bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings
Authors: Kucharski Adam , Klepac Petra , Conlan Andrew , Kissler Stephen , Tang Maria , Fry Hannah , Gog Julia , Edmunds John ,   CMMID COVID-19 working group
Published: April 2020

AbstractBackgroundIsolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures – including novel digital tracing approaches and less intensive physical distancing – may be required to reduce transmission.MethodsUsing a model of individual-level transmission stratified by setting (household, work, school, other) based on BBC Pandemic data from 40,162 UK participants, we simulated the impact of a range of different testing, isolation, tracing and physical distancing scenarios. As well as estimating reduction in effective reproduction number, we estimated, for a given level of COVID-19 incidence, the number of contacts that would be newly quarantined each day under different strategies.ResultsUnder optimistic but plausible assumptions, we estimated that combined testing and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50–65% compared to 2–30%). If limits are placed on gatherings outside of home/school/work (e.g. maximum of 4 daily contacts in other settings), then manual contact tracing of acquaintances only could have a similar effect on transmission reduction as detailed contact tracing. In a scenario where there were 10,000 new symptomatic cases per day, we estimated in most contact tracing strategies, 140,000 to 390,000 contacts would be newly quarantined each day.ConclusionsConsistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimates that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number that is below one in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control.FundingWellcome Trust, EPSRC, European Commission.
Epidemiological and clinical characteristics of discharged patients infected with SARS-CoV-2 on the Qinghai plateau
Authors: Xi Aiqi , Zhuo Ma , Dai Jingtao , Ding Yuehe , Ma Xiuzhen , Ma Xiaoli , Wang Xiaoyi , Shi Lianmeng , Bai Huanying , Zheng Hongying , Nuermberger Eric , Xu Jian 
Published: April 2020

AbstractSince the outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, a series of confirmed cases of COVID-19 were found on the Qinghai-Tibet plateau. We aimed to describe the epidemiological, clinical characteristics, and outcomes of all confirmed cases in Qinghai, a province at high altitude. With efficient measures to stop the spread of coronavirus, no new cases were found in Qinghai Province for 60 consecutive days between Feb 6 and April 6, 2020. Of all 18 patients with confirmed SARS-CoV-2 infection, 15 patients comprising 4 transmission clusters were identified. Three patients were infected by direct contact without travel history to Wuhan. Seven patients were asymptomatic on admission. Of 18 patients, 10 patients showed bilateral pneumonia and 2 patients showed no abnormalities. Three patients with comorbidities such as hypertension, liver diseases or diabetes developed severe illness. High C-reactive protein levels and elevations of both ALT and AST were observed in 3 severely ill patients on admission. All 18 patients were eventually discharged, including the 3 severe patients who recovered after treatment with non-invasive mechanical ventilation, convalescent plasma and other therapies. Our findings confirmed human-to-human transmission of SARS-CoV-2 in clusters. The strategies of early diagnosis, early isolation, and early treatment are important to prevent the spread of COVID-19 and improve the cure rate. Patients with comorbidities are more likely to develop severe illness and could benefit from convalescent plasma transfusion.
Clinical Characteristics and Short-Term Outcomes of Severe Patients with COVID-19 in Wuhan, China
Authors: Feng Xiaobo , Li Peiyun , Ma Liang , Liang Hang , Lei Jie , Li Wenqiang , Wang Kun , Song Yu , Li Shuai , Yang Wei , Yang Cao 
Published: April 2020

