bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics of Coronavirus Disease 2019 (COVID-19): An Updated Systematic Review
Authors: Fang Zhangfu , Yi Fang , Wu Kang , Lai Kefang , Sun Xizhuo , Zhong Nanshan , Liu Zhigang 
Published: March 2020

AbstractOBJECTIVEClinical characteristics of novel coronavirus disease (COVID-19) have been described in numerous studies but yielded varying results. We aimed to conduct a systematic review on scientific literatures and to synthesize critical data on clinical traits of COVID-19 from its initial outbreak to pandemic.METHODSSystematic searches were conducted to identify retrospective observational study that contained clinical characteristics on COVID-19 through multiple databases. Two reviewers independently evaluated eligible publications. Data on clinical characteristics of COVID-19 were extracted and analyzed.RESULTSSeventy-two retrospective studies demonstrating the clinical characteristics of COVID-19 were included. A total of 3470 COVID-19 patients were synthesized to the final analysis in an unbiased manner. The most common symptom was fever (2878 [83.0%]), and 63.4% of the patients presented fever as onset symptom. There were 2528 [88.2%] of 2866 cases had abnormal lung findings on chest CT scan. Laboratory findings showed that 1498 [62.8%] of 2387 cases had lymphopenia, and 1354 [64.8%] of 2091 cases had an increased level of C-reactive protein (CRP). A total of 185 [11.5%] patients were admitted to intensive care unit (ICU) while the overall case fatality rate (CFR) was 3.7%. Compared to patients admitted outside of Hubei, China, those from Hubei had a significant higher ICU admission rate (21.9% vs. 2.5%, p<0.001). Also, CFR attributed to COVID-19 was significantly higher in Hubei than that of non-Hubei admissions (10.4% vs. 0.6%, p<0.001).INTERPRETATIONThis large patient-based systematic review presents a more precise profiling of the COVID-19 from its outbreak to current pandemic. Dynamic evolvements of COVID-19 are needed to be characterized in future studies.
Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection
Authors: Hong Xu-wei , Chi Ze-pai , Liu Guo-yuan , Huang Hong , Guo Shun-qi , Fan Jing-ru , Lin Xian-wei , Qu Liao-zhun , Chen Rui-lie , Wu Ling-jie , Wang Liang-yu , Zhang Qi-chuan , Wu Su-wu , Pan Ze-qun , Lin Hao , Zhou Yu-hua , Zhang Yong-hai 
Published: March 2020

AbstractObjectivesThe aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19.DesignThe study was an observational, descriptive study.SettingThis study was carried out in a tertiary hospital in Guangdong, China.Participants12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020.Primary and secondary outcome measuresThe primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury.ResultsWhile all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury.ConclusionsEarly renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.
Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak
Authors: Liu Yuan , Ning Zhi , Chen Yu , Guo Ming , Liu Yingle , Gali Nirmal Kumar , Sun Li , Duan Yusen , Cai Jing , Westerdahl Dane , Liu Xinjin , Ho Kin-fai , Kan Haidong , Fu Qingyan , Lan Ke 
Published: March 2020

AbstractBackgroundThe ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied.MethodsThirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration.ResultsThe ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow.ConclusionsRoom ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2.
Comparison of Radiologist-Assigned Categories and Quantitative Measures of Background Parenchymal Enhancement on Breast MRI
Authors: Niell Bethany L , Abdalah Mahmoud , Stringfield Olya , Pereira Malesa , Ataya Dana , Balagurunathan Yoga , Gillies Robert , Raghunand Natarajan 
Published: March 2020

AbstractBackground parenchymal enhancement (BPE) on multi-parametric breast magnetic resonance imaging (mpMRI) reflects the volume and intensity of gadolinium uptake. We developed a semi-automated segmentation algorithm to extract and quantify measures of BPE and investigated the agreement of computed measures of BPE with radiologist-assigned categories. We retrospectively identified 123 high risk patients with breast mpMRI performed for screening indications. Pre- and post-gadolinium T1-weighted series with and without fat suppression were co-registered. Using Otsu’s method and an active contours method, the breast tissue was segmented from the chest wall and non-fat voxels were clustered to identify the amount of fibroglandular tissue. Median and inter-quartile ranges for the absolute volume of BPE (BPE cm3) and the percentage of BPE (BPE%) using a threshold PE of 30% were computed within the segmented FGT on the first post-contrast phase. Student’s t-test was used to evaluate BPE volume and BPE% by radiologist-assigned categories. Both BPE volume and BPE% differed significantly between minimal/mild and moderate/marked radiologist assigned categories (p=0.030 and 0.004, respectively). Using our newly developed semi-automated segmentation pipeline, we quantified fibroglandular tissue and BPE. The overlapping ranges of quantitative BPE corresponding to the radiologist-assigned BPE categories showcases the inter-reader variability with visual estimation of BPE.
Ascertainment rate of novel coronavirus disease (COVID-19) in Japan
Authors: Omori Ryosuke , Mizumoto Kenji , Nishiura Hiroshi 
Published: March 2020

