bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing clinical concept extraction with contextual embeddings
Authors: Si Yuqi , Wang Jingqi , Xu Hua , Roberts Kirk 
Published: May 2019

AbstractObjectiveNeural network–based representations (“embeddings”) have dramatically advanced natural language processing (NLP) tasks, including clinical NLP tasks such as concept extraction. Recently, however, more advanced embedding methods and representations (eg, ELMo, BERT) have further pushed the state of the art in NLP, yet there are no common best practices for how to integrate these representations into clinical tasks. The purpose of this study, then, is to explore the space of possible options in utilizing these new models for clinical concept extraction, including comparing these to traditional word embedding methods (word2vec, GloVe, fastText).Materials and MethodsBoth off-the-shelf, open-domain embeddings and pretrained clinical embeddings from MIMIC-III (Medical Information Mart for Intensive Care III) are evaluated. We explore a battery of embedding methods consisting of traditional word embeddings and contextual embeddings and compare these on 4 concept extraction corpora: i2b2 2010, i2b2 2012, SemEval 2014, and SemEval 2015. We also analyze the impact of the pretraining time of a large language model like ELMo or BERT on the extraction performance. Last, we present an intuitive way to understand the semantic information encoded by contextual embeddings.ResultsContextual embeddings pretrained on a large clinical corpus achieves new state-of-the-art performances across all concept extraction tasks. The best-performing model outperforms all state-of-the-art methods with respective F1-measures of 90.25, 93.18 (partial), 80.74, and 81.65.ConclusionsWe demonstrate the potential of contextual embeddings through the state-of-the-art performance these methods achieve on clinical concept extraction. Additionally, we demonstrate that contextual embeddings encode valuable semantic information not accounted for in traditional word representations.
Effects of Host Age and Density on the Performance of Apanteles hemara (Hymenoptera: Braconidae), a Larval Endoparasitoid of Spoladea recurvalis (Lepidoptera: Crambidae)
Authors: Othim S T O , Ramasamy S , Kahuthia-Gathu R , Dubois T , Ekesi S , Fiaboe K K M 
Published: May 2019

AbstractThe amaranth leaf-webber, Spoladea recurvalis (Fabricius; Lepidoptera: Crambidae), is a serious pest of Amaranthus sp. in Africa and Asia. Apanteles hemara (Nixon; Hymenoptera: Braconidae) is by far the most important larval endoparasitoid of the amaranth leaf-webber. We examined the effects of host density and age on the biological characteristics of A. hemara. The regression model of the number of hosts supplied to A. hemara against the number of larvae parasitized resulted in a curve corresponding to type II functional response, with a significant increase in the number of hosts parasitized up to the density of 30 hosts before being constant up to 40 hosts. In contrast, the parasitism rate decreased linearly with increasing host densities. Development time, sex ratio, and adult longevity were not significantly affected by host density. The immature parasitoid mortality was significantly higher at higher host densities. Apanteles hemara did not parasitize 7-d-old larvae and beyond, while parasitism was significantly higher among 1- to 2-d-old compared with 3- to 4-d-old larvae. Immature parasitoid mortality was 2.6 times higher in 1- to 2-d-old larvae compared with 5- to 6-d-old larvae. The developmental period of the parasitoid from egg to adult was longest among 1- to 2-d-old larvae and least among 5- to 6-d-old larvae. Nonreproductive mortality was markedly higher among 1- to 2-d-old larvae compared with the older larvae. Adult female A. hemara were significantly larger on 3- to 4-d-old larvae compared with either 1- to 2-d-old or 5- to 6-d-old larvae. We discuss the implications of our results for the interpretation of functional response in parasitoids, mass rearing, conservation, and augmentative biological control of S. recurvalis.
ESTIMATING DIVERSION RATIOS IN HOSPITAL MERGERS
Authors: Rossi Cecilia , Whitehouse Russell , Moore Alex 
Published: May 2019

ABSTRACT
Understanding patient choice is vital in assessing the closeness of competition between hospitals. The standard technique used in the UK is to estimate substitution patterns based on historical general practitioner (GP) referrals. In this paper we compare the results of the ‘GP referral’ methodology to a demand estimation approach. Using patient-level data over a 3-year period (2012/13–2014/15) we apply both methodologies to every hypothetical merger between hospitals in England, for three specialties. We find a high degree of consistency between the two approaches, suggesting that GP referral analysis is a useful and reliable filter in merger cases. There are a small number of cases, however, in which the GP referral approach filters out potentially problematic mergers. This is particularly true for ‘borderline’ cases. Filtering should therefore be done with caution and in conjunction with additional evidence.
‘The Only Thing “Womanish” is the Composer’: Music at Nineteenth-Century Exhibitions of Women’s Work
Authors: Kirby Sarah 
Published: May 2019

