bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2In VitroVirus Neutralization in Convalescent Plasma
Authors: Salazar Eric , Kuchipudi Suresh V. , Christensen Paul A. , Eagar Todd N. , Yi Xin , Zhao Picheng , Jin Zhicheng , Long S. Wesley , Olsen Randall J. , Chen Jian , Castillo Brian , Leveque Christopher , Towers Dalton M. , Lavinder Jason , Gollihar Jimmy D. , Cardona Jose , Ippolito Gregory C. , Nissly Ruth H. , Bird Ian M. , Greenawalt Denver , Rossi Randall M. , Gontu Abinhay , Srinivasan Sreenidhi , Poojary Indira B. , Cattadori Isabella M. , Hudson Peter J. , Joselyn Nicole , Prugar Laura , Huie Kathleen , Herbert Andrew , Bernard David W. , Dye John , Kapur Vivek , Musser James M. 
Published: June 2020

AbstractNewly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two differentin vitroassays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, andin vitroVN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.
ClipKIT: a multiple sequence alignment-trimming algorithm for accurate phylogenomic inference
Authors: Steenwyk Jacob L. , Buida Thomas J. , Li Yuanning , Shen Xing-Xing , Rokas Antonis 
Published: June 2020

AbstractHighly divergent sites in multiple sequence alignments, which stem from erroneous inference of homology and saturation of substitutions, are thought to negatively impact phylogenetic inference. Trimming methods aim to remove these sites before phylogenetic inference, but recent analysis suggests that doing so can worsen inference. We introduce ClipKIT, a trimming method that instead aims to retain phylogenetically-informative sites; phylogenetic inference using ClipKIT-trimmed alignments is accurate, robust, and time-saving.
Multiplexed imaging of human tuberculosis granulomas uncovers immunoregulatory features conserved across tissue and blood
Authors: McCaffrey Erin F. , Donato Michele , Keren Leeat , Chen Zhenghao , Fitzpatrick Megan , Jojic Vladimir , Delmastro Alea , Greenwald Noah F. , Baranski Alex , Graf William , Bosse Marc , Ramdial Pratista K. , Forgo Erna , Van Valen David , van de Rijn Matt , Bendall Sean C. , Banaei Niaz , Steyn Adrie J.C. , Khatri Purvesh , Angelo Michael 
Published: June 2020

AbstractTuberculosis (TB) is an infectious disease caused byMycobacterium tuberculosisthat is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with T-cell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.
Stability of SARS-CoV-2 Phylogenies
Authors: Turakhia Yatish , Thornlow Bryan , Gozashti Landen , Hinrichs Angie S. , Fernandes Jason D. , Haussler David , Corbett-Detig Russell 
Published: June 2020

AbstractThe SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab-specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation and/or recombination among viral lineages. We suggest how samples can be screened and problematic mutations removed. We also develop tools for comparing and visualizing differences among phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse.ForewordWe wish to thank all groups that responded rapidly by producing these invaluable and essential sequence data. Their contributions have enabled an unprecedented, lightning-fast process of scientific discovery---truly an incredible benefit for humanity and for the scientific community. We emphasize that most lab groups with whom we associate specific suspicious alleles are also those who have produced the most sequence data at a time when it was urgently needed. We commend their efforts. We have already contacted each group and many have updated their sequences. Our goal with this work is not to highlight potential errors, but to understand the impacts of these and other kinds of highly recurrent mutations so as to identify commonalities among the suspicious examples that can improve sequence quality and analysis going forward.
Information Content of Trees: Three-taxon Statements Inference Rules and Dependency
Authors: Rineau Valentin , Zaragüeta René , Bardin Jérémie 
Published: June 2020

