bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale virtual screening optimization for shotgun drug repurposing using the CANDO platform
Authors: Hudson Matthew L. , Samudrala Ram 
Published: August 2020

AbstractDrug repurposing, the practice of utilizing existing drugs for novel clinical indications, has tremendous potential for improving human health outcomes and increasing therapeutic development efficiency. The goal of multidisease multitarget drug repurposing, also known as shotgun drug repurposing, is to develop platforms that assess the therapeutic potential of each existing drug for every clinical indication. Our Computational Analysis of Novel Drug Opportunities (CANDO) platform for shotgun multitarget repurposing implements several pipelines via large scale modelling and simulation of interactions between comprehensive libraries of drugs/compounds and protein structures. In these pipelines, each drug is described by an interaction signature that is then compared to all other signatures that are then sorted and ranked based on similarity. Pipelines within the platform are benchmarked based on their ability to recover known drugs for all indications in our library, and predictions are generated based on the hypothesis that (novel) drugs with similar signatures may be repurposed for the same indication(s). The drug-protein interactions in the platform used to create the drug-proteome signatures may be determined by any screening or docking method but the primary approach used thus far has been an in house similarity docking protocol. In this study, we calculated drug-proteome interaction signatures using the publicly available molecular docking method Autodock Vina and created hybrid decision tree pipelines that combined our original bio- and cheminformatic approach with the goal of assessing and benchmarking their drug repurposing capabilities and performance. The hybrid decision tree pipeline outperformed the corresponding two docking-