AbstractObjectiveTo estimate the ascertainment rate of novel coronavirus (COVID-19).MethodsWe analyzed the epidemiological dataset of confirmed cases with COVID-19 in Japan as of 28 February 2020. A statistical model was constructed to describe the heterogeneity of reporting rate by age and severity. We estimated the number of severe and non-severe cases, accounting for under-ascertainment.ResultsThe ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50), indicating that unbiased number of non-cases would be more than twice the reported count.ConclusionsSevere cases are twice more likely diagnosed and reported than other cases. Considering that reported cases are usually dominated by non-severe cases, the adjusted total number of cases is also about a double of observed count. Our finding is critical in interpreting the reported data, and it is advised to interpret mild case data of COVID-19 as always under-ascertained.Highlights-Epidemiological dataset of COVID-19 in Japan was analyzed.-The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval: 0.37, 0.50).-Severe cases are twice more likely diagnosed and reported than other cases.-Mild cases of COVID-19 are under-ascertained.
A TgfβRI/Snai1-dependent developmental module at the core of vertebrate axial elongation
Authors: Dias André , Lozovska Anastasiia , Wymeersch Filip J. , Nóvoa Ana , Binagui-Casas Anahi , Sobral Daniel , Martins Gabriel G. , Wilson Valerie , Mallo Moisés 
Published: March 2020

ABSTRACTFormation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary body) through the activity of the primitive streak (PS) on axial progenitors within the epiblast. The embryo then switches to generate the secondary body (post-sacral structures), which depends on axial progenitors in the tail bud. Here we show that the mammalian tail bud is generated through an independent developmental module, concurrent but functionally different to that generating the primary body. This module is triggered by convergent TgfβRI and Snai1 activities that promote an incomplete epithelial to mesenchymal transition (EMT) on a subset of epiblast axial progenitors. This EMT is functionally different to that coordinated by the PS, as it does not lead to mesodermal differentiation but brings axial progenitors into a transitory state, keeping their progenitor activity to drive further axial body extension.
IncreasedAPOEε4expression is associated with reactive A1 astrocytes and the difference in Alzheimer Disease risk from diverse ancestral backgrounds
Authors: Griswold A. J. , Celis K. , Bussies P. , Rajabli F. , Whitehead P. , Hamilton-Nelson K. , Beecham G. W. , Dykxhoorn D. M. , Nuytemans K. , Wang L. , Gardner O. K. , Dorfsman D. , Bigio E.H. , Mesulam M. , Weintraub S. , Geula C. , Gearing M. , Martinez-McGrath E. , Dalgard C.L. , Scott W. K. , Haines J. L. , Pericak-Vance M.A. , Young J. I. , Vance J. M. 
Published: March 2020

AbstractAPOEε4African local genomic ancestry (LA) confers less risk for Alzheimer disease (AD) relative to European LA (LA) carriers. Single nucleus RNA sequencing from AD-APOEε4/4frontal cortex found European LA carriers have a 1.45-fold greaterAPOEε4expression (p< 1.8 E10−313) and are associated with a unique A1 reactive astrocyte cluster. This suggests a potential mechanism for the increased risk for AD seen in European LA carriers ofAPOEε4.
Robust inference of positive selection on regulatory sequences in human brain
Authors: Liu Jialin , Robinson-Rechavi Marc 
Published: March 2020

AbstractA long standing hypothesis is that divergence between humans and chimpanzees might have been driven more by regulatory level adaptions than by protein sequence adaptations. This has especially been suggested for regulatory adaptions in the evolution of the human brain. There is some support for this hypothesis, but it has been limited by the lack of a reliable and powerful way to detect positive selection on regulatory sequences. We present a new method to detect positive selection on transcription factor binding sites, based on Orr’s sign test applied to a machine learning model of binding. Unlike other methods, this requires neither defining a priori neutral sites, nor detecting accelerated evolution, thus removing major sources of bias. The method is validated in flies, mice, and primates, by a McDonald-Kreitman-like measure of polymorphism vs. divergence, by experimental binding site gains and losses, and by changes in expression levels. We scanned the signals of positive selection for CTCF binding sites in 29 human and 11 mouse tissues or cell types. We found that human brain related cell types have the highest proportion of positive selection. This is consistent with the importance of adaptive evolution on gene regulation in the evolution of the human brain.
Benchmark of lasso-like penalties in the Cox model for TCGA datasets reveal improved performance with pre-filtering and wide differences between cancers
Authors: Jardillier Rémy , Chatelain Florent , Guyon Laurent 
Published: March 2020

