bluuebunny/crossref_metadata_2025_split huggingface dataset:
A two-phase stochastic dynamic model for COVID-19 mid-term policy recommendations in Greece: a pathway towards mass vaccination
Authors: Rachaniotis N.P. , Dasaklis T.K. , Fotopoulos F. , Tinios P. 
Published: January 2021

AbstractFrom November 7th, 2020, Greece adopted a second nationwide lockdown policy to mitigate the transmission of SARS-CoV-2 (the first took place from March 23rdtill May 4th, 2020), just as the second wave of COVID-19 was advancing, as did other European countries. In the light of the very promising voluntary mass vaccination, which will start in January 2021, it is of utmost importance for the country to plan to complement vaccination with mid-term Non-Pharmaceutical Interventions (NPIs). The objective is to minimize human losses and to limit social and economic costs. In this paper a two-phase stochastic dynamic network compartmental model (a pre-vaccination SEIR until February 15th, 2021 and a post-vaccination SVEIR from February 15th, 2021 to June 30th, 2021) is developed. Three scenarios are assessed in the first phase: (a) abaseline scenario, which lifts the national lockdown and all NPIs on January 2021, (b) a“semi-lockdown” scenario with school opening, partial retail sector operation, universal mask wearing and social distancing/teleworking on January 2021 and (c) a “rolling lockdown” scenario combining apartial lifting of measuresin January 2021 followed by a third imposed nationwide lockdown in February 2021. In the second phase three scenarios with different vaccination rates are assessed. Publicly available data along with some preliminary first results of the SHARE COVID-19 survey conducted in Greece are used as input. The results regarding the first phase indicate that the “semi-lockdown” scenario outperforms the third lockdown scenario (5.7% less expected fatalities), whereas in the second phase it is of great importance to ensure a sufficient vaccine supply and high vaccination rates.
Timeliness of provisional United States mortality data releases during the COVID-19 pandemic: delays associated with electronic death registration system and weekly mortality
Authors: Rosenbaum Janet E. , Stillo Marco , Graves Nathaniel , Rivera Roberto 
Published: January 2021

AbstractAll-cause mortality counts allow public health authorities to identify populations experiencing excess deaths from pandemics, natural disasters, and other emergencies. Delays in the completeness of mortality counts may contribute to misinformation because death counts take weeks to become accurate. We estimate the timeliness of all-cause mortality releases during the Covid-19 pandemic for the dates 3 April to 5 September 2020 by estimating the number of weekly data releases of the NCHS Fluview Mortality Surveillance System until mortality comes within 99% of the counts in the 19 March 19 2021 provisional mortality data release. States’ mortality counts take 5 weeks at median (interquartile range 4--7 weeks) to completion. The fastest states were Maine, New Hampshire, Vermont, New York, Utah, Idaho, and Hawaii. States that had not adopted the electronic death registration system (EDRS) were 4.8 weeks slower to achieve complete mortality counts, and each weekly death per 10^8 was associated with a 0.8 week delay. Emergency planning should improve the timeliness of mortality data by improving state vital statistics digital infrastructure.
High prevalence of long-term psychophysical olfactory dysfunction in patients with COVID-19
Authors: Boscolo-Rizzo Paolo , Menegaldo Anna , Fabbris Cristoforo , Spinato Giacomo , Borsetto Daniele , Vaira Luigi Angelo , Calvanese Leonardo , Pettorelli Andrea , Sonego Massimo , Frezza Daniele , Bertolin Andy , Cestaro Walter , Rigoli Roberto , Tirelli Giancarlo , Mosto Maria Cristina Da , Menini Anna , Polesel Jerry , Hopkins Claire 
Published: January 2021

AbstractThis study prospectively assessed the long-term prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 54 (37.2) being mildly microsmic, 16 (11.0%) moderately microsmic, 7 (4.8%) severely microsmic, and 10 patients (6.9%) being anosmic. At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of sense of smell or taste and olfactory test scores (Spearman’s r=-0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of SARS-CoV-2 infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-CoV-2 infection.
Causal Mediation Analysis with Multiple Causally Ordered and Non-ordered Mediators based on Summarized Genetic Data
Authors: Hou Lei , Yu Yuanyuan , Sun Xiaoru , Liu Xinhui , Yu Yifan , Yan Ran , Li Hongkai , Xue Fuzhong 
Published: January 2021

