bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of self-reported symptoms and testing for COVID in Canada using a nationally representative survey
Authors: Wu Daphne C , Jha Prabhat , Lam Teresa , Brown Patrick , Gelband Hellen , Nagelkerke Nico , Birnboim H. Chaim , Reid Angus 
Published: June 2020

AbstractIn April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about their COVID experience in March, early in the epidemic. We examined determinants of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys—including high-risk older populations—of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future.
Perceptual gating of a brainstem reflex facilitates speech understanding in human listeners
Authors: Hernandez-Perez Heivet , Mikiel-Hunter Jason , McAlpine David , Dhar Sumitrajit , Boothalingam Sriram , Monaghan Jessica J.M. , McMahon Catherine M. 
Published: June 2020

AbstractNavigating “cocktail party” situations by enhancing foreground sounds over irrelevant background information is typically considered from a cortico-centric perspective. However, subcortical circuits, such as the medial olivocochlear (MOC) reflex that modulates inner ear activity itself, have ample opportunity to extract salient features from the auditory scene prior to any cortical processing. To understand the contribution of auditory subcortical nuclei and the cochlea, physiological recordings were made along the auditory pathway while listeners differentiated non(sense)-words and words. Both naturally-spoken and intrinsically-noisy, vocoded speech — filtering that mimics processing by a cochlear implant—significantly activated the MOC reflex, whereas listening to speech-in-background noise revealed instead engagement of midbrain and cortical resources. An auditory periphery model reproduced these speech degradation-specific effects, providing a rationale for goal-directed gating of the MOC reflex to enhance representation of speech features in the auditory nerve. Our data reveals the co-existence of two strategies in the auditory system that may facilitate speech understanding in situations where the speech signal is either intrinsically degraded or masked by extrinsic auditory information.
Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft
Authors: Klein Joshua A. , Zaia Joseph 
Published: June 2020

AbstractWidely-available LC-MS instruments and methods allow users to acquire glycoproteomics data. Complex glycans, however, add a dimension of complexity to the data analysis workflow. In a sense, complex glycans are post-translationally modified post-translational modifications, reflecting a series of biosynthetic reactions in the secretory pathway that are spatially and temporally regulated. One problem is that complex glycan is micro-heterogeneous, multiplying the complexity of the proteome. Another is that glycopeptide glycans undergo dissociation during tandem MS that must be considered for tandem MS interpretation algorithms and quantitative tools. Fortunately, there are a number of algorithmic tools available for analysis of glycoproteomics LC-MS data. We summarize the principles for glycopeptide data analysis and show use of our GlycReSoft tool to analyze SARS-CoV-2 spike protein site-specific glycosylation.
Ribosomal Protein Large subunit RPL6 modulates salt tolerance in rice
Authors: Moin Mazahar , Saha Anusree , Bakshi Achala , Madhav M. S. , Kirti P B 
Published: June 2020

AbstractThe extra-ribosomal functions of ribosomal proteins RPL6 and RPL23a in stress-responsiveness have emanated from our previous studies on activation tagged mutants of rice screened for water-use efficiency (Moinet al., 2016a). In the present study, we functionally validated theRPL6, a Ribosomal Protein Large subunit member for salt stress tolerance in rice. The overexpression ofRPL6resulted in tolerance to moderate (150 mM) to high (200 mM) levels of salt (NaCl) in rice. The transgenic rice plants expressingRPL6constitutively showed better phenotypic and physiological responses with high quantum efficiency, accumulation of more chlorophyll and proline contents, and an overall increase in seed yield compared with the wild type in salt stress treatments. An iTRAQ-based comparative proteomic analysis revealed the high expression of about 333 proteins among the 4,378 DEPs in a selected overexpression line ofRPL6treated with 200 mM of NaCl. The functional analysis showed that these highly expressed proteins (HEPs) are involved in photosynthesis, ribosome and chloroplast biogenesis, ion transportation, transcription and translation regulation, phytohormone and secondary metabolite signal transduction. Anin siliconetwork analysis of HEPs predicted that RPL6 binds with translation-related proteins and helicases, which coordinately affects the activities of a comprehensive signaling network, thereby inducing tolerance and promoting growth and yield in response to salt stress. Our overall findings identified a novel candidate, RPL6 whose characterization contributed to the existing knowledge on the complexity of salt tolerance mechanism in plants.
Neurofunctional basis underlying audiovisual integration of print and speech sound in Chinese children
Authors: Xia Zhichao , Yang Ting , Cui Xin , Hoeft Fumiko , Liu Hong , Zhang Xianglin , Shu Hua , Liu Xiangping 
Published: June 2020