AbstractMotivationPrediction of patient survival from tumor molecular ‘omics’ data is a key step toward personalized medicine. With this aim, the databases available are growing, with the collection of various ‘omics’ characterizations of patient tumors, together with their associated clinical outcomes for weeks to years of follow-up. Cox models with variable selection used with RNA profiling datasets are popular for identification of prognostic biomarkers and for clinical predictions. However, these models are confronted with the ‘curse of dimensionality’, as the numberpof covariates (genes) can greatly exceed the numbernof patients. To tackle this problem, variance-based pre-filtering and penalization methods are popular for dimension reduction. In the present paper, we study the impact of a pre-filtering step based on gene variability, and we evaluate the performance of the lasso penalization of the Cox model and four variants (i.e., elastic net, adaptive elastic net, ridge, univariate Cox) in terms of prediction, selection and stability.ResultsFirst, we show that the prediction capacity with the Cox penalties method is cancer dependent. Second, we develop a methodology to fix a threshold to filter out genes with low variability without losing prediction capacity. Third, we show that it is best not to use the Cox model to select prognostic biomarkers, as its false discovery proportion is always ≥ 50%. Finally, to predict overall survival, we can suggest the use of the ridge penalty, or the elastic net if a more parsimonious model is needed, after the pre-filtering step.AvailabilityWe provide the R script generated to reproduce all of the figures presented in this article.Supplementary informationSupplementary Figures and R scripts are available.
Ecological consequences of intraspecific variation in coevolutionary systems
Authors: Senthilnathan Athmanathan , Gavrilets Sergey 
Published: March 2020

AbstractThe patterns and outcomes of coevolution are expected to depend on intraspecific trait variation. Various evolutionary factors can change this variation in time. As a result, modeling coevolutionary processes solely in terms of mean trait values may not be sufficient; one may need to study the dynamics of the whole trait distribution. Here, we develop a theoretical framework for studying the effects of evolving intraspecific variation in two-species coevolutionary systems. In particular, we build and study mathematical models of competition, exploiter-victim interactions, and mutualism in which the strength of within- and between-species interactions depends on the difference in continuously varying traits. We use analytical approximations based on the invasion analysis and supplement it with a numerical method. We find that intraspecific variation can be maintained if stabilizing selection is weak in at least one species. When intraspecific variation is maintained, stable coexistence is promoted by small ranges of interspecific interaction in two-species competition and mutualism, and large ranges in exploiter-victim interactions. We show that trait distributions can become multimodal. Our approach and results contribute to the understanding of the ecological consequences of intraspecific variation in coevolutionary systems by exploring its effects on population densities and trait distributions.
Massively parallel encapsulation of single cells with structured microparticles and secretion-based flow sorting
Authors: de Rutte Joseph , Dimatteo Robert , Archang Maani M , van Zee Mark , Koo Doyeon , Lee Sohyung , Sharrow Allison C. , Krohl Patrick J. , Mellody Michael P. , Zhu Sheldon , Eichenbaum James , Kizerwetter Monika , Udani Shreya , Ha Kyung , Bertozzi Andrea L. , Spangler Jamie B. , Damoiseaux Robert , Carlo Dino Di 
Published: March 2020

AbstractTechniques to analyze and sort single cells based on functional outputs, such as secreted products, have the potential to transform our understanding of cellular biology, as well as accelerate the development of next generation cell and antibody therapies. However, secreted molecules rapidly diffuse away from cells, and analysis of these products requires specialized equipment and expertise to compartmentalize individual cells and capture their secretions. Herein we demonstrate the use of suspendable microcontainers to sort single viable cells based on their secreted products at high-throughput using only commonly accessible laboratory infrastructure. Our microparticles act as solid supports which facilitate cell attachment, partition uniform aqueous compartments, and capture secreted proteins. Using this platform, we demonstrate high-throughput screening of stably- and transiently-transfected producer cells based on relative IgG production as well as screening of B lymphocytes and hybridomas based on antigen-specific antibody production using commercially available flow sorters. Leveraging the high-speed sorting capabilities of standard sorters, we sorted >1,000,000 events in less than an hour. The reported microparticles can be easily stored, and distributed as a consumable reagent amongst researchers, democratizing access to high-throughput functional cell screening.
Evolutionary variation in MADS-box dimerization affects floral development and protein stability
Authors: Juarez Maria Jazmin Abraham , Schrager-Lavelle Amanda , Man Jarrett , Whipple Clinton , Handakumbura Pubudu , Babbitt Courtney , Bartlett Madelaine 
Published: March 2020

