bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-discharge Acute Care and Outcomes in the Era of Readmission Reduction
Authors: Khera Rohan , Wang Yongfei , Bernheim Susannah M. , Lin Zhenqiu , Krumholz Harlan M. 
Published: July 2019

ABSTRACTBackgroundWith incentives to reduce readmission rates, there are concerns that patients who need hospitalization after a recent hospital discharge may be denied access, which would increase their risk of mortality.ObjectiveWe determined whether patients with hospitalizations for conditions covered by national readmission programs who received care in emergency department (ED) or observation units but were not hospitalized within 30 days had an increased risk of death. We also evaluated temporal trends in post-discharge acute care utilization in inpatient units, emergency department (ED) and observation units for these patients.Design, Setting, and ParticipantsIn this observational study, national Medicare claims data for 2008-2016, we identified patients ≥65 years hospitalized with heart failure (HF), acute myocardial infarction (AMI), or pneumonia, conditions included in the HRRP.Main Outcomes and MeasuresPost-discharge 30-day mortality according to patients’ 30-day acute care utilization. Acute care utilization in inpatient and observation units, and the ED during the 30-day and 31-90-day post-discharge period.ResultsThere were 3,772,924 hospitalizations for HF, 1,570,113 for AMI, and 3,131,162 for pneumonia. The overall post-discharge 30-day mortality was 8.7% for HF, 7.3% for AMI, and 8.4% for pneumonia. Post-discharge mortality increased annually by 0.16% (95% CI, 0.11%, 0.22%) for HF, decreased by 0.15% (95% CI, -0.18%, -0.12%) for AMI, and did not significantly change for pneumonia. Specifically, mortality only increased for HF patients who did not utilize any post-discharge acute care, increasing at a rate of 0.16% per year (95% CI, 0.11%, 0.22%), accounting for 99% of the increase in post-discharge mortality in heart failure. Concurrent with a reduction in 30-day readmission rates, 30-day observation stays and visits to the ED increased across all 3 conditions during and beyond the post-discharge 30-day period. There was no significant change in overall 30-day post-acute care utilization (P-trend >0.05 for all).Conclusions and RelevanceThe only condition with an increasing mortality through the study period was HF; the increase preceded the policy and was not present among those received ED or observation unit care without hospitalization. Overall, during this period, there was not a significant change in the overall 30-day post-discharge acute care utilization.
The sharedneoantigen landscape of MSI cancers reflects immunoediting during tumor evolution
Authors: Ballhausen Alexej , Przybilla Moritz Jakob , Jendrusch Michael , Haupt Saskia , Pfaffendorf Elisabeth , Draxlbauer Markus , Seidler Florian , Krausert Sonja , Ahadova Aysel , Kalteis Martin Simon , Heid Daniel , Gebert Johannes , Bonsack Maria , Schott Sarah , Bläker Hendrik , Seppälä Toni , Mecklin Jukka-Pekka , Broeke Sanne Ten , Nielsen Maartje , Heuveline Vincent , Krzykalla Julia , Benner Axel , Riemer Angelika Beate , von Knebel Doeberitz Magnus , Kloor Matthias 
Published: July 2019

AbstractThe immune system can recognize and attack cancer cells, especially those with a high load of mutation-inducedneoantigens. Suchneoantigens are particularly abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and toneoantigen-inducing translational frameshifts. The abundance of mutationalneoantigens renders MSI cancers sensitive to immune checkpoint blockade. However, the neoantigen landscape of MMR-deficient cancers has not yet been systematically mapped. In the present study, we used a novel tool to monitorneoantigen-inducing indel mutations in MSI colorectal and endometrial cancer. Our results show that MSI cancers share several highly immunogenicneoantigens that result from specific, recurrent indel mutation events. Notably, the frequency of such indel mutations was negatively correlated to the predicted immunogenicity of the resultingneoantigens. These observations suggest continuous immunoediting of emerging MMR-deficient cells during tumor evolution.One sentence summaryQuantitative indel mutation analysis reveals evidence of immune selection in mismatch repair-deficient cancers
Genomic re-assessment of the transposable element landscape of the potato genome
Authors: Zavallo Diego , Crescente Juan Manuel , Gantuz Magdalena , Leone Melisa , Vanzetti Leonardo Sebastian , Masuelli Ricardo Williams , Asurmendi Sebastian 
Published: July 2019