Abstract
The 1880s saw a burgeoning of exhibitions of ‘Women’s Work’ across the world. These events focused on the artistic and industrial abilities of women, signifying an unprecedented shift away from the emphasis usually placed on maleness and masculinized technology in contemporary exhibition culture. The first Exhibition, held in Bristol in 1885, included a musical novelty: a concert entirely of works composed by women. The next, in Sydney in 1888, included a whole series of such concerts. These concerts—containing works by Kate Loder, Clara Wieck, Fanny Hensel, Agnes Zimmermann, and Maude Valérie White—were extraordinarily well received, applauded in both concept and execution. Yet, their reception appears paradoxical against the contemporary critical climate. In both Britain and Australia, the ‘question’ of women composers was widely debated, and works met with condescension or hostility. By exploring the expectations surrounding displays of ‘women’s work’, I argue that it was the exhibition context itself that influenced the reception of this music. While Exhibitions were conventionally seen as male-gendered events, ‘Women’s’ Exhibitions allowed organizers to blur the distinctions between private and public space. Similarly, while women composers were criticized for their encroachment in the male concert sphere, these Exhibitions also blurred these boundaries and gave critics an appropriate ‘feminine’ framework through which to view and critique the works.
A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG)
Authors: Huang Huachao , Kong Weili , Jean Maxime , Fiches Guillaume , Zhou Dawei , Hayashi Tsuyoshi , Que Jianwen , Santoso Netty , Zhu Jian 
Published: May 2019

AbstractAlthough combination antiretroviral therapy is potent to block active replication of HIV-1 in AIDS patients, HIV-1 persists as transcriptionally inactive proviruses in infected cells. These HIV-1 latent reservoirs remain a major obstacle for clearance of HIV-1. Investigation of host factors regulating HIV-1 latency is critical for developing novel antiretroviral reagents to eliminate HIV-1 latent reservoirs. From our recently accomplished CRISPR/Cas9 sgRNA screens, we identified that the histone demethylase, MINA53, is potentially a novel HIV-1 latency-promoting gene (LPG). We next validated MINA53’s function in maintenance of HIV-1 latency by depleting MINA53 using the alternative RNAi approach. We further identified that in vitro MINA53 preferentially demethylates the histone substrate, H3K36me3 and that in cells MINA53 depletion by RNAi also increases the local level of H3K36me3 at LTR. The effort to map the downstream effectors unraveled that H3K36me3 has the cross-talk with another epigenetic mark H4K16ac, mediated by KAT8 that recognizes the methylated H3K36 and acetylated H4K16. Removing the MINA53-mediated latency mechanisms could benefit the reversal of post-integrated latent HIV-1 proviruses for purging of reservoir cells. We further demonstrated that a pan jumonji histone demethylase inhibitor, JIB-04, inhibits MINA53-mediated demethylation of H3K36me3, and JIB-04 synergizes with other latency-reversing agents (LRAs) to reactivate latent HIV-1.
Efficient HIV-1 Trans Infection of CD4+ T Cells Occurs in the Presence of Antiretroviral Therapy
Authors: Rappocciolo Giovanna , Sluis-Cremer Nicolas , Rinaldo Charles R 
Published: May 2019

Abstract

Background
Antiretroviral therapy (ART) has dramatically improved the quality of life of people with HIV-1 infection (PWH). However, it is not curative, and interruption of ART results in rapid viral rebound. Cell-to-cell transfer of HIV-1, or trans infection, is a highly efficient mechanism of virus infection of CD4+ T cells by professional antigen-presenting cells (APCs), that is, dendritic cells (DCs), macrophages, and B lymphocytes.

Methods
APC from HIV seronegative donors treated with ART in vitro (CCR5 agonist, NRTI, PI and NNRTI, alone or in combination), were loaded with HIV R5-tropic HIVBal and mixed with autologous or heterologous CD4+ T lymphocytes to assess trans infection. Ex vivo APC from chronic HIV-infected MACS participants before and after initiation of ART, were also loaded with HIV R5-tropic HIVBal and tested for trans infection against autologous or heterologous CD4+ T lymphocytes. Virus replication was measured by p24 ELISA.

Results
Here we show in vitro that antiretroviral drugs did not block the ability of DCs and B cells to trans-infect CD4+ T cells, although they were effective in blocking direct cis infection of CD4+ T cells. Moreover, ex vivo DCs and B cells from ART-suppressed PWH mediated efficient HIV-1 trans infection of CD4+ T cells, which were resistant to direct cis infection.

