bluuebunny/crossref_metadata_2025 huggingface dataset:
Population-scale Longitudinal Mapping of COVID-19 Symptoms, Behavior, and Testing Identifies Contributors to Continued Disease Spread in the United States
Authors: Allen William E. , Altae-Tran Han , Briggs James , Jin Xin , McGee Glen , Shi Andy , Raghavan Rumya , Kamariza Mireille , Nova Nicole , Pereta Albert , Danford Chris , Kamel Amine , Gothe Patrik , Milam Evrhet , Aurambault Jean , Primke Thorben , Li Weijie , Inkenbrandt Josh , Huynh Tuan , Chen Evan , Lee Christina , Croatto Michael , Bentley Helen , Lu Wendy , Murray Robert , Travassos Mark , Coull Brent A. , Openshaw John , Greene Casey S. , Shalem Ophir , King Gary , Probasco Ryan , Cheng David R. , Silbermann Ben , Zhang Feng , Lin Xihong
Published: June 2020

Summary Paragraph

Despite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users’ health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self-reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self-reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self-reported data to fight the COVID-19 pandemic.
Clinical, dietary, and psychosocial effectiveness of interdisciplinary care in child and juvenile obesity
Authors: Menezes Carlos Alberto , Vasconcelos Rayzza Santos
Published: June 2020

The aim of this study is to evaluate the effectiveness of interdisciplinary care in modifying anthropometric clinical parameters (BMI and waist circumference), psychosocial profile and eating behavior in a group of children and adolescents with obesity. This is a clinical study involving 200 children and adolescents with obesity who are participants of the “Serviço de Medicina Preventiva” program, and the “Centro de Especialidades Médicas de Crianças e Adolescentes” both in Aracaju, Sergipe, Brazil. At the end of the interdisciplinary intervention, there was a decrease in the number of hours devoted to electronic games and television and an increase in physical activity, which was associated with a reduction in reports of dissatisfaction and symptoms of depression. In addition, the sadness and prejudice related to obesity suffered at school and in the family environment were also attenuated, despite the percentage increase in the anxiety indicator. Regarding the anthropometric measurement, there was a reduction in body mass index, waist circumference, in caloric consumption. It is concluded that interdisciplinary programs are an effective strategy to reduce the negative repercussions of obesity in the daily lives of obese children and adolescents, as there were improvements in anthropometric parameters, in addition to psychosocial and dietary aspects.

O objetivo deste estudo é avaliar a eficácia do atendimento interdisciplinar na modificação de parâmetros clínicos antropométricos (IMC e circunferência da cintura), perfil psicossocial e comportamento alimentar em um grupo de crianças e adolescentes com obesidade. Trata-se de um estudo clínico envolvendo 200 crianças e adolescentes com obesidade participantes do programa “Serviço de Medicina Preventiva” e do “Centro de Especialidades Médicas de Crianças e Adolescentes”, ambos em Aracaju, Sergipe, Brasil. Ao final da intervenção interdisciplinar, houve uma diminuição no número de horas dedicadas a jogos eletrônicos e televisão e um aumento na atividade física, o que foi associado à redução nos relatos de insatisfação e sintomas de depressão. Além disso, a tristeza e o preconceito relacionados à obesidade sofrida na escola e no ambiente familiar também foram atenuados, apesar do aumento percentual no indicador de ansiedade. Em relação à medida antropométrica, houve redução do índice de massa corporal, circunferência da cintura e consumo calórico. Conclui-se que os programas interdisciplinares são uma estratégia eficaz para reduzir as repercussões negativas da obesidade no cotidiano de crianças e adolescentes obesos, pois houve melhorias nos parâmetros antropométricos, além de aspectos psicossociais e alimentares.
Implications of the reverse associations between obesity prevalence and coronavirus disease (COVID-19) cases and related deaths in the United States
Authors: Zhang Ning , Cordeiro Lorraine S. , Liu Zhenhua
Published: June 2020

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was most recently discovered, quickly evolved into a global pandemic. Studies suggested that obesity was a major risk factor for its hospitalization and severity of symptoms. This study investigated the associations between obesity prevalence with overall COVID-19 cases and related deaths across states in the United States. General regression and Chi-square tests were used to examine those associations. The analyses indicated that obesity prevalence (%) across states were negatively associated with COVID-19 cases (p= 0.0448) and related deaths (p= 0.0181), with a decrease of 158 cases/100K population and 13 deaths/100K for every 5% increase of the obesity prevalence. When the states were divided based on the median of obesity prevalence (30.9%) into a group of states with low obesity prevalence and a group with high obesity prevalence, both the cases (671 vs 416 cases/100k population) and deaths (39 vs 21 deaths/100k population) were significantly different (p< 0.001) across groups. These findings provided important information for the relationship between the dual pandemic threats of obesity and COVID-19. These results should not currently be considered as an indication that obesity is a protective factor for COVID-19, and would rather be used as a warning of the public advice that obese people is more vulnerable to COVID-19 infection, which may lead to a false safety message probably given to people with normal body weight.
A new bioinformatic tool to interpret metagenomics / metatranscriptomics results based on the geometry of the clustering network and its differentially gene ontologies (GANGO)
Authors: Monleon-Getino Antonio , Paytuví-Gallart Andreu , Sanseverino Walter , Méndez Javier
Published: June 2020

