bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incubation Period and Reproduction Number for novel coronavirus (COVID-19) infections in India
Authors: Patrikar SR , Kotwal A , Bhatti VK , Banerjee A , Chatterjee K , Kunte R , Tambe M 
Published: June 2020

AbstractNovel coronavirus (COVID-19) rapidly spread from China to other parts of the world. Knowledge of incubation period and reproduction number is important in controlling any epidemic. The distribution of these parameters helps estimate the epidemic size and transmission potential of the disease. We estimated incubation period and reproduction number of COVID-19 for India utilizing data reported by Ministry of Health and Family Welfare (MoHFW), Government of India (GOI) and data in public domain. The mean incubation period seems to be larger at 6.93 (SD=±5.87, 95% CI: 6.11-7.75). and 95th percentile estimate for best fit normal distribution is 17.8 days. Weibull distribution, the best fit for the reproduction number estimated pre lockdown reproduction number as 2.6 (95% CI=2.34 - 2.86) and post lockdown reduced to 1.57 (95% CI=1.3 – 1.84) implying effectiveness of the epidemic response strategies. The herd immunity is estimated between 36-61% for R0 of 1.57 and 2.6 respectively.
Estimating the infection fatality risk of COVID-19 in New York City during the spring 2020 pandemic wave
Authors: Yang Wan , Kandula Sasikiran , Huynh Mary , Greene Sharon K. , Wye Gretchen Van , Li Wenhui , Chan Hiu Tai , McGibbon Emily , Yeung Alice , Olson Don , Fine Anne , Shaman Jeffrey 
Published: June 2020

AbstractBackgroundAs the COVID-19 pandemic continues to unfold, the infection fatality risk (IFR, i.e. risk of death among all infections including asymptomatic and mild infections) is crucial for gauging the burden of death due to COVID-19 in the coming months or years. Here we estimate the IFR of COVID-19 in New York City (NYC), the first epidemic center in the United States where the IFR remains unclear.MethodsWe developed a meta-population network model-inference system to estimate underlying SARS-CoV-2 infection rates in NYC during the 2020 spring pandemic wave using case, mortality, and mobility data. Based on these estimates, we further estimated the IFR for all ages overall and for 5 age groups (i.e. <25, 25-44, 45-64, 65-74, and 75+ years) separately, during March 1 – June 6, 2020 (i.e., before NYC began its phased reopening).FindingsDuring March 1 – June 6, 2020, 205,639 laboratory-confirmed COVID-19 cases were diagnosed and 21,447 confirmed and probable COVID-19 deaths occurred among NYC residents. We estimated an overall IFR of 1.39% (95% Credible Interval: 1.04-1.77%) in NYC. Estimated IFR for the two oldest age groups (65-74 and 75+ years) was much higher than the younger age groups and about double estimates reported for elsewhere. In particular, weekly IFR was estimated as high as 6.7% for 65-74 year-olds and 19.1% for 75+ year-olds.InterpretationThese results are based on more complete ascertainment of COVID-19-associated deaths in NYC and thus likely more accurately reflect the true, higher burden of death due to COVID-19 than previously reported elsewhere.
Characterizing the molecular regulation of inhibitory immune checkpoints with multi-modal single-cell screens
Authors: Papalexi Efthymia , Mimitou Eleni , Butler Andrew W. , Foster Samantha , Bracken Bernadette , Mauck William M. , Wessels Hans-Hermann , Yeung Bertrand Z. , Smibert Peter , Satija Rahul 
Published: June 2020

ABSTRACTThe expression of inhibitory immune checkpoint molecules such asPD-L1is frequently observed in human cancers and can lead to the suppression of T cell-mediated immune responses. Here we apply ECCITE-seq, a technology which combines pooled CRISPR screens with single-cell mRNA and surface protein measurements, to explore the molecular networks that regulatePD-L1expression. We also develop a computational framework,mixscape, that substantially improves the signal-to-noise ratio in single-cell perturbation screens by identifying and removing confounding sources of variation. Applying these tools, we identify and validate regulators ofPD-L1, and leverage our multi-modal data to identify both transcriptional and post-transcriptional modes of regulation. In particular, we discover that the kelch-like proteinKEAP1and the transcriptional activatorNRF2, mediate levels ofPD-L1upregulation after IFNγ stimulation. Our results identify a novel mechanism for the regulation of immune checkpoints and present a powerful analytical framework for the analysis of multi-modal single-cell perturbation screens.
Quantitative trait locus mapping identifiesCol4a6as a novel regulator of striatal dopamine level and axonal branching in mice
Authors: Thomas Mélanie H. , Gui Yujuan , Garcia Pierre , Karout Mona , Jaeger Christian , Hodak Zdenka , Michelucci Alessandro , Kollmus Heike , Centeno Arthur , Schughart Klaus , Balling Rudi , Mittelbronn Michel , Nadeau Joseph H. , Williams Robert W. , Sauter Thomas , Sinkkonen Lasse , Buttini Manuel 
Published: June 2020

