bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naïve and Experienced COVID-19 Patients
Authors: Chen Hongyi , Zhang Zhicheng , Wang Li , Huang Zhihua , Gong Fanghua , Li Xiaodong , Chen Yahong , Wu Jinzi J. 
Published: March 2020

AbstractAs coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo®) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naïve and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naïve and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.
High risk of infection caused Posttraumatic Stress symptoms in individuals with poor sleep quality: A study on influence of Coronavirus disease (COVID-19) in China
Authors: Zhang Fan , Shang Zhilei , Ma Haiying , Jia Yanpu , Sun Luna , Guo Xin , Wu Lili , Sun Zhuoer , Zhou Yaoguang , Wang Yan , Liu Nianqi , Liu Weizhi 
Published: March 2020

AbstractThe influence of the outbreak of coronavirus disease (COVID-19) on mental health was poorly understood. The present study aimed to exam sleep problems and posttraumatic stress symptoms (PTSS) in Chinese immediately after the massive outbreak of COVID-19. A total of 2027 Chinese participated in the present study. Wuhan-expose history, sleep quality and PTSS were measured with self-rating scales. Results showed that there were significant differences of PCL-5 and of sleep quality scores in different data-collection dates (ps<0.05). There were significant differences of PCL-5 scores (t=-2.93, p<0.05) and latency onset of sleep (χ2=9.77, p<0.05) between participants with and without Wuhan-expose history. The interaction effect of Wuhan exposure history× sleep quality significantly influenced PCL-5 (ps<0.05). These results indicate that keeping good sleep quality in individuals with high infectious risk is a way to prevent PTSS.
The impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak - evidence from China
Authors: Shi Peng , Dong Yinqiao , Yan Huanchang , Li Xiaoyang , Zhao Chenkai , Liu Wei , He Miao , Tang Shixing , Xi Shuhua 
Published: March 2020

ABSTRACTOBJECTIVETo investigate the impact of temperature and absolute humidity on the coronavirus disease 2019 (COVID-19) outbreak.DESIGNEcological study.SETTING31 provincial-level regions in mainland China.MAIN OUTCOME MEASURESData on COVID-19 incidence and climate between Jan 20 and Feb 29, 2020.RESULTSThe number of new confirm COVID-19 cases in mainland China peaked on Feb 1, 2020. COVID-19 daily incidence were lowest at -10 °C and highest at 10 °C, while the maximum incidence was observed at the absolute humidity of approximately 7 g/m3. COVID-19 incidence changed with temperature as daily incidence decreased when the temperature rose. No significant association between COVID-19 incidence and absolute humidity was observed in distributed lag nonlinear models. Additionally, A modified susceptible-exposed-infectious-recovered (M-SEIR) model confirmed that transmission rate decreased with the increase of temperature, leading to further decrease of infection rate and outbreak scale.CONCLUSIONTemperature is an environmental driver of the COVID-19 outbreak in China. Lower and higher temperatures might be positive to decrease the COVID-19 incidence. M-SEIR models help to better evaluate environmental and social impacts on COVID-19.What is already known on this topicMany infectious diseases present an environmental pattern in their incidence.Environmental factors, such as climate and weather condition, could drive the space and time correlations of infectious diseases, including influenza.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted through aerosols, large droplets, or direct contact with secretions (or fomites) as influenza virus can.Little is known about environmental pattern in COVID-19 incidence.What this study addsThe significant association between COVID-19 daily incidence and temperature was confirmed, using 3 methods, based on the data on COVID-19 and weather from 31 provincial-level regions in mainland China.Environmental factors were considered on the basis of SEIR model, and a modified susceptible-exposed-infectious-recovered (M-SEIR) model was developed.Simulations of the COVID-19 outbreak in Wuhan presented similar effects of temperature on incidence as the incidence decrease with the increase of temperature.
Repurposing the yeast peroxisome to compartmentalize a toxic enzyme enables improved (S)-reticuline production
Authors: Grewal Parbir S. , Samson Jennifer A. , Baker Jordan J. , Choi Brian , Dueber John E. 
Published: March 2020

AbstractEukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with other factors in the cytosol. Increasingly, engineers are researching ways in which synthetic compartmentalization could be used to address challenges in metabolic engineering. Here, we identified that norcoclaurine synthase (NCS), the enzyme which catalyzes the first committed reaction in benzylisoquinoline alkaloid (BIA) biosynthesis, is toxic when expressed cytosolically inSaccharomyces cerevisiaeand, consequently, restricts (S)-reticuline production. We developed a compartmentalization strategy that alleviates NCS toxicity while promoting increased (S)-reticuline titer, achieved through efficient targeting of toxic NCS to the peroxisome while, crucially, taking advantage of the free flow of metabolite substrates and product across the peroxisome membrane. We identified that peroxisome protein capacity inS. cerevisiaebecomes a limiting factor for further improvement of BIA production and demonstrate that expression of engineered transcription factors can mimic the oleate response for larger peroxisomes, further increasing BIA titer without the requirement for peroxisome induction with fatty acids. This work specifically addresses the challenges associated with toxic NCS expression and, more broadly, highlights the potential for engineering organelles with desired characteristics for metabolic engineering.
Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth
Authors: Lloyd Colton J. , Monk Jonathan , Yang Laurence , Ebrahim Ali , Palsson Bernhard O. 
Published: March 2020

AbstractSustaining a robust metabolic network requires a balanced and fully functioning proteome. In addition to amino acids, many enzymes require cofactors (coenzymes and engrafted prosthetic groups) to function properly. Extensively validated genome-scale models of metabolism and gene expression (ME-models) have the unique ability to compute an optimal proteome composition underlying a metabolic phenotype, including the provision of all required cofactors. Here we use the ME-model forEscherichia coliK-12 MG1655 to computationally examine how environmental conditions change the proteome and its accompanying cofactor usage. We found that: (1) The cofactor requirements computed by the ME model mostly agree with the standard biomass objective function used in models of metabolism alone (M models); (2) ME-model computations reveal non-intuitive variability in cofactor use under different growth conditions; (3) An analysis of ME-model predicted protein use in aerobic and anaerobic conditions suggests an enrichment in the use of prebiotic amino acids in the proteins used to sustain anaerobic growth (4) The ME-model could describe how limitation in key protein components affect the metabolic state ofE. coli.Genome-scale models have thus reached a level of sophistication where they reveal intricate properties of functional proteomes and how they support differentE. colilifestyles.
Unsupervised manifold learning of collective behavior
Authors: Titus Mathew , Hagstrom George , Watson James R. 
Published: March 2020

AbstractCollective behavior is an emergent property of numerous complex systems, from financial markets to cancer cells to predator-prey ecological systems. Characterizing modes of collective behavior is often done through human observation, training generative models, or other supervised learning techniques. Each of these cases requires knowledge of and a method for characterizing the macro-state(s) of the system. This presents a challenge for studying novel systems where there may be little prior knowledge. Here, we present a new unsupervised method of detecting emergent behavior in complex systems, and discerning between distinct collective behaviors. We require only metrics,d(1),d(2), defined on the set of agents,X, which measure agents’ nearness in variables of interest. We apply the method of diffusion maps to the systems (X, d(i)) to recover efficient embeddings of their interaction networks. Comparing these geometries, we formulate a measure of similarity between two networks, called the map alignment statistic (MAS). A large MAS is evidence that the two networks are codetermined in some fashion, indicating an emergent relationship between the metricsd(1)andd(2). Additionally, the form of the macro-scale organization is encoded in the covariances among the two sets of diffusion map components. Using these covariances we discern between different modes of collective behavior in a data-driven, unsupervised manner. This method is demonstrated on empirical fish schooling data. We show that our state classification subdivides the known behaviors of the school in a meaningful manner, leading to a finer description of the system’s behavior.Author summaryMany complex systems in society and nature exhibit collective behavior where individuals’ local interactions lead to system-wide organization. One challenge we face today is to identify and characterize these emergent behaviors, and here we have developed a new method for analyzing data from individuals, to detect when a given complex system is exhibiting system-wide organization. Importantly, our approach requires no prior knowledge of the fashion in which the collective behavior arises, or the macro-scale variables in which it manifests. We apply the new method to an agent-based model and empirical observations of fish schooling. While we have demonstrated the utility of our approach to biological systems, it can be applied widely to financial, medical, and technological systems for example.
Potential role of theXcircular code in the regulation of gene expression
Authors: Thompson Julie D. , Ripp Raymond , Mayer Claudine , Poch Olivier , Michel Christian J. 
Published: March 2020