High-throughput experimental techniques, such as metagenomics or metatranscriptomics, produce large amounts of data, which interpretation and conversion into understandable knowledge can be challenging and out of reach. We present GANGO, a new algorithm based on the ecological concept of consortium (groups biologically connected) and by using clustering network analysis, gene ontologies and powerful hypothesis test allows the identification and interpretation of complex ecological networks, allowing the identification of the relationship between taxa/genes, the number of groups, their relations and their functionalities using the annotated genes of an organism in a database (e.g. UniProt or Ensembl). Three examples of the use of GANGO are shown: a simulated mixture of fungi and bacteria, alterations in soil fungi communities after a diesel-oil spill and genomic changes inSaccharomyces cerevisaedue to abiotic stress.
Sentinelp16INK4a+ cells in the basement membrane form a reparative niche in the lung
Authors: Reyes de Mochel Nabora , Cheong Ka Neng , Cassandras Monica , Wang Chaoqun , Krasilnikov Maria , Matatia Peri , Molofsky Ari , Campisi Judith , Peng Tien
Published: June 2020

Senescent cells are recognized drivers of aging-related decline in organ function, but deciphering the biology of senescencein vivohas been hindered by the paucity of tools to track and isolate senescent cells in tissues1–4. Deleting senescent cells from transgenic murine models have demonstrated therapeutic benefits in numerous age-related diseases5–11, but the identity, behavior, and function of the senescent cells deletedin vivoremain elusive. We engineered an ultra-sensitive reporter ofp16INK4a, a biomarker of senescence12, to isolate and trackp16INK4a+ cellsin vivo. Surprisingly,p16INK4a+ mesenchymal cells appear in the basement membrane adjacent to epithelial progenitors in the lung shortly after birth, and these cells demonstrate senescent characteristicsin vivoandex vivo. Transcriptomic analysis ofp16INK4a+ mesenchymal cells from non-aged lungs demonstrates a transition to a secretory phenotype upon airway epithelial injury. Heterotypic 3D organoid assays show that injuredp16INK4a+ mesenchymal cells enhance epithelial progenitor proliferation, and we identified EREG as a novel airway progenitor mitogen produced by the secretoryp16INK4a+ mesenchymal cells. Mesenchymal-specific deletion of thep16INK4agene abrogates features of senescencein vivo, but also attenuates normal epithelial repair. Thus,p16INK4a+ mesenchymal cells can act as sentinels for the airway epithelial stem cell niche, poised to transition to a senescence-associated secretory phenotype to support barrier repair. Our data identify possible cellular targetsin vivofor a rapidly growing list of senolytic therapies, but also raises important questions about the hidden cost of targeting senescent cells present in normal organs.
SPECIFIC ECTODERMAL ENHANCERS CONTROL THE EXPRESSION OFHoxcGENES IN DEVELOPING MAMMALIAN INTEGUMENTS
Authors: Fernandez-Guerrero Marc , Yakushiji-Kaminatsui Nayuta , Lopez-Delisle Lucille , Zdral Sofía , Darbellay Fabrice , Perez-Gomez Rocío , Bolt Christopher Chase , Sanchez-Martin Manuel A. , Duboule Denis , Ros Maria A.
Published: June 2020

VertebrateHoxgenes are key players in the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that theHoxCgene cluster was globally co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of theHoxCcluster led to mice lacking nails (anonychia) and also hairs (alopecia), a condition stronger than the previously reported loss of function ofHoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two ectodermal, mammalian-specific enhancers located upstream of theHoxCgene cluster, which act synergistically to regulateHoxcgene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation ofHoxcgenes in the ectoderm, suggesting that these two enhancers may have evolved along with mammals to provide the level of HOXC proteins necessary for the full development of hairs and nails.