AbstractThe features of dopaminergic neurons (DAns) of nigrostriatal circuitry are orchestrated by a multitude of yet unknown factors, many of them genetic. Genetic variation between individuals at baseline can lead to differential susceptibility to and severity of diseases. As decline of DAns, a characteristic of Parkinson’s disease, heralds a significant decrease in dopamine level, measuring dopamine can reflect the integrity of DAns. To identify novel genetic regulators of the integrity of DAns, we used the Collaborative Cross (CC) mouse strains as model system to search for quantitative trait loci (QTLs) related to dopamine levels in the dorsal striatum. The dopamine levels in dorsal striatum varied greatly in the eight CC founder strains, and the differences were inheritable in 32 derived CC strains. QTL mapping in these CC strains identified a QTL associated with dopamine level on chromosome X containing 393 genes. RNA-seq analysis of the ventral midbrain of two of the founder strains with large striatal dopamine difference (C57BL/6J and A/J) revealed 24 differentially expressed genes within the QTL. The protein-coding gene with the highest expression difference wasCol4a6, which exhibited a 9-fold reduction in A/J compared to C57BL/6J, consistent with decreased dopamine levels in A/J. Publicly available single cell RNA-seq data from developing human midbrain suggests thatCol4a6is highly expressed in radial glia-like cells and neuronal progenitors, indicating possible involvement in neurogenesis. Interestingly, the lowered dopamine levels were accompanied by reduced striatal axonal branching of striatal DAns in A/J compared to C57BL/6J. BecauseCol4a6is known to control axogenesis in non-mammal model organisms, we hypothesize that different dopamine levels in mouse dorsal striatum are due to differences in axogenesis induced by varying COL4A6 levels during neural development.
SCARECROWgene function is required for photosynthetic development in maize
Authors: Hughes Thomas E. , Langdale Jane A. 
Published: June 2020

AbstractC4photosynthesis in grasses relies on a specialized leaf anatomy. In maize, this ‘Kranz’ leaf anatomy is patterned in part by the duplicatedSCARECROW (SCR)genesZmSCR1andZmSCR1h. Here we show that in addition to patterning defects, chlorophyll content and levels of transcripts encoding Golden2-like regulators of chloroplast development are significantly lower inZmscr1;Zmscr1hmutants than in wild-type. These perturbations are not associated with changes in chloroplast number, size or ultrastructure. However, the maximum rates of carboxylation by ribulose bisphosphate carboxylase/oxygenase (RuBisCO, Vcmax) and phosphoenolpyruvate carboxylase (PEPC, Vpmax) are both reduced, leading to perturbed plant growth. The CO2compensation point and13C‰of Zmscr1;Zmscr1hplants are both normal, indicating that a canonical C4cycle is operating, albeit at reduced overall capacity. Taken together, our results reveal that the maizeSCRgenes, either directly or indirectly, play a role in photosynthetic development.Significance statementSCARECROW (SCR) is one of the best studied plant developmental regulators, however, its role in downstream plant physiology is less well-understood. Here, we have demonstrated that SCR is required to establish and/or maintain photosynthetic capacity in maize leaves.
The SAGE genetic toolkit enables highly efficient, iterative site-specific genome engineering in bacteria
Authors: Elmore Joshua R. , Dexter Gara N. , Francis Ryan , Riley Lauren , Huenemann Jay , Baldino Henri , Guss Adam M. , Egbert Robert 
Published: June 2020

