bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive mapping of the human cytokine gene regulatory network
Authors: Santoso CS , Li Z , Lal S , Yuan S , Gan KA , Agosto LM , Liu X , Carrasco Pro S , Sewell JA , Henderson A , Atianand MK , Fuxman Bass JI 
Published: May 2020

SummaryProper cytokine gene expression is essential in development, homeostasis, and immune responses. Studies on the transcriptional control of cytokine genes have mostly focused on highly researched transcription factors (TFs) and cytokines, resulting in an incomplete portrait of cytokine gene regulation. Here, we use enhanced yeast one-hybrid (eY1H) assays to derive a comprehensive network comprising 1,380 interactions between 265 TFs and 108 cytokine gene promoters, greatly expanding the known repertoire of TF-cytokine gene interactions. We found an enrichment of nuclear receptors and confirmed their role in cytokine regulation in primary macrophages. Additionally, we used the eY1H-derived network as a framework to identify pairs of TFs that synergistically modulate cytokine gene expression, and to identify novel TF-cytokine regulatory axes in immune diseases and immune cell lineage development. Overall, the eY1H data provides a rich resource to study cytokine regulation in a variety of physiological and disease contexts.
Programmable gene regulation for metabolic engineering using decoy transcription factor binding sites
Authors: Wang Tiebin , Tague Nathan , Whelan Stephen , Dunlop Mary J. 
Published: May 2020

ABSTRACTTranscription factor decoy binding sites are short DNA sequences that can serve as “sponges” to titrate a transcription factor away from its natural binding site, therefore regulating gene expression. In this study, we harness decoy sites to develop synthetic transcription factor sponge systems to regulate gene expression for metabolic pathways inEscherichia coli.We show that transcription factor sponges can effectively regulate expression of native and heterologous genes. Tunability of the sponge can be engineered via changes in copy number or modifications to the DNA decoy site sequence. Using arginine biosynthesis as a showcase, we observe a 16-fold increase in arginine production when we introduce the sponge system to steer metabolic flux towards increased arginine biosynthesis, with negligible growth differences compared to the wild type strain. The sponge-based production strain shows high genetic stability; in contrast to a gene knock-out approach where mutations were common, we detected no mutations in the production system using the sponge-based strain. We further show that transcription factor sponges are amenable to multiplexed library screening by demonstrating enhanced tolerance to pinene with a combinatorial sponge library. Our study shows that transcription factor sponges are a powerful and compact tool for metabolic engineering.
Optimal protocols for sequence-based characterization of the human vaginal microbiome
Authors: Hugerth Luisa W. , Pereira Marcela , Zha Yinghua , Seifert Maike , Kaldhusdal Vilde , Boulund Fredrik , Krog Maria C , Bashir Zahra , Hamsten Marica , Fransson Emma , Svarre-Nielsen Henriette , Schuppe-Koistinen Ina , Engstrand Lars 
Published: May 2020

AbstractThe vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment, but also to the use of conflicting methodologies to study its microbial composition. Here we systematically assess best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region has the best theoretical properties, but limitations of current sequencing technologies mean that the V3-V4 region performs equally well. Both of these approaches present very good agreement with qPCR quantification of key taxa, provided an appropriate bioinformatic pipeline is used. Shotgun metagenomic sequencing presents an interesting alternative to 16S amplification and sequencing, but it is not without its challenges. We have assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and – use, reference database of vaginal taxa. This strategy performed as well as the best performing previously published strategies. Despite the many advantages of shotgun sequencing none of the shotgun approaches assessed here had as good agreement with the qPCR data as 16S rRNA gene sequencing.ImportanceThe vaginal microbiome has been connected to a wide range of health outcomes, from susceptibility to sexually transmitted infections to gynecological cancers and pregnancy outcomes. This has led to a thriving research environment, but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail for them to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.
The spatial percept of tinnitus is associated with hearing asymmetry: subgroup comparisons
Authors: Genitsaridi Eleni , Kypraios Theodore , Edvall Niklas K. , Trpchevska Natalia , Canlon Barbara , Hoare Derek J. , Cederroth Christopher R. , Hall Deborah A. 
Published: May 2020

