bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractal kinetics of COVID-19 pandemic (with update 3/1/20)
Authors: Ziff Anna L. , Ziff Robert M. 
Published: February 2020

AbstractWe give an update to the original paper posted on 2/17/20 – now (as of 3/1/20) the China deaths are rapidly decreasing, and we find an exponential decline to the power law similar to the that predicted by the network model of Vazquez [2006]. At the same time, we see non-China deaths increasing rapidly, and similar to the early behavior of the China statistics. Thus, we see three stages of the spread of the disease in terms of number of deaths: exponential growth, power-law behavior, and then exponential decline in the daily rate.(Original abstract) The novel coronavirus (COVID-19) continues to grow rapidly in China and is spreading in other parts of the world. The classic epidemiological approach in studying this growth is to quantify a reproduction number and infection time, and this is the approach followed by many studies on the epidemiology of this disease. However, this assumption leads to exponential growth, and while the growth rate is high, it is not following exponential behavior. One approach that is being used is to simply keep adjusting the reproduction number to match the dynamics. Other approaches use rate equations such as the SEIR and logistical models. Here we show that the current growth closely follows power-law kinetics, indicative of an underlying fractal or small-world network of connections between susceptible and infected individuals. Positive deviations from this growth law might indicate either a failure of the current containment efforts while negative deviations might indicate the beginnings of the end of the pandemic. We cannot predict the ultimate extent of the pandemic but can get an estimate of the growth of the disease.
Estimating the case fatality ratio of the COVID-19 epidemic in China
Authors: Wang Xing , Ma Zihui , Ning Yi , Chen Chen , Chen Rujin , Chen Qiwen , Zhang Heng , Li Chunming , He Yan , Wang Tao , Tong Cheng , Wu Junqing , Li Yuyan , Ma Handong , Zhang Shaodian , Zhao Hongxin 
Published: February 2020

AbstractBackgroundCorona Virus Disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China since late December 2019. Crude case fatality ratio (CFR) with dividing the number of known deaths by the number of confirmed cases does not represent the true CFR and might be off by orders of magnitude. We aim to provide a precise estimate of the CFR of COVID-19 using statistical models at the early stage of the epidemic.MethodsWe extracted data from the daily released epidemic report published by the National Health Commission P. R. China from 20 Jan 2020, to 1 March 2020. Competing risk model was used to obtain the cumulative hazards for death, cure, and cure-death hazard ratio. Then the CFR was estimated based on the slope of the last piece in joinpoint regression model, which reflected the most recent trend of the epidemic.ResultsAs of 1 March 2020, totally 80,369 cases were diagnosed as COVID-19 in China. The CFR of COVID-19 were estimated to be 70.9% (95% CI: 66.8%-75.6%) during Jan 20-Feb 2, 20.2% (18.6%-22.1%) during Feb 3-14, 6.9% (6.4%-7.4%) during Feb 15-23, 1.5% (1.4%-1.6%) during Feb 24-March 1 in Hubei province, and 20.3% (17.0%-25.3%) during Jan 20-28, 1.9% (1.8%-2.1%) during Jan 29-Feb 12, 0.9% (0.8%-1.1%) during Feb 13-18, 0.4% (0.4%-0.5%) during Feb 19-March 1 in other areas of China, respectively.ConclusionsBased on analyses of public data, we found that the CFR in Hubei was much higher than that of other regions in China, over 3 times in all estimation. The CFR would follow a downwards trend based on our estimation from recently released data. Nevertheless, at early stage of outbreak, CFR estimates should be viewed cautiously because of limited data source on true onset and recovery time.
Leading causes of mortality and prescription drug coverage in Canada and New Zealand
Authors: Rawson Nigel S B 
Published: February 2020