Significance Statement

In this study, we report a unique and necessary function for theHoxCgene cluster in the development of some ectodermal organs, as illustrated both by the hair and nail phenotype displayed by mice lacking theHoxc13function and by the congenital anonychia (absence of nails) in fullHoxCcluster mutants. We show thatHoxcgenes are activated in a colinear manner in the embryonic limb ectoderm and are subsequently transcribed in developing nails and hairs. We identify two mammalian-specific enhancers located upstream of theHoxCcluster with and exclusive ectodermal specificity. Individual or combined enhancer deletions suggest that they act in combination to raise the transcription level of severalHoxcgenes during hairs and nails development.
A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance
Authors: Al-Akhrass Hussein , Conway James R.W. , Aavild Poulsen Annemarie Svane , Paatero Ilkka , Kaivola Jasmin , Padzik Artur , Andersen Olav M. , Ivaska Johanna
Published: June 2020

Current evidence indicates that resistance to HER2-targeted therapies is frequently associated with HER3 and active signalingviaHER2-HER3 dimers, particularly in the context of breast cancer. Thus, understanding the response to HER2-HER3 signaling and the regulation of the dimerper seremains essential to decipher therapy relapse mechanisms. Here, we demonstrate that signaling by HER3 growth factor ligands, heregulins, support the transcription of a type-1 transmembrane sorting receptor, sortilin-related receptor (SorLA;SORL1) downstream of the mitogen-activated protein kinase pathway. In addition, we demonstrate that SorLA interacts directly with HER3, forming a trimeric complex with HER2 and HER3 to attenuate lysosomal degradation of the dimer through a Rab4-dependent manner. In line with a role for SorLA in supporting the stability of the HER2 and HER3 receptors, loss of SorLA compromised heregulin-induced cell proliferation and sensitized metastatic anti-HER2 therapy-resistant breast cancer cells to neratinib in cancer spheroidsin vitroandin vivoin a zebrafish brain xenograft model. Collectively, our results demonstrate a novel feed-forward loop consisting of heregulin, HER2-HER3 and SorLA, which controls breast cancer growth and anti-HER2 therapy resistancein vitroandin vivo.

Significance

HER3 signaling, through ERK/MAPK, upregulates SorLA and SorLA controls the trafficking and stability of HER3 to support cancer proliferation and neratinib resistance.
Functional modules from variable genes: Leveraging percolation to analyze noisy, high-dimensional data
Authors: Werner Steffen , Rozemuller W Mathijs , Ebbing Annabel , Alemany Anna , Traets Joleen , van Zon Jeroen S. , van Oudenaarden Alexander , Korswagen Hendrik C. , Stephens Greg J. , Shimizu Thomas S.
Published: June 2020

While measurement advances now allow extensive surveys of gene activity (large numbers of genes across many samples), interpretation of these data is often confounded by noise — expression counts can differ strongly across samples due to variation of both biological and experimental origin. Complimentary to perturbation approaches, we extract functionally related groups of genes by analyzing the standing variation within a sampled population. To distinguish biologically meaningful patterns from uninterpretable noise, we focus on correlated variation and develop a novel density-based clustering approach that takes advantage of a percolation transition generically arising in random, uncorrelated data. We apply our approach to two contrasting RNA sequencing data sets that sample individual variation — across single cells of fission yeast and whole animals ofC. elegansworms — and demonstrate robust applicability and versatility in revealing correlated gene clusters of diverse biological origin, including cell cycle phase, development/reproduction, tissue-specific functions, and feeding history. Our technique exploits generic features of noisy high-dimensional data and is applicable, beyond gene expression, to feature-rich data that sample population-level variability in the presence of noise.

Significance Statement

Gene expression largely determines the fate of each cell and ultimately the development and behavior of the whole organism. Whereas most of our knowledge on gene regulatory networks has been obtained from perturbation experiments (e.g. manipulating environmental conditions, genotype, or other physiological variables), here we develop an alternative approach based on the analysis of naturally occurring variations across individuals within a population. Using both single-cell and whole-animal RNA sequencing data, we demonstrate how a rich set of co-regulated gene modules can be uncovered from transcriptomic variability of individuals within unperturbed populations. To robustly extract interpretable clusters from the strong noise background, we devise a novel, versatile clustering approach based on network theory. With a foundation in the generic behavior of random networks near their percolation critical point, our method is broadly applicable, beyond gene expression, to any noisy, high-dimensional data that sample variation across individuals within a population.
FASTQuick: Rapid and comprehensive quality assessment of raw sequence reads
Authors: Zhang Fan , Kang Hyun Min
Published: June 2020

Background

Rapid and thorough quality assessment of sequenced genomes in an ultra-high-throughput scale is crucial for successful large-scale genomic studies. Comprehensive quality assessment typically requires full genome alignment, which costs a significant amount of computational resources and turnaround time. Existing tools are either computational expensive due to full alignment or lacking essential quality metrics by skipping read alignment.