AbstractObjectiveA novel pneumonia (COVID-19) which is sweeping the globe was started in December, 2019, in Wuhan, China. Most deaths occurred in severe and critically cases, but information on prognostic risk factors for severe ill patients is incomplete. Further research is urgently needed to guide clinicians, so we prospectively evaluate the clinical outcomes of 114 severe ill patients with COVID-19 for short-term in the Union Hospital in Wuhan, China.MethodsIn this single-centered, prospective and observational study, we enrolled 114 severe ill patients with confirmed COVID-19 from Jan 23, 2020 to February 22, 2020. Epidemiological, demographic and laboratory information were collected at baseline, data on treatment and outcome were collected until the day of death or discharge or for the first 28 days after severe ill diagnosis, whichever was shorter. Univariate and multivariate Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of poor outcome.ResultsAmong enrolled 114 patients, 94 (82.5%) had good outcome while 20 (17.5%) had poor outcome. No significant differences were showed in age, gender and the prevalence of coexisting disorders between outcome groups. Results of multivariate Cox analyses indicated that higher levels of oxygen saturation (HR, 0.123; 95% CI, 0.041-0.369), albumin (HR, 0.060; 95% CI, 0.008-0.460) and arterial partial pressure of oxygen (HR, 0.321; 95% CI, 0.106-0.973) were associated with decreased risk of developing poor outcome within 28 days. In the other hand, higher levels of leucocytes (HR, 5.575; 95% CI, 2.080-14.943), neutrophils (HR, 2.566; 95% CI, 1.022-6.443), total bilirubin (HR, 6.171; 95% CI, 2.458- 15.496), globulin (HR, 2.526; 95% CI, 1.027-6.211), blood urea nitrogen (HR, 5.640; 95% CI, 2.193-14.509), creatine kinase-MB (HR, 3.032; 95% CI, 1.203-7.644), lactate dehydrogenase (HR, 4.607; 95% CI, 1.057-20.090), hypersensitive cardiac troponin I (HR, 5.023; 95% CI, 1.921-13.136), lactate concentration (HR,15.721; 95% CI, 2.099-117.777), Interleukin-10 (HR, 3.551; 95% CI, 1.280-9.857) and C-reactive protein (HR, 5.275; 95% CI, 1.517-18.344) were associated with increased risk of poor outcome development. We also found that traditional Chinese medicine can significantly improve the patient’s condition, which is conducive to the transformation from severe to mild.ConclusionIn summary, we firstly reported this single-centered, prospective and observational study for short-term outcome in severe patients with COVID-19. We found that cytokine storm and uncontrolled inflammation responses, liver, kidney, cardiac dysfunction may play important roles in final outcome of severe ill patients with COVID-19. Our study will provide clinicians to be benefit to rapidly estimate the likelihood risk of short-term poor outcome for severe patients.
Contextualizing covid-19 spread: a county level analysis, urban versus rural, and implications for preparing for the next wave
Authors: Rao J. Sunil , Zhang Hang , Mantero Alejandro 
Published: April 2020

AbstractParaphrasing [Morano and Holt, 2017], contextual determinants of health including social, environmental, healthcare and others, are a so-called deck of cards one is dealt. The ability to modify health outcomes varies then based upon how one’s hand is played. It is thus of great interest to understand how these determinants associate with the emerging pandemic covid-19. To this end, we conducted a deep-dive analysis into this problem using a recently curated public dataset on covid-19 that connects infection spread over time to a rich collection of contextual determinants for all counties of the U.S and Washington, D.C. Using random forest machine learning methodology, we identified a relevant constellation of contextual factors of disease spread which manifest differently for urban and rural counties. The findings also have clear implications for better preparing for the next wave of disease.
The Relationship between Cannabis Use and Cognition in People with Bipolar Disorder: A Systematic Scoping Review
Authors: Walter T. Jordan , Pocuca Nina , Young Jared W. , Geyer Mark A. , Minassian Arpi , Perry William 
Published: April 2020

ABSTRACTBipolar disorder (BD) and cannabis use are highly comorbid and are each associated with cognitive impairment. It is therefore important to understand the relationship between cannabis use and cognition in people with BD, as cannabis use in BD may be associated with greater cognitive impairment. We performed a scoping review to determine how much and what is currently known in this field. We systematically searched PubMed, Embase, CINAHL, Web of Science, and PsycINFO for studies on the relationship between cannabis and cognition in people with BD or relevant animal models. Six observational human studies met inclusion criteria. Two studies found cannabis use in BD was associated with better performance in some cognitive domains, while three studies found no association. One study found cannabis use in BD was associated with worse overall cognition. Overall, most identified studies suggest cannabis use is not associated with significant cognitive impairment in BD; however, the scope of knowledge in this field is limited, and more systematic studies are clearly required. Future studies should focus on longitudinal and experimental trials, as well as well-controlled observational studies with rigorous quantification of the onset, frequency, quantity, duration, and type of cannabis use.
Intra-host site-specific polymorphisms of SARS-CoV-2 is consistent across multiple samples and methodologies
Authors: Rose Rebecca , Nolan David J. , Moot Samual , Feehan Amy , Cross Sissy , Garcia-Diaz Julia , Lamers Susanna L. 
Published: April 2020

