bluuebunny/crossref_metadata_2025_split huggingface dataset:
scVAE: variational auto-encoders for single-cell gene expression data
Authors: Grønbech Christopher Heje , Vording Maximillian Fornitz , Timshel Pascal N , Sønderby Casper Kaae , Pers Tune H , Winther Ole 
Published: May 2020

Abstract

Motivation
Models for analysing and making relevant biological inferences from massive amounts of complex single-cell transcriptomic data typically require several individual data-processing steps, each with their own set of hyperparameter choices. With deep generative models one can work directly with count data, make likelihood-based model comparison, learn a latent representation of the cells and capture more of the variability in different cell populations.

Results
We propose a novel method based on variational auto-encoders (VAEs) for analysis of single-cell RNA sequencing (scRNA-seq) data. It avoids data preprocessing by using raw count data as input and can robustly estimate the expected gene expression levels and a latent representation for each cell. We tested several count likelihood functions and a variant of the VAE that has a priori clustering in the latent space. We show for several scRNA-seq datasets that our method outperforms recently proposed scRNA-seq methods in clustering cells and that the resulting clusters reflect cell types.

Availability and implementation
Our method, called scVAE, is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://github.com/scvae/scvae.

Supplementary information
Supplementary data are available at Bioinformatics online.
Palantir: a springboard for the analysis of secondary metabolite gene clusters in large-scale genome mining projects
Authors: Meunier Loïc , Tocquin Pierre , Cornet Luc , Sirjacobs Damien , Leclère Valérie , Pupin Maude , Jacques Philippe , Baurain Denis 
Published: May 2020

Abstract

Summary
To support small and large-scale genome mining projects, we present Post-processing Analysis tooLbox for ANTIsmash Reports (Palantir), a dedicated software suite for handling and refining secondary metabolite biosynthetic gene cluster (BGC) data annotated with the popular antiSMASH pipeline. Palantir provides new functionalities building on NRPS/PKS predictions from antiSMASH, such as improved BGC annotation, module delineation and easy access to sub-sequences at different levels (cluster, gene, module and domain). Moreover, it can parse user-provided antiSMASH reports and reformat them for direct use or storage in a relational database.

Availability and implementation
Palantir is released both as a Perl API available on CPAN (https://metacpan.org/release/Bio-Palantir) and as a web application (http://palantir.uliege.be). As a practical use case, the web interface also features a database built from the mining of 1616 cyanobacterial genomes, of which 1488 were predicted to encode at least one BGC.

Supplementary information
Supplementary data are available at Bioinformatics online.
Pathogenic SREK1 decrease in Huntington’s disease lowers TAF1 mimicking X-linked dystonia parkinsonism
Authors: Hernández Ivó H , Cabrera Jorge R , Santos-Galindo María , Sánchez-Martín Manuel , Domínguez Verónica , García-Escudero Ramón , Pérez-Álvarez María J , Pintado Belén , Lucas José J 
Published: May 2020

Abstract
Huntington’s disease and X-linked dystonia parkinsonism are two monogenic basal ganglia model diseases. Huntington’s disease is caused by a polyglutamine-encoding CAG repeat expansion in the Huntingtin (HTT) gene leading to several toxic interactions of both the expanded CAG-containing mRNA and the polyglutamine-containing protein, while X-linked dystonia parkinsonism is caused by a retrotransposon insertion in the TAF1 gene, which decreases expression of this core scaffold of the basal transcription factor complex TFIID. SRSF6 is an RNA-binding protein of the serine and arginine-rich (SR) protein family that interacts with expanded CAG mRNA and is sequestered into the characteristic polyglutamine-containing inclusion bodies of Huntington’s disease brains. Here we report decreased levels of the SRSF6 interactor and regulator SREK1—another SR protein involved in RNA processing—which includes TAF1 as one of its targets. This led us to hypothesize that Huntington’s disease and X-linked dystonia parkinsonism pathogeneses converge in TAF1 alteration. We show that diminishing SRSF6 through RNA interference in human neuroblastoma cells leads to a decrease in SREK1 levels, which, in turn, suffices to cause diminished TAF1 levels. We also observed decreased SREK1 and TAF1 levels in striatum of Huntington’s disease patients and transgenic model mice. We then generated mice with neuronal transgenic expression of SREK1 (TgSREK1 mice) that, interestingly, showed transcriptomic alterations complementary to those in Huntington’s disease mice. Most importantly, by combining Huntington’s disease and TgSREK1 mice we verify that SREK1 overexpression corrects TAF1 deficiency and attenuates striatal atrophy and motor phenotype of Huntington’s disease mice. Our results therefore demonstrate that altered RNA processing upon SREK1 dysregulation plays a key role in Huntington’s disease pathogenesis and pinpoint TAF1 as a likely general determinant of selective vulnerability of the striatum in multiple neurological disorders.
M1 muscarinic acetylcholine receptor dysfunction in moderate Alzheimer’s disease pathology
Authors: Yi Jee Hyun , Whitcomb Daniel J , Park Se Jin , Martinez-Perez Celia , Barbati Saviana A , Mitchell Scott J , Cho Kwangwook 
Published: May 2020