AbstractThe spatial percept of tinnitus is hypothesized as an important variable for tinnitus subtyping. Hearing asymmetry often associates with tinnitus laterality, but not always. One of the methodological limitations for cross-study comparisons is how the variables for hearing asymmetry and tinnitus spatial perception are defined. In this study, data from two independent datasets were combined (n= 833 adults, age ranging from 20 to 91 years, 404 males, 429 females) to investigate characteristics of subgroups with different tinnitus spatial perception focusing on hearing asymmetry. Three principle findings emerged. First, a hearing asymmetry variable emphasizing the maximum interaural difference most strongly discriminated unilateral from bilateral tinnitus. Merging lateralized bilateral tinnitus (perceived in both ears but worse in one side) with unilateral tinnitus weakened this relationship. Second, there was an association between unilateral tinnitus and ipsilateral asymmetric hearing. Third, unilateral and bilateral tinnitus were phenotypically distinct, with unilateral tinnitus being characterized by older age, asymmetric hearing, more often wearing one hearing aid, older age at tinnitus onset, shorter tinnitus duration, and higher percentage of time being annoyed by tinnitus. We recommend that careful consideration is given to the definitions of hearing asymmetry and tinnitus spatial perception in order to improve the comparability of findings across studies.
Extending A Chronological and Geographical Analysis of Personal Reports of COVID-19 on Twitter to England, UK
Authors: Golder S , Klein Ari Z. , Magge Arjun , O’Connor Karen , Cai Haitao , Weissenbacher Davy , Gonzalez-Hernandez Graciela 
Published: May 2020

AbstractThe rapidly evolving COVID-19 pandemic presents challenges for actively monitoring its transmission. In this study, we extend a social media mining approach used in the US to automatically identify personal reports of COVID-19 on Twitter in England, UK. The findings indicate that natural language processing and machine learning framework could help provide an early indication of the chronological and geographical distribution of COVID-19 in England.
Longitudinal peripheral blood transcriptional analysis of COVID-19 patients captures disease progression and reveals potential biomarkers
Authors: Yan Qihong , Li Pingchao , Ye Xianmiao , Huang Xiaohan , Mo Xiaoneng , Wang Qian , Zhang Yudi , Luo Kun , Chen Zhaoming , Luo Jia , Niu Xuefeng , Feng Ying , Ji Tianxing , Feng Bo , Wang Jinlin , Li Feng , Zhang Fuchun , Li Fang , Wang Jianhua , Feng Liqiang , Chen Zhilong , Lei Chunliang , Qu Linbing , Chen Ling 
Published: May 2020

ABSTRACTCOVID-19, caused by SARS-CoV-2, is an acute self-resolving disease in most of the patients, but some patients can develop a severe illness or even death. To characterize the host responses and identify potential biomarkers during disease progression, we performed a longitudinal transcriptome analysis for peripheral blood mononuclear cells (PBMCs) collected from 4 COVID-19 patients at 4 different time points from symptom onset to recovery. We found that PBMCs at different COVID-19 disease stages exhibited unique transcriptome characteristics. SARS-CoV-2 infection dysregulated innate immunity especially type I interferon response as well as the disturbed release of inflammatory cytokines and lipid mediators, and an aberrant increase of low-density neutrophils may cause tissue damage. Activation of cell death, exhaustion and migratory pathways may lead to the reduction of lymphocytes and dysfunction of adaptive immunity. COVID-19 induced hypoxia may exacerbate disorders in blood coagulation. Based on our analysis, we proposed a set of potential biomarkers for monitoring disease progression and predicting the risk of severity.
Global genetic diversity patterns and transmissions of SARS-CoV-2
Authors: Chen Zhi-wei , Li Zhao , Li Hu , Ren Hong , Hu Peng 
Published: May 2020

