bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is p-value 0.05 enough? A study on the statistical evaluation of classifiers
Authors: Neumann Nadine M. , Plastino Alexandre , Pinto Junior Jony A. , Freitas Alex A. 
Published: November 2020

Abstract
Statistical significance analysis, based on hypothesis tests, is a common approach for comparing classifiers. However, many studies oversimplify this analysis by simply checking the condition p-value < 0.05, ignoring important concepts such as the effect size and the statistical power of the test. This problem is so worrying that the American Statistical Association has taken a strong stand on the subject, noting that although the p-value is a useful statistical measure, it has been abusively used and misinterpreted. This work highlights problems caused by the misuse of hypothesis tests and shows how the effect size and the power of the test can provide important information for better decision-making. To investigate these issues, we perform empirical studies with different classifiers and 50 datasets, using the Student’s t-test and the Wilcoxon test to compare classifiers. The results show that an isolated p-value analysis can lead to wrong conclusions and that the evaluation of the effect size and the power of the test contributes to a more principled decision-making.
Projections of Landscape Evolution on a 10,000 Year Timescale With Assessment and Partitioning of Uncertainty Sources
Authors: Barnhart Katherine R. , Tucker Gregory E. , Doty Sandra G. , Glade Rachel C. , Shobe Charles M. , Rossi Matthew W. , Hill Mary C. 
Published: November 2020

AbstractLong‐term erosion can threaten infrastructure and buried waste, with consequences for management of natural systems. We develop erosion projections over 10 ky for a 5 km2 watershed in New York, USA. Because there is no single landscape evolution model appropriate for the study site, we assess uncertainty in projections associated with model structure by considering a set of alternative models, each with a slightly different governing equation. In addition to model structure uncertainty, we consider the following uncertainty sources: selection of a final model set; each model's parameter values estimated through calibration; simulation boundary conditions such as the future incision of downstream rivers and future climate; and initial conditions (e.g., site topography which may undergo near‐term anthropogenic modification). We use an analysis‐of‐variance approach to assess and partition uncertainty in projected erosion into the variance attributable to each source. Our results suggest one sixth of the watershed will experience erosion exceeding 5 m in the next 10 ky. Uncertainty in projected erosion increases with time, and the projection uncertainty attributable to each source manifests in a distinct spatial pattern. Model structure uncertainty is relatively low, which reflects our ability to constrain parameter values and reduce the model set through calibration to the recent geologic past. Beyond site‐specific findings, our work demonstrates what information prediction‐under‐uncertainty studies can provide about geomorphic systems. Our results represent the first application of a comprehensive multi‐model uncertainty analysis for long‐term erosion forecasting.
RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response
Authors: Liu Zezhong , Xu Wei , Xia Shuai , Gu Chenjian , Wang Xinling , Wang Qian , Zhou Jie , Wu Yanling , Cai Xia , Qu Di , Ying Tianlei , Xie Youhua , Lu Lu , Yuan Zhenghong , Jiang Shibo 
Published: November 2020

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.
Fruquintinib inhibits VEGF/VEGFR2 axis of choroidal endothelial cells and M1-type macrophages to protect against mouse laser-induced choroidal neovascularization
Authors: Liu Xiaojuan , Guo Aisong , Tu Yuanyuan , Li Wendie , Li Lele , Liu Wangrui , Ju Yuanyuan , Zhou Yamei , Sang Aimin , Zhu Manhui 
Published: November 2020