AbstractBackgroundCanada may soon see the introduction of a national pharmaceutical insurance system. New Zealand has a government-funded healthcare system used by all residents that operates within a tight cost-containment budget.ObjectiveTo compare the main mortality causes in Canada and New Zealand and examine listings in current Canadian provincial public drug plans and the New Zealand national drug formulary.MethodsAge-standardized mortality rates from 1985 to 2014 and data on hospital discharges and average length of stay in hospital for Canada and New Zealand were obtained from the Organization for Economic Cooperation and Development’s website. Information on insured medications was obtained from Canadian provincial drug plan lists and the New Zealand Pharmaceutical Schedule current in mid-2019.ResultsMortality rates for acute myocardial infarction, ischemic heart disease and cerebrovascular disease were higher, on average over the 30-year observation period, in New Zealand, but rates for malignancies and respiratory disorders were similar in the two countries. Reimbursement listing rates for drugs for cancer and some cardiovascular indications were lower in New Zealand than in Canada.ConclusionsNew Zealand’s drug coverage system has contained costs, but it restricts or denies access to new innovative medicines with the potential to improve patients’ lives. Although a New Zealand-style national pharmacare scheme in Canada would offer the opportunity to restrain drug expenditure, it would likely fail to satisfy patients and healthcare providers and diminish health outcomes, resulting in higher costs in other healthcare sectors.
Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver
Authors: He Bingbing , Peng Wenbo , Huang Jia , Zhang Hang , Zhou Yingsi , Yang Xiali , Liu Jing , Li Zhijie , Xu Chunlong , Xue Mingxing , Yang Hui , Huang Pengyu 
Published: February 2020

AbstractRNA knockdownin vivocarries significant potential for disease modelings and therapies. Despite the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes, strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of the genome DNA is not appropriate, and RNA virus infection diseases when pathogenic DNA is not available (such as SARS-Cov-2 and MERS infections). Recently, Cas13d, a family of RNA-targeting CRISPR effectors, has been shown to accomplish robust down-regulation of cellular RNAs in mammalian cellsin vitro. Among the various Cas13d subtypes, CasRx (RfxCas13d) showed the most potent RNA knockdown efficiency in HEK293T cells. However, the RNA-targeting activity of Cas13d still needs to be verifiedin vivo. In this study, the CasRx system was demonstrated to efficiently and functionally knock down genes related to metabolism functions, includingPten, Pcsk9andlncLstr, in mouse hepatocytes. CasRx-mediated simultaneous knockdown of multiple genes was also achieved by sgRNA arrays, providing a useful strategy to modulate complex metabolism networks. Moreover, the AAV (adeno-associated virus)-mediated delivery ofCasRxandPcsk9sgRNAs into mouse liver successfully decreased serum PCSK9, resulting in significant reduction of serum cholesterol levels. Importantly, CasRx-mediated knockdown ofPcsk9is reversible andPcsk9could be repeatedly down-regulated, providing an effective strategy to reversibly modulate metabolic genes. The present work supplies a successful proof-of-concept trial that suggests efficient and regulatory knockdown of target metabolic genes for a designed metabolism modulation in the liver.
Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins
Authors: Xiao Kangpeng , Zhai Junqiong , Feng Yaoyu , Zhou Niu , Zhang Xu , Zou Jie-Jian , Li Na , Guo Yaqiong , Li Xiaobing , Shen Xuejuan , Zhang Zhipeng , Shu Fanfan , Huang Wanyi , Li Yu , Zhang Ziding , Chen Rui-Ai , Wu Ya-Jiang , Peng Shi-Ming , Huang Mian , Xie Wei-Jun , Cai Qin-Hui , Hou Fang-Hui , Liu Yahong , Chen Wu , Xiao Lihua , Shen Yongyi 
Published: February 2020

AbstractThe outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.
Integrative omics approach to identify the molecular architecture of inflammatory protein levels in healthy older adults
Authors: Hillary Robert F. , Trejo-Banos Daniel , Kousathanas Athanasios , McCartney Daniel L. , Harris Sarah E. , Stevenson Anna J. , Patxot Marion , Ojavee Sven Erik , Zhang Qian , Liewald David C. , Ritchie Craig W. , Evans Kathryn L. , Tucker-Drob Elliot M. , Wray Naomi R. , McRae Allan F. , Visscher Peter M. , Deary Ian J. , Robinson Matthew R. , Marioni Riccardo E. 
Published: February 2020

AbstractThe molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets. Therefore, in this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink®inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified three CpG sites spread across three proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to one polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease, and between IL12B and Crohn’s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.
Hand-reared wolves show attachment comparable to dogs and use human caregiver as a social buffer in the Strange Situation Test
Authors: Wheat Christina Hansen , Larsson Linn , Berner Patricia , Temrin Hans 
Published: February 2020