AbstractShifting interactions between MADS-box transcription factors may have been critical in the emergence of the flower, and in floral diversification. However, how evolutionary variation in MADS-box interactions affects the development and evolution of floral form remains unknown. Interactions between B-class MADS-box proteins are variable across the grass family. Here, we test the functional consequences of this evolutionary variability using maize as an experimental system. We found that differential B-class dimerization was associated with subtle, quantitative differences in stamen shape. In contrast, differential dimerization resulted in large-scale changes to protein complex composition and downstream gene expression. Differential dimerization also affected B-class complex abundance, independent of RNA levels. Thus, differential dimerization may affect protein stability. This reveals an important consequence for evolutionary variability in MADS-box interactions, adding complexity to the evolution of developmental gene networks. Our results show that floral development is robust to molecular change, even coding change in a master regulator of development. This robustness may contribute to the evolvability of floral form.
Evidence for non-methanogenic metabolisms in globally distributed archaeal clades basal to theMethanomassiliicoccales
Authors: Zinke Laura A. , Evans Paul N. , Schroeder Alena L. , Parks Donovan H. , Varner Ruth K. , Rich Virginia I. , Tyson Gene W. , Emerson Joanne B. 
Published: March 2020

AbstractRecent discoveries ofmcrandmcr-like complexes in genomes from diverse archaeal lineages suggest that methane (and more broadly alkane) metabolism is an ancient pathway with complicated evolutionary histories. The conventional view is that methanogenesis is an ancestral metabolism of the archaeal classThermoplasmata. Through comparative genomic analysis of 12Thermoplasmatametagenome-assembled genomes (MAGs), we show that these microorganisms do not encode the genes required for methanogenesis, which suggests that this metabolism may have been laterally acquired by an ancestor of the orderMethanomassiliicoccales. These MAGs include representatives from four orders basal to theMethanomassiliicoccales, including a high-quality MAG (95% complete) that likely represents a new order,Ca.Lunaplasma lacustris ord. nov. sp. nov. These MAGs are predicted to use diverse energy conservation pathways, such as heterotrophy, sulfur and hydrogen metabolism, denitrification, and fermentation. Two of these lineages are globally widespread among anoxic, sedimentary environments, with the exception ofCa.Lunaplasma lacustris, which has thus far only been detected in alpine caves and subarctic lake sediments. These findings advance our understanding of the metabolic potential, ecology, and global distribution of theThermoplasmataand provide new insights into the evolutionary history of methanogenesis within theThermoplasmata.
The demographic decline of a sea lion population followed multi-decadal sea surface warming
Authors: Adame Karen , Elorriaga-Verplancken Fernando R. , Beier Emilio , Acevedo-Whitehouse Karina , Pardo Mario A. 
Published: March 2020

AbstractBackgroundThe population growth of top predators depends largely on environmental conditions suitable for aggregating sufficient and high-quality prey. We reconstructed numerically the population size dynamics of a resident population of California sea lions in the Gulf of California during 1978 – 2019, and its relation with the gulf’s multi-decadal sea surface temperature trend. This are the first long-term insights to the oceanic environment of the Gulf of California and to the population trend of one of its major predators.ResultsOur results indicate that a three-decade sustained warming explains statistically the population’s trend, including a ∼65% decline between 1991 – 2019, accounting for 92% of the variance. Long-term warming conditions started in the late 80’s, followed by the population’s decline, from a peak of 43,834 animals (range: 34,080 - 58,274) in 1991 to only 15,291 (range: range: 11,861 - 20,316) in 2019. The models suggested a century-scale optimum sea surface habitat for the population occurring in mildly temperate waters, from 0.18 to 0.39°C above the 100- year mean of 22.24°C.ConclusionsThe negative relation of the population size with warming sea surface conditions was evident, and the predictability of the former from the sea surface temperature 100-year anomalies was high. The mechanistic links of this relation are still untested, but an apparent diversification of pelagic fish catches suggests a reduction of high quality prey. We propose that this sea lion population should be considered as vulnerable to any disturbance that could add to the negative effects of the current sea surface warming conditions in the Gulf of California.