AbstractBackgroundSince it was firstly discovered in China, the SARS-CoV-2 epidemic has caused a substantial health emergency and economic stress in the world. However, the global genetic diversity and transmissions are still unclear.Methods3050 SARS-CoV-2 genome sequences were retrieved from GIASID database. After aligned by MAFFT, the mutation patterns were identified by phylogenetic tree analysis.ResultsWe detected 17 high frequency (>6%) mutations in the 3050 sequences. Based on these mutations, we classed the SARS-CoV-2 into four main groups and 10 subgroups. We found that group A was mainly presented in Asia, group B was primarily detected in North America, group C was prevailingly appeared in Asia and Oceania and group D was principally emerged in Europe and Africa. Additionally, the distribution of these groups was different in age, but was similar in gender. Group A, group B1 and group C2 were declined over time, inversely, group B2, group C3 and group D were rising. At last, we found two apparent expansion stages (late Jan-2020 and late Feb-2020 to early Mar-2020, respectively). Notably, most of groups are quickly expanding, especially group D.ConclusionsWe classed the SARS-CoV-2 into four main groups and 10 subgroups based on different mutation patterns at first time. The distribution of the 10 subgroups was different in geography, time and age, but not in gender. Most of groups are rapidly expanding, especially group D. Therefore, we should attach importance to these genetic diversity patterns of SARS-CoV-2 and take more targeted measures to constrain its spread.
The First Wave of COVID-19 in Israel – Initial Analysis of Publicly Available Data
Authors: Last Mark 
Published: May 2020

AbstractThe first case of COVID-19 was confirmed in Israel on February 21, 2020. Within approximately 30 days, the total number of confirmed cases climbed up to 1,000, accompanied by a doubling period of less than 3 days. About one week later, after this number exceeded 4, 000 cases, and following some extreme lockdown measures taken by the Israeli government, the daily infection rate started a sharp decrease from the peak value of 1,131 down to slightly more than 100 new confirmed cases on April 30. Motivated by this encouraging data, similar to the trends observed in many other countries, along with the growing economic pressures, the Israeli government has quickly lifted most of its emergency regulations. Throughout May, the daily number of new cases stayed at a very low level of 20 – 40 until at the end of May it started a steady increase, exceeding 1, 000 by the end of June and 2,000 on July 22. As suggested by some experts and popular media, this disturbing trend may be even a part of a “second wave”. This article attempts to analyze the currently available data on Israel, compared to three European countries (Greece, Italy, and Sweden), in order to understand the local dynamics of COVID-19, assess the effect of the implemented intervention measures, and discuss some plausible scenarios for the foreseeable future.
Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results
Authors: Kinloch Natalie N. , Ritchie Gordon , Brumme Chanson J. , Dong Winnie , Dong Weiyan , Lawson Tanya , Jones R. Brad , Montaner Julio S.G. , Leung Victor , Romney Marc G. , Stefanovic Aleksandra , Matic Nancy , Lowe Christopher F. , Brumme Zabrina L. 
Published: May 2020

AbstractImproper nasopharyngeal swab collection could contribute to false-negative COVID-19 results. In support of this, specimens from confirmed or suspected COVID-19 cases that tested negative or indeterminate (i.e. suspected false-negatives) contained less human DNA (a stable molecular marker of sampling quality) compared to a representative pool of specimens submitted for testing.
COVID-19 Infection in Children: Estimating Pediatric Morbidity and Mortality
Authors: Barton Michelle , Mehta Kayur , Kumar Kriti , Lu Jielin , Le Saux Nicole , Sampson Margaret , Robinson Joan 
Published: May 2020

ABSTRACTBACKGROUNDEstimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic.METHODSGovernment websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series.RESULTSData on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases.CONCLUSIONChildren accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.
Cancer phylogenetic tree inference at scale from 1000s of single cell genomes
Authors: Salehi Sohrab , Dorri Fatemeh , Chern Kevin , Kabeer Farhia , Rusk Nicole , Funnell Tyler , Williams Marc J , Lai Daniel , Andronescu Mirela , Campbell Kieran R. , McPherson Andrew , Aparicio Samuel , Roth Andrew , Shah Sohrab , Bouchard-Côté Alexandre 
Published: May 2020