AbstractCausal mediation analysis aims to investigate the mechanism linking an exposure and an outcome. Dealing with the impact of unobserved confounders among the exposure, mediator and outcome has always been an issue of great concern. Moreover, when multiple mediators exist, this causal pathway intertwines with other causal pathways, making it more difficult to estimate of path-specific effects (PSEs). In this article, we propose a method (PSE-MR) to identify and estimate PSEs of an exposure on an outcome through multiple causally ordered and non-ordered mediators using Mendelian Randomization, when there are unmeasured confounders among the exposure, mediators and outcome. Additionally, PSE-MR can be used when pleiotropy exists, and can be implemented using only summarized genetic data. We also conducted simulations to evaluate the finite sample performances of our proposed estimators in different scenarios. The results show that the causal estimates of PSEs are almost unbiased with good coverage and Type I error properties. We illustrate the utility of our method through a study of exploring the mediation effects of lipids in the causal pathways from body mass index to cardiovascular disease.Author summaryA new method (PSE-MR) is proposed to identify and estimate PSEs of an exposure on an outcome through multiple causally ordered and non-ordered mediators using summarized genetic data, when there are unmeasured confounders among the exposure, mediators and outcome. Lipids play important roles in the causal pathways from body mass index to cardiovascular disease
Differential encoding of safe and risky offers
Authors: Maisson David J-N. , Michael Yoo Seng Bum , Wang Maya Zhe , Cash-Padgett Tyler V. , Zimmermann Jan , Hayden Benjamin Y. 
Published: January 2021

ABSTRACTCommon currency theories in neuroeconomics hold that neurons in specific brain regions specifically encode subjective values of offers and not stimulus-specific information. The rationale behind these theories is that abstract value encoding lets the decision maker compare qualitatively different options. Alternatively, expectancy-based theories hold that the brain preferentially tracks the relationship between options and their outcomes, and thus does not abstract away details of offers. To adjudicate between these theories, we examined responses of neurons in six reward regions to risky and safe offers while macaques performed a gambling task. In all regions, responses to safe options are unrelated to responses evoked by equally preferred risky options. Nor does any region appear to contain a specialized subset of value-selective neurons. Finally, in all regions, responses to risky and safe options occupy distinct response subspaces, indicating that the organizational framework for encoding risky and safe offers is different. Together, these results argue against the idea that putative reward regions carry abstract value signals, and instead support the idea that these regions carry information that links specific options to their outcomes in support of a broader cognitive map.
Multi-antigen recognition circuits overcome challenges of specificity, heterogeneity, and durability in T cell therapy for glioblastoma
Authors: Choe Joseph H. , Watchmaker Payal B. , Simic Milos S. , Gilbert Ryan D. , Li Aileen W. , Krasnow Nira A. , Carrera Diego A. , Yu Wei , Downey Kira M. , Celli Anna , Cho Juhyun , Briones Jessica D. , Dannenfelser Ruth , Cardarelli Lia , Sidhu Sachdev S. , Roybal Kole T. , Okada Hideho , Lim Wendell A. 
Published: January 2021

ABSTRACTTreatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of target antigens that are both tumor-specific and homogeneously expressed. We show that multiantigen prime-and-kill recognition circuits have the flexibility and precision to overcome these challenges in attacking glioblastoma. A synNotch receptor that recognizes a specific priming antigen – the heterogeneous glioblastoma neoantigen EGFRvIII or a brain tissue-specific antigen – is used to locally induce expression of a CAR, enabling thorough but controlled tumor killing by targeting of homogeneous antigens that are not absolutely tumor specific. Moreover, regulated CAR expression maintains a higher fraction of the T cells in the naïve-like state which is associated with higher durabilityin vivo. In summary, using circuits that integrate recognition of multiple imperfect but complementary antigens, we improve the specificity and persistence of T cells directed against glioblastoma, providing a general recognition strategy applicable to other solid tumors.
Telomerase Prevents Emphysema in Old Mice by Sustaining Subpopulations of Endothelial and AT2 Cells
Authors: Breau Marielle , Cayrou Christelle , Churikov Dmitri , Fouillade Charles , Curras-Alonso Sandra , Bauwens Serge , Jourquin Frederic , Braud Laura , Fiore Frederic , Castellano Rémy , Josselin Emmanuelle , Sánchez-Ferrer Carlota , Giovinazzo Giovanna , Gilson Eric , Flores Ignacio , Londono-Vallejo Arturo , Adnot Serge , Géli Vincent 
Published: January 2021