AbstractAggregation of amyloid beta and loss of cholinergic innervation in the brain are predominant components of Alzheimer’s disease pathology and likely underlie cognitive impairment. Acetylcholinesterase inhibitors are one of the few treatment options for Alzheimer’s disease, where levels of available acetylcholine are enhanced to counteract the cholinergic loss. However, these inhibitors show limited clinical efficacy. One potential explanation for this is a concomitant dysregulation of cholinergic receptors themselves as a consequence of the amyloid beta pathology. We tested this hypothesis by examining levels of M1 muscarinic acetylcholine receptors in the temporal cortex from seven Alzheimer’s disease and seven non-disease age-matched control brain tissue samples (control: 85 ± 2.63 years old, moderate Alzheimer’s disease: 84 ± 2.32 years old, P-value = 0.721; eight female and six male patients). The samples were categorized into two groups: ‘control’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘No Alzheimer’s disease’, and Braak staging pathology of I–II) and ‘moderate Alzheimer’s disease’ (Consortium to Establish a Registry for Alzheimer’s Disease diagnosis of ‘possible/probable Alzheimer’s disease’, and Braak staging pathology of IV). We find that in comparison to age-matched controls, there is a loss of M1 muscarinic acetylcholine receptors in moderate Alzheimer’s disease tissue (control: 2.17 ± 0.27 arbitrary units, n = 7, Mod-AD: 0.83 ± 0.16 arbitrary units, n = 7, two-tailed t-test, t = 4.248, P = 0.00113). Using a functional rat cortical brain slice model, we find that postsynaptic muscarinic acetylcholine receptor function is dysregulated by aberrant amyloid beta-mediated activation of metabotropic glutamate receptor 5. Crucially, blocking metabotropic glutamate receptor 5 restores muscarinic acetylcholine receptor function and object recognition memory in 5XFAD transgenic mice. This indicates that the amyloid beta-mediated activation of metabotropic glutamate receptor 5 negatively regulates muscarinic acetylcholine receptor and illustrates the importance of muscarinic acetylcholine receptors as a potential disease-modifying target in the moderate pathological stages of Alzheimer’s disease.
Degeneracy and Redundancy in Active Inference
Authors: Sajid Noor , Parr Thomas , Hope Thomas M , Price Cathy J , Friston Karl J 
Published: May 2020

AbstractThe notions of degeneracy and redundancy are important constructs in many areas, ranging from genomics through to network science. Degeneracy finds a powerful role in neuroscience, explaining key aspects of distributed processing and structure–function relationships in the brain. For example, degeneracy accounts for the superadditive effect of lesions on functional deficits in terms of a “many-to-one” structure–function mapping. In this paper, we offer a principled account of degeneracy and redundancy, when function is operationalized in terms of active inference, namely, a formulation of perception and action as belief updating under generative models of the world. In brief, “degeneracy” is quantified by the “entropy” of posterior beliefs about the causes of sensations, while “redundancy” is the “complexity” cost incurred by forming those beliefs. From this perspective, degeneracy and redundancy are complementary: Active inference tries to minimize redundancy while maintaining degeneracy. This formulation is substantiated using statistical and mathematical notions of degenerate mappings and statistical efficiency. We then illustrate changes in degeneracy and redundancy during the learning of a word repetition task. Finally, we characterize the effects of lesions—to intrinsic and extrinsic connections—using in silico disconnections. These numerical analyses highlight the fundamental difference between degeneracy and redundancy—and how they score distinct imperatives for perceptual inference and structure learning that are relevant to synthetic and biological intelligence.
An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019
Authors: Bordoni Veronica , Sacchi Alessandra , Cimini Eleonora , Notari Stefania , Grassi Germana , Tartaglia Eleonora , Casetti Rita , Giancola Maria Letizia , Bevilacqua Nazario , Maeurer Markus , Zumla Alimuddin , Locatelli Franco , De Benedetti Fabrizio , Palmieri Fabrizio , Marchioni Luisa , Capobianchi Maria R , D’Offizi Gianpiero , Petrosillo Nicola , Antinori Andrea , Nicastri Emanuele , Ippolito Giuseppe , Agrati Chiara 
Published: May 2020

AbstractIncreased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.
Case Fatality Risk of the First Pandemic Wave of Coronavirus Disease 2019 (COVID-19) in China
Authors: Deng Xiaowei , Yang Juan , Wang Wei , Wang Xiling , Zhou Jiaxin , Chen Zhiyuan , Li Jing , Chen Yinzi , Yan Han , Zhang Juanjuan , Zhang Yongli , Wang Yan , Qiu Qi , Gong Hui , Wei Xianglin , Wang Lili , Sun Kaiyuan , Wu Peng , Ajelli Marco , Cowling Benjamin J , Viboud Cecile , Yu Hongjie 
Published: May 2020

Abstract

Background
To assess the case fatality risk (CFR) of COVID-19 in mainland China, stratified by region and clinical category, and estimate key time-to-event intervals.