AbstractEffortless print-sound integration is essential to reading development, and the superior temporal cortex (STC) is the most critical brain region. However, to date, the conclusion is almost restricted to alphabetic orthographies. To examine the neural basis in non-alphabetic languages and its relationship with reading abilities, we conducted a functional magnetic resonance imaging study in typically developing Chinese children. Two neuroimaging-based indicators of audiovisual processing—additive enhancement (higher activation in the congruent than the average activation of unimodal conditions) and neural integration (different activations between the congruent versus incongruent conditions)—were used to investigate character-sounds (opaque) and pinyin-sounds (transparent) processing. We found additive enhancement in bilateral STCs processing both character and pinyin stimulations. Moreover, the neural integrations in the left STC for the two scripts were strongly correlated. In terms of differentiation, first, areas beyond the STCs showed additive enhancement in processing pinyin-sounds. Second, while the bilateral STCs, left inferior/middle frontal and parietal regions manifested a striking neural integration (incongruent > congruent) for character-sounds, no significant clusters were revealed for pinyin-sounds. Finally, the neural integration in the left middle frontal gyrus for characters was specifically associated with silent reading comprehension proficiency, indicating automatic semantic processing during implicit character-sound integration. In contrast, the neural integration in the left STC for pinyin was specifically associated with oral reading fluency that relies on grapho-phonological mapping. To summarize, this study revealed both script-universal and script-specific neurofunctional substrates of print-sound integration as well as their processing- and region-dependent associations with reading abilities in typical Chinese children.HighlightsThe bilateral superior temporal cortices display additive enhancement in processing print-sound information regardless of orthographies.The location, direction, and strength of the neural audiovisual integration are modulated by orthographic transparency.The neural integration in the left middle frontal gyrus in processing character-sounds is correlated to reading comprehension.The neural integration in the left superior temporal gyrus for pinyin is correlated with oral reading fluency.The neural integrations of character-sounds and pinyin-sounds show spatial overlap and inter-subject correlation in the left superior temporal cortex.
Bacterial influence on the maintenance of symbiotic yeast throughDrosophilametamorphosis
Authors: Guilhot Robin , Rombaut Antoine , Xuéreb Anne , Howell Kate , Fellous Simon 
Published: June 2020

AbstractInteractions between microbial symbionts of metazoan hosts are emerging as key features of symbiotic systems. Little is known about the role of such interactions on the maintenance of symbiosis through host’s life cycle. We studied the influence of symbiotic bacteria on the maintenance of symbiotic yeast through metamorphosis of the flyDrosophila melanogaster. To this end we mimicked the development of larvae in natural fruit. In absence of bacteria yeast was never found in young adults. However, yeast could maintain through metamorphosis when larvae were inoculated with symbiotic bacteria isolated fromD. melanogasterfaeces. Furthermore, an Enterobacteriaceae favoured yeast transstadial maintenance. Because yeast is a critical symbiont ofD. melanogasterflies, bacterial influence on host-yeast association may have consequences for the evolution of insect-yeast-bacteria tripartite symbiosis and their cooperation.Summary statementBacterial symbionts ofDrosophilainfluence yeast maintenance through fly metamorphosis, a novel observation that may have consequences for the evolution of insect-yeast-bacteria interactions.
Phenome-wide association study of a comprehensive health check-up database in a Korea population: Clinical application & trans-ethnic comparison
Authors: Choe Eun Kyung , Shivakumar Manu , Verma Anurag , Verma Shefali Setia , Choi Seung Ho , Kim Joo Sung , Kim Dokyoon 
Published: June 2020