AbstractWet age-related macular degeneration, which is characterized by choroidal neovascularization (CNV) and induces obvious vision loss. Vascular endothelial growth factor (VEGF) family member VEGF-A (also named as VEGF) and its receptor VEGFR2 contribute to the pathogenesis of CNV. Choroidal endothelial cells (CECs) secret C–C motif chemokine ligand 2 (CCL2), which attracts macrophages to CNV lesion and promotes macrophage M1 polarization. Accordingly, infiltrating macrophages secret inflammatory cytokines to promote CNV. In vivo, intravitreal injection of fruquintinib (HMPL-013), an antitumor neovascularization drug, alleviated mouse CNV formation without obvious ocular toxicity. Meanwhile, HMPL-013 inhibited VEGF/VEGFR2 binding in CECs and macrophages, as well as macrophage M1 polarization. In vitro, noncontact coculture of human choroidal vascular endothelial cells (HCVECs) and macrophages under hypoxia conditions was established. HMPL-013 downregulated VEGF/VEGFR2/phosphoinositide-3-kinase/protein kinase B (AKT)/nuclear factor kappa B pathway and CCL2 secretion in HCVECs, as well as VEGF/VEGFR2-induced macrophage M1 polarization under hypoxia condition. In addition, HMPL-013 inhibited HCEVC derived CCL2-induced macrophage migration and M1 polarization, along with macrophage M1 polarization-induced HCVECs proliferation, migration, and tube formation. Altogether, HMPL-013 alleviated CNV formation might via breaking detrimental cross talk between CECs and macrophages.
A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer
Authors: Gormley Mark , Dudding Tom , Sanderson Eleanor , Martin Richard M. , Thomas Steven , Tyrrell Jessica , Ness Andrew R. , Brennan Paul , Munafò Marcus , Pring Miranda , Boccia Stefania , Olshan Andrew F. , Diergaarde Brenda , Hung Rayjean J. , Liu Geoffrey , Davey Smith George , Richmond Rebecca C. 
Published: November 2020

AbstractThe independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.
Feedforward prediction error signals during episodic memory retrieval
Authors: Haque Rafi U. , Inati Sara K. , Levey Allan I. , Zaghloul Kareem A. 
Published: November 2020

AbstractOur memories enable us to form expectations for our future experiences, yet the precise neural mechanisms underlying how we compare any experience to our memory remain unknown. Here, using intracranial EEG recordings, we show that episodic memories formed after a single visual experience establish expectations for future experience within neocortical-medial temporal lobe circuits. When subsequent experiences violate these expectations, we find a 80–120 Hz prediction error signal that emerges in both visual association areas and the medial temporal lobe. Critically, this error signal emerges in visual association areas first and then propagates to the medial temporal lobe. This error signal is accompanied by alpha coherence between the two regions. Our data therefore suggest that internal models formed from episodic memories are generated throughout the visual hierarchy after just a single exposure, and that these internal models are then used for comparison with future experiences.
Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates
Authors: Savastano Adriana , Ibáñez de Opakua Alain , Rankovic Marija , Zweckstetter Markus 
Published: November 2020

AbstractThe etiologic agent of the Covid-19 pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral membrane of SARS-CoV-2 surrounds a helical nucleocapsid in which the viral genome is encapsulated by the nucleocapsid protein. The nucleocapsid protein of SARS-CoV-2 is produced at high levels within infected cells, enhances the efficiency of viral RNA transcription, and is essential for viral replication. Here, we show that RNA induces cooperative liquid–liquid phase separation of the SARS-CoV-2 nucleocapsid protein. In agreement with its ability to phase separate in vitro, we show that the protein associates in cells with stress granules, cytoplasmic RNA/protein granules that form through liquid-liquid phase separation and are modulated by viruses to maximize replication efficiency. Liquid–liquid phase separation generates high-density protein/RNA condensates that recruit the RNA-dependent RNA polymerase complex of SARS-CoV-2 providing a mechanism for efficient transcription of viral RNA. Inhibition of RNA-induced phase separation of the nucleocapsid protein by small molecules or biologics thus can interfere with a key step in the SARS-CoV-2 replication cycle.
Exploring the trade-offs between electric heating policy and carbon mitigation in China
Authors: Wang Jianxiao , Zhong Haiwang , Yang Zhifang , Wang Mu , Kammen Daniel M. , Liu Zhu , Ma Ziming , Xia Qing , Kang Chongqing 
Published: November 2020