AbstractDomesticated animals are generally assumed to display increased sociability towards humans compared to their wild ancestors. Dogs (Canis familiaris) have a remarkable ability to form social relationships with humans, including lasting attachment, a social bond based on emotional dependency. Since it has specifically been suggested that the ability to form attachment with humans evolved post-domestication in dogs, attempts to quantify attachment in wolves (Canis lupus), the ancestor of dogs, have subsequently been performed. However, while these rare wolf studies do highlight the potential for wolves to express attachment behaviour towards humans, the varied, and in some cases, contrasting results also emphasize the need for further testing of wolves. Here we used the standardized Strange Situation Test to investigate attachment behaviour expressed in wolves and dogs hand-reared and socialized under identical conditions. We found that 23 weeks old wolves and dogs equally discriminated between a stranger and a familiar person, and expressed similar attachment behaviours toward a familiar person. Additionally, wolves, but not dogs, expressed significantly elevated stress behaviour during the test, but this stress response was buffered by the presence of a familiar person. Wolves also expressed quantifiable fear responses to the stranger, whereas no such response was detectable in dogs. Together, our results suggest that wolves can show attachment toward humans comparable to that of dogs. Importantly, our findings demonstrate that the ability to form attachment with humans exists in relatives of the wild ancestor of dogs, thus refuting claims that such attachment is unique to post-domestication dog lineages.
Mutation bias can shape adaptation in large asexual populations experiencing clonal interference
Authors: Gomez Kevin , Bertram Jason , Masel Joanna 
Published: February 2020

AbstractThe Extended Evolutionary Synthesis invokes a role for development in shaping adaptive evolution, which in population genetics terms corresponds to mutation-biased adaptation. Critics have claimed that clonal interference makes mutation-biased adaptation rare. We consider the behavior of two simultaneously adapting traits, one with larger mutation rateU, the other with larger selection coefficients, using asexual traveling wave models. We find that adaptation is dominated by whichever trait has the faster rate of adaptationvin isolation, with the other trait subject to evolutionary stalling. Reviewing empirical claims for mutation-biased adaptation, we find that not all occur in the “origin-fixation” regime of population genetics wherevis only twice as sensitive tosas toU. In some cases, differences inUare at least ten to twelve times larger than differences ins, as needed to cause mutation-biased adaptation even in the “multiple mutations” regime. Surprisingly, whenU>sin the “diffusive-mutation” regime, the required sensitivity ratio is also only two, despite pervasive clonal interference. Given two traits with identicalv, the benefit of having highersis surprisingly small, occurring largely when one trait is at the boundary between the origin-fixation and multiple mutations regimes.
Identification of Characteristic Genomic Markers in Human Hepatoma Huh7 and Huh7.5.1-8 Cell Lines
Authors: Kawamoto Masaki , Yamaji Toshiyuki , Saito Kyoko , Satomura Kazuhiro , Endo Toshinori , Fukasawa Masayoshi , Hanada Kentaro , Osada Naoki 
Published: February 2020

AbstractThe human hepatoma-derived Huh7 cell line and its derivatives (Huh7.5 and Huh7.5.1) have been widely used as a convenient experimental substitute for primary hepatocytes. In particular, these cell lines represent host cells suitable for propagating the hepatitis C virus (HCV)in vitro. The Huh7.5.1-8 cell line, a subline of Huh7.5.1, can propagate HCV more efficiently than its parental cells. To provide genomic information for cells’ quality control, we performed whole-genome sequencing of Huh7 and Huh7.5.1-8 and identified their characteristic genomic deletions, some of which are applicable to an in-house test for cell authentication. Among the genes related to HCV infection and replication, 53 genes were found to carry missense or loss-of-function mutations likely specific to the Huh7 and/or Huh7.5.1-8. Eight genes, includingDDX58(RIG-I),BAX, EP300, andSPP1(osteopontin), contained mutations observed only in Huh7.5.1-8 or mutations with higher frequency in Huh7.5.1-8. These mutations might be relevant to phenotypic differences between the two cell lines and may also serve as genetic markers to distinguish Huh7.5.1-8 cells from the ancestral Huh7 cells.
IHS: an integrative method for the identification of network hubs
Authors: Salavaty Abbas , Ramialison Mirana , Currie Peter D 
Published: February 2020

AbstractBiological systems are composed of highly complex networks and decoding the functional significance of individual network components is critical for understanding healthy and diseased states. Several algorithms have been designed to identify the most influential regulatory points, or hub nodes, within a network. However, none of the current methods correct for inherent positional biases which limits their applicability. In addition, none of the currently available hub detection algorithms effectively combine network centrality measures together. To overcome this computational deficit, we undertook a statistical assessment of 200 real-world and simulated networks to decipher associations between centrality measures, and developed a novel algorithm termed “integrated hubness score” (IHS), which integrates the most important and commonly used network centrality measures, namely degree centrality, betweenness centrality and neighbourhood connectivity, in an unbiased way. When compared against the four most commonly used hub identification methods on four independent validated biological networks, the IHS algorithm outperformed all other assessed methods. Using this novel and universal method, researchers of any discipline can now identify the most influential network nodes.
Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy
Authors: Takata Norio , Sato Nobuhiko , Komaki Yuji , Okano Hideyuki , Tanaka Kenji F. 
Published: February 2020