Findings

We developed a set of rapid and accurate methods to produce comprehensive quality metrics directly from raw sequence reads without full genome alignment. Our methods offer orders of magnitude faster turnaround time than existing full alignment-based methods while providing comprehensive and sophisticated quality metrics, including estimates of genetic ancestry and contamination.

Conclusions

By rapidly and comprehensively performing the quality assessment, our tool will help investigators detect potential issues in ultra-high-throughput sequence reads in real-time within a low computational cost, ensuring high-quality downstream analysis and preventing unexpected loss in time, money, and invaluable specimens.
Anticipation of ventricular tachyarrhythmias by a novel mathematical method: Further insights towards an early warning system in implantable cardioverter defibrillators
Authors: Zamudio Gabriel S. , Márquez Manlio F. , José Marco V.
Published: June 2020

Background

Implantable cardioverter defibrillators (ICD) are the most effective therapy to terminate malignant ventricular arrhythmias (VA) and therefore to prevent sudden cardiac death. Until today, there is no way to predict the onset of such VA. Our aim was to develop a mathematical model that could predict VA in a timely fashion.

Methods

We analyzed the time series of R-R intervals from 3 groups. Two groups from the Spontaneous Ventricular Tachyarrhythmia Database (v 1.0) were analyzed from a set of 81 pairs of R-R interval time series records from patients, each pair containing one record before the VT episode (Dataset 1A) and one control record which was obtained during the follow up visit (Dataset 1B). A third data set was composed of the RR interval time series of 54 subjects without a significant arrhythmia heart disease (Dataset 2). We developed a new method to transform a time series into a network for its analysis, theε−regular graphs. This novel approach transforms a time series into a network which is sensitive to the quantitative properties of the time series, it has a single parameter (ε) to be adjusted, and it can trace long-range correlations. This procedure allows to use graph theory to extract the dynamics of any time series.

Results

The average of the difference between the VT and the control record graph degree of each patient, at each time window, reached a global minimum value of −2.12 followed by a drastic increase of the average graph until reaching a local maximum of 5.59. The global minimum and the following local maxima occur at the windows 276 and 393, respectively. This change in the connectivity of the graphs distinguishes two distinct dynamics occurring during the VA, while the states in between the 276 and 393, determine a transitional state. We propose this change in the dynamic of the R-R intervals as a measurable and detectable “early warning” of the VT event, occurring an average of 514.625 seconds (8 : 30 minutes) before the onset of the VT episode.

Conclusions

It is feasible to detect retrospectively early warnings of the VA episode using their correspondingε−regular graphs, with an average of 8 : 30 minutes before the ICD terminates the VA event.
Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters
Authors: Osterrieder Nikolaus , Bertzbach Luca D. , Dietert Kristina , Abdelgawad Azza , Vladimirova Daria , Kunec Dusan , Hoffmann Donata , Beer Martin , Gruber Achim D. , Trimpert Jakob
Published: June 2020

In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans1. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals2. Because age-dependent differences of COVID-19 were identified in humans3, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss.In situhybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information as this small-animal model appears to mirror age-dependent differences in human patients.
A steady-state algebraic model for the time course of covalent enzyme inhibition
Authors: Kuzmič Petr
Published: June 2020

This report describes a double-exponential algebraic equation for the time course of irreversible enzyme inhibition following the two-step mechanismE+I⇌E·I→EI, under the steady-state approximation. Under the previously invoked rapid-equilibrium approximation [Kitz & Wilson (1962)J. Biol. Chem.237, 3245] it was assumed that the rate constant for the reversible dissociation of the initial noncovalent complex is very much faster than the rate constant for the irreversible inactivation step. The steady-state algebraic equation reported here removes any restrictions on the relative magnitude of microscopic rate constants. The resulting formula was used in heuristic simulations designed to test the performance of the standard rapid-equilibrium kinetic model. The results show that if the inactivation rate constant is significantly higher than the dissociation rate constant, the conventional “kobs” method is incapable of correctly distinguishing between the two-step inhibition mechanism and a simpler one-step variant,E+I→EI, even for inhibitors that have very high binding affinity in the reversible noncovalent step.
Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger Cyclin K degradation
Authors: Lv Lu , Chen Peihao , Cao Longzhi , Li Yamei , Zeng Zhi , Cui Yue , Wu Qingcui , Li Jiaojiao , Wang Jian-Hua , Dong Meng-Qiu , Qi Xiangbing , Han Ting
Published: June 2020