AbstractTheXcircular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that theXcircular code has the important mathematical property of being an error-correcting code. Thus, motifs of theXcircular code, i.e. a series of codons belonging toX, which are significantly enriched in the genes, allow identification and maintenance of the reading frame in genes.Xmotifs have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role ofXmotifs as functional elements in the regulation of gene expression. Surprisingly, the definition of a simple parameter identifies several relations between theXcircular code and gene expression. First, we identify a correlation between the 20 codons of theXcircular code and the optimal codons/dicodons that have been shown to influence translation efficiency. Using previously published experimental data, we then demonstrate that the presence ofXmotifs in genes can be used to predict the level of gene expression. Based on these observations, we propose the hypothesis that theXmotifs represent a new genetic signal, contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.Author SummaryThe standard genetic code is used by (quasi-) all organisms to translate information in genes into proteins. Recently, other codes have been identified in genomes that increase the versatility of gene decoding. Here, we focus on the circular codes, an important class of genome codes, that have the ability to detect and maintain the reading frame during translation. Motifs of theXcircular code are enriched in protein-coding genes from most organisms from bacteria to eukaryotes, as well as in important molecules in the gene translation machinery, including transfer RNA (tRNA) and ribosomal RNA (rRNA). Based on these observations, it has been proposed that theXcircular code represents an ancestor of the standard genetic code, that was used in primordial systems to simultaneously decode a smaller set of amino acids and synchronize the reading frame. Using previously published experimental data, we highlight several links between the presence ofXmotifs in genes and more efficient gene expression, supporting the hypothesis that theXcircular code still contributes to the complex dynamics of gene regulation in extant genomes.
DrosophilaActivin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes
Authors: Kim Myung-Jun , O’Connor Michael B. 
Published: March 2020

SummaryThe Myostatin/Activin branch of the TGFβ superfamily acts as a negative regulator of mammalian skeletal muscle size, in part, through downregulation of insulin/IGF-1 signaling. Surprisingly, recent studies inDrosophilaindicate that Activin signaling acts as a positive regulator of muscle size. Here we demonstrate thatDrosophilaActivin signaling promotes growth of the muscle cells along all three axes; width, length and thickness. In addition, Activin signaling positively regulates the InR/dTORC1 pathway and the level of MHC, an essential sarcomeric protein, via promoting the transcription ofPdk1andAkt1. Enhancing InR/dTORC1 signaling in the muscle of Activin pathway mutants restores MHC levels close to wild-type, but only increased the width of muscle cells. In contrast, hyperactivation of the Activin pathway increases the length of muscle cells even when MHC levels were lowered by suppression of dTORC1. Together, these results indicate thatDrosophilaActivin pathway regulates larval muscle geometry via promoting InR/dTORC1-dependent MHC production and the differential assembly of sarcomeric components into either pre-existing (width) or new (length) sarcomeric units depending on the balance of InR/dTORC1 and Activin signals.
Deletion of FUNDC2 and CMC4 on chromosome Xq28 is sufficient to cause hypergonadotropic hypogonadism in men
Authors: Deng Xinxian , Fang He , Pathak Asha , Zou Angela M. , Neufeld-Kaiser Whitney , Malouf Emily A. , Failor R. Alan , Hisama Fuki M. , Liu Yajuan J. 
Published: March 2020

AbstractBackgroundHypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated.MethodsHere, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Furthermore, expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion.ResultsOur patient’s Xq28 deletion is 44,806bp and contains only two genes FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier regulation, apoptosis, inflammatory response and gonadotropin-releasing regulation. Indeed, our patient has an elevated FSH level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation is skewed towards the deleted X, suggesting a mechanism to avoid FSH dysregulation.ConclusionCompared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and/or CMC4 results in dysregulation of apoptosis, inflammation and FSH, and is sufficient to cause Xq28-associated HH.
Reliability evaluation index for the integrated supply chain utilising BIM and lean approaches
Authors: Zhang Jingxiao , Li Hui , Golizadeh Hamed , Zhao Chuandang , Lyu Sainan , Jin Ruoyu 
Published: March 2020