ABSTRACTDespite the potential relevance to clinical outcome, intra-host dynamics of SARS-CoV-2 are unclear. Here, we quantify and characterize intra-host variation in SARS-CoV-2 raw sequence data uploaded to SRA as of 14 April 2020, and compare results between two sequencing methods (amplicon and RNA-Seq). Raw fastq files were quality filtered and trimmed using Trimmomatic, mapped to the WuhanHu1 reference genome using Bowtie2, and variants called with bcftools mpileup. To ensure sufficient coverage, we only included samples with 10X coverage for >90% of the genome (n=406 samples), and only variants with a depth >=10. Derived (i.e. non-reference) alleles were found at 408 sites. The number of polymorphic sites (i.e. sites with multiple alleles) within samples ranged from 0-13, with 72% of samples (295/406) having at least one polymorphic site. Correlation between number of polymorphic sites and coverage was very low for both sequencing methods (R2 < 0.1, p < 0.05). Polymorphisms were observed >1 sample at 66 sites (range: 2-38 samples). The minor allele frequency (MAF) at each shared polymorphic site was 0.03% - 48.5%. 33/66 sites occurred in ORF1a1b, and 37/66 changes were non-synonymous. At 10/66 sites, derived alleles were found in samples sequenced using both methods. Polymorphic amplicon samples were found at 10/10 positions, while polymorphic RNA-Seq samples were found at 7/10 positions. In conclusion, our results suggest that intra-host variation is prevalent among clinical samples. While mutations resulting from amplification and/or sequencing errors cannot be excluded, the observation of shared polymorphic sites with high MAF across multiple samples and sequencing methods is consistent with true underlying variation. Further investigation into intra-host evolutionary dynamics, particularly with longitudinal sampling, is critical for broader understanding of disease progression.
KAT7 is a therapeutic vulnerability ofMLL-rearranged acute myeloid leukemia
Authors: Au Yan Zi , Gu Muxin , De Braekeleer Etienne , Yu Jason , Ong Swee Hoe , Gozdecka Malgorzata , Chen Xi , Tzelepis Konstantinos , Huntly Brian J.P , Vassiliou George , Yusa Kosuke 
Published: April 2020

AbstractHistone acetyltransferases (HATs) catalyze the transfer of an acetyl group from acetyl-CoA to lysine residues of histones and play a central role in transcriptional regulation in diverse biological processes. Dysregulation of HAT activity can lead to human diseases including developmental disorders and cancer. Through genome-wide CRISPR-Cas9 screens, we identified several HATs of the MYST family as fitness genes for acute myeloid leukaemia (AML). Here we investigate the essentiality of lysine acetyltransferase KAT7 in AMLs driven by theMLL-Xgene fusions. We found that KAT7 loss leads to a rapid and complete loss of both H3K14ac and H4K12ac marks, in association with reduced proliferation, increased apoptosis and differentiation of AML cells. Acetyltransferase activity of KAT7 is essential for the proliferation of these cells. Mechanistically, our data propose that acetylated histones provide a platform for the recruitment of MLL-fusion-associated adaptor proteins such as BRD4 and AF4 to gene promoters. Upon KAT7 loss, these factors together with RNA polymerase II rapidly dissociate from several MLL-fusion target genes that are essential for AML cell proliferation, includingMEIS1, PBX3andSENP6. Our findings reveal that KAT7 is a plausible therapeutic target for this poor prognosis AML subtype.
Epidemiological and clinical characteristics of the early phase of the COVID-19 epidemic in Brazil
Authors: de Souza William Marciel , Buss Lewis Fletcher , Candido Darlan da Silva , Carrera Jean-Paul , Li Sabrina , Zarebski Alexander E. , Vincenti-Gonzalez Maria F. , Messina Janey , Silva Sales Flavia Cristina da , Santos Andrade Pamela dos , Prete Carlos A. , Nascimento Vítor Heloiz , Ghilardi Fabio , Moraes Pereira Rafael Henrique , Souza Santos Andreza Aruska de , Abade Leandro , Gutierrez Bernardo , Kraemer Moritz U. G. , Aguiar Renato Santana , Alexander Neal , Mayaud Philippe , Brady Oliver J. , de Souza Izabel Oliva Marcilio , Gouveia Nelson , Li Guangdi , Tami Adriana , de Oliveira Silvano Barbosa , Gomes Porto Victor Bertollo , Ganem Fabiana , de Almeida Walquiria Aparecida Ferreira , Tardetti Fantinato Francieli Fontana Sutile , Macário Eduardo Marques , de Oliveira Wanderson Kleber , Pybus Oliver G. , Wu Chieh-Hsi , Croda Julio , Sabino Ester C. , Faria Nuno Rodrigues 
Published: April 2020

