bluuebunny/crossref_metadata_2025 huggingface dataset:
The melissopalynological investigation in the Eastern Dry Zone of Karnataka, India
Authors: Shishira D. , Uthappa A. R. , Kumar Veeresh , Shringeshwara  , Kuberappa G. C.
Published: July 2020

Melissopalynology, the analysis of pollen grains present in honey, indicates about the pollen and nectar sources in a region utilized by bees, which is used to determine the bee floral resources and botanical origin of the honey. This study investigated the melissopalynological analysis of the honey samples from the Eastern Dry zone of Karnataka. 24 honey samples were examined based on pollen analyses, among them 14 samples were unifloral, rest were multifloral. The unifloral honey had pollens ofCallistemon viminalis, Areca catechu, Citrussp.,Mallotus philippensis, Cocos nucifera, Eucalyptussp.,Ocimumsp.,Moringa oleiferaandPongamia pinnata. Samples collected in October, November, December, and January were rich in pollens ofEucalyptussp.. Similarly, samples collected in January, February and March had pollen of tree speciesviz.,Swietenia mahagoni, Canthium parviflorum, Simarouba glauca, Eucalyptussp.,Moringa oleifera, Syzygium cumini, Tabebuiasp.,Pongamia pinnata, Acanthaceae, Anacardium occidentale, Cocos nucifera, Areca catechu, Mallotus philippensis, Bauhinia variegata, Psidium guajava, Alangiaceae, Euphorbiaceae, Ulmaceae, Capparis zeylanica, Convolvulaceae. GKVK-11 followed by GKVK-12 sample recorded the highest Shannon diversity and GKVK-9 followed by GKVK-7 sample recorded the least diversity. Based on the similar floral composition samples were classified into four clusters. The PCA revealed that most of the samples grouped into a single cluster, except 7, 19, 20, 21, and 22 which were placed away from the origin. The presence of pollen in the honey of a particular plant species during different months is related to the blooming of that particular plant species from which the bees forage. The flora of honey changes with the season. The diversity of pollen grains in honey varied with location to location. The present study provides scientific knowledge to the beekeepers by indicating important plants for the development of the regional apiculture, through the identification of pollen types.
Compression of quantification uncertainty for scRNA-seq counts
Authors: Van Buren Scott , Sarkar Hirak , Srivastava Avi , Rashid Naim U. , Patro Rob , Love Michael I.
Published: July 2020

Motivation

Quantification estimates of gene expression from single-cell RNA-seq (scRNA-seq) data have inherent uncertainty due to reads that map to multiple genes. Many existing scRNA-seq quantification pipelines ignore multi-mapping reads and therefore underestimate expected read counts for many genes.alevinaccounts for multi-mapping reads and allows for the generation of “inferential replicates”, which reflect quantification uncertainty. Previous methods have shown improved performance when incorporating these replicates into statistical analyses, but storage and use of these replicates increases computation time and memory requirements.

Results

We demonstrate that storing only the mean and variance from a set of inferential replicates (“compression”) is sufficient to capture gene-level quantification uncertainty. Using these values, we generate “pseudo-inferential” replicates from a negative binomial distribution and propose a general procedure for incorporating these replicates into a proposed statistical testing framework. We show reduced false positives when applying this procedure to trajectory-based differential expression analyses. We additionally extend theSwishmethod to incorporate pseudo-inferential replicates and demonstrate improvements in computation time and memory consumption without any loss in performance. Lastly, we show that the removal of multi-mapping reads can result in significant underestimation of counts for functionally important genes in a real dataset.

Availability and implementation

makeInfRepsandsplitSwishare implemented in the development branch of the R/Bioconductorfishpondpackage available athttp://bioconductor.org/packages/devel/bioc/html/fishpond.html. Sample code to calculate the uncertainty-awarep-values can be found on GitHub athttps://github.com/skvanburen/scUncertaintyPaperCode.

Contact

michaelisaiahlove@gmail.com
Clean Enzymatic depolymerization of highly crystalline polyethylene terephthalate in moist-solid reaction mixtures
Authors: Kaabel Sandra , Therien J. P. Daniel , Deschênes Catherine E. , Duncan Dustin , Friščić Tomislav , Auclair Karine
Published: July 2020

Less than 9% of the plastic produced is recycled after use, contributing to the global plastic pollution problem. While polyethylene terephthalate (PET) is one of the most common plastics, its thermomechanical recycling generates a material of lesser quality. Enzymes are highly selective, renewable catalysts active at mild temperatures; however, the current consensus is that they lack activity towards the more crystalline forms of PET. We report here that when used in moist-solid reaction mixtures instead of the typical dilute aqueous solutions, enzymes can directly depolymerize high crystallinity PET in 13-fold higher space-time yield and a 15-fold higher enzyme efficiency than prior reports. Further, this process shows a 26-fold selectivity for terephthalic acid over other hydrolysis products, which allows the direct synthesis of UiO-66 metal-organic framework.
Numerical Model for Formation and Evolution of the Bleb
Authors: Feng J. , Tang L. , Liu Z. , Dong S. , Zhou L. , Liu Y. , Jiang Z.
Published: July 2020