AbstractsBackgroundThe expanding use of the phenome-wide association study (PheWAS) faces challenges in the context of using International Classification of Diseases billing codes for phenotype definition, imbalanced study population ethnicity, and constrained application of the results to clinical practice or research.MethodsWe performed a PheWAS utilizing deep phenotypes corroborated by comprehensive health check-ups in a Korean population, along with trans-ethnic comparisons through the UK Biobank and Biobank Japan Project. Network analysis, visualization of cross-phenotype mapping, and causal inference mapping with Mendelian randomization were conducted in order to make robust, clinically applicable interpretations.ResultsOf the 136 phenotypes extracted from the health check-up database, the PheWAS associated 65 phenotypes with 14,101 significant variants (P< 4.92×10−10). In the association study for body mass index, our population showed 583 exclusive loci relative to the Japanese population and 669 exclusive loci relative to the European population. In the meta-analysis with Korean and Japanese populations, 72.5% of phenotypes had uniquely significant variants. Tumor markers and hematologic phenotypes had a high degree of phenotype-phenotype pairs. By Mendelian randomization, one skeletal muscle mass phenotype was causal and two were outcomes. Among phenotype pairs from the genotype-driven cross-phenotype associations, 71.65% also demonstrated penetrance in correlation analysis using a clinical database.ConclusionsThis comprehensive analysis of PheWAS results based on a health check-up database will provide researchers and clinicians with a panoramic overview of the networks among multiple phenotypes and genetic variants, laying groundwork for the practical application of precision medicine.
A consensus-based and readable extension ofLinearCode forReactionRules (LiCoRR)
Authors: Kellman Benjamin P. , Zhang Yujie , Logomasini Emma , Meinhardt Eric , Chiang Austin W. T. , Sorrentino James T. , Liang Chenguang , Bao Bokan , Zhou Yusen , Akase Sachiko , Sogabe Isami , Kouka Thukaa , Wilson Iain B.H. , Campbell Matthew P. , Neelamegham Sriram , Krambeck Frederick J. , Aoki-Kinoshita Kiyoko F. , Lewis Nathan E. 
Published: June 2020

AbstractSystems glycobiology aims to provide models and analysis tools that account for the biosynthesis, regulation, and interactions with glycoconjugates. To facilitate these methods, there is a need for a clear glycan representation accessible to both computers and humans. Linear Code, a linearized and readily parsable glycan structure representation, is such a language. For this reason, Linear Code was adapted to represent reaction rules, but the syntax has drifted from its original description to accommodate new and originally unforeseen challenges. Here, we delineate the consensuses and inconsistencies that have arisen through this adaptation. We recommend options for a consensus-based extension of Linear Code that can be used for reaction rule specification going forward. Through this extension and specification of Linear Code to reaction rules, we aim to minimize inconsistent symbology thereby making glycan database queries easier. With a clear guide for generating reaction rule descriptions, glycan synthesis models will be more interoperable and reproducible thereby moving glycoinformatics closer to compliance with FAIR standards. Reaction rule-extended Linear Code is an unambiguous representation for describing glycosylation reactions in both literature and code.
Robust and scalable manifold learning via landmark diffusion for long-term medical signal processing
Authors: Shen Chao , Lin Yu-Ting , Wu Hau-Tieng 
Published: June 2020

AbstractMotivated by analyzing long-term physiological time series, we design a robust and scalable spectral embedding algorithm, coined the algorithm RObust and Scalable Embedding via LANdmark Diffusion (ROSE-LAND). The key is designing a diffusion process on the dataset, where the diffusion is forced to interchange on a small subset called thelandmark set. In addition to demonstrating its application to spectral clustering and image segmentation, the algorithm is applied to study the long-term arterial blood pressure waveform dynamics during a liver transplant operation lasting for 12 hours long.
Mannose-binding lectin gene polymorphisms in the East Siberia and Russian Arctic populations
Authors: Tereshchenko Sergey Yu , Smolnikova Marina V , Freidin Maxim B 
Published: June 2020