Molecular glues are small molecules that exert their biologic or therapeutic activities by inducing gain-of-function interactions between pairs of proteins. In particular, molecular-glue degraders, which mediate interactions between target proteins and components of the ubiquitin proteasome system to cause targeted protein degradation, hold great promise as a unique modality for therapeutic targeting of proteins that are currently intractable. Here, we report a new molecular glue HQ461 discovered by high-throughput screening of small molecules that inhibited NRF2 activity. Using unbiased loss-of-function and gain-of-function genetic screening followed by biochemical reconstitution, we show that HQ461 acts by promoting interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, leading to polyubiquitination and proteasomal degradation of CDK12’s interacting protein Cyclin K (CCNK). Degradation of CCNK mediated by HQ461 compromised CDK12 function, leading to reduced phosphorylation of CDK12 substrate, downregulation of DNA damage response genes, and cell death. Structure-activity relationship analysis of HQ461 revealed the importance of a 5-methylthiazol-2-amine pharmacophore and resulted in an HQ461 derivate with improved potency. Our studies reveal a new molecular glue that engages its target protein directly with DDB1 to bypass the requirement of a substrate-specific receptor, presenting a new strategy for targeted protein degradation.
Human Whole Genome Sequencing in South Africa
Authors: Glanzmann Brigitte , Jooste Tracey , Ghoor Samira , Gordon Richard , Mia Rizwana , Mao Jun , Li Hao , Charls Patrick , Douman Craig , Kotze Maritha J. , Peeters Armand V. , Loots Glaudina , Esser Monika , Tiemessen Caroline T. , Wilkinson Robert J , Louw Johan , Gray Glenda , Warren Robin M. , Möller Marlo , Kinnear Craig
Published: June 2020

The advent and evolution of next generation sequencing has considerably impacted genomic research. Until recently, South African researchers were unable to access affordable platforms capable of human whole genome sequencing locally and DNA samples had to be exported. Here we report the whole genome sequences of the first six human DNA samples sequenced and analysed at the South African Medical Research Council’s Genomics Centre. We demonstrate that the data obtained is of high quality, with an average sequencing depth of 36.41, and that the output is comparable to data generated internationally on a similar platform. The Genomics Centre creates an environment where African researchers are able to access world class facilities, increasing local capacity to sequence whole genomes as well as store and analyse the data.
Single nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell type-specific gene regulatory variation
Authors: Gui Yujuan , Grzyb Kamil , Thomas Mélanie H. , Ohnmacht Jochen , Garcia Pierre , Buttini Manuel , Skupin Alexander , Sauter Thomas , Sinkkonen Lasse
Published: June 2020

Cell types in ventral midbrain are involved in diseases with variable genetic susceptibility such as Parkinson’s disease and schizophrenia. Many genetic variants affect regulatory regions and alter gene expression. We report 20 658 single nuclei chromatin accessibility profiles of ventral midbrain from two genetically and phenotypically distinct mouse strains. We distinguish ten cell types based on chromatin profiles and analysis of accessible regions controlling cell identity genes highlights cell type-specific key transcription factors. Regulatory variation segregating the mouse strains manifests more on transcriptome than chromatin level. However, cell type-level data reveals changes not captured at tissue level. To discover the scope and cell-type specificity ofcis-acting variation in midbrain gene expression, we identify putative regulatory variants and show them to be enriched at differentially expressed loci. Finally, we find TCF7L2 to mediatetrans-acting variation selectively in midbrain neurons. Our dataset provides an extensive resource to study gene regulation in mesencephalon.
Relating Bone Strain to Local Changes in Radius Microstructure Following 12 Months of Axial Forearm Loading in Women
Authors: Mancuso Megan E. , Troy Karen L.
Published: June 2020

Work in animal models suggest that bone structure adapts to local bone strain, but this relationship has not been comprehensively studied in humans. Here, we quantified the influence of strain magnitude and gradient on bone adaptation in the forearm of premenopausal women performing compressive forearm loading (n=11) and non-loading controls (n=10). High resolution peripheral quantitative computed tomography (HRpQCT) scans of the distal radius acquired at baseline and 12 months of a randomized controlled experiment were used to identify local sites of bone formation and resorption. Bone strain was estimated using validated finite element (FE) models. Trabecular strain magnitude and gradient were higher near (within 200 µm) formation versus resorption (p<0.05). Trabecular formation and resorption occurred preferentially near very high (>95th percentile) versus low (<5th percentile) strain magnitude and gradient elements, and very low strain elements were more likely to be near resorption than formation (p<0.05). In the cortical compartment, strain gradient was higher near formation versus resorption (p<0.05), and both formation and resorption occurred preferentially near very high versus low strain gradient elements (p<0.05). At most, 54% of very high and low strain elements were near formation or resorption only, and similar trends were observed in the control and load groups. These findings suggest that strain, likely in combination with other physiological factors, influences adaptation under normal loads and in response to a novel loading intervention, and represents an important step toward defining exercise interventions to maximize bone strength.
Assessment of metagenomic sequencing and qPCR for detection of influenza D virus in bovine respiratory tract samples
Authors: Zhang Maodong , Huang Yanyun , Godson Dale L. , Fernando Champika , Alexander Trevor W. , Hill Janet E.
Published: June 2020