AbstractTransposable elements (TEs) are DNA sequences with the ability to auto-replicate and move throughout the host genome. TEs are major drivers in stress response and genome evolution. Given their significance, the development of clear and efficient TE annotation pipelines has become essential for many species. The latest de novo TE discovery tools, along with available TEs from Repbase and sRNA-seq data, allowed us to perform a reliable potato TEs detection, classification and annotation through an open-source and freely available pipeline (https://github.com/DiegoZavallo/TE_Discovery). Using a variety of tools, approaches and rules, our pipeline revealed that ca. 16% of the potato genome can be clearly annotated as TEs. Additionally, we described the distribution of the different types of TEs across the genome, where LTRs and MITEs present a clear clustering pattern in pericentromeric and subtelomeric/telomeric regions respectively. Finally, we analyzed the insertion age and distribution of LTR retrotransposon families which display a distinct pattern between the two major superfamilies. While older Gypsy elements concentrated around heterochromatic regions, younger Copia elements located predominantly on euchromatic regions. Overall, we delivered not only a reliable, ready-to-use potato TE annotation files, but also all the necessary steps to perform de novo detection for other species.Key MessageWe provide a comprehensive and reliable potato TE landscape, based on a wide variety of identification tools and integrative approaches, producing clear and ready-to-use outputs for the scientific community.
Impaired early visual categorization of fear in social anxiety
Authors: Meynadasy Melissa , Clancy Kevin , Simon Jessica , Wu Wei , Li Wen 
Published: July 2019

AbstractSocial anxiety is associated with biased social perception, especially of ambiguous cues. While aberrations in high-level processes, including cognitive appraisal and interpretation of social signals, have been implicated in such biases, contributions of early, low-level stimulus processing remain unclear. Categorical perception is known to be an efficient process to resolve signal ambiguity, and categorical emotion perception can swiftly classify sensory input, “tagging” biologically important stimuli at early stages of processing to facilitate ecological response. However, early threat categorization could be disrupted by exaggerated threat processing in anxiety, resulting in biased perception of ambiguous signals. We tested this hypothesis among individuals with low and high trait social anxiety (LSA and HSA), who performed a 2-alternative-forced-choice (fear or neutral) task on facial expressions parametrically varied along a neutral-fear continuum. Clear divergence between the groups emerged in the profiles of reaction time (RT) and early visual response along the neutral-fear continuum. The LSA group exhibited a RT profile characteristic of categorical perception with drastically increased RT from neutral to intermediate (boundary) fear intensities, contrasting monotonous, non-significant RT changes in the HSA group. Neurometric analysis along the continuum identified an early fear-neutral categorization operation (arising in the P1, an early visual event-related potential/ERP at 100 ms) in the LSA (but not HSA) group. Absent group differences in higher-level cognitive operations (identified by later ERPs), current findings highlight a dispositional cognitive vulnerability in early visual categorization of social threat, which could precipitate further cognitive aberrations and, eventually, the onset of social anxiety disorder.
Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds
Authors: Vahaba Daniel M. , Hecsh Amelia , Remage-Healey Luke 
Published: July 2019