Methods
We collected individual information and aggregated data on COVID-19 cases from publicly available official sources from 29 December 2019 to 17 April 2020. We accounted for right-censoring to estimate the CFR and explored the risk factors for mortality. We fitted Weibull, gamma, and log-normal distributions to time-to-event data using maximum-likelihood estimation.

Results
We analyzed 82 719 laboratory-confirmed cases reported in mainland China, including 4632 deaths and 77 029 discharges. The estimated CFR was 5.65% (95% confidence interval [CI], 5.50–5.81%) nationally, with the highest estimate in Wuhan (7.71%) and lowest in provinces outside Hubei (0.86%). The fatality risk among critical patients was 3.6 times that of all patients and 0.8–10.3-fold higher than that of mild-to-severe patients. Older age (odds ratio [OR], 1.14 per year; 95% CI, 1.11–1.16) and being male (OR, 1.83; 95% CI, 1.10–3.04) were risk factors for mortality. The times from symptom onset to first healthcare consultation, to laboratory confirmation, and to hospitalization were consistently longer for deceased patients than for those who recovered.

Conclusions
Our CFR estimates based on laboratory-confirmed cases ascertained in mainland China suggest that COVID-19 is more severe than the 2009 H1N1 influenza pandemic in hospitalized patients, particularly in Wuhan. Our study provides a comprehensive picture of the severity of the first wave of the pandemic in China. Our estimates can help inform models and the global response to COVID-19.
The riskscapes of re/insurance
Authors: Taylor Zac J , Weinkle Jessica L 
Published: May 2020

Abstract
Property catastrophe re/insurance plays a crucial yet underexplored role in the governance of disparate geographies of risk. This article extends the concept of the riskscape to the study of re/insurance in two ways. We first develop a four-part framework for understanding re/insurance markets as a series of conjoined riskscapes. Second, we apply this approach to a case study analysis of Florida’s hurricane wind re/insurance market and its restructuring after the destructive 2004/2005 hurricane seasons. Using this riskscapes framework and the Florida case, we advance a critical geographical understanding of re/insurance markets as conjunctural and open-ended political economic projects.
Clinical Performance of Two SARS-CoV-2 Serologic Assays
Authors: Tang Mei San , Hock Karl G , Logsdon Nicole M , Hayes Jennifer E , Gronowski Ann M , Anderson Neil W , Farnsworth Christopher W 
Published: May 2020

Abstract

Background
The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a rapid proliferation of serologic assays. However, little is known about their clinical performance. Here, we compared two commercial SARS-CoV-2 IgG assays.

Methods
103 specimens from 48 patients with PCR-confirmed SARS-CoV-2 infections and 153 control specimens were analyzed using SARS-CoV-2 serologic assays by Abbott and EUROIMMUN (EI). Duration from symptom onset was determined by medical record review. Diagnostic sensitivity, specificity, and concordance were calculated.

Results
The Abbott SARS-CoV-2 assay had a diagnostic specificity of 99.4% (95% CI; 96.41–99.98%), and sensitivity of 0.0% (95% CI; 0.00–26.47%) at &lt;3 days post symptom onset, 30.0% (95% CI; 11.89–54.28) at 3–7d, 47.8% (95% CI; 26.82–69.41) at 8–13d and 93.8% (95% CI; 82.80–98.69) at ≥14d. Diagnostic specificity on the EI assay was 94.8% (95% CI; 89.96–97.72) if borderline results were considered positive and 96.7% (95% CI; 92.54–98.93) if borderline results were considered negative. The diagnostic sensitivity was 0.0% (95% CI; 0.00–26.47%) at &lt;3d, 25.0% (95% CI; 8.66–49.10) at 3–7d, 56.5% (95% CI; 34.49–76.81) at 3–7d and 85.4% (95% CI; 72.24–93.93) at ≥14d if borderline results were considered positive. The qualitative concordance between the assays was 0.83 (95% CI; 0.75–0.91).