High throughput sequencing is currently revolutionizing the genomics field and providing new approaches to the detection and characterization of microorganisms. The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. An IDV-specific qPCR was performed on 232 samples (116 nasal swabs and 116 tracheal washes) that had been previously subject to virome sequencing using MiSeq. Nanopore sequencing was performed on 19 samples positive for IDV by either MiSeq or qPCR. Nanopore sequence data was analyzed by two bioinformatics methods: What’s In My Pot (WIMP, on the EPI2ME platform), and an in-house developed analysis pipeline. The agreement of IDV detection between qPCR and MiSeq was 82.3%, between qPCR and Nanopore was 57.9% (in-house) and 84.2% (WIMP), and between MiSeq and Nanopore was 89.5% (in-house) and 73.7% (WIMP). IDV was detected by MiSeq in 14 of 17 IDV qPCR-positive samples with Cq (cycle quantification) values below 31, despite multiplexing 50 samples for sequencing. When qPCR was regarded as the gold standard, the sensitivity and specificity of MiSeq sequence detection were 28.3% and 98.9%, respectively. We conclude that both MiSeq and Nanopore sequencing are capable of detecting IDV in clinical specimens with a range of Cq values. Sensitivity may be further improved by optimizing sequence data analysis, improving virus enrichment, or reducing the degree of multiplexing.
A comprehensive and centralized database for exploring omics data in Autoimmune Diseases
Authors: Martorell-Marugán Jordi , Lopez-Dominguez Raul , Garcia-Moreno Adrian , Toro-Dominguez Daniel , Villatoro-Garcia Juan Antonio , Barturen Guillermo , Martin-Gomez Adoracion , Troule Kevin , Gomez-Lopez Gonzalo , Al-Shahrour Fatima , Gonzalez-Rumayor Victor , Peña-Chilet Maria , Dopazo Joaquin , Saez-Rodriguez Julio , Alarcon-Riquelme Marta E. , Carmona-Saez Pedro
Published: June 2020

Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field. Here, we present ADEx (https://adex.genyo.es), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis.
Knowledge, attitudes, and practices among the general population during COVID-19 outbreak in Iran: A national cross-sectional survey
Authors: Kakemam Edris , Ghoddoosi-Nejad Djavad , Chegini Zahra , Momeni Khalil , Salehinia Hamid , Hassanipour Soheil , Ameri Hosein , Arab-Zozani Morteza
Published: June 2020

Background

COVID-19, which emerged in December 2019, is the largest pandemic ever to occur. During the early phase, little was known about public awareness relating to Coronavirus disease. This study was designed to determine knowledge, attitudes and practices (KAP) among the Iranian public towards COVID-19.

Methods

A cross-sectional online survey was carried out in Iran from 2 March to 8 April 2020 using a self-administered questionnaire on 1,480 people. COVID-19-related KAP questions were adapted from other internationally validated questionnaires specific to infectious diseases.

Results

All participants were aware of COVID-19. When asked unprompted, 80% of respondents could correctly cite fever, difficulty breathing and cough as signs/symptoms of COVID-19. Most of our sample population knew that by staying at home and staying isolated (95.3%, 95 % CI: 94.2-96.3) as well as constant hand washing and using disinfectants (92.5%, 95 % CI: 91.1-93.8) could prevent COVID-19. However, there was also widespread misconceptions such as the belief that COVID-19 can be transmitted by wild animals (58%, 95 % CI: 55.5-60.5) and by air (48.3%, 95 % CI: 45.7-50.8). Unprompted, self-reported actions taken to avoid COVID-19 infection included hand washing with soap and water (95.4%, 95 % CI: 94.3-96.4), avoiding crowded places (93%, 95 % CI: 91.7-94.3), cleaning hands with other disinfectants (80.9 %, 95 % CI: 78.9-82.9), and covering mouths and noses when coughing and sneezing (76.1 %, 95 % CI: 73.9-78.2). The internet and social media (94.5%, 95 % CI: 93.3-95.6) were the main Coronavirus information sources. However, the most trusted information sources on Coronavirus were health and medical professionals (79.3%, 95 % CI: 77.2-81.3). The majority of participants (77.0%, 95 % CI: 74.8-79.1) wanted more information about Coronavirus to be available.