Conclusions
Our study supports a role for HIV-1 trans infection in maintenance of the HIV-1 reservoir during ART.
Internal and External Objects of Cognition
Authors: Ayers Michael 
Published: May 2019

Abstract
Detailed analysis is conducted of the different constructions in which ‘know’, ‘believe’, ‘see’, and cognate verbs appear in ordinary or natural language, of their functions and of the relations and differences between them: e.g. noun-clauses of the form ‘that P’ serve different purposes after each of these classes of verb, partly reflected in the proposition–fact distinction—although ‘facts’ are ontologically unsuited to be what it is in the world we know. Some relevant views of Timothy Williamson (e.g. ‘e=k’) are discussed. The emphasis in current epistemology on the ‘know/see that P’ construction is criticized—no construction, and no use of the term ‘evidence’, is philosophically best, since it is no accident that we have them all. The philosophical task is to understand how they work together—the footprints in language of our cognitive relation to reality, manifestations of what knowledge, belief, and perception are.
A Macroeconomic Model with Financial Panics
Authors: Gertler Mark , Kiyotaki Nobuhiro , Prestipino Andrea 
Published: May 2019

AbstractThis article incorporates banks and banking panics within a conventional macroeconomic framework to analyse the dynamics of a financial crisis of the kind recently experienced. We are particularly interested in characterizing the sudden and discrete nature of banking panics as well as the circumstances that make an economy vulnerable to such panics in some instances but not in others. Having a conventional macroeconomic model allows us to study the channels by which the crisis affects real activity both qualitatively and quantitatively. In addition to modelling the financial collapse, we also introduce a belief driven credit boom that increases the susceptibility of the economy to a disruptive banking panic.
Novel Rhabdovirus and an almost complete drain fly transcriptome recovered from two independent contaminations of clinical samples
Authors: Brito Francisco , Manni Mosè , Laubscher Florian , Schibler Manuel , Hartley Mary-Anne , Keitel Kristina , Mlaganile Tarsis , d’Acremont Valerie , Cordey Samuel , Kaiser Laurent , Zdobnov Evgeny M 
Published: May 2019

AbstractMetagenomic approaches enable an open exploration of microbial communities without requiring a priori knowledge of a sample’s composition by shotgun sequencing the total RNA or DNA of the sample. Such an approach is valuable for exploratory diagnostics of novel pathogens in clinical practice. Yet, one may also identify surprising off-target findings. Here we report a mostly complete transcriptome from a drain fly (likely Psychoda alternata) as well as a novel Rhabdovirus-like virus recovered from two independent contaminations of RNA sequencing libraries from clinical samples of cerebral spinal fluid (CSF) and serum, out of a total of 724 libraries sequenced at the same laboratory during a 2-year time span. This drain fly genome shows a considerable divergence from previously sequenced insects, which may obscure common clinical metagenomic analyses not expecting such contaminations. The classification of these contaminant sequences allowed us to identify infected drain flies as the likely origin of the novel Rhabdovirus-like sequence, which could have been erroneously linked to human pathology, had they been ignored.
Risk assessment of Ebola virus disease spreading in Uganda using a multilayer temporal network
Authors: Riad Mahbubul H , Sekamatte Musa , Ocom Felix , Makumbi Issa , Scoglio Caterina M 
Published: May 2019

ABSTRACTNetwork-based modelling of infectious diseases apply compartmental models on a contact network, which makes the epidemic process crucially dependent on the network structure. For highly contagious diseases such as Ebola virus disease (EVD), the inter-personal contact plays the most vital role in the human to human transmission. Therefore, for accurate representation of the EVD spreading, the contact network needs to resemble the reality. Prior research work has mainly focused on static networks (only permanent contacts) or activity driven networks (only temporal contacts) for Ebola spreading. A comprehensive network for EVD spreading should include both these network structures, as there are always some permanent contacts together with temporal contacts. Therefore, we propose a multilayer temporal network for Uganda, which is at risk of Ebola outbreak from the neighboring Democratic Republic of Congo (DRC) epidemic. The network has a permanent layer representing permanent contacts among individuals within family level, and a data driven temporal network for human movements motivated by cattle trade, fish trade, or general communications. We propose a Gillespie algorithm with the susceptible-infected-recovered (SIR) compartmental model to simulate the evolution of the EVD spreading as well as to evaluate the risk throughout our network. As an example, we applied our method to a multilayer network consisting of 23 districts along different movement routes in Uganda starting from bordering districts of DRC to Kampala. Simulation results shows that some regions are at higher risk of infection, suggesting some focal points for Ebola preparedness and providing direction to inform interventions in the field. Simulation results also shows that decreasing physical contacts as well as increasing preventive measures result in a reduction of chances to develop an outbreak. Overall, the main contribution of this paper lies in the novel method for risk assessment, the accuracy of which can be increased by increasing the amount and the accuracy of the data used to build the network and the model.
APEC: an accesson-based method for single-cell chromatin accessibility analysis
Authors: Li Bin , Li Young , Li Kun , Zhu Lianbang , Yu Qiaoni , Cai Pengfei , Fang Jingwen , Zhang Wen , Du Pengcheng , Jiang Chen , Qu Kun 
Published: May 2019

