in GelMA hydrogels with these combined cytokines increases the ratio of hematopoietic progenitors to committed progeny after a 7-day culture 7.52 ± 3.65 fold compared to non-stimulated monocultures. Findings suggest a cocktail of the downselected cytokines amplify hematopoietic maintenance potential of HSCs beyond that of MSPC-secreted factors alone. This work integrates empirical and computation methods to identify cytokine combinations to improve HSC maintenance within an engineered HSC niche, suggesting a route towards identifying feeder-free culture platforms for HSC expansion.InsightHematopoietic stem cells within an artificial niche receive maintenance cues in the form of soluble factors from hematopoietic and mesenchymal progeny. Applying a proteomic regression analysis, we identify a reduced set of soluble factors correlated to maintenance of a hematopoietic phenotype during culture in a biomaterial model of the bone marrow niche. We identify a minimum factor cocktail that promotes hematopoietic maintenance potential in a gelatin-based culture, regardless of the presence of mesenchymal feeder-cells. By combining empirical and computational methods, we report an experimentally feasible number of factors from a large dataset, enabling exogenous integration of soluble factors into an engineered hematopoietic stem cell for enhance maintenance potential of a quiescent stem cell population.
Exploring the remarkable diversity ofEscherichia coliPhages in the Danish Wastewater Environment, Including 91 Novel Phage Species
Authors: Olsen Nikoline S. , Kot Witold , Junco Laura M. F. , Hansen Lars H. 
Published: January 2020

AbstractPhages drive bacterial diversity - profoundly influencing diverse microbial communities, from microbiomes to the drivers of global biogeochemical cycling. The vast genomic diversity of phages is gradually being uncovered as >8000 phage genomes have now been sequenced. Aiming to broaden our understanding ofEscherichia coli(MG1655, K-12) phages, we screened 188 Danish wastewater samples (0.5 ml) and identified 136 phages of which 104 are unique phage species and 91 represent novel species, including several novel lineages. These phages are estimated to represent roughly a third of the true diversity ofEscherichiaphages in Danish wastewater. The novel phages are remarkably diverse and represent four different familiesMyoviridae, Siphoviridae, PodoviridaeandMicroviridae. They group into 14 distinct clusters and nine singletons without any substantial similarity to other phages in the dataset. Their genomes vary drastically in length from merely 5 342 bp to 170 817 kb, with an impressive span of GC contents ranging from 35.3% to 60.0%. Hence, even for a model host bacterium, in the go-to source for phages, substantial diversity remains to be uncovered. These results expand and underlines the range ofEscherichiaphage diversity and demonstrate how far we are from fully disclosing phage diversity and ecology.