Conclusion

Our findings suggest that people’s knowledge and attitude towards COVID-19 at the time of its outbreak was of a high level. Therefore, health systems should use multiple ways, such as mass media, phone applications, electronic, print, and tele-education to increase KAP related to COVID-19.
Intangibles and innovation-labor-biased technical change
Authors: Piekkola Hannu
Published: June 2020

Purpose

This paper analyzes the productivity effects of structural capital such as research and development (R&D) and organizational capital (OC). Innovation work also produces innovation-labor-biased technical change (IBTC) and knowledge spillovers. Analyses use full register-based dataset of Finnish firms for the period 1994–2014 from Statistics Finland.

Design/methodology/approach

Intangibles are derived from the labor costs of innovation-type occupations using linked employer-employee data. The approach is consistent with National Accounting and offered as one method in OECD (2010) and applied in statistical offices, e.g. in measuring software. The EU 7th framework Innodrive project 2008–2011 extended this method to cover R&D and OC.

Findings

Methodology is implementable at firm-level and offers way to link personnel reporting to intangible assets. The OC-IBTC as well as total resources allocated to OC are relevant for productivity growth. The R&D stock is relatively higher but R&D-IBTC is smaller than OC-IBTC. Public policy should, besides technology policy, account for OC and OC-IBTC and related knowledge spillovers in the industries that are most important among the SMEs (low market-share-firms).

Research limitations/implications

The data are based on remote access to Statistics Finland; the data cannot be disseminated.

Originality/value

Intangible assets are measured from innovation work that encompasses not only R&D work. IBTC is proxied in production function estimation by relative compensations on IA work. The non-competing nature of IAs is captured by IA knowledge spillovers. The sample sizes are much higher than in earlier studies on horizontal knowledge spillovers (such as for SMEs,) thus bringing additional generality to the results.
Interdependency in coordinating networked maintenance and modification operations
Authors: Engelseth Per , Törnroos Jan-Åke , Zhang Yufeng
Published: June 2020

Purpose

The purpose of this research is to detect, through applying a process-based view, how to manage economisation of the maintenance and modification operations in offshore petroleum logistics operations.

Design/methodology/approach

A single case study of engineering services, more specifically, maintenance and modification service operations, on a Norwegian Sea oil platform reveals the dynamics of building network capabilities in a consistent network structure. Two layers of coordination are studied: the engineering process and its context, represented by its network of interconnected firms. This case study empirically grounds how engineering service involves managing reciprocally interdependent exchange processes in the network structure.

Findings

Pooled interdependencies are vital in understanding the nature of service provision and use, and sequential interdependencies are vital in narrating the timing of processes to reveal the nature of process emergence to coordinate strings of production events. Furthermore, the network structure, when characterised by multiple interdependent projects, is also dynamic but at a slower pace.

Originality/value

Through the case study, operations management is revealed to be associated with project emergence at two levels: the core process level regarding daily continuous change, including the changing interaction of multiple different and interdependent projects, and the contextual level, where features of interdependency and integration change, affecting engineering service production. This provides guidance as to the economisation of engineering services. They change not only interactions in the flow of production but also its context.
Consumers and their celebrity brands: how personal narratives set the stage for attachment
Authors: Eng Bennie , Jarvis Cheryl Burke
Published: June 2020

Purpose

This paper aims to demonstrate how consumer attachment to celebrity brands is driven by perceived narratives about the celebrity’s persona, which triggers communal (i.e. altruistic) relationship norms. The research investigates the differential role of narratives about celebrities’ personal vs professional lives in creating attachment and identifies and tests moderating effects of narrative characteristics including perceived source of fame, valence and authenticity.

Design/methodology/approach

Three online experiments tested the proposed direct, meditating and moderating relationships. Data was analyzed using mediation analysis and multiple ANOVAs.

Findings

The results suggest relationship norms that are more altruistic in nature fully mediate the relationship between narrative type and brand attachment. Additionally, personal narratives produce stronger attachment than professional narratives; the celebrity’s source of fame moderates narrative type and attachment; and on-brand narratives elicit higher attachment than off-brand narratives, even when these narratives are negative.

Practical implications

The authors offer recommendations for how marketers can shape celebrity brand narratives to build stronger consumer attachment. Notably, personal (vs professional) narratives are critical in building attachment, especially for celebrity brands that are perceived to have achieved their fame. Both positive and negative personal narratives can strengthen attachment for achieved celebrity brands, but only if they are on-brand with consumer expectations.