The bleb morphology and its changes are an important mechanism of cell’s amoeboid migration. By releasing bonds between the membrane and the cortex of a cell, the formation of bleb can be observed experimentally, but the mechanism that affects the size and shape of this kind of bleb is waiting for further study. In this paper, a two-dimensional fluid-solid coupling model is established to describe a cell with membrane, cortex and cytoplasm in a solution, and a numerical solving method for the fluid-solid coupling model is developed to simulate the behaviors of cell bleb. The effects of parameters, such as the number of broken bonds, the viscosity coefficient of the cortex, and the cell’s membrane modulus on the size and the shape of the bleb were investigated. Numerical results show that the model is effective to simulate the formation and evolution of cell’s bleb, and derive the contribution of several affecting factors to the bleb shape and size clearly.

SIGNIFICANCE

To understand the process of cell migration with bleb pseudopods in the amoeba cell migration, it is necessary to study the formation mechanism of cells protruding bleb. In this paper, we propose a reasonable and reliable cell numerical model. With this model we successfully simulate the bleb phenomenon consistent with the experimental phenomenon by changing the key impact factors. The method in this paper is applicable to the cell model of amoeba cell migration pattern, which helps to understand the important role of blebs in the process of cell migration.
X-chromosome upregulation is dynamically linked to the X-inactivation state
Authors: Lentini Antonio , Coucoravas Christos , Andrews Nathanael , Enge Martin , Deng Qiaolin , Reinius Björn
Published: July 2020

Mammalian X-chromosome dosage balance is regulated by X-chromosome inactivation (XCI) and X-chromosome upregulation (XCU), but the dynamics of XCU as well as the interplay between the two mechanisms remain poorly understood. Here, we mapped XCU throughout early mouse embryonic development at cellular and allelic resolution, revealing sex- and lineage-specific dynamics along key events in X-chromosome regulation. Our data show that XCU is linearly proportional to the degree of XCI, indicating that dosage compensation ensues based on mRNA levels rather than number of active X chromosomes. In line with this, we reveal that the two active X chromosomes in female naïve embryonic stem cells are not hyperactive as previously thought. In all lineages, XCU was underlain by increased transcriptional burst frequencies, providing a mechanistic basis in vivo. Together, our results demonstrate unappreciated flexibility of XCU in balancing X-chromosome expression, and we propose a general model for allelic dosage balance, applicable for wider mechanisms of transcriptional regulation.
SOX9 promotes stress-responsive transcription of VGF nerve growth factor inducible gene in kidney epithelial cells
Authors: Kim Ji Young , Bai Yuntao , Jayne Laura A. , Abdulkader Ferdos , Gandhi Megha , Parikh Samir V. , Song Min-Ae , Bajwa Amandeep , Pabla Navjot Singh
Published: July 2020

Acute kidney injury (AKI) is a common clinical condition associated with diverse etiologies and abrupt loss of renal function. In patients with sepsis, rhabdomyolysis, cancer, as well as cardiovascular disorders, the underlying disease or associated therapeutic interventions can cause hypoxic, cytotoxic, and inflammatory insults to renal tubular epithelial cells (RTECs) resulting in the onset of AKI. To uncover stress-responsive disease-modifying genes, here we have carried out renal transcriptome profiling in three distinct murine models of AKI. We find that Vgf nerve growth factor inducible gene upregulation is a common transcriptional stress response in RTECs to ischemia, cisplatin, and rhabdomyolysis-associated renal injury. The Vgf gene encodes a secretory peptide precursor protein that has critical neuro-endocrine functions; however, its role in the kidneys remains unknown. Our functional studies show that RTEC-specific Vgf gene ablation exacerbates ischemia, cisplatin, and rhabdomyolysis-associated AKI in vivo and cisplatin-induced RTEC cell death in vitro. Importantly, addback experiments showed that aggravation of cisplatin-induced renal injury caused by Vgf gene ablation is partly reversed by TLQP-21, a Vgf-derived peptide. Finally, in vitro and in vivo mechanistic studies showed that injury-induced Vgf upregulation in RTECs is driven by the transcriptional regulator Sox9. These findings reveal a crucial downstream target of the Sox9-directed transcriptional program and identify Vgf as a stress-responsive protective gene in kidney epithelial cells.
ArabidopsisUGT76B1 glycosylatesN-hydroxy-pipecolic acid and inactivates systemic acquired resistance in tomato
Authors: Holmes Eric C. , Chen Yun-Chu , Mudgett Mary Beth , Sattely Elizabeth S.
Published: July 2020