Conclusion
The Abbott SARS-CoV-2 assay had fewer false positive and false negative results than the EI assay. However, diagnostic sensitivity was poor in both assays during the first 14 days of symptoms.
QoS Enhancement In VoD Systems: Load Management And Replication Policy Optimization Perspectives
Authors: Alaya Bechir , Khan Rehanullah 
Published: May 2020

AbstractThe amount of online video content is exponentially increasing, which spurs its access demands. Providing optimal quality of service (QoS) for this ever-increasing video data is a challenging task due to the number of QoS constraints. The system resources, the distributed system platform and the transport protocol thus all need to collaborate to guarantee an acceptable level of QoS for the optimal video streaming process. In this paper, we present a comprehensive survey on QoS management for the video-on-demand systems. First, we focus on load management and replication algorithms in content delivery networks and peer-to-peer (P2P) networks for their shortcomings. We also address the problem of admission control and resource allocation with the objectives of congestion avoidance and frame-loss reduction. Besides, we introduce and discuss various replication schemes. For both the client–server architecture and P2P networks, we highlight the need for a specific storage management policy to preserve system reliability and content availability. We also focus on content distribution and streaming protocols scaling. We deduce that content availability is linked to the characteristics and the performance of the streaming protocols. Finally, we create a comparison table that presents the different contributions of the discussed approaches as well as their limitations. We believe that such a comprehensive survey provides useful insights and contributes to the related domains.
Safety and Optimal Timing of BCG Vaccination in Infants Born to Mothers Receiving Anti-TNF Therapy for Inflammatory Bowel Disease
Authors: Park Sang Hyoung , Kim Hyo Jong , Lee Chang Kyun , Song Eun Mi , Kang Sang-Bum , Jang Byung Ik , Kim Eun Soo , Kim Kyeong Ok , Lee Yoo Jin , Kim Eun Young , Jung Yun Jin , Park Soo-Kyung , Park Dong Il , Ye Byong Duk , Jung Sung-Ae , Yang Suk-Kyun 
Published: May 2020

Abstract

Backgrounds and Aims
We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease.

Methods
Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30.

Results
After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death.

Conclusions
BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.
VALIDation of the IBD-Disk Instrument for Assessing Disability in Inflammatory Bowel Diseases in a French Cohort: The VALIDate Study
Authors: Le Berre Catherine , Flamant Mathurin , Bouguen Guillaume , Siproudhis Laurent , Dewitte Marie , Dib Nina , Cesbron-Metivier Elodie , Goronflot Thomas , Hanf Matthieu , Gourraud Pierre-Antoine , Kerdreux Elise , Poinas Alexandra , Bourreille Arnaud , Trang-Poisson Caroline 
Published: May 2020

Abstract

Background and Aims
Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time.

Methods
From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3–12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits.

Results
A total of 447 patients [71% Crohn’s disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p &lt;0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach’s α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time.

Conclusions
This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC.
Applications of Beauveria bassiana (Hypocreales: Cordycipitaceae) to Control Populations of Spotted Lanternfly (Hemiptera: Fulgoridae), in Semi-Natural Landscapes and on Grapevines
Authors: Clifton Eric H , Hajek Ann E , Jenkins Nina E , Roush Richard T , Rost John P , Biddinger David J 
Published: May 2020

Abstract
Spotted lanternfly, Lycorma delicatula (White), is an invasive Asian insect that was initially found in Berks County, Pennsylvania, in 2014. As of early 2020, this pest had been found in five more eastern states and it is expected to continue to expand its geographical range. Lycorma delicatula is highly polyphagous but seems to prefer tree-of-heaven, Ailanthus altissima. However, grape growers in Pennsylvania have reported significant damage and loss of vines caused by L. delicatula adults. In fall 2018, two fungal entomopathogens (Beauveria bassiana and Batkoa major) drove localized collapses in L. delicatula populations in Berks County, Pennsylvania. In 2019, we tested applications of a commercialized mycoinsecticide based on B. bassiana strain GHA on L. delicatula populations in a public park in southeastern Pennsylvania. A single application of B. bassiana reduced fourth instar nymphs by 48% after 14 d. Applications of B. bassiana to L. delicatula adults in the same park resulted in 43% mortality after 14 d. Beauveria bassiana spores remained viable on foliage for 5–7 d after spraying. We also conducted semi-field bioassays with B. bassiana GHA (formulated as BoteGHA and Aprehend) and another mycoinsecticide containing Isaria fumosorosea Apopka Strain 97 against L. delicatula adults feeding on potted grapes. All the mycoinsecticides killed ≥90% of adults after 9 d using direct applications. Aprehend killed 99% of adults after 9 d with exposure to residues on sprayed grapes. These data show that fungal entomopathogens can help to suppress populations of L. delicatula in agroecosystems and natural areas.