ABSTRACTBackgroundMannose-binding lectin (MBL) encoded byMBL2gene is a protein with the ability to form carbohydrate complexes with microbial wall promoting their subsequent elimination. Genetically determined levels of MBL can modify the risk and clinical characteristics of many infectious diseases. The frequency ofMBL2genotypes exhibits significant population differences. The data on the distribution ofMBL2genotypes among the aborigines of the Russian Arctic territories have not yet been published.MethodsA total of 880 specimens of dried blood spots of the newborns were genotyped. The newborns represented four populations: Nenets, Dolgan-Nganasans, Mixed aboriginal population, and Russians (Caucasians, Krasnoyarsk). Six polymorphisms of theMBL2gene were studied: rs11003125, rs7096206, rs7095891, rs5030737, rs1800450, and rs1800451.ResultsThe frequency of the combined rare O allele (composed of the coding region variants rs5030737, rs1800450, and rs1800451) in the homozygous state was significantly higher in Russians: 10% vs 2% in Nenets and 1% in Dolgan-Nganosans (p<0.001 for Russians vs other populations). The frequency of the high-producing haplotype (HYPA) was 35.4% in the Russian newborns, in keeping with European populations (27-33%); 64% for Nenets and 56% for Dolgan-Nganasans, similar to the estimates obtained for Eskimos and North Amerinds (64-81%).ConclusionOur study results are in line with the hypothesis that human evolution has been moving in the direction of accumulation of the genotypes associated with low activity of the lectin complement activation pathway because of the prevalence of some intracellular infections such as tuberculosis, whereby low MBL activity may have a protective effect.
Direct detection of RNA modifications and structure using single molecule nanopore sequencing
Authors: Stephenson William , Razaghi Roham , Busan Steven , Weeks Kevin M. , Timp Winston , Smibert Peter 
Published: June 2020

ABSTRACTMany methods exist to detect RNA modifications by short-read sequencing, relying on either antibody enrichment of transcripts bearing modified bases or mutational profiling approaches which require conversion to cDNA. Endogenous modifications are present on several major classes of RNA including tRNA, rRNA and mRNA and can modulate diverse biological processes such as genetic recoding, mRNA export and RNA folding. In addition, exogenous modifications can be introduced to RNA molecules to reveal RNA structure and dynamics. Limitations on read length and library size inherent in short-read-based methods dissociate modifications from their native context, preventing single molecule analysis and modification phasing. Here we demonstrate direct RNA nanopore sequencing to detect endogenous and exogenous RNA modifications over long sequence distance at the single molecule level. We demonstrate comprehensive detection of endogenous modifications inE. coliandS. cerevisiaeribosomal RNA (rRNA) using current signal deviations. Notably 2’-O-methyl (Nm) modifications generated a discernible shift in current signal and event level dwell times. We show that dwell times are mediated by the RNA motor protein which sits atop the nanopore. Further, we characterize a recently described small adduct-generating 2’-O-acylation reagent, acetylimidazole (AcIm) for exogenously labeling flexible nucleotides in RNA. Finally, we demonstrate the utility of AcIm for single molecule RNA structural probing using nanopore sequencing.Graphical abstract
Detecting copy number alterations in RNA-Seq using SuperFreq
Authors: Flensburg Christoffer , Oshlack Alicia , Majewski Ian J. 
Published: June 2020

AbstractCalling copy number alterations (CNAs) from RNA-Seq is challenging, because differences in gene expression mean that read depth across genes varies by several orders of magnitude and there is a paucity of informative single nucleotide polymorphisms (SNPs). We previously developed SuperFreq to analyse exome data of tumours by combining variant calling and copy number estimation in an integrated pipeline. Here we have used the SuperFreq framework for the analysis of RNA sequencing (RNA-Seq) data, which allows for the detection of absolute and allele sensitive CNAs. SuperFreq uses an error-propagation framework to combine and maximise the information available in the read depth and B-allele frequencies of SNPs (BAFs) to make CNA calls on RNA-seq data. We used data from The Cancer Genome Atlas (TCGA) to evaluate the CNA called from RNA-Seq with those generated from SNP-arrays. When ploidy estimates were consistent, we found excellent agreement with CNAs called from DNA of over 98% of the genome for acute myeloid leukaemia (TCGA-AML, n=116) and 87% for colorectal cancer (TCGA-CRC, n=377), which has a much higher CNA burden. As expected, the sensitivity of CNA calling from RNA-Seq was dependent on gene density. Nonetheless, using RNA-Seq SuperFreq detected 78% of CNA calls covering 100 or more genes with a precision of 94%. Recall dropped markedly for focal events, but this also depended on the signal intensity. For example, in the CRC cohort SuperFreq identified 100% (7/7) of cases with high-level amplification of ERBB2, where the copy number was typically >20, but identified only 6% (1/17) of cases with moderate amplification of IGF2, typically 4 or 5 copies over a smaller region (median 5 flanking genes for IGF2, compared to 20 for ERBB2). We were able to reproduce the relationship between mutational load and CNA profile in CRC using RNA-Seq alone. SuperFreq offers an integrated platform for identification of CNAs and point mutations from RNA-seq in cancer transcriptomes.The software is implemented in R and is available through GitHub:https://github.com/ChristofferFlensburg/SuperFreq.
Delirium Incidence, Duration and Severity in Critically Ill Patients with COVID-19
Authors: Khan Sikandar H , Lindroth Heidi , Perkins Anthony J. , Jamil Yasser , Wang Sophia , Roberts Scott , Farber Mark , Rahman Omar , Gao Sujuan , Marcantonio Edward R. , Boustani Malaz , Machado Roberto , Khan Babar A. 
Published: June 2020