Systemic acquired resistance (SAR) is a mechanism that plants utilize to connect a local pathogen infection to global defense responses.N-hydroxy-pipecolic acid (NHP) and a glycosylated derivative are produced during SAR, yet their individual roles in the response have not yet been elucidated. Here we report thatArabidopsis thalianaUGT76B1 can generate glycosylated NHP (NHP-Glc)in vitroand when transiently expressed alongside Arabidopsis NHP biosynthetic genes in two Solanaceous plants. During infection, Arabidopsisugt76b1mutants do not accumulate NHP-Glc and accumulate less glycosylated salicylic acid (SA-Glc) than wild type plants. The metabolic changes inugt76b1mutant plants are accompanied by enhanced defense to the bacterial pathogenPseudomonas syringae, suggesting that glycosylation of SAR molecules NHP and SA by UGT76B1 plays an important role in defense modulation. Transient expression of ArabidopsisUGT76B1with the Arabidopsis NHP biosynthesis genesALD1andFMO1in tomato increases NHP-Glc production and reduces NHP accumulation in local tissue, and abolishes the systemic resistance seen when expressing NHP-biosynthetic genes alone. These findings reveal that the glycosylation of NHP by UGT76B1 alters defense priming in systemic tissue and provide further evidence for the role of the NHP aglycone as the active metabolite in SAR signaling.
Neutrophil extracellular traps impair regeneration
Authors: Wier Eric , Asada Mayumi , Wang Gaofeng , Alphonse Martin P. , Li Ang , Hintelmann Chase , Youn Christine , Pielstick Brittany , Ortines Roger , Miller Lloyd S. , Archer Nathan K. , Garza Luis A.
Published: July 2020

Fibrosis is a major health burden across diseases and organs. To remedy this, we study wound induced hair follicle regeneration (WIHN) as a model of non-fibrotic healing that recapitulates embryogenesis for de novo hair follicle morphogenesis after wounding. We have previously demonstrated that TLR3 promotes WIHN through binding dsRNA, but the source of which is still unclear. Here, we demonstrate that multiple distinct contexts of high WIHN all show a strong neutrophil signature, and given the likelihood of nuclear dsRNA release during the production of neutrophil extracellular trap (NETs), we hypothesized that mature neutrophils and NETs might promote WIHN. Consistent with this, in addition to the presence of mature neutrophils shortly after wounding, neutrophils remain within the wound after the barrier is reestablished, where they produce extracellular traps (NETs) that likely release spliceosomal U1 dsRNA. Contrary to our hypothesis, genetic models of neutrophil depletion show enhanced WIHN. Pad4 null mice that are defective in NET production also augment WIHN. Finally, using single-cell RNA sequencing, we identified a dramatic increase in mature neutrophils in the wound beds of low regenerating Tlr3-/- mice. Taken together, these results demonstrate that although mature neutrophils are stimulated by a common pro-regenerative cue, their presence and NETs hinder WIHN.
Quantitative profiling of native RNA modifications and their dynamics using nanopore sequencing
Authors: Begik Oguzhan , Lucas Morghan C , Pryszcz Leszek P , Ramirez Jose Miguel , Medina Rebeca , Milenkovic Ivan , Cruciani Sonia , Liu Huanle , Vieira Helaine Graziele Santos , Sas-Chen Aldema , Mattick John S , Schwartz Schraga , Novoa Eva Maria
Published: July 2020

A broad diversity of modifications decorate RNA molecules. Originally conceived as static components, evidence is accumulating that some RNA modifications may be dynamic, contributing to cellular responses to external signals and environmental circumstances. A major difficulty in studying these modifications, however, is the need of tailored protocols to map each modification type individually. Here, we present a new approach that uses direct RNA nanopore sequencing to identify and quantify RNA modifications present in native RNA molecules. First, we show that each RNA modification type results in a distinct and characteristic base-calling ‘error’ signature, which we validate using a battery of genetic strains lacking either pseudouridine (Y) or 2’-O-methylation (Nm) modifications. We then demonstrate the value of these signatures forde novoprediction of Y modifications transcriptome-wide, confirming known Y-modified sites as well as uncovering novel Y sites in mRNAs, ncRNAs and rRNAs, including a previously unreported Pus4-dependent Y modification in yeast mitochondrial rRNA, which we validate using orthogonal methods. To explore the dynamics of pseudouridylation across environmental stresses, we treat the cells with oxidative, cold and heat stresses, finding that yeast ribosomal rRNA modifications do not change upon environmental exposures, contrary to the general belief. By contrast, our method reveals many novel heat-sensitive Y-modified sites in snRNAs, snoRNAs and mRNAs, in addition to recovering previously reported sites. Finally, we develop a novel software,nanoRMS, which we show can estimate per-site modification stoichiometries from individual RNA molecules by identifying the reads with altered current intensity and trace profiles, and quantify the RNA modification stoichiometry changes between two conditions. Our work demonstrates that Y RNA modifications can be predictedde novoand in a quantitative manner using native RNA nanopore sequencing.
Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection
Authors: Rathnasinghe Raveen , Strohmeier Shirin , Amanat Fatima , Gillespie Virginia L. , Krammer Florian , García-Sastre Adolfo , Coughlan Lynda , Schotsaert Michael , Uccellini Melissa
Published: July 2020