ABSTRACTThe development of sequencing technologies has promoted the survey of genome-wide chromatin accessibility at single-cell resolution; however, comprehensive analysis of single-cell epigenomic profiles remains a challenge. Here, we introduce an accessibility pattern-based epigenomic clustering (APEC) method, which classifies each individual cell by groups of accessible regions with synergistic signal patterns termed “accessons”. By integrating with other analytical tools, this python-based APEC package greatly improves the accuracy of unsupervised single-cell clustering for many different public data sets. APEC also predicts gene expressions, identifies significant differential enriched motifs, discovers super enhancers, and projects pseudotime trajectories. Furthermore, we adopted a fluorescent tagmentation-based single-cell ATAC-seq technique (ftATAC-seq) to investigated the per cell regulome dynamics of mouse thymocytes. Associated with ftATAC-seq, APEC revealed a detailed epigenomic heterogeneity of thymocytes, characterized the developmental trajectory and predicted the regulators that control the stages of maturation process. Overall, this work illustrates a powerful approach to study single-cell epigenomic heterogeneity and regulome dynamics.
Interruption of Continuous Opioid Exposure Exacerbates Drug-Evoked Adaptations in the Mesolimbic Dopamine System
Authors: Lefevre Emilia M. , Pisansky Marc T. , Toddes Carlee , Baruffaldi Federico , Pravetoni Marco , Tian Lin , Kono Thomas J. Y. , Rothwell Patrick E. 
Published: May 2019

ABSTRACTDrug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may therefore represent a strategy to minimize iatrogenic effects on brain reward circuits.
The Effect of Aging, Parkinson’s Disease, and Exogenous Dopamine on the Neural Response Associated with Auditory Regularity Processing
Authors: Jaja Abdullah Al , Grahn Jessica A. , Herrmann Björn , MacDonald Penny A. 
Published: May 2019

AbstractProcessing regular patterns in auditory scenes is important for navigating complex environments. Electroencephalography (EEG) studies find enhancement of sustained brain activity, correlating with the emergence of a regular pattern in sounds. How aging, aging-related diseases such as Parkinson’s disease (PD), and treatment of PD affect this fundamental function remain unknown. We addressed this knowledge gap. Healthy younger and older adults, and PD patients listened to sounds that contained or were devoid of regular patterns. Healthy older adults and PD patients were tested twice—on and off dopaminergic medication in counterbalanced order. Regularity-evoked, sustained EEG activity was reduced in older, compared to younger adults. PD patients and older controls had comparable attenuation of the sustained response. Dopaminergic therapy further weakened the sustained response in both groups. These findings suggest that fundamental regularity processing is impacted by aging-related neural changes but not those underlying PD. The finding that dopaminergic therapy attenuates rather than improves the sustained response coheres with the dopamine overdose response and implicates brain regions receiving dopamine from the ventral tegmental area in regularity processing.
Circulating bacterial DNA as a tool towards non-invasive biomarkers for colorectal cancer and adenoma
Authors: Xiao Qian , Lu Wei , Kong Xiangxing , Shao Yang W. , Hu Yeting , Wang Ao , Bao Hua , Liu Kaihua , Wang Xiaonan , Wu Xue , Zheng Shu , Yuan Ying , Ding Kefeng 
Published: May 2019

AbstractObjectiveThe gut microbiota is closely associated with colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating microbial DNA in colorectal neoplasia patients remained unexplored. This study aimed to characterize microbial DNA in plasma samples and build a machine learning model for colorectal neoplasia early detection.DesignWe performed whole genome sequencing of plasma samples from 25 colorectal cancer (CRC) patients, 10 colorectal adenoma (CRA) patients and 22 healthy controls (HC). Microbial DNA was obtained by removing the host genome and relative abundance was measured by mapping reads into microbial genomes. Significant biomarker species were identified in the discovery cohort and built into a random forest model, which was tested in the validation cohort.ResultsIn the discovery cohort, there were 127 significant species between CRC patients and HC. Based on the random forest model, 28 species were selected from the discovery cohort (AUC=0.944) and yielded an AUC of 1 in the validation cohort. Interestingly, relative abundance of most biomarker species in CRA patients were between CRC patients and HC with a trend towards CRC patients. Furthermore, pathway enrichment analysis also showed similar pattern where CRA patients had intermediate relative abundance of significant pathways compared to CRC patients and HC. Finally, species network analysis revealed that CRC and HC displayed distinct patterns of species association.ConclusionsWe demonstrated characteristic alteration of circulating bacterial DNA in colorectal neoplasia patients. The predictive model accurately distinguished CRC and CRA from HC, suggesting the utility of circulating bacterial biomarkers as a non-invasive tool for colorectal neoplasia screening and early diagnosis.