ABSTRACTBirdsong, like human speech, is learned early in life by first memorizing an auditory model. Once memorized, birds compare their own burgeoning vocalizations to their auditory memory, and adjust their song to match the model. While much is known about this latter part of vocal learning, less is known about how initial auditory experiences are formed and consolidated. In both adults and developing songbirds, there is strong evidence suggesting the caudomedial nidopallium (NCM), a higher order auditory forebrain area, is the site of auditory memory consolidation. However, the mechanisms that facilitate this consolidation are poorly understood. One likely mechanism is 17β-estradiol (E2), which is associated with speech-language development and disorders in humans, and is abundant in both mammalian temporal cortex and songbird NCM. Circulating E2 is also elevated during the auditory memory phase, and in NCM immediately after song learning sessions, suggesting it functions to encode recent auditory experience. Therefore, we tested a role for E2 production in auditory memory consolidation during development using a comprehensive set of investigations to ask this question at the level of neuroanatomy, neurophysiology, and behavior. Our results demonstrate that while systemic estrogen synthesis blockade regulates juvenile song production, inhibiting E2 synthesis locally within NCM does not adversely affect song learning outcomes. Surprisingly, early life E2 manipulations in NCM modify the neural representations of birds’ own song and the model tutor song in both NCM and a downstream sensorimotor nucleus (HVC). Further, we show that the capacity to synthesize neuroestrogens remains high throughout development alongside substantial changes in NCM cell density across age. Taken together, these findings suggest that E2 plays a multifaceted role during development, and demonstrate that contrary to prediction, unilateral post-training estrogen synthesis blockade in the auditory cortex does not negatively impact vocal learning. Acute downregulation of neuroestrogens are therefore likely permissive for juvenile auditory memorization, while neuroestrogen synthesis influences communication production and representation in adulthood.
ChassiDex: A microbial database useful for synthetic biology applications
Authors: Kailash B P , Karthik D , Shinde Mousami , Damaraju Nikhita , Muthukrishnan Anantha Barathi , Prasad Shashi Bala , Jayaraman Guhan 
Published: July 2019

ChassiDex is an open-source, non-profit online host organism database that houses a repository of molecular, biological and genetic data for model organisms with applications in synthetic biology. The structured user-friendly environment makes it easy to browse information. The database consists of a page for each model organism subdivided into sections such as Growth Characteristics, Strain diversity, Culture sources, Maintenance protocol, Transformation protocol, BioBrick parts and commonly used vectors. With tools such as CUTE built for codon usage table generator, it is also easy to generate and download accurate novel codon tables for unconventional hosts in suitable formats. This database was built as a project for the International Genetically Engineered Machine Competition in 2017 with the mission of making it easy to shift from working with one host organism to another unconventional host organism for any researcher in the field of synthetic biology. The code along with other instructions for the usage of the database and tools are publicly available at the GitHub page. We encourage the synthetic biology community to contribute to the database by adding data for any additional or existing host organism.https://chassidex.org;https://github.com/ChassiDex
Evolution of barrier loci at an intermediate stage of speciation with gene flow
Authors: Liu Xiaodong , Glémin Sylvain , Karrenberg Sophie 
Published: July 2019

AbstractUnderstanding the origin of new species is a central goal in evolutionary biology. Diverging lineages often evolve highly heterogeneous patterns of differentiation; however, the underlying mechanisms are not well understood. We used an integrated approach to investigate evolutionary processes governing genetic differentiation between the hybridizing campions (Silene dioica (L.) Clairv. and S. latifolia Poiret). Demographic modeling indicated that the two species diverged with continuous gene flow. The best-supported scenario with heterogeneity in both migration rate and effective population size suggested that 5% of the loci evolved without gene flow. Differentiation (FST) and sequence divergence (dXY) were correlated and both tended to peak in the middle of most linkage groups, consistent with reduced gene flow at highly differentiated loci. Highly differentiated loci further exhibited signatures of selection and differentiation was significantly elevated around previously identified QTLs associated with assortative mating. In between-species population pairs, isolation by distance was stronger for genomic regions with low between-species differentiation than for highly differentiated regions that may contain barrier loci. Moreover, differentiation landscapes within and between species were only weakly correlated suggesting that the interplay of background selection and conserved genomic features is not the dominant determinant of genetic differentiation in these lineages. Instead, our results suggest that divergent selection drove the evolution of barrier loci played and the genomic landscape of differentiation between the two species, consistent with predictions for speciation in the face of gene flow.
Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data
Authors: Bhati Meenu , Kadri Naveen Kumar , Crysnanto Danang , Pausch Hubert 
Published: July 2019