AbstractBackgroundDelirium incidence, duration and severity in patients admitted to the intensive care unit (ICU) due to COVID-19 is not known.MethodsWe conducted an observational study at two large urban academic Level 1 trauma centers. Consecutive patients admitted to the ICU with a positive SARS-CoV-2 nasopharyngeal swab polymerase chain reaction test from March 1st, 2020 to April 27, 2020 were included. Individuals younger than 18 years of age, without any documented delirium assessments (CAM-ICU), or without a discharge disposition were excluded. The primary outcomes were delirium rates and delirium duration and the secondary outcome was delirium severity. Outcomes were assessed for up to the first 14 days of ICU stay.ResultsOf 243 consecutive patients with confirmed COVID-19 admitted to the ICU, 144 met eligibility criteria and were included in the analysis. Delirium occurred in 73.6% (106/144) and delirium or coma occurred in 76.4% (110/144). Sixty-three percent of patients were positive for delirium on the first CAM-ICU assessment. The median duration of delirium and coma was 7 days (IQR: 3-10), and the median delirium duration was 5 days (IQR: 2-7). The median CAM-ICU-7 score was 6 (IQR: 4-7) representing severe delirium. Mechanical ventilation was associated with greater odds of developing delirium (OR: 42.1, 95%CI: 13.0-137.1). Mortality was 26.4% in patients with delirium compared to 15.8% in patients without delirium.Conclusions73.6% of patients admitted to the ICU with COVID-19 experience delirium that persists for approximately 1 week. Invasive mechanical ventilation is significantly associated with odds of delirium. Clinical attention to prevent and manage delirium and reduce delirium duration and severity is urgently needed for patients with COVID-19.
Changes in Reproductive Rate of SARS-CoV-2 Due to Non-pharmaceutical Interventions in 1,417 U.S. Counties
Authors: Wu Jie Ying , Killeen Benjamin D. , Nikutta Philipp , Thies Mareike , Zapaishchykova Anna , Chakraborty Shreya , Unberath Mathias 
Published: June 2020

AbstractIn response to the rapid spread of the novel coronavirus, SARS-CoV-2, the U.S. has largely delegated implementation of non-pharmaceutical interventions (NPIs) to local governments on the state and county level. This staggered implementation combined with the heterogeneity of the U.S. complicates quantification the effect of NPIs on the reproductive rate of SARS-CoV-2.We describe a data-driven approach to quantify the effect of NPIs that relies on county-level similarities to specialize a Bayesian mechanistic model based on observed fatalities. Using this approach, we estimate change in reproductive rate, Rt, due to implementation of NPIs in 1,417 U.S. counties.We estimate that as of May 28th, 2020 1,177 out of the considered 1,417 U.S. counties have reduced the reproductive rate of SARS-CoV-2 to below 1.0. The estimated effect of any individual NPI, however, is different across counties. Stay-at-home orders were estimated as the only effective NPI in metropolitan and urban counties, while advisory NPIs were estimated to be effective in more rural counties. The expected level of infection predicted by the model ranges from 0 to 28.7% and is far from herd immunity even in counties with advanced spread.Our results suggest that local conditions are pertinent to containment and re-opening decisions.