AbstractThe three-taxon statement is the fundamental unit of rooted trees in Cladistics, stating that for three terminal taxa, two are more related to each other than to a third. Because of their fundamental role in phylogenetics, three-taxon statements are present in methodological research of various disciplines in evolutionary biology, as in consensus methods, supertree methods, species-tree methods, distance metrics, and even phylogenetic reconstruction. However, three-taxon statements methods are subject to important flaws related to information redundancy. We aim to study the behavior of three-taxon statements and the interactions among them in order to enhance their performance in evolutionary studies. We show here how specific interactions between three-taxon statements are responsible of the emergence of redundancy and dependency within trees, and how they can be used for the improvement of weighting procedures. Our proposal is subsequently empirically tested in the supertree framework using simulations. We show that three-taxon statements using fractional weights perform drastically better than classical methods such as MRP or methods using unweighted statements. Our study shows that appropriate fractional weighting of three taxon statements is of critical importance for removing redundancy in any method using three-taxon statements, as in consensus, supertrees, distance metrics, and phylogenetic or biogeographic analyses.
Unravelling lactate-acetate conversion to butyrate by intestinalAnaerobutyricumandAnaerostipesspecies
Authors: Shetty Sudarshan A. , Boeren Sjef , Nam Bui Thi Phuong , Smidt Hauke , de Vos Willem M. 
Published: June 2020

SummaryThe D-and L-forms of lactate are important fermentation metabolites produced by intestinal bacteria but have been found to negatively affect mucosal barrier function and human health. Of interest, both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, includingAnaerobutyricumandAnaerostipesspp. This is a low energy yielding process with a partially unknown pathway inAnaerobutyricumandAnaerostipesspp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We focused onAnaerobutyricum soehngeniiand compared its growth on lactate with that on sucrose and sorbitol. Comparative proteomics revealed a unique active gene cluster that was abundantly expressed when grown on lactate. This active gene cluster,lctABCDEF, encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), along with a nickel-dependent racemase (lctE) and a lactate permease (lctF). Extensive search of available genomes of intestinal bacteria revealed this gene cluster to be highly conserved in onlyAnaerobutyricumandAnaerostipesspp. The present study demonstrates thatA. soehngeniiand several relatedAnaerobutyricumandAnaerostipesspp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.
Vascular Injury Changes Topology of Vessel Network to Adapt to Partition of Blood Flow for New Arteriovenous Specification
Authors: In Baek Kyung , Chang Shyr-Shea , Chang Chih-Chiang , Roustei Mehrdad , Ding Yichen , Wang Yixuan , Chen Justin , O’donnelle Ryan , Chen Hong , Ashby Julianne W. , Mack Julia J. , Xu Xiaolei , Cavallero Susana , Roper Marcus , Hsiai Tzung K. 
Published: June 2020

AbstractWithin vascular networks, wall shear stress (WSS) modulates endothelial cell proliferation and arteriovenous specification. Mechano-responsive signaling pathways enable vessels within a connected network to structurally adapt to properly partition blood flow between different parts of organ systems. Here, we study vascular regeneration in a zebrafish model system, performing tail amputation of the Dorsal Aorta (DA)-Posterior Cardinal Vein (PCV) embryonic circulatory loop (ECL) at 3 days post fertilization (dpf). Following severing the ECL, the topology of the micro-circular network is reorganized to engender local increase in blood flow and peak WSS in the closest Segmental Artery (SeA) to the amputation site. Remodeling of this artery increases its radius, and blood flow. These hemodynamic WSS cues activate post-angiogenic Notch-ephrinb2 signaling to guide network reconnection and restore microcirculation. Gain- and loss-of-function analyses of Notch and ephrinb2 pathways, manipulations of WSS by modulating myocardial contractility and blood viscosity directly implicate that hemodynamically activated post-angiogenic Notch-ephrinb2 signaling guides network reconnection and restore microcirculation. Taken together, amputation of the DA-PCV loop induces changes in microvascular topology to partition blood flow and increase WSS-mediated Notch-ephrinb2 pathway, driving the new DLAV-PCV loop formation for restoring local microcirculation.
Diffuse neural coupling mediates complex network dynamics through the formation of quasi-critical brain states
Authors: Müller Eli J. , Munn Brandon , Shine James M. 
Published: June 2020