SummaryBackgroundThe first case of COVID-19 was detected in Brazil on February 25, 2020. We report the epidemiological, demographic, and clinical findings for confirmed COVID-19 cases during the first month of the epidemic in Brazil.MethodsIndividual-level and aggregated COVID-19 data were analysed to investigate demographic profiles, socioeconomic drivers and age-sex structure of COVID-19 tested cases. Basic reproduction numbers (R0) were investigated for São Paulo and Rio de Janeiro. Multivariate logistic regression analyses were used to identify symptoms associated with confirmed cases and risk factors associated with hospitalization. Laboratory diagnosis for eight respiratory viruses were obtained for 2,429 cases.FindingsBy March 25, 1,468 confirmed cases were notified in Brazil, of whom 10% (147 of 1,468) were hospitalised. Of the cases acquired locally (77·8%), two thirds (66·9% of 5,746) were confirmed in private laboratories. Overall, positive association between higher per capita income and COVID-19 diagnosis was identified. The median age of detected cases was 39 years (IQR 30-53). The median R0 was 2·9 for São Paulo and Rio de Janeiro. Cardiovascular disease/hypertension were associated with hospitalization. Co-circulation of six respiratory viruses, including influenza A and B and human rhinovirus was detected in low levels.InterpretationSocioeconomic disparity determines access to SARS-CoV-2 testing in Brazil. The lower median age of infection and hospitalization compared to other countries is expected due to a younger population structure. Enhanced surveillance of respiratory pathogens across socioeconomic statuses is essential to better understand and halt SARS-CoV-2 transmission.FundingSão Paulo Research Foundation, Medical Research Council, Wellcome Trust and Royal Society.
A Simple Covid-19 Epidemic Model and Containment Policy in France
Authors: Quadrat J.-P. 
Published: April 2020

AbstractWe show that the standard SIR model is not effective to predict the 2019-20 coronavirus pandemic propagation. We propose a new model where the logarithm of the detected population number follows a linear dynamical system. We estimate the parameters of this system and compare models obtained with data observed from different countries. Based on the given estimator and results obtained with the Pr. Raoult’s treatment, we affirm with a reasonable degree of confidence that his “test-treat-noconfine” policy was less expensive in human lives than the”confine and wait for a proved treatment” policy adopted by the French government.
Protein synthesis is suppressed in sporadic and familial Parkinson’s Disease by LRRK2
Authors: Deshpande Prasannakumar , Flinkman Dani , Hong Ye , Goltseva Elena , Siino Valentina , Sun Lihua , Peltonen Sirkku , Elo Laura , Kaasinen Valtteri , James Peter , Coffey Eleanor T. 
Published: April 2020

ABSTRACTGain of function LRRK2-G2019S is the most common mutation associated with both familial and sporadic Parkinson’s disease. It is expected therefore that understanding the cellular function of LRRK2 will provide much needed insight on the pathological mechanism of sporadic Parkinson’s, which is the most common form. Here we show that constitutive LRRK2 activity represses nascent protein synthesis in rodent neurons. Specifically, enzymatic inhibition of LRRK2, gene silencing or gene knockout of Lrrk2 increase translation. In the rotenone model of Parkinson’s, LRRK2 activity increases, leading to repression of translation and dopaminergic neuron atrophy both of which are prevented by LRRK2 inhibition. This is accompanied by altered phosphorylation of eIF2α-S52(↑), eIF2s2-S2(↓) and eEF2-T57(↑) in striatum/substantia nigra in a direction that signifies inhibition of protein synthesis. Significantly, LRRK2 is activated and translation is 40% reduced in Parkinson’s patient fibroblasts (G2019S and sporadic) and LRRK2 inhibition restores normal translation. In contrast, translation is unchanged in cells from multiple system atrophy patients, implying disease specificity. These findings suggest that LRRK2-dependent repression of translation may be a proximal function of LRRK2 in Parkinson’s pathology.
Detection of Merkel cell polyomavirus using whole exome sequencing data
Authors: Garcia-Mulero Sandra , Moratalla-Navarro Ferran , Curiel-Olmo Soraya , Moreno Victor , Vaqué José Pedro , Sanz-Pamplona Rebeca , María Piulats Josep 
Published: April 2020