Originality/value

This research is an introductory examination of the fundamental theoretical process by which celebrity brand relationships develop from brand persona narratives and how characteristics of those narratives influence consumer-brand attachment.
The microRNA miR‐184 regulates the CYP303A1 transcript level to control molting of Locusta migratoria
Authors: Wang Yan‐Li , Wu Li‐Xian , Li Hui‐Yong , Wen Xue‐Qin , Ma En‐Bo , Zhu Kun‐Yan , Zhang Jian‐Zhen
Published: June 2020

Cytochrome P450 monooxygenases (CYPs) play essential physiological functions in insects. CYP303A1 is highly conserved in insect species studied to date, and shows an indispensable role for adult eclosion in both Locusta migratoria and Drosophila melanogaster. However, how CYP303A1 is regulated to control insect developmental processes remains uninvestigated. In this study, we discovered functional binding sites for miR‐184 in the coding sequence of LmCYP303A1. The luciferase reporter assay showed that miR‐184 could target LmCYP303A1 and regulate its expression in vitro. Furthermore, overexpression of miR‐184 through microinjection of agomir to locusts reduced the transcripts of LmCYP303A1 and led to abnormal molting, which is similar to the phenotype of silencing LmCYP303A1 by direct injection of dsLmCYP303A1 to locusts. Meanwhile, down‐regulation of miR‐184 by injection of antagomir increased the LmCYP303A1 transcript and caused molting defects. These findings suggested that miR‐184 could target LmCYP303A1 to regulate the molting process in L. migratoria, which might be considered as a novel target for pest control.
Alcohol Consumption and Risk of Hospitalizations and Mortality in the Atherosclerosis Risk in Communities Study
Authors: Daya Natalie R. , Rebholz Casey M. , Appel Lawrence J. , Selvin Elizabeth , Lazo Mariana
Published: June 2020

Background

Public health recommendations on the benefits and harms of moderate alcohol intake require a thorough and unbiased understanding of all potential effects of various levels and patterns of alcohol consumption. We seek to evaluate the associations between patterns of current and past alcohol consumption with hospitalizations and mortality.

Methods

Data came from a prospective cohort of 12,327 adults (56% women, 78% white, mean age 60 years) participating in the Atherosclerosis Risk in Communities study visit 3 (1993 to 1995). Current and past alcohol consumption was based on self‐report. Hospitalizations and mortality were ascertained through December 31, 2017. Negative binomial and Cox proportional hazards regressions were used.

Results

24.8% of the study population reported never drinking, 48.3% reported currently drinking without a history of heavy drinking, 4.2% reported currently drinking with a history of heavy drinking, 19.2% reported being former drinkers without a history of heavy drinking, and 3.4% reported being former drinkers with a history of heavy drinking. Compared to those who reported drinking ≤1 to 7 drinks/wk, never drinkers (incident rate ratio [IRR]: 1.21 (95% confidence interval 1.13, 1.29) and former drinkers with (IRR: 1.43 [1.26, 1.63]) or without (IRR: 1.21 [1.13, 1.30]) a history of heavy drinking had a positive association with all‐cause hospitalization (p < 0.001). Those who reported drinking ≤1 to 7 drinks/wk had the lowest all‐cause mortality rate (19.2 per 1,000 person‐years [18.4, 20.1]) and former drinkers with a history of heavy drinking had the highest (43.7 per 1,000 person‐years [39.0, 49.1]).

Conclusions

The positive associations with hospitalization and mortality were stronger among never and former drinkers compared to those who consume ≤1 to 7 drinks/wk. Former drinkers with a history of heavy drinking had a stronger positive association with adverse health outcomes than former drinkers without a history of heavy drinking, highlighting the impact of this pattern of alcohol consumption.
Epidermolysis Bullosa Pruriginosa successfully treated with concomitant topical and systemic agents
Authors: Ferreira Sandra , Azevedo Alexandra , Velho Glória C , Sanches Madalena , Selores Manuela
Published: June 2020

Epidermolysis bullosa pruriginosa, a genetic mechanobullous disease, manifests at birth or late in life and is characterised by intense pruritus, resulting in lichenified or nodular prurigo‐like lesions and scarring most prominent on the shins. Treatment is unsatisfactory. We report a patient treated with success using a combination of topical and systemic agents.
Mediators Linking Information Quality and the Cost of Equity Capital*
Authors: Bae Seong Mi , An Hyoung‐Tae , Kim Jong Dae
Published: June 2020

This study investigates the mechanisms underlying the relationship between accounting information quality and the cost of equity capital. Information quality is negatively correlated with the cost of equity capital, with the relationship possibly driven by mediators linking the two variables. The empirical results indicate that about 42% of the total effects of information quality on the cost of equity capital is attributable to the indirect effects mediated by information asymmetry, market risk, and liquidity risk in that order, although the relative magnitude of the mediation depends on which mediator is considered first in the model. This study is the first to examine the mediating effect of liquidity risk using path analysis. Furthermore, no previous study has examined and compared the relative impact of the three mediators. In particular, liquidity risk mediates the relationship between information quality and the cost of equity capital, and the mediating effect of liquidity risk is almost as significant as information asymmetry and market risk with a marginal difference when considered individually.