AbstractThe biological mechanisms that allow the brain to balance flexibility and integration remain poorly understood. A potential solution to this mystery may lie in a unique aspect of neurobiology, which is that numerous brain systems contain diffuse synaptic connectivity. In this manuscript, we demonstrate that increasing diffuse cortical coupling within a validated biophysical corticothalamic model traverses the system through a quasi-critical regime in which spatial heterogeneities in input noise support transient critical dynamics in distributed sub-regions. We then demonstrate that the presence of quasi-critical states coincides with known signatures of complex, adaptive brain network dynamics. Finally, we demonstrate the presence of similar dynamic signatures in empirical whole brain human neuroimaging data. Together, our results establish that modulating the balance between local and diffuse synaptic coupling in a thalamocortical model subtends the emergence of quasi-critical brain states that act to flexibly transition the brain between unique modes of information processing.
Relative humidity predominantly determines long-term biocrust-forming lichen survival under climate change
Authors: Baldauf Selina , Porada Philipp , Raggio José , Maestre Fernando T. , Tietjen Britta 
Published: June 2020

AbstractManipulative experiments show a decrease in dryland biological soil crust cover and altered species composition under climate change. However, the underlying mechanisms are not fully understood, and long-term interacting effects of different drivers are largely unknown due to the short-term nature of the studies conducted so far.We addressed this gap and successfully parameterized a process-based model for the biocrust-forming lichenDiploschistes diacapsisas a common and globally distributed representative of biocrust communities to quantify how changing atmospheric CO2, temperature, rainfall amount and relative humidity affect its photosynthetic activity and cover. We also mimicked a long-term manipulative climate change experiment to understand the mechanisms underlying observed patterns in the field.The model reproduced observed experimental findings: warming reduced lichen cover whereas less rainfall had no effect. This warming effect was caused by the associated decrease in relative humidity and non-rainfall water inputs as major water sources for lichens. Warming alone, however, increased cover because higher temperatures promoted photosynthesis during the cool morning hours with high lichen activity. When combined, climate variables showed non-additive effects on lichen cover, and fertilization effects of CO2leveled off with decreasing levels of relative humidity.Synthesis.Our results show that a decrease in relative humidity, rather than an increase in temperature may be the key factor for the survival of dryland lichens under climate change and that CO2fertilization effects might be offset by a reduction in non-rainfall water inputs in the future. Because of a global trend towards warmer and thus drier air, this will affect lichen-dominated dryland biocrust communities and their role in regulating ecosystem functions, worldwide.
Multiple types of navigational information are independently encoded in the population activities of the dentate gyrus neurons
Authors: Murano Tomoyuki , Nakajima Ryuichi , Nakao Akito , Hirata Nao , Amemori Satoko , Murakami Akira , Kamitani Yukiyasu , Yamamoto Jun , Miyakawa Tsuyoshi 
Published: June 2020

AbstractThe dentate gyrus (DG) plays critical roles in cognitive functions such as learning, memory, and spatial coding, and its dysfunction is implicated in various neuropsychiatric disorders. However, it remains largely unknown how information is represented in this region. Here, we recorded neuronal activity in the DG using Ca2+imaging in freely moving mice and analysed this activity using machine learning. The activity patterns of populations of DG neurons enabled us to successfully decode position, speed, and motion direction in an open field as well as current and future location in a T-maze, and each individual neuron was diversely and independently tuned to these multiple information types. In αCaMKII heterozygous knockout mice, which present deficits in spatial remote and working memory, the decoding accuracy of position in the open field and future location in the T-maze were selectively reduced. These results suggest that multiple types of information are independently distributed in DG neurons.
Microbiota-derived short chain fatty acids promote Aβ plaque deposition
Authors: Colombo Alessio Vittorio , Sadler Rebecca K. , Llovera Gemma , Singh Vikramjeet , Roth Stefan , Heindl Steffanie , Monasor Laura Sebastian , Verhoeven Aswin , Peters Finn , Parhizkar Samira , Kamp Frits , de Agüero Mercedes Gomez , Macpherson Andrew J. , Winkler Edith , Herms Jochen , Benakis Corinne , Dichgans Martin , Steiner Harald , Giera Martin , Haass Christian , Tahirovic Sabina , Liesz Arthur 
Published: June 2020