AbstractAccumulation of senescent cells has been causally linked to the development of age-related pathologies. Here, we characterized a new mouse model (p21+/Tert) whose telomerase (TERT) is expressed from the p21 promoter that can be activated in response to telomere dysfunction. Lung parenchyma from p21+/Tertold mice accumulated fewer senescent cells with age and this correlated with a reduction in age-related alveolar space enlargement, a feature of pulmonary emphysema. This protection against emphysema depends on TERT catalytic activity and is associated with increased proliferation of pulmonary endothelial cells (EC) and capillary density. Single-cell RNA sequencing of lung cells revealed that TERT expression was associated with the enrichment of ECs expressing genes involved in vessel regeneration and in AT2 cells overexpressing S/G2M markers. These findings indicate that p21-promoter-dependent expression of catalytically active telomerase prevents emphysema by sustaining the proliferation of subclasses of EC and AT2 cells.
Interplay between intrinsic reprogramming potential and microenvironment controls neuroblastoma cell plasticity and identity
Authors: Thirant Cécile , Peltier Agathe , Durand Simon , Kramdi Amira , Louis-Brennetot Caroline , Pierre-Eugène Cécile , Costa Ana , Grelier Amandine , Zaïdi Sakina , Gruel Nadège , Jimenez Irène , Lapouble Eve , Pierron Gaëlle , Brisse Hervé J. , Gauthier Arnaud , Fréneaux Paul , Grossetête-Lalami Sandrine , Baudrin Laura G. , Raynal Virginie , Baulande Sylvain , Bellini Angela , Bhalshankar Jaydutt , Carcaboso Angel M. , Geoerger Birgit , Rohrer Hermann , Surdez Didier , Boeva Valentina , Schleiermacher Gudrun , Delattre Olivier , Janoueix-Lerosey Isabelle 
Published: January 2021

AbstractTwo cell identities, noradrenergic and mesenchymal, have been characterized in neuroblastoma cell lines according to their epigenetic landscapes relying on specific circuitries of transcription factors. Yet, their relationship and relative contribution in patient tumors remain poorly defined. Here, we demonstrate that the knock-out ofGATA3, but not ofPHOX2AorPHOX2B, in noradrenergic cells induces a mesenchymal phenotype. Our results document spontaneous plasticity in several models between both identities and show that plasticity relies on epigenetic reprogramming. We demonstrate that anin vivomicroenvironment provides a powerful pressure towards a noradrenergic identity for these models. Consistently, tumor cells with a mesenchymal identity are not detected in a series of PDX models. Further study of the intra-tumor noradrenergic heterogeneity reveals two distinct cell populations exhibiting features of chromaffin-like or sympathoblast-like cells. This work emphasizes that both external cues of the environment and intrinsic factors control plasticity and cell identity in neuroblastoma.
Creating wounds in cell monolayers using micro-jets
Authors: Soitu Cristian , Panea Mirela , Castrejón-Pita Alfonso A. , Cook Peter R. , Walsh Edmond J. 
Published: January 2021