PurposeThis research aims to develop an approach to assess the reliability of integrated construction supply chainsviaan integrated model of building information modelling (BIM) and the lean supply chain (LSC). It reflects the synergistic workflow between BIM and LSC as a novel approach to improve the reliability of construction projects.Design/methodology/approachThis research evaluates the reliability of the BIM-LSC approach through a combination of entropy theory, set pair analysis (SPA), and Markov chains (EESM). An exploratory survey was conducted to collect data from 316 industry professionals experienced in BIM and LSC. Subsequently, multiple cycles of calculations were performed with indirect data inputs. Finally, a reliability evaluation index is established for the BIM-LSC approach and potential applications are identified.FindingsThe results show that the EESM model of BIM-LSC developed in this study can handle not only supply chain reliability evaluation at a given state but also the prediction of reliability in supply chain state transitions due to changing project conditions. This is particularly relevant to the current environment of the construction project, which is characterised by an increasing level of complexity in terms of labour, technology, and resource interactions.Research limitations/implicationsFuture research could consider the accuracy and validity of the proposed model in real-life scenarios with by considering both quantitative and qualitative data across the entire lifecycle of projects.Practical implicationsThe research offers a model to evaluate the reliability of the BIM-LSC approach. The accuracy of BIM supply chain reliability analysis and prediction in an uncertain environment is improved.Originality/valueThe BIM-LSC reliability evaluation and prediction presented in this study provides a theoretical foundation to enhance understanding of the BIM-LSC in the construction project context.
What drives job satisfaction in IT companies?
Authors: Moro Sérgio , Ramos Ricardo F. , Rita Paulo 
Published: March 2020

PurposeStrategic goal achievement in every sector of a company relies fundamentally on the firm's employees. This study aims to disclose the factors that spur employees of major Information Technology (IT) companies in the United States (US).Design/methodology/approachIn this paper, 15,000 reviews from the top 15 United States IT companies were collected from the social media platform Glassdoor to uncover the factors that satisfy IT employees. To learn the most meaningful features that influence the scores, positive and negative remarks, as well as advice to the management team, were analyzed through a support vector machine.FindingsResults highlight a positive attitude of coworkers, contributing to a positive environment and job satisfaction. However, unsatisfied IT employees reveal that work exhaustion is the main reason for their job dissatisfaction.Practical implicationsIT human resource departments can use these valuable insights to align their strategies in accordance with their employees' desires and expectations in order to thrive.Originality/valueThe study highlights the relevance of IT companies to understand the reasons behind their employees' satisfaction. Up until now, little is known concerning the variants of job satisfaction among IT employees, enriching the understanding in this particular professional area.
An integrative framework of supply chain flexibility
Authors: Liao Ying 
Published: March 2020

PurposeIt is crucial to recognize that supply chain flexibility is important to build sustainable competitive edge in coping with uncertainty. This study puts forth an empirically supported integrative framework to understand supply chain flexibility from market-oriented and network-oriented perspectives, interrelationships among its dimensions and the effect of supply chain complexity as a contingent factor.Design/methodology/approachThe online survey data were collected from 201 manufacturing companies and checked for common method variance, validity and reliability. Structural equation modeling was then used to test the hypotheses.FindingsThe results of this study demonstrate that there are interrelationships among market-oriented and network-oriented supply chain flexibility dimensions. It is the flexibility embedded in the supply chain network configuration that plays critical roles in superior performance in flexibility capabilities to create customer values. The interrelated effect among flexibility dimensions is contingent on the magnitude of the supply chain complexity corresponding to the number of supply chain tiers.Originality/valueThis study takes a step to advance understanding of supply chain flexibility from an integrative point of view consisting of market-oriented and network-oriented perspectives. This study is expected to provide practitioners the foundation to implement supply chain flexibility considering the interrelationships among flexibility dimensions. Our results suggest that to carry out a supply chain flexibility strategy, the vertical complexity of the supply chain structure needs to be taken into consideration.