AbstractPrevious studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, the mechanisms of microbiome-brain interaction in AD, including the microbial mediators and their cellular targets in the brain, were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as key metabolites along the gut-brain axis in AD. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice was sufficient to increase the Aβ plaque load to levels of conventionally colonized animals. While Aβ generation was only mildly affected, we observed strong microglial activation and upregulation of ApoE upon the SCFA supplementation. Taken together, our results demonstrate that microbiota-derived SCFA are the key mediators along the gut-brain axis resulting in increased microglial activation, ApoE upregulation and Aβ deposition.
Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis
Authors: Liu Yong , Li Chao , Dong Lijin , Li Ping , Chen Xuewei , Fan Rong 
Published: June 2020

AbstractBackgroundColorectal cancer (CRC) is the third most lethal malignancy in the world, wherein colon adenocarcinoma (COAD) is the most prevalent type of CRC. Exploring biomarkers is important for the diagnosis, treatment, and prevention of COAD.MethodsWe used GEO2R and Venn online software for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software, real-time PCR and immunohistochemistry.ResultsIn this study, we screened 323 common differentially expressed genes from four GSE datasets. Furthermore, four hub genes were selected for survival correlation analysis and expression level verification, three of which were shown to be statistically significant.ConclusionOur study suggests that SERPINE1, SPP1 and TIMP1 may be biomarkers closely related to the prognosis of CRC patients.
Prolonged SARS-CoV-2 Viral Shedding in Patients with COVID-19 was Associated with Delayed Initiation of Arbidol Treatment: a retrospective cohort study
Authors: Zhou Yaya , He Xinliang , Zhang Jianchu , Xue Yu’e , Liang Mengyuan , Yang Bohan , Ma Wanli , Zhou Qiong , Chen Long , Wang Xiaorong 
Published: June 2020

AbstractObjectivesEvaluate the risk factors of prolonged SARS-CoV-2 virus shedding and the impact of arbidol treatment on SARS-CoV-2 virus shedding.MethodsData were retrospective collected from adults hospitalized with COVID-19 in Wuhan Union Hospital. We described the clinical features and SARS-CoV-2 RNA shedding of patients with COVID-19 and evaluated factors associated with prolonged virus shedding by multivariate regression analysis.ResultsAmong 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) used arbidol, 58.4% (139/238) used arbidol combination with interferon. The median time from illness onset to start arbidol was 8 days (IQR, 5-14 days) and the median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8–30 days). SARS-CoV-2 RNA clearance was significantly delayed in patients who received arbidol >7 days after illness onset, compared with those in whom arbidol treatment was started≤7 days after illness onset (HR, 1.738 [95% CI, 1.339–2.257], P < .001). Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol more than seven days after symptom onset (OR 2.078, 95% CI [1.114-3.876], P .004), more than 7 days from onset of symptoms to first medical visitation (OR 3.321, 95% CI[1.559-7.073], P .002), illness onset before Jan.31, 2020 (OR 3.223, 95% CI[1.450-7.163], P .021). Arbidol combination with interferon was also significantly associated with shorter virus shedding (OR .402, 95% CI[.206-.787], P .008).ConclusionsEarly initiation of arbidol and arbidol combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.
Addressing capacities of local communities in a changing context in Nepal
Authors: Rolsted Morten , Raju Emmanuel 
Published: June 2020

PurposeThe field study aimed at exploring how capacities are influenced by external factors in the context of community-based disaster risk reduction (CBDRR).Design/methodology/approachThe field study was conducted in a small rural area called Lapsibot in Lamjung district in Nepal. The article is based on a fieldwork conducted in April 2018. The different tools of data collection were inspired by the vulnerability and capacity assessment approach with a focus on various aspects of vulnerabilities and capacities with regard to disaster risk reduction (DRR) in Lapsibot.FindingsThe paper highlights that communities, in fact, need enhanced and extended capacities, not only existing inherent capacities, which are usually the main subject of capacity development in rural communities.Originality/valueWhile there is absolutely no question of strong capacities at the community level, this paper appeals for a more in-depth investigation of an extended notion of capacities, where the effects of the rapid changes and increasing impact of the outside world are taken into consideration.