AbstractChina has enacted a series of policies since 2015 to substitute electricity for in-home combustion for rural residential heating. The Electric Heating Policy (EHP) has contributed to significant improvements in air quality, benefiting hundreds of millions of people. This shift, however, has resulted in a sharp increase in electric loads and associated carbon emissions. Here, we show that China’s EHP will greatly increase carbon emissions. We develop a theoretical model to quantify the carbon emissions from power generation and rural residential heating sectors. We found that in 2015, an additional 101.69–162.89 megatons of CO2could potentially be emitted if EHP was implemented in 45–55% of rural residents in Northern China. In 2020, the incremental carbon emission is expected to reach 130.03–197.87 megatons. Fortunately, the growth of carbon emission will slow down due to China’s urbanization progress. In 2030, the carbon emission increase induced by EHP will drop to 119.19–177.47 megatons. Finally, we conclude two kinds of practical pathways toward low-carbon electric heating, and provide techno-economic analyses.
Tumor evolutionary trajectories during the acquisition of invasiveness in early stage lung adenocarcinoma
Authors: Wang Siwei , Du Mulong , Zhang Jingyuan , Xu Weizhang , Yuan Qianyu , Li Ming , Wang Jie , Zhu Hongyu , Wang Yuzhuo , Wang Cheng , Gong Yuhua , Wang Xiaonan , Hu Zhibin , Christiani David C. , Xu Lin , Shen Hongbing , Yin Rong 
Published: November 2020

AbstractThe evolutionary trajectories of early lung adenocarcinoma (LUAD) have not been fully elucidated. We hypothesize that genomic analysis between pre-invasive and invasive components will facilitate the description of LUAD evolutionary patterns. We micro-dissect malignant pulmonary nodules (MPNs) into paired pre-invasive and invasive components for panel-genomic sequencing and recognize three evolutionary trajectories. Evolutionary mode 1 (EM1) demonstrates none of the common driver events between paired components, but another two modes, EM2A and EM2B, exhibit critical private alterations restricted to pre-invasive and invasive components, respectively. When ancestral clones harbor EGFR mutations, truncal mutation abundance significantly decrease after the acquisition of invasiveness, which may be associated with the intratumoral accumulation of infiltrated B cells. Harboring EGFR mutations is critical to the selective pressure and further impacts the prognosis. Our findings extend the understanding of evolutionary trajectories during invasiveness acquisition in early LUAD.
Nutrients cause grassland biomass to outpace herbivory
Authors: Borer E. T. , Harpole W. S. , Adler P. B. , Arnillas C. A. , Bugalho M. N. , Cadotte M. W. , Caldeira M. C. , Campana S. , Dickman C. R. , Dickson T. L. , Donohue I. , Eskelinen A. , Firn J. L. , Graff P. , Gruner D. S. , Heckman R. W. , Koltz A. M. , Komatsu K. J. , Lannes L. S. , MacDougall A. S. , Martina J. P. , Moore J. L. , Mortensen B. , Ochoa-Hueso R. , Olde Venterink H. , Power S. A. , Price J. N. , Risch A. C. , Sankaran M. , Schütz M. , Sitters J. , Stevens C. J. , Virtanen R. , Wilfahrt P. A. , Seabloom E. W. 
Published: November 2020

AbstractHuman activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs (‘consumer-controlled’). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food (‘resource-controlled’). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.
Viral Bcl2s’ transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis
Authors: García-Murria Maria Jesús , Duart Gerard , Grau Brayan , Diaz-Beneitez Elisabet , Rodríguez Dolores , Mingarro Ismael , Martínez-Gil Luis 
Published: November 2020

AbstractViral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death.
Three host peculiarities of a cycloalkane-based micelle toward large metal-complex guests
Authors: Hanafusa Mamiko , Tsuchida Yamato , Matsumoto Kyosuke , Kondo Kei , Yoshizawa Michito 
Published: November 2020

AbstractLinear alkanes are essential building blocks for natural and artificial assemblies in water. As compared with typical, linear alkane-based micelles and recent aromatic micelles, we herein develop a cycloalkane-based micelle, consisting of bent amphiphiles with two cyclohexyl frameworks. This uncommon type of micelle, with a spherical core diameter of ~ 2 nm, forms in water in a spontaneous and quantitative manner. The cycloalkane-based, hydrophobic cavity displays peculiar host abilities as follows: (i) highly efficient uptake of sterically demanding Zn(II)-tetraphenylporphyrin and rubrene dyes, (ii) selective uptake of substituted Cu(II)-phthalocyanines and spherical nanocarbons, and (iii) uptake-induced solution-state emission of [Au(I)-dimethylpyrazolate]3 in water. These host functions toward the large metal-complex and other guests studied herein remain unaccomplished by previously reported micelles and supramolecular containers.
Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma
Authors: Federico Cinzia , Alhallak Kinan , Sun Jennifer , Duncan Kathleen , Azab Feda , Sudlow Gail P. , de la Puente Pilar , Muz Barbara , Kapoor Vaishali , Zhang Luna , Yuan Fangzheng , Markovic Matea , Kotsybar Joseph , Wasden Katherine , Guenthner Nicole , Gurley Shannon , King Justin , Kohnen Daniel , Salama Noha N. , Thotala Dinesh , Hallahan Dennis E. , Vij Ravi , DiPersio John F. , Achilefu Samuel , Azab Abdel Kareem 
Published: November 2020