AbstractMerkel cell carcinoma (MCC) is a highly malignant neuroendocrine tumor of the skin in which Merkel cell polyomavirus (MCV) DNA virus insertion can be detected in 75–89% of cases. Etiologic and phenotypic differences exist between MCC tumors with and without the inserted virus, thus it is important to distinguish between MCV+ MCC and MCV-MCC cases. Currently, MCV insertions in MCC genomes are detected using laboratory techniques. Here we report a freely available bioinformatics methodology to identify MCV+ MCC tumors using whole exome sequencing (WES) data. WES data could be also used to infer the virus insertion site into the tumor genome. Our method has been validated in a set of MCC samples previously characterized in the laboratory as MCV+ or MCV-, achieving 100% sensitivity and 62,5% specificity. Thus, with enough depth of sequencing, it is possible to use WES to the presence of MCV insertions in cancer samples.
Developmentally regulated PERK activity renders dendritic cells insensitive to subtilase cytotoxin-induced integrated stress response
Authors: Mendes Andreia , Gigan Julien P. , Rodrigues Christian Rodriguez , Choteau Sébastien A. , Sanseau Doriane , Barros Daniela , Almeida Catarina , Camosseto Voahirana , Argüello Rafael J. , Chasson Lionel , Paton Adrienne W. , Paton James C. , Lennon-Duménil Ana-Maria , Gatti Evelina , Pierre Philippe 
Published: April 2020

AbstractIn stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response (ISR). We show here that dendritic cells (DCs) display unusually high eIF2α phosphorylation, which is mostly caused by a developmentally regulated activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, differentiated DCs display active protein synthesis and no signs of a chronic ISR. eIF2α phosphorylation does not majorly impact DC differentiation nor cytokines production. It is however important to adapt protein homeostasis to the variations imposed on DCs by the immune or physiological contexts. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by subtilase cytotoxin or upon DC stimulation with bacterial lipopolysaccharides. This is also exemplified by the influence of the actin cytoskeleton dynamics on eIF2α phosphorylation and the migratory deficit observed in PERK-deficient DCs.
Relating network analyses to phylogenetic relatedness to infer protistan co-occurrences and co-exclusions in marine and terrestrial environments
Authors: Lentendu Guillaume , Dunthorn Micah 
Published: April 2020

AbstractWe used two large-scale metabarcoding datasets to evaluate phylogenetic signals at global marine and regional terrestrial scales using co-occurrence and co-exclusion networks. Phylogenetic relatedness was estimated using either global pairwise sequence distance or phylogenetic distance and the significance of observed patterns relating networks and phylogenies were evaluated against two null models. In all datasets, we found that phylogenetically close OTUs significantly co-occurred more often, and OTUs with intermediate phylogenetic relatedness co-occurred less often, than expected by chance. Phylogenetically close OTUs co-excluded less often than expected by chance in the marine datasets only. Simultaneous excess of co-occurrences and co-exclusions were observed in the inversion zone between close and intermediate phylogenetic distance classes in marine surface. Similar patterns were observed by using either pairwise sequence or phylogenetic distances, and by using both null models. These results suggest that environmental filtering and dispersal limitation are the preponderant forces driving co-occurrence of protists in both environments, while signal of competitive exclusion was only detected in the marine surface environment. The discrepancy in the co-exclusion pattern is potentially linked to the individual environments: water bodies are more homogeneous while tropical forest soils contain a myriad of nutrient rich micro-environment reducing the strength of mutual exclusion.