AbstractMany wound-healing assays are used in cell biology and biomedicine; they are often labor intensive and/or require specialized and costly equipment. We describe a contactless method to create wounds with any imaginable 2D pattern in cell monolayers using micro-jets of either media or an immiscible and biocompatible fluorocarbon (i.e., FC40). We also combine this with another method that allows automation and multiplexing using standard Petri dishes. A dish is filled with a thin film of media overlaid with FC40, and the two liquids reshaped into an array of microchambers in minutes. Each chamber in such a grid is isolated from others by fluid walls of FC40. Cells are now added, allowed to grow into a monolayer, and wounds created using the microjets; then, healing is monitored by microscopy. As arrays of chambers can be made using the media and Petri dishes familiar to biologists, and as dishes fit seamlessly into their incubators, microscopes, and workflows, we anticipate this assay will find wide application in biomedicine.
DeepFrag: A Deep Convolutional Neural Network for Fragment-based Lead Optimization
Authors: Green Harrison , Koes David R. , Durrant Jacob D. 
Published: January 2021

1AbstractMachine learning has been increasingly applied to the field of computer-aided drug discovery in recent years, leading to notable advances in binding-affinity prediction, virtual screening, and QSAR. Surprisingly, it is less often applied to lead optimization, the process of identifying chemical fragments that might be added to a known ligand to improve its binding affinity. We here describe a deep convolutional neural network that predicts appropriate fragments given the structure of a receptor/ligand complex. In an independent benchmark of known ligands with missing (deleted) fragments, our DeepFrag model selected the known (correct) fragment from a set over 6,500 about 58% of the time. Even when the known/correct fragment was not selected, the top fragment was often chemically similar and may well represent a valid substitution. We release our trained DeepFrag model and associated software under the terms of the Apache License, Version 2.0. A copy can be obtained free of charge fromhttp://durrantlab.com/deepfragmodel.
Invasive grass dominance over native forbs is linked to shifts in the bacterial rhizosphere microbiome
Authors: LaForgia Marina L. , Kang Hannah , Ettinger Cassandra L. 
Published: January 2021

AbstractRhizosphere microbiomes have received growing attention in recent years for their role in plant health, stress tolerance, soil nutrition, and invasion. Still, relatively little is known about how these microbial communities are altered under plant competition, and even less about whether these shifts are tied to competitive outcomes between native and invasive plants. We investigated the structure and diversity of rhizosphere bacterial and fungal microbiomes of native annual forbs and invasive annual grasses individually and in competition using high-throughput amplicon sequencing of the bacterial 16S rRNA gene and the fungal ITS region. We assessed how differentially abundant microbial families correlate to plant biomass under competition We find that bacterial diversity and structure differ between native forbs and invasive grasses, but fungal diversity and structure do not. Further, bacterial community structures under competition are distinct from individual bacterial community structures. We also identified five bacterial families that varied in normalized abundance between treatments and that were correlated with plant biomass under competition. We speculate that invasive grass dominance over these natives may be partially due to effects on the rhizosphere community, with changes in specific bacterial families potentially benefiting invaders at the expense of natives.
Using dual-calibrated functional MRI to map brain oxygen supply and consumption in multiple sclerosis
Authors: Chandler Hannah L , Stickland Rachael C , Germuska Michael , Patitucci Eleonora , Foster Catherine , Bhome-Dhaliwal Shona , Lancaster Thomas M , Saxena Neeraj , Khot Sharmila , Tomassini Valentina , Wise Richard G 
Published: January 2021