AbstractDrug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity. We aim to improve treatments for MM by (1) using nanoparticle delivery to enhance efficacy and reduce toxicity; (2) targeting the tumor-associated endothelium for specific delivery of the cargo to the tumor area, and (3) synchronizing the delivery of chemotherapy (bortezomib; BTZ) and BMME-disrupting agents (ROCK inhibitor) to overcome BMME-induced drug resistance. We find that targeting the BMME with P-selectin glycoprotein ligand-1 (PSGL-1)-targeted BTZ and ROCK inhibitor-loaded liposomes is more effective than free drugs, non-targeted liposomes, and single-agent controls and reduces severe BTZ-associated side effects. These results support the use of PSGL-1-targeted multi-drug and even non-targeted liposomal BTZ formulations for the enhancement of patient outcome in MM.
Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19
Authors: Li Kening , Huang Bin , Wu Min , Zhong Aifang , Li Lu , Cai Yun , Wang Zhihua , Wu Lingxiang , Zhu Mengyan , Li Jie , Wang Ziyu , Wu Wei , Li Wanlin , Bosco Bakwatanisa , Gan Zhenhua , Qiao Qinghua , Wu Jian , Wang Qianghu , Wang Shukui , Xia Xinyi 
Published: November 2020

AbstractDeciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.
Survival of the weakest in non-transitive asymmetric interactions among strains of E. coli
Authors: Liao Michael J. , Miano Arianna , Nguyen Chloe B. , Chao Lin , Hasty Jeff 
Published: November 2020

AbstractHierarchical organization in ecology, whereby interactions are nested in a manner that leads to a dominant species, naturally result in the exclusion of all but the dominant competitor. Alternatively, non-hierarchical competitive dynamics, such as cyclical interactions, can sustain biodiversity. Here, we designed a simple microbial community with three strains of E. coli that cyclically interact through (i) the inhibition of protein production, (ii) the digestion of genomic DNA, and (iii) the disruption of the cell membrane. We find that intrinsic differences in these three major mechanisms of bacterial warfare lead to an unbalanced community that is dominated by the weakest strain. We also use a computational model to describe how the relative toxin strengths, initial fractional occupancies, and spatial patterns affect the maintenance of biodiversity. The engineering of active warfare between microbial species establishes a framework for exploration of the underlying principles that drive complex ecological interactions.
Comprehensive prediction of secondary metabolite structure and biological activity from microbial genome sequences
Authors: Skinnider Michael A. , Johnston Chad W. , Gunabalasingam Mathusan , Merwin Nishanth J. , Kieliszek Agata M. , MacLellan Robyn J. , Li Haoxin , Ranieri Michael R. M. , Webster Andrew L. H. , Cao My P. T. , Pfeifle Annabelle , Spencer Norman , To Q. Huy , Wallace Dan Peter , Dejong Chris A. , Magarvey Nathan A. 
Published: November 2020

AbstractNovel antibiotics are urgently needed to address the looming global crisis of antibiotic resistance. Historically, the primary source of clinically used antibiotics has been microbial secondary metabolism. Microbial genome sequencing has revealed a plethora of uncharacterized natural antibiotics that remain to be discovered. However, the isolation of these molecules is hindered by the challenge of linking sequence information to the chemical structures of the encoded molecules. Here, we present PRISM 4, a comprehensive platform for prediction of the chemical structures of genomically encoded antibiotics, including all classes of bacterial antibiotics currently in clinical use. The accuracy of chemical structure prediction enables the development of machine-learning methods to predict the likely biological activity of encoded molecules. We apply PRISM 4 to chart secondary metabolite biosynthesis in a collection of over 10,000 bacterial genomes from both cultured isolates and metagenomic datasets, revealing thousands of encoded antibiotics. PRISM 4 is freely available as an interactive web application at http://prism.adapsyn.com.