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2)(1-3). Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in both the lung and brain leading to lethality. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the lung, and no clinical signs of infection with a challenge dose of 104 plaque forming units. The K18-hACE2 model provides a stringent model for testing the ability of vaccines and antivirals to protect against disease, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
Stress-induced epigenetic regulation of transcription in neocortical excitatory neurons drives depression-like behavior
Authors: Kwon Deborah Y. , Hu Peng , Zhao Ying-Tao , Beagan Jonathan A. , Nofziger Jonathan H. , Cui Yue , Xu Bing , Zaitseva Daria , Phillips-Cremins Jennifer E. , Blendy Julie A. , Wu Hao , Zhou Zhaolan
Published: July 2020

Prolonged stress exposure is a major risk factor for the development of depression and comorbid anxiety. Efforts to understand how recurrent stress induces behavioral maladaptation have largely concentrated on the neuronal synapse with limited understanding of the underlying epigenetic mechanisms. Here, we performed complementary bulk nuclei- and single-nucleus transcriptome profiling and mapped fine-scale chromatin architecture in mice subjected to chronic unpredictable stress (CUS) to identify the cell type-specific epigenetic alterations that drive complex behavior. We find that neocortical excitatory neurons are particularly vulnerable to chronic stress and acquire signatures of transcription and chromatin configuration that denote reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in excitatory neurons of the prefrontal cortex (PFC) enhances stress sensitivity in mice, inducing depressive- and anxiety-related behaviors and deregulating the expression of stress-associated genes following an abbreviated stress exposure. Notably, we find that loss of YY1 in PFC excitatory neurons provokes more maladaptive behaviors in stressed females than males. These findings demonstrate how chronic stress provokes maladaptive behavior by epigenetically shaping excitatory neurons in the PFC, identifying a novel molecular target for therapeutic treatment of stress-related mood and anxiety disorders.
Role of SARS-CoV-2 in altering the RNA binding protein and miRNA directed post-transcriptional regulatory networks in humans
Authors: Srivastava Rajneesh , Daulatabad Swapna Vidhur , Srivastava Mansi , Janga Sarath Chandra
Published: July 2020

The outbreak of a novel coronavirus SARS-CoV-2 responsible for COVID-19 pandemic has caused worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2 mediated alteration on post-transcriptional gene regulation across human tissues remains elusive. In this study, we analyze publicly available genomic datasets to systematically dissect the crosstalk and dysregulation of human post-transcriptional regulatory networks governed by RNA binding proteins (RBPs) and micro-RNAs (miRs), due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV-2 encoded proteins directly interact with 51 human RBPs of which majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed a functional analysis of differentially expressed genes in mock-treated versus SARS-CoV-2 infected lung cells that revealed enrichment for immune response, cytokine-mediated signaling, and metabolism associated genes. This study also characterized the alternative splicing events in SARS-CoV-2 infected cells compared to control demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to viral infection. Motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed the enrichment for RBPs such as SRSFs, PCBPs, ELAVs, and HNRNPs suggesting the sponging of RBPs by SARS-CoV-2 genome. A similar analysis to study the interactions of miRs with SARS-CoV-2 revealed functionally important miRs that were highly expressed in immune cells, suggesting that these interactions may contribute to the progression of the viral infection and modulate host immune response across other human tissues. Given the need to understand the interactions of SARS-CoV-2 with key post-transcriptional regulators in the human genome, this study provides a systematic computational analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs, across tissues types during SARS-CoV-2 infection.
AdmixPipe: Population analyses in Admixture for non-model organisms
Authors: Mussmann Steven M. , Douglas Marlis R. , Chafin Tyler K. , Douglas Michael E.
Published: July 2020

Background

Research on the molecular ecology of non-model organisms, while previously constrained, has now been greatly facilitated by the advent of reduced-representation sequencing protocols. However, tools that allow these large datasets to be efficiently parsed are often lacking, or if indeed available, then limited by the necessity of a comparable reference genome as an adjunct. This, of course, can be difficult when working with non-model organisms. Fortunately, pipelines are currently available that avoid this prerequisite, thus allowing data to bea prioriparsed. An oft-used molecular ecology program (i.e., Structure), for example, is facilitated by such pipelines, yet they are surprisingly absent for a second program that is similarly popular and computationally more efficient (i.e., Admixture). The two programs differ in that Admixtureemploys a maximum-likelihood framework whereas Structureuses a Bayesian approach, yet both produce similar results. Given these issues, there is an overriding (and recognized) need among researchers in molecular ecology for bioinformatic software that will not only condense output from replicated Admixtureruns, but also infer from these data the optimal number of population clusters (K).