AbstractBackgroundAutochthonous cattle breeds represent an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and food conditions. Original Braunvieh (OB) is a local cattle breed of Switzerland used for beef and milk production in alpine areas. Using whole-genome sequencing (WGS) data of 49 key ancestors, we characterize genomic diversity, genomic inbreeding, and signatures of selection in Swiss OB cattle at nucleotide resolution.ResultsWe annotated 15,722,811 million SNPs and 1,580,878 million Indels including 10,738 and 2,763 missense deleterious and high impact variants, respectively, that were discovered in 49 OB key ancestors. Six Mendelian trait-associated variants that were previously detected in breeds other than OB, segregated in the sequenced key ancestors including variants causal for recessive xanthinuria and albinism. The average nucleotide diversity (1.6 × 10-3) was higher in OB than many mainstream European cattle breeds. Accordingly, the average genomic inbreeding quantified using runs of homozygosity (ROH) was relatively low (FROH=0.14) in the 49 OB key ancestor animals. However, genomic inbreeding was higher in more recent generations of OB cattle (FROH=0.16) due to a higher number of long (> 1 Mb) runs of homozygosity. Using two complementary approaches, composite likelihood ratio test and integrated haplotype score, we identified 95 and 162 genomic regions encompassing 136 and 157 protein-coding genes, respectively, that showed evidence (P< 0.005) of past and ongoing selection. These selection signals were enriched for quantitative trait loci related to beef traits including meat quality, feed efficiency and body weight and pathways related to blood coagulation, nervous and sensory stimulus.ConclusionsWe provide a comprehensive overview of sequence variation in Swiss OB cattle genomes. With WGS data, we observe higher genomic diversity and less inbreeding in OB than many European mainstream cattle breeds. Footprints of selection were detected in genomic regions that are possibly relevant for meat quality and adaptation to local environmental conditions. Considering that the population size is low and genomic inbreeding increased in the past generations, the implementation and adoption of optimal mating strategies seems warranted to maintain genetic diversity in the Swiss OB cattle population.
Testing for population decline using maximal linkage disequilibrium blocks
Authors: Kerdoncuff Elise , Lambert Amaury , Achaz Guillaume 
Published: July 2019

AbstractOnly 6% of known species have a conservation status. Methods that assess conservation statuses are often based on individual counts and are thus too laborious to be generalized to all species. Population genomics methods that infer past variations in population size are easy to use but limited to the relatively distant past. Here we propose a population genomics approach that tests for recent population decline and may be used to assess species conservation statuses. More specifically, we study Maximal Recombination Free (MRF) blocks, that are segments of a sequence alignment inherited from a common ancestor without recombination. MRF blocks are relatively longer in small than in large populations. We use the distribution of MRF block lengths rescaled by their mean to test for recent population decline. However, because MRF blocks are difficult to detect, we also consider Maximal Linkage Disequilibrium (MLD) blocks, which are runs of single nucleotide polymorphisms compatible with a single tree. We develop a new method capable of inferring a very recent decline (e.g. with a detection power of 50% for populations which size was halved toN, 0.05 ×Ngenerations ago) from rescaled MLD block lengths. Our framework could serve as a basis for quantitative tools to assess conservation status in a wide range of species.
Predicting protein functional motions: an old recipe with a new twist
Authors: Grudinin Sergei , Laine Elodie , Hoffmann Alexandre 
Published: July 2019