AbstractSustainable enhancements to crop productivity and increased resilience to adverse conditions are critical for modern agriculture, and application of plant growth promoting rhizobacteria (PGPR) is a promising method to achieve these goals. However, many desirable PGPR traits are highly regulated in their native microbe, limited to certain plant rhizospheres, or insufficiently active for agricultural purposes. Synthetic biology can address these limitations, but its application is limited by availability of appropriate tools for sophisticated, high-throughput genome engineering that function in environments where selection for DNA maintenance is impractical. Here we present an orthogonal, Serine-integrase Assisted Genome Engineering (SAGE) system, which enables iterative, site-specific integration of up to 10 different DNA constructs at efficiency on par or better than replicating plasmids. SAGE does not require use of replicating plasmids to deliver recombination machinery, and employs a secondary serine-integrase to excise and recycle selection markers. Furthermore, unlike the widely utilized pBBR1 origin, DNA transformed using SAGE is stable without selection. We highlight SAGE’s utility by constructing a 287-member constitutive promoter library with a ∼40,000-fold dynamic range in P. fluorescens SBW25. We show that SAGE functions robustly in diverse α- and γ-proteobacteria, thus providing evidence that it will be broadly useful for engineering industrial or environmental bacteria.
The deubiquitinase Usp9x regulates PRC2-mediated chromatin reprogramming during mouse development
Authors: Macrae Trisha A. , Ramalho-Santos Miguel 
Published: June 2020

ABSTRACTPluripotent cells of the mammalian embryo undergo extensive chromatin rewiring to prepare for lineage commitment after implantation. Repressive H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2), is reallocated from large gene-distal blankets in pre-implantation embryos to mark promoters of developmental genes. The factors that mediate this global redistribution of H3K27me3 are unknown. Here we report a post-translational mechanism that destabilizes PRC2 to constrict H3K27me3 during lineage commitment. Using an auxin-inducible degron system, we show that the deubiquitinase Usp9x is required for mouse embryonic stem (ES) cell self-renewal. Usp9x-high ES cells have high PRC2 levels and bear a chromatin and transcriptional signature of the pre-implantation embryo, whereas Usp9x-low ES cells resemble the post-implantation, gastrulating epiblast. We show that Usp9x interacts with, deubiquitinates and stabilizes PRC2. Deletion ofUsp9xin post-implantation embryos results in the derepression of genes that normally gain H3K27me3 after gastrulation, followed by the appearance of morphological abnormalities at E9.5, pointing to a recurrent link between Usp9x and PRC2 during development. Usp9x is a marker of “stemness” and is mutated in various neurological disorders and cancers. Our results unveil a Usp9x-PRC2 regulatory axis that is critical at peri-implantation and may be redeployed in other stem cell fate transitions and disease states.
Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCa1.1, in Sinus Node Function and Arrhythmia Risk
Authors: Pineda Santiago , Nikolova-Krstevski Vesna , Leimena Christiana , Atkinson Andrew J. , Altekoester Ann-Kristin , Cox Charles D. , Jacoby Arie , Huttner Inken G. , Ju Yue-Kun , Soka Magdalena , Ohanian Monique , Trivedi Gunjan , Kalvakuri Sreehari , Johnson Renee , Molenaar Peter , Kuchar Dennis , Allen David G. , van Helden Dirk F. , Harvey Richard P. , Hill Adam P. , Bodmer Rolf , Vogler Georg , Dobrzynski Halina , Ocorr Karen , Fatkin Diane 
Published: June 2020

ABSTRACTBackgroundKCNMA1encodes the α-subunit of the large-conductance Ca2+-activated K+channel, KCa1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into the cardiac functions of KCa1.1 are limited andKCNMA1has not been investigated as an AF candidate gene.Methods and ResultsKCNMA1sequencing in 118 patients with familial AF identified a novel complex variant in one kindred. To evaluate potential disease mechanisms, we first evaluated the distribution of KCa1.1 in normal hearts using immunostaining and immunogold electron microscopy. KCa1.1 was seen throughout the atria and ventricles in humans and mice, with strong expression in the sinus node. In anex vivomurine sinoatrial node preparation, addition of the KCa1.1 antagonist, paxilline, blunted the increase in beating rate induced by adrenergic receptor stimulation. Knockdown of the KCa1.1 ortholog,kcnma1b, in zebrafish embryos resulted in sinus bradycardia with dilatation and reduced contraction of the atrium and ventricle. Genetic inactivation of theDrosophilaKCa1.1 ortholog,slo, systemically or in adult stages, also slowed the heartbeat and produced cardiac arrhythmias.Electrophysiological characterization ofslo-deficient flies revealed bursts of action potentials, reflecting increased events of fibrillatory arrhythmias. Flies with cardiac-specific overexpression of the humanKCNMA1mutant also showed increased heart period and bursts of action potentials, similar to the KCa1.1 loss-of-function models.ConclusionsOur data point to a highly conserved role of KCa1.1 in sinus node function in humans, mice, zebrafish and fly and suggest that KCa1.1 loss of function may predispose to AF.
Membrane tethering potency of Rab-family small GTPases is defined by the C-terminal hypervariable regions
Authors: Ueda Sanae , Tamura Naoki , Mima Joji 
Published: June 2020