Results

Here we provide such a program (i.e., AdmixPipe) that (a) filters SNPs to allow the delineation of population structure in Admixture, then (b) parses the output for summarization and graphical representation via Clumpak. Our benchmarks effectively demonstrate how efficient the pipeline is for processing large, non-model datasets generated via double digest restriction-site associated DNA sequencing (ddRAD). Outputs not only parallel those from Structure, but also visualize the variation among individual Admixtureruns, so as to facilitate selection of the most appropriateK-value.

Conclusions

AdmixPipesuccessfully integrates Admixtureanalysis with popular variant call format (VCF) filtering software to yield file types readily analyzed by Clumpak. Large population genomic datasets derived from non-model organisms are efficiently analyzed via the parallel-processing capabilities of Admixture. AdmixPipeis distributed under the GNU Public License and freely available for Mac OSX and Linux platforms at:https://github.com/stevemussmann/admixturePipeline.
The effect of sequence learning on sensorimotor adaptation
Authors: Liu Yang , Block Hannah J.
Published: July 2020

Motor skill learning involves both sensorimotor adaptation (calibrating the response to task dynamics and kinematics), and sequence learning (executing the task elements in the correct order at the necessary speed). These processes typically occur together in natural behavior and share much in common, such as working memory demands, development, and possibly neural substrates. However, sensorimotor and sequence learning are usually studied in isolation in research settings, for example as force field adaptation or serial reaction time tasks (SRTT), respectively. It is therefore unclear whether having predictive sequence information during sensorimotor adaptation would facilitate performance, perhaps by improving sensorimotor planning, or if it would impair performance, perhaps by occupying neural resources needed for sensorimotor learning. Here we evaluated adaptation to a distance-dependent force field in two different SRTT contexts: In Experiment 1, 28 subjects reached between 4 targets in a sequenced or random order. In Experiment 2, 40 subjects reached to one target, but 3 force field directions were applied in a sequenced or random order. We did not observe any consistent influence of target position sequence on force field adaptation in Experiment 1. However, sequencing of force field directions facilitated sensorimotor adaptation and retention in Experiment 2. This is inconsistent with the idea that sensorimotor and sequence learning share neural resources in any mutually exclusive fashion. These findings indicate that under certain conditions, perhaps especially when the sequence is related to the sensorimotor perturbation itself as in Experiment 2, sequence learning may interact with sensorimotor learning in a facilitatory manner.
Dynamics of Prion Proliferation Under Combined Treatment of Pharmacological Chaperones and Interferons via a Mathematical Model
Authors: Garzón Doménica N. , Castillo Yair , Navas-Zuloaga M. Gabriela , Culik Nora , Darwin Leah , Hardin Abigail , Yang Anji , Castillo-Garsow Carlos , Ríos-Soto Karen , Arriola Leon , Ghosh Aditi
Published: July 2020

Prion diseases are lethal neurodegenerative disorders such as mad cow disease in bovines, chronic wasting disease in cervids, and Creutzfeldt-Jakob disease in humans. They are caused when the prion protein PrPCmisfolds into PrPSc, which is capable of inducing further misfolding in healthy PrPCproteins. Recentin vivoexperiments show that pharmacological chaperones can temporarily prevent this conversion by binding to PrPCmolecules, and thus constitute a possible treatment. A second strategic approach uses interferons to decrease the concentration of PrPSc. In order to study the quantitative effects of these treatments on prion proliferation, we develop a model using a non-linear system of ordinary differential equations. By evaluating their efficacy and potency, we find that interferons act at lower doses and achieve greater prion decay rates. However, there are benefits in combining them with pharmacological chaperones in a two-fold therapy. This research is crucial to guide future prion experiments and inform potential treatment protocols.
Early Identification of Patients with Acute Gastrointestinal Bleeding using Electronic Health Record Phenotyping
Authors: Shung Dennis , Tsay Cynthia , Laine Loren , Thomas Prem , Partridge Caitlin , Simonov Michael , Hsiao Allen , Taylor Andrew
Published: July 2020

Background and Aim

Guidelines recommend risk stratification scores in patients presenting with gastrointestinal bleeding (GIB), but such scores are uncommonly employed in practice. Automation and deployment of risk stratification scores in real time within electronic health records (EHRs) would overcome a major impediment. This requires an automated mechanism to accurately identify (“phenotype”) patients with GIB at the time of presentation. The goal is to identify patients with acute GIB by developing and evaluating EHR-based phenotyping algorithms for emergency department (ED) patients.

Methods

We specified criteria using structured data elements to create rules for identifying patients, and also developed a natural-language-processing (NLP)-based algorithm for automated phenotyping of patients, tested them with tenfold cross-validation (n=7144) and external validation (n=2988), and compared them with the standard method for encoding patient conditions in the EHR, Systematized Nomenclature of Medicine (SNOMED). The gold standard for GIB diagnosis was independent dual manual review of medical records. The primary outcome was positive predictive value (PPV).