AbstractA new generation of scalable single cell whole genome sequencing (scWGS) methods allows unprecedented high resolution measurement of the evolutionary dynamics of cancer cell populations. Phylogenetic reconstruction is central to identifying sub-populations and distinguishing the mutational processes that gave rise to them. Existing phylogenetic tree building models do not scale to the tens of thousands of high resolution genomes achievable with current scWGS methods. We constructed a phylogenetic model and associated Bayesian inference procedure, sitka, specifically for scWGS data. The method is based on a novel phylogenetic encoding of copy number (CN) data, the sitka transformation, that simplifies the site dependencies induced by rearrangements while still forming a sound foundation to phylogenetic inference. The sitka transformation allows us to design novel scalable Markov chain Monte Carlo (MCMC) algorithms. Moreover, we introduce a novel point mutation calling method that incorporates the CN data and the underlying phylogenetic tree to overcome the low per-cell coverage of scWGS. We demonstrate our method on three single cell datasets, including a novel PDX series, and analyse the topological properties of the inferred trees. Sitka is freely available athttps://github.com/UBC-Stat-ML/sitkatree.git.
Mutations inMYLPFcause a novel segmental amyoplasia that manifests as distal arthrogryposis
Authors: Chong Jessica X. , Talbot Jared C. , Teets Emily M. , Previs Samantha , Martin Brit L. , Shively Kathryn M. , Marvin Colby T. , Aylsworth Arthur S. , Saadeh-Haddad Reem , Schatz Ulrich A. , Inzana Francesca , Ben-Omran Tawfeg , Almusafri Fatima , Al-Mulla Mariam , Buckingham Kati J. , Harel Tamar , Mor-Shaked Hagar , Radhakrishnan Periyasamy , Girisha Katta M , Nayak Shalini S. , Shukla Anju , Dieterich Klaus , Faure Julien , Rendu John , Capri Yline , Latypova Xenia , Nickerson Deborah A. , Warshaw David , Janssen Paul M. ,   University of Washington Center for Mendelian Genomics, Amacher Sharon L. , Bamshad Michael J. 
Published: May 2020

AbstractWe identified ten persons in six consanguineous families with Distal Arthrogryposis (DA) who had congenital contractures, scoliosis, and short stature. Exome sequencing revealed that each affected person was homozygous for one of two different rare variants (c.470G>T, p.(Cys157Phe) or c.469T>C, p.(Cys157Arg)) affecting the same residue ofmyosin light chain, phosphorylatable, fast skeletal muscle(MYLPF). In a seventh family, a c.487G>A, p.(Gly163Ser) variant inMYLPFarosede novoin a father, who transmitted it to his son. In an eighth family comprised of seven individuals with dominantly-inherited DA, a c.98C>T, p.(Ala33Val) variant segregated in all four persons tested. Variants inMYLPFunderlie both dominant and recessively inherited DA. Mylpf protein models suggest that the residues associated with dominant DA interact with myosin whereas the residues altered in families with recessive DA only indirectly impair this interaction. Pathological and histological exam of a foot amputated from an affected child revealed complete absence of skeletal muscle (i.e., segmental amyoplasia). To investigate the mechanism for this finding, we generated an animal model for partial MYLPF impairment by knocking out zebrafishmylpfa. Themylpfamutant had reduced trunk contractile force and complete pectoral fin paralysis, demonstrating thatmylpfimpairment most severely affects limb movement.mylpfamutant muscle weakness was most pronounced in an appendicular muscle and was explained by reduced myosin activity and fiber degeneration. Collectively, our findings demonstrate that partial loss of MYLPF function can lead to congenital contractures, likely as a result of degeneration of skeletal muscle in the distal limb.
Microglial phagocytosis dysfunction is related to local neuronal activity in a genetic model of epilepsy
Authors: Sierra-Torre Virginia , Plaza-Zabala Ainhoa , Bonifazi Paolo , Abiega Oihane , Díaz-Aparicio Irune , Tegelberg Saara , Lehesjoki Anna-Elina , Valero Jorge , Sierra Amanda 
Published: May 2020