AbstractMembrane tethering is a crucial step to determine the spatiotemporal specificity of secretory and endocytic trafficking pathways in all eukaryotic endomembrane systems. Recent biochemical studies by a chemically-defined reconstitution approach reveal that, in addition to the structurally-diverse classic tethering factors such as coiled-coil tethering proteins and multisubunit tethering complexes, Rab-family small GTPases also retain the inherent membrane tethering functions to directly and physically bridge two distinct lipid bilayers by themselves. Although Rab-mediated membrane tethering reactions are fairly efficient and specific in the physiological context, its mechanistic basis is yet to be understood. Here, to explore whether and how the intrinsic tethering potency of Rab GTPases is controlled by their C-terminal hypervariable region (HVR) domains that link the conserved small GTPase domains (G-domains) to membrane anchors at the C-terminus, we quantitatively compared tethering activities of two representative Rab isoforms in humans (Rab5a, Rab4a) and their HVR-deleted mutant forms. Strikingly, deletion of the HVR linker domains enabled both Rab5a and Rab4a isoforms to enhance their intrinsic tethering potency, exhibiting 5-to 50-fold higher initial velocities of tethering for the HVR-deleted mutants than those for the full-length, wild-type Rabs. Furthermore, we revealed that the tethering activity of full-length Rab5a was significantly reduced by the omission of anionic lipids and cholesterol from membrane lipids and, however, membrane tethering driven by HVR-deleted Rab5a mutant was completely insensitive to the headgroup composition of lipids. Reconstituted membrane tethering assays with the C-terminally-truncated mutants of Rab4a further uncovered that the N-terminal residues in the HVR linker, located adjacent to the G-domain, are critical for regulating the intrinsic tethering activity. In conclusion, our current findings establish that the non-conserved, flexible C-terminal HVR linker domains define membrane tethering potency of Rab-family small GTPases through controlling the close attachment of the globular G-domains to membrane surfaces, which confers the active tethering-competent state of the G-domains on lipid bilayers.
Extracorporeal Cytokine Hemadsorption in Severe COVID-19 Respiratory Failure
Authors: Damiani Marianna , Gandini Lucia , Landi Francesco , Fabretti Fabrizio , Gritti Giuseppe , Riva Ivano 
Published: June 2020

AbstractDespite the extracorporeal cytokine hemadsorption device CytoSorb was granted FDA emergency approval for critically ill COVID19 patients, to our knowledge no published studies are currently available to support its use. This manuscript reports the experience of the use of CytoSorb during COVID19 pandemic in Bergamo, Italy. In our pilot study, eleven COVID19 patients requiring invasive mechanical ventilation for a rapidly progressive ARDS were treated with 24 to 48 hours of extracorporeal cytokine hemadsorption.Respiratory and laboratory parameters, including a full set of inflammatory cytokines, were evaluated at different time points. A significant but transient reduction of the hyperinflammatory status was observed, along with the amelioration of the clinical and respiratory parameters.We believe that this manuscript will provide them with important preliminary data on the use of cytokine hemadsorption devices.
Quantification of Epicardial Fat Volume as a Novel Cardiovascular Risk Marker in Asymptomatic Subjects for Early Detection of Cardiovascular Disease
Authors: Shahawy Mahfouz El , Izadi Lillee , Sabatini Antonella , Tucker Susan , Patella Jessica , Shahawy Omar El , Yturralde Frederick 
Published: June 2020