AbstractEvidence suggests that cerebrovascular function and oxygen consumption are altered in multiple sclerosis (MS). Here, we quantified the vascular and oxygen metabolic MRI burden in patients with MS (PwMS) and assessed the relationship between these MRI measures of and metrics of damage and disability. In PwMS and in matched healthy volunteers, we applied a newly developed dual-calibrated fMRI method of acquisition and analysis to map grey matter (GM) cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen consumption (CMRO2) and effective oxygen diffusivity of the capillary network (DC). We also quantified physical and cognitive function in PwMS and controls. There was no significant difference in GM volume between 22 PwMS and 20 healthy controls (p=0.302). Significant differences in CBF (PwMS vs. controls: 44.91 ± 6.10 vs. 48.90 ± 5.87 ml/100g/min,p=0.010), CMRO2(117.69 ± 17.31 vs. 136.49 ± 14.48 μmol/100g/minp<0.001) and DC(2.70 ± 0.51 vs. 3.18 ± 0.41 μmol/100g/mmHg/min,p=0.002) were observed in the PwMS. No significant between-group differences were observed for OEF (PwMS vs. controls: 0.38 ± 0.09 vs. 0.39 ± 0.02,p=0.358). Regional analysis showed widespread reductions in CMRO2and DCfor PwMS compared to healthy volunteers. There was a significant correlation between physiological measures and T2 lesion volume, but no association with current clinical disability. Our findings demonstrate concurrent reductions in oxygen supply and consumption in the absence of an alteration in oxygen extraction that may be indicative of a reduced demand for oxygen (O2), an impaired transfer of O2from capillaries to mitochondria, and/or a reduced ability to utilise O2that is available at the mitochondria. With no between-group differences in GM volume, our results suggest that changes in brain physiology may precede MRI-detectable GM loss and thus may be one of the pathological drivers of neurodegeneration and disease progression.
Transcriptomics provides a genetic signature of vineyard site with insight into vintage-independent regional wine characteristics
Authors: Reiter Taylor , Montpetit Rachel , Byer Shelby , Frias Isadora , Leon Esmeralda , Viano Robert , Mcloughlin Michael , Halligan Thomas , Hernandez Desmon , Figueroa-Balderas Rosa , Cantu Dario , Steenwerth Kerri , Runnebaum Ron , Montpetit Ben 
Published: January 2021

AbstractIn wine fermentations, the metabolic activity of bothSaccharomyces cerevisiaeand non-Saccharomycesorganisms impact wine chemistry. Ribosomal DNA amplicon sequencing of grape musts has demonstrated that microorganisms occur non-randomly and are associated with the vineyard of origin, suggesting a role for the vineyard, grape, and wine microbiome in shaping wine fermentation outcomes. We used ribosomal DNA amplicon sequencing of grape must and RNA sequencing of primary fermentations to profile fermentations from 15 vineyards in California and Oregon across two vintages. We find that the relative abundance of fungal organisms detected by ribosomal DNA amplicon sequencing did not correlate with transcript abundance from those organisms within the RNA sequencing data, suggesting that the majority of the fungi detected in must by ribosomal DNA amplicon sequencing are not active during these inoculated fermentations. Additionally, we detect genetic signatures of vineyard site and region during fermentation that are predictive for each vineyard site, identifying nitrogen, sulfur, and thiamine metabolism as important factors for distinguishing vineyard site and region.ImportanceThe wine industry generates billions of dollars of revenue annually, and economic productivity is in part associated with regional distinctiveness of wine sensory attributes. Microorganisms associated with grapes and wineries are influenced by region of origin, and given that some microorganisms play a role in fermentation, it is thought that microbes may contribute to the regional distinctiveness of wine. We show that while the presence of microbial DNA is associated with wine region and vineyard site, the presence of microbial DNA is not associated with gene expression of those microorganisms during fermentation. We further show that detected gene expression signatures associated with wine region and vineyard site provide a means to address differences in fermentations that may drive regional distinctiveness.
MassMark: A Highly Scalable Multiplex NGS-based Method for High-Throughput, Accurate and Sensitive Detection of SARS-CoV-2 for Mass Testing
Authors: Ngeow Kao Chin , Xie Chao , Teo Alvin Kuo Jing , Hsu Li Yang , Tan Min Han , Choudhury Yukti 
Published: January 2021

AbstractMass testing has been proposed as a strategy to address and contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic1,2. We have developed MassMark, a novel and highly scalable multiplex method that employs next generation sequencing for high-throughput, accurate and sensitive detection of SARS-CoV-2, while minimizing handling complexity and resources by utilizing a serial pooling strategy to accommodate over 9,000 samples per workflow. Analytical validation showed that MassMark was able to detect SARS-CoV-2 RNA down to a level of 100 copies per reaction. We evaluated the clinical performance of MassMark in a simulated screening testing with 22 characterized samples from three different sources (nasopharyngeal swabs, nasal swabs and saliva), comprising of 12 SARS-CoV-2 positive samples with mid to late Ct values (range: 22.98-32.72) and 10 negative samples. There was one false negative and no false positives, giving an overall sensitivity and specificity of 91.67% and 100% respectively, when compared against an optimized RT-PCR test with a target size within 70 bp (CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel3).