AbstractA brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher’s necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed,i.e.combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1,381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC)acrossthe anatomical hierarchy andamongcortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.Highlights–A flexible annotation atlas (FAA) for the mouse brain is proposed.–FAA is expected to improve whole brain ROI-definition consistency among laboratories.–The ROI can be combined or divided objectively while maintaining anatomical hierarchy.–FAA realizes functional connectivity analysisacrossthe anatomical hierarchy.–Codes for FAA reconstruction is available athttps://github.com/ntakata/flexible-annotation-atlas–Datasets for resting-state fMRI in awake mice are available athttps://openneuro.org/datasets/ds002551
Estimating maximal oxygen consumption from heart rate response to submaximal ramped treadmill test
Authors: Gonzales Tomas I. , Westgate Kate , Hollidge Stefanie , Lindsay Tim , Jeon Justin , Brage Søren 
Published: February 2020

AbstractThe Cambridge Ramped Treadmill Test (CRTT) is an incremental, multistage exercise test (I: steady-state walk, II: walk ramped speed, III: walk ramped incline, and IV: run ramped speed on flat). It is typically deployed as a submaximal test with flexible test termination criteria, making it an attractive option for population-based studies of cardiorespiratory fitness. We conducted a study in healthy adults to test the validity of maximal oxygen consumption estimates (VO2 max; ml O2·kg-1·min-1) predicted from CRTT heart rate response using several methods: a heart rate-to-work rate linear regression method across several test termination criteria, either when a percentage of age-predicted maximal heart rate was achieved (50% through 100%) or at the end of distinct CRTT stages (II, III, and IV); and two single-point walk-test calibration methods using data from either CRTT stage I (low-point method) or stage II (high-point method). For estimates from the linear regression method, prediction bias ranged from −3.0 to −1.6 ml O2·kg-1·min-1 and Pearson’s r ranged from 0.57 to 0.79 for endpoints at percentages of age-predicted maximal heart rate; results were similar for stages III and IV endpoints, but predictions using data only up to stage II had poorer agreement. Agreement was moderate when using the low-point (mean bias: −4.3 ml O2·kg-1·min-1; Pearson’s r: 0.71) and high-point (mean bias: −3.5 ml O2·kg-1·min-1; Pearson’s r: 0.69) methods. Heart rate response to the CRTT can be used to predict VO2max with acceptable validity in common epidemiological scenarios.
Is migraine associated to brain anatomical alterations? New data and coordinate-based meta-analysis
Authors: Masson Rémy , Demarquay Geneviève , Meunier David , Lévêque Yohana , Hannoun Salem , Bidet-Caulet Aurélie , Caclin Anne 
Published: February 2020

AbstractA growing number of studies investigate brain anatomy in migraine using voxel-(VBM) and surface-based morphometry (SBM), as well as diffusion tensor imaging (DTI). The purpose of this article is to identify consistent patterns of anatomical alterations associated with migraine. First, 19 migraineurs without aura and 19 healthy participants were included in a brain imaging study. T1-weighted MRIs and DTI sequences were acquired and analyzed using VBM, SBM and tract-based spatial statistics. No significant alterations of gray matter (GM) volume, cortical thickness, cortical gyrification, sulcus depth and white-matter tract integrity could be observed. However, migraineurs displayed decreased white matter (WM) volume in the left superior longitudinal fasciculus. Second, a systematic review of the literature employing VBM, SBM and DTI was conducted to investigate brain anatomy in migraine. Meta-analysis was performed using Seed-based d Mapping via permutation of subject images (SDM-PSI) on GM volume, WM volume and cortical thickness data. Alterations of GM volume, WM volume, cortical thickness or white-matter tract integrity were reported in 72%, 50%, 56% and 33% of published studies respectively. Spatial distribution and direction of the disclosed effects were highly inconsistent across studies. The SDM-PSI analysis revealed neither significant decrease nor significant increase of GM volume, WM volume or cortical thickness in migraine. Overall there is to this day no strong evidence of specific brain anatomical alterations reliably associated to migraine. Possible explanations of this conflicting literature are discussed.Trial registration numberNCT02791997, registrated February 6th, 2015.