AbstractEpicardial fat volume (EFV), also known as epicardial adipose tissue (EAT), sometimes acts as a protector against heart problems; however, in excess volume was found to be associated with cardiovascular structural and functional abnormalities. This study aims to establish a threshold between normal and abnormal values for EFV/EAT in asymptomatic subjects, as well as to assess whether excess EFV/EAT is associated with significant structural and functional abnormalities, including coronary artery calcium score (CACS). A total of 220 asymptomatic patients, were screened utilizing Early Cardiovascular Disease Risk Score (ECVDRS), and CT for CACS and EFV/EAT quantification. Out of the 220 subjects, 69 had a 0 CACS and were included in this analysis. These 69 were then further categorized into 3 groups: Group 1 (Normal subjects; n=20) with ECVDRS < 3, and ACC/AHA risk score < 5%; Group 2 (n= 16) with elevated EFV/EAT and no abdominal visceral obesity; Group 3 (n=33) with elevated EFV/EAT and abdominal visceral obesity. The average EFV/EAT was identified to be 69 cm3± 20 in females and 68 cm3± 15 in males among Group 1, which indicate the normal values for EFV/EAT. It was also found that elevated EFV/EAT without (Group 2) or with (Group 3) abdominal visceral adiposity was associated with significant vascular abnormalities, as compared to the normal group among these populations of asymptomatic patients with 0 CACS. Elevated EFV/EAT is a novel cardiovascular risk marker regardless of gender, which might be the culprit for major cardiovascular risk factors.
Estimation of COVID-19 dynamics in the different states of the United States using Time-Series Clustering
Authors: Rojas Fernando , Valenzuela Olga , Rojas Ignacio 
Published: June 2020

AbstractEstimation of COVID-19 dynamics and its evolution is a multidisciplinary effort, which requires the unification of heterogeneous disciplines (scientific, mathematics, epidemiological, biological/bio-chemical, virologists and health disciplines to mention the most relevant) to work together in a better understanding of this pandemic. Time series analysis is of great importance to determine both the similarity in the behavior of COVID-19 in certain countries/states and the establishment of models that can analyze and predict the transmission process of this infectious disease. In this contribution, an analysis of the different states of the United States will be carried out to measure the similarity of COVID-19 time series, using dynamic time warping distance (DTW) as a distance metric. A parametric methodology is proposed to jointly analyze infected and deceased persons. This metric allows to compare time series that have a different time length, making it very appropriate for studying the United States, since the virus did not spread simultaneously in all the states/provinces. After a measure of the similarity between the time series of the states of United States was determined, a hierarchical cluster was created, which makes it possible to analyze the behavioral relationships of the pandemic between different states and to discover interesting patterns and correlations in the underlying data of COVID-19 in the United States. With the proposed methodology, nine different clusters were obtained, showing a different behavior in the eastern zone and western zone of the United States. Finally, to make a prediction of the evolution of COVID-19 in the states, Logistic, Gompertz and SIR model was computed. With these mathematical model it is possible to have a more precise knowledge of the evolution and forecast of the pandemic.
Implementing the principles of Academagogy for effective learning facilitation in corporate organizations: a case study
Authors: Murthy Shekhar , Pattanayak Biswajeet 
Published: June 2020

Purpose
The purpose of this study is to adapt the principles of Academagogy (McAuliffe et al., 2009; McAuliffe and Winter, 2014) in Corporate Training. Academagogy is an amalgamation of learning theories, viz. pedagogy (teacher-centered learning); andragogy (student-centered learning); and, heutagogy (self-determined learning). 10;While the original paper by McAuliffe et al. focused on the application of Academagogical principles to higher education in a university, this case study extends Academagogy into corporate training.

Design/methodology/approach
Academagogy-based learning interventions were implemented in training programs conducted at IIC Academy. The study-sample comprised 144 trainees divided into the experiment and the control groups. Academagogical interventions were applied to the experiment group, whereas the control group followed conventional methods. Controlled quasi-experiment and statistical analyses were used as research tools in this case study.

Findings
The performance scores of the participants' at entry-level were analyzed through propensity score matching and chi-square tests. The results concluded that the experiment and the control group had no selection bias. 10; 10;The treatment effect applied to the experiment group was studied using scatter-plots and effect size analyses. 10; 10;The results indicate that the academagogical interventions markedly improved behavioral and professional skills among participants of the experiment group, which showed up in their superior performance, both during training and at work.

Research limitations/implications
This case study has two major limitations, viz. the sample population was homogenous; the batch-size was limited to 15 participants, which facilitated closer monitoring of the course.

Originality/value
Academagogical interventions were implemented in a corporate setting as opposed to earlier studies which focused on a university setting and academic environs.