ABSTRACTMicroglial phagocytosis of apoptotic cells is an essential component of the brain regenerative response in neurodegenerative diseases. Phagocytosis is very efficient in physiological conditions, as well as during apoptotic challenge induced by excitotoxicity or inflammation, but is impaired in mouse and human mesial temporal lobe epilepsy (MTLE). Here we extend our studies to a genetic model of progressive myoclonus epilepsy type 1 (EPM1) in mice lacking cystatin B (CSTB), an inhibitor of cysteine proteases involved in lysosomal proteolysis. We first demonstrated that microglial phagocytosis was impaired in the hippocampus inCstbknock-out (KO) mice when seizures arise and hippocampal atrophy begins, at 1 month of age. To test if this blockage was related to the lack ofCstbin microglia, we used anin vitromodel of phagocytosis and siRNAs to acutely reduceCstbexpression but we found no significant effect in the phagocytosis of apoptotic cells. We then tested whether seizures were involved in the phagocytosis impairment, similar to MTLE, and analyzedCstbKO mice before seizures begin, at postnatal day 14. Here, phagocytosis impairment was restricted to the granule neuron layer but not to the subgranular zone, where there are no active neurons. Furthermore, we observed apoptotic cells (both phagocytosed and not phagocytosed) inCstbdeficient mice at close proximity to active, cFos+neurons and used mathematical modeling to demonstrate that the physical relationship between apoptotic cells and cFos+ neurons was specific forCstbKO mice. These results suggest a complex crosstalk between apoptosis, phagocytosis and neuronal activity, hinting that local neuronal activity could be related to phagocytosis dysfunction inCstbKO mice. Overall, this data suggest that phagocytosis impairment is an early feature of hippocampal damage in epilepsy and opens novel therapeutic approaches for epileptic patients based on targeting microglial phagocytosis.
Full-length 16S rRNA gene amplicon analysis of human gut microbiota using MinION™ nanopore sequencing confers species-level resolution
Authors: Matsuo Yoshiyuki , Komiya Shinnosuke , Yasumizu Yoshiaki , Yasuoka Yuki , Mizushima Katsura , Takagi Tomohisa , Kryukov Kirill , Fukuda Aisaku , Morimoto Yoshiharu , Naito Yuji , Okada Hidetaka , Bono Hidemasa , Nakagawa So , Hirota Kiichi 
Published: May 2020

AbstractBackgroundSpecies-level genetic characterization of complex bacterial communities has important clinical applications in both diagnosis and treatment. Amplicon sequencing of the 16S ribosomal RNA (rRNA) gene has proven to be a powerful strategy for the taxonomic classification of bacteria. This study aims to improve the method for full-length 16S rRNA gene analysis using the nanopore long-read sequencer MinION™. We compared it to the conventional short-read sequencing method in both a mock bacterial community and human fecal samples.ResultsWe modified our existing protocol for full-length 16S amplicon sequencing by MinION™. A new strategy for library construction with an optimized primer set overcame PCR-associated bias and enabled taxonomic classification across a broad range of bacterial species. We compared the performance of full-length and short-read 16S amplicon sequencing for the characterization of human gut microbiota with a complex bacterial composition. The relative abundance of dominant bacterial genera was highly similar between full-length and short-read sequencing. At the species level, MinION™ long-read sequencing had better resolution for discriminating between members of particular taxa such asBifidobacterium, allowing an accurate representation of the sample bacterial composition.ConclusionsOur present microbiome study, comparing the discriminatory power of full-length and short-read sequencing, clearly illustrated the analytical advantage of sequencing the full-length 16S rRNA gene, which provided the requisite species-level resolution and accuracy in clinical settings.