Results

A decision rule using GIB-specific terms from ED triage and from ED review-of-systems assessment performed better than SNOMED on internal validation (PPV=91% [90%-93%] vs. 74% [71%-76%], P<0.001) and external validation (PPV=85% [84%-87%] vs. 69% [67%-71%], P<0.001). The NLP algorithm (external validation PPV=80% [79-82%]) was not superior to the structured-datafields decision rule.

Conclusions

An automated decision rule employing GIB-specific triage and review-of-systems terms can be used to trigger EHR-based deployment of risk stratification models to guide clinical decision-making in real time for patients with acute GIB presenting to the ED.
Adverse Events in Surgical Neurology: The Novel Therapy-Disability-Neurology (TDN) Grade
Authors: Romain Terrapon Alexis Paul , Zattra Costanza Maria , Voglis Stefanos , Velz Julia , Vasella Flavio , Akeret Kevin , Held Ulrike , Schiavolin Silvia , Bozinov Oliver , Ferroli Paolo , Broggi Morgan , Sarnthein Johannes , Regli Luca , Neidert Marian Christoph
Published: July 2020

Background

The most widely used classifications of adverse events (AE) in surgical neurology assign a grade to AE that depends on the therapy used to treat them or on new neurologic deficits. Both concepts have substantial shortcomings in grading AE severity. We present a novel multidimensional approach to this challenge and aim at validating the new grading system.

Methods

The new Therapy-Disability-Neurology (TDN) grading system classifies AE into five grades, depending on the associated therapy, disability, and neurologic deficits. We conducted a two-center study on 6071 interventions covering the whole neurosurgical spectrum with data prospectively recorded between January 2013 and September 2019 at the University Hospital Zurich (USZ) and at the Fondazione IRCCS Istituto Neurologico Carlo Besta (FINCB).

Findings

Using data from USZ, a positive correlation was found between the severity of AE and the length of hospital stay (LOS) as well as treatment cost. Each grade was associated with a greater deterioration of the Karnofsky Performance Status Scale (KPS) at discharge and at follow-up. Additionally, there was a correlation between the severity of AE and absolute KPS values. When using the same methods on an external validation cohort from FINCB, correlations between the grade of AE, LOS, and KPS at discharge were even more pronounced.

Interpretation

Our results suggest that the TDN grade is consistent with clinical and economic repercussions of AE and thus reflects AE severity. It is objective, practical, easily interpreted, and enables comparison between different medical centers. The TDN grade will constitute an important step forward towards a more precise and standardized documentation of AE and ultimately lead to a more critical and patient-centered appraisal of process and outcome measures in surgical neurology.

Funding

None.
Impact of COVID-19 Attributable Deaths on Longevity, Premature Mortality and DALY: Estimates of USA, Italy, Sweden and Germany
Authors: Mohanty Sanjay K , Dubey Manisha , Mishra Udaya S , Sahoo Umakanta
Published: July 2020

In a short span of four months, the COVID-19 pandemic has added over 0.4 million deaths worldwide, which are untimely, premature and unwarranted. The USA, Italy, Germany and Sweden are four worst affected countries, accounting to over 40% of COVID-19 deaths globally. The main objective of this study is to examine the impact of COVID-19 attributable deaths on longevity, years of potential life lost (YPLL) and disability adjusted life years (DALY) in USA, Italy, Germany and Sweden. Data from United Nation Population Projection, Statista and centre for disease control and prevention were used in the analyses. Life expectancy, YPLL and DALY were estimated under four scenarios; no COVID-19 deaths, actual number of COVID-19 death as of 22ndMay, 2020 and anticipating COVID-19 death share of 6% and 10% respectively. The COVID-19 attributable deaths have lowered the life expectancy by 0.4 years each in USA and Sweden, 0.5 years in Italy and 0.1 years in Germany. The loss of YPLL was 1.5, 0.5, 0.1 and 0.5 million in USA, Italy, Germany and Sweden respectively. The DALY (per 1000 population) due to COVID-19 was 4 in USA, 6 in Italy, 1 each in Germany and Sweden. Compression in life expectancy and increase in YPLL and DALY may intensify further if death continues to soar. COVID-19 has a marked impact on mortality. Reduction in longevity premature mortality and loss of DALY is higher among elderly.
Molecular tracing of SARS-CoV-2 in Italy in the first three months of the epidemic
Authors: Lai Alessia , Bergna Annalisa , Caucci Sara , Clementi Nicola , Vicenti Ilaria , Dragoni Filippo , Cattelan Anna Maria , Menzo Stefano , Pan Angelo , Callegaro Annapaola , Tagliabracci Adriano , Caruso Arnaldo , Caccuri Francesca , Ronchiadin Silvia , Balotta Claudia , Zazzi Maurizio , Vaccher Emanuela , Clementi Massimo , Galli Massimo , Zehender Gianguglielmo
Published: July 2020

The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central Italy until the end of April 2020.

All but one of the newly characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B.

A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution.

tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (Re) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented.

Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.
Clinical characteristics and epidemiology survey of lung transplantation recipients accepting surgeries during the COVID-19 pandemic : from area near Hubei Province
Authors: Qiu Lingxiao , Chen Shan shan , Wang Cong , Liu Caihong , Wang Huaqi , Zhao Xiaoguang , Fang Zeming , Chang Siyuan , Zhao Gaofeng , Zhang Guojun
Published: July 2020

Lung transplantation recipients (LTx) were susceptible to severe acute respiratory syndrome-corona virus-2 (SARS-Cov-2) and suffered a higher mortality risk than healthy subjects. Here we aim to analyze whether it was appropriate or and valuable to maintain lung transplant programs in medical institutions accepting coronavirus disease 2019 (COVID-19) patients. In this study, the clinical characteristics, laboratory testing and epidemiology survey results of 10 LTx recipients undergoing allograft lung transplantation surgeries in the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic were collected. A web-based epidemiology questionnaire was used to collect the information of LTx recipients after discharge. Up to now, none of the LTx recipients or their family members get infected with SARS-CoV-2 during the novel coronavirus pandemic. In conclusion, under the premise of taking appropriate preventive measures during hospitalization and after discharge, the lung transplant program can be maintained in the medical institution that accepts patients with COVID-19.
Digitized smart surveillance in malaria elimination programme in Mangaluru city, Karnataka, India ― a detailed account of operationalization in post-digitization years
Authors: Baliga B. Shantharam , Baliga Shrikala , Jain Animesh , Kulal Naveen , Kumar Manu , Koduvattat Naren , Kumar B. G. Prakash , Kumar Arun , Ghosh Susanta K.
Published: July 2020

Background

An indigenously developed digital handheld Android-based geographical information system (GIS)-tagged tablets (TABs) device has been deployed in Mangaluru city, Karnataka, India for smart surveillance in malaria elimination programme from October 2014. Here a detailed account is enumerated in the post-digitization years. The study was aimed to assess the effectiveness of the digitized surveillance system under the ongoing health system in Mangaluru city.

Methods

A software developed for digitization of malaria surveillance was continued in the post-digitization years (PDY). The same digitization year (DY) protocol was followed in the post-digitization periods also. Secondary data from the malaria control software, total nunber of cases, active surveillance, malaria indices, and feedback from stakeholders were looked at and analyzed.

Results

Digital surveillance was sustained and the performance improved in the 5th year with participation of all stakeholders. Malaria indices significantly reduced to about 65% in the digitization years compared with digitization year (p<0.001). Slide positivity rate (SPR) decreased from 10.36 (DY) to 4.3 (PDY4). Annual parasite incidence (API) decreased from 16.17 (DY) to 5.4 (PDY4). There was a tempo-spatial correlation between closure of cases on 14th day and incidence of malaria. There was a negative correlation between contact smears and incidence of malaria (r = -0.907). Good impact was recorded in the pre-monsoon months (∼85%) and low impact in July and August months (∼40%).

Conclusion

Software helped to improve incidence-centric active surveillance, complete treatment with documentation of elimination of parasite, targeted vector control measures. The learnings and analytical output from the data helped to modify strategies for local control of both disease and the vector.
Early Detection Of COVID-19 Using A Smartwatch
Authors: Mishra Tejaswini , Wang Meng , Metwally Ahmed A. , Bogu Gireesh K , Brooks Andrew W , Bahmani Amir , Alavi Arash , Celli Alessandra , Higgs Emily , Dagan-Rosenfeld Orit , Fay Bethany , Kirkpatrick Susan , Kellogg Ryan , Gibson Michelle , Wang Tao , Rolnik Benjamin , Ganz Ariel B , Li Xiao , Snyder Michael P
Published: July 2020

Wearable devices digitally measuring vital signs have been used for monitoring health and illness onset and have high potential for real-time monitoring and disease detection. As such they are potentially useful during public health crises, such as the current COVID-19 global pandemic. Using smartwatch data from 31 infected individuals identified from a cohort of over 5000 participants, we investigated the use of wearables for early, presymptomatic detection of COVID-19. From physiological and activity data, we first demonstrate that COVID-19 infections are associated with alterations in heart rate, steps and sleep in 80% of COVID-19 infection cases. Failure to detect these changes in the remaining patients often occurred in those with chronic respiratory/lung disease. Importantly the physiological alterations were detected prior to, or at, symptom onset in over 85% of the positive cases (21/24), in some cases nine or more days before symptoms. Through daily surveys we can track physiological changes with symptom onset and severity. Finally, we develop a method to detect onset of COVID-19 infection in real-time which detects 67% of infection cases at or before symptom onset. Our study provides a roadmap to a rapid and universal diagnostic method for the large-scale detection of respiratory viral infections in advance of symptoms, highlighting a useful approach for managing epidemics using digital tracking and health monitoring.
COVID-19 screening strategies that permit the safe re-opening of college campuses
Authors: Paltiel A. David , Zheng Amy , Walensky Rochelle P.
Published: July 2020

Importance

The COVID-19 pandemic poses an existential threat to many US residential colleges: either they open their doors to students in September or they risk serious financial consequences.