Large macromolecules, including proteins and their complexes, very often adopt multiple conformations. Some of them can be seen experimentally, for example with X-ray crystallography or cryo-electron microscopy. This structural heterogeneity is not occasional and is frequently linked with specific biological function. Thus, the accurate description of macromolecular conformational transitions is crucial for understanding fundamental mechanisms of life’s machinery. We report on a real-time method to predict such transitions by extrapolating from instantaneous eigen-motions, computed using the normal mode analysis, to a series of twists. We demonstrate the applicability of our approach to the prediction of a wide range of motions, including large collective opening-closing transitions and conformational changes induced by partner binding. We also highlight particularly difficult cases of very small transitions between crystal and solution structures. Our method guaranties preservation of the protein structure during the transition and allows to access conformations that are unreachable with classical normal mode analysis. We provide practical solutions to describe localized motions with a few low-frequency modes and to relax some geometrical constraints along the predicted transitions. This work opens the way to the systematic description of protein motions, whatever their degree of collectivity. Our method is available as a part of the NOn-Linear rigid Block (NOLB) package athttps://team.inria.fr/nano-d/software/nolb-normal-modes/.Significance StatementProteins perform their biological functions by changing their shapes and interacting with each other. Getting access to these motions is challenging. In this work, we present a method that generatesplausiblephysics-based protein motions and conformations. We model a protein as a network of atoms connected by springs and deform it along the least-energy directions. Our main contribution is to perform the deformations in a nonlinear way, through a series of twists. This allows us to produce a wide range of motions, some of them previously inaccessible, and to preserve the structure of the protein during the motion. We are able to simulate the opening or closing of a protein and the changes it undergoes to adapt to a partner.
A new species of Lepanthopsis (Orchidaceae, Pleurothallidinae) in the Atlantic Forest in São Paulo, Brazil
Authors: Zandoná L.R. , Catharino E.L.M. , Maragni A.G. , Jesus M.M.F. 
Published: July 2019

AbstractA new species of Lepanthopsis is discovered and described for the Atlantic Forest of southeastern Brazil, the species called Lepanthopsis legadensis is distinguished from other Brazilian species, notably by the petals and long-acuminate sepals.
Myosoft: an automated muscle histology analysis tool using machine learning algorithm utilizing FIJI/ImageJ software
Authors: Encarnacion-Rivera Lucas , Foltz Steven , Hartzell H. Criss , Choo Hyo-Jung 
Published: July 2019

AbstractBackgroundSkeletal muscle is comprised of a heterogeneous population of muscle fibers which can be classified by their metabolic and contractile properties (fiber “types”). Fiber type is a primary determinant of muscle function along with fiber size (cross-sectional area). The fiber type composition of a muscle responds to physiological changes like exercise and aging and is often altered in disease states. Thus, analysis of fiber size and type in histological muscle preparations is a useful method for quantifying key indicators of muscle function and for measuring responses to a variety of stimuli or stressors. These analyses are near-ubiquitous in the fields of muscle physiology and myopathy, but are most commonly performed manually, which is highly labor- and time-intensive. To offset this obstacle, we developed Myosoft, a novel method to automate morphometric and fiber type analysis in muscle sections stained with fluorescent antibodies.MethodsMuscle sections were stained for cell membrane (laminin) and myofiber type (myosin heavy chain isoforms). Myosoft, running in the open access software platform FIJI (ImageJ), was used to analyze myofiber size and type in transverse sections of entire gastrocnemius/soleus muscles.ResultsMyosoft provides accurate analysis of muscle histology >50-times faster than manual analysis. We demonstrate that Myosoft is capable of handling high-content images even when image or staining quality is suboptimal, which is a marked improvement over currently available, comparable programs.ConclusionsMyosoft is a reliable, accurate, high-throughput, and convenient tool to analyze high-content muscle histology. Myosoft is freely available to download from Github athttps://github.com/Hyojung-Choo/Myosoft/tree/Myosoft-hub.