Objective

To define SARS-CoV-2 screening performance standards that would permit the safe return of students to campus for the Fall 2020 semester.

Design

Decision and cost-effectiveness analysis linked to a compartmental epidemic model to evaluate campus screening using tests of varying frequency (daily-weekly), sensitivity (70%-99%), specificity (98%-99.7%), and cost ($10-$50/test). Reproductive numbers Rt = {1.5, 2.5, 3.5} defined three epidemic scenarios, with additional infections imported via exogenous shocks. We generally adhered to US government guidance for parameterization data.

Participants

A hypothetical cohort of 5000 college-age, uninfected students.

Main Outcome(s) and Measure(s)

Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. All measured over an 80-day, abbreviated semester.

Results

With Rt = 2.5, daily screening with a 70% sensitive, 98% specific test produces 85 cumulative student infections and isolation dormitory daily census averaging 108 (88% false positives). Screening every 2 (7) days nets 135 (3662) cumulative infections and daily isolation census 66 (252) with 73% (4%) false positives. Across all scenarios, test frequency exerts more influence on outcomes than test sensitivity. Cost-effectiveness analysis selects screening every {2, 1, 7} days with a 70% sensitive test as the preferred strategy for Rt = {2.5, 3.5, 1.5}, implying a screening cost of {$470, $920, $120} per student per semester.

Conclusions & Relevance

Rapid, inexpensive and frequently conducted screening – even if only 70% sensitive – would be cost-effective and produce a modest number of COVID-19 infections. While the optimal screening frequency hinges on the success of behavioral interventions to reduce the base severity of transmission (Rt), this could permit the safe return of student to campus.

KEY POINTS

Question

What SARS-CoV-2 screening and isolation program will keep U.S. residential college students safe and permit the reopening of campuses?

Findings

Frequent screening (every 2 or 3 days) of all students with a low-sensitivity, high-specificity test will control outbreaks with manageable isolation dormitory utilization at a justifiable cost.

Meaning

Campuses can safely reopen in the Fall 2020 but success hinges on frequent screening and uncompromising, continuous attention to basic prevention and behavioral interventions to reduce the baseline severity of transmission.
Parallel structure of six wheel-legged robot trajectory tracking control with heavy payload under uncertain physical interaction
Authors: Li Jiehao , Wang Junzheng , Wang Shoukun , Peng Hui , Wang Bomeng , Qi Wen , Zhang Longbin , Su Hang
Published: July 2020

Purpose

This paper aims on the trajectory tracking of the developed six wheel-legged robot with heavy load conditions under uncertain physical interaction. The accuracy of trajectory tracking and stable operation with heavy load are the main challenges of parallel mechanism for wheel-legged robots, especially in complex road conditions. To guarantee the tracking performance in an uncertain environment, the disturbances, including the internal friction, external environment interaction, should be considered in the practical robot system.

Design/methodology/approach

In this paper, a fuzzy approximation-based model predictive tracking scheme (FMPC) for reliable tracking control is developed to the six wheel-legged robot, in which the fuzzy logic approximation is applied to estimate the uncertain physical interaction and external dynamics of the robot system. Meanwhile, the advanced parallel mechanism of the electric six wheel-legged robot (BIT-NAZA) is presented.

Findings

Co-simulation and comparative experimental results using the BIT-NAZA robot derived from the developed hybrid control scheme indicate that the methodology can achieve satisfactory tracking performance in terms of accuracy and stability.

Originality/value

This research can provide theoretical and engineering guidance for lateral stability of intelligent robots under unknown disturbances and uncertain nonlinearities and facilitate the control performance of the mobile robots in a practical system.
Linking digital platforms' service dimensions to customers' purchase
Authors: Saberian Fatemeh , Amirshahi Mirahmad , Ebrahimi Mahdi , Nazemi Asieh
Published: July 2020

Purpose

This paper aims to identify the dimensions of digital platforms' services quality and their impact on customers' purchase intent based on customer experience.

Design/methodology/approach

The research has a mixed method. Qualitative data is gathered by using of systematic literature review and Delphi method and quantitative data is gathered through survey of 412 experts from three well-known restaurant industry platforms. These restaurant digital platforms were Snapfood, Changal and Chelivery.

Findings

The results indicate the effect of platforms' service quality dimensions on customer hedonic and cognitive experiences. Also, the results indicate that the platforms' customers attach different priority to the various dimensions of platforms' services quality which are platform services' ease of use, platform information quality, services and products quality, platform customers interaction, platform design, platform response speed, platform services' trustiness, platform services' security and platform responsibility. Finally, the results showed that all of these dimensions have positive impact on customers' purchase intent based on their experiences.

Originality/value

The development of digital service platforms despite being new, has recently great progress, but, many dimensions of digital platforms' services quality have been not well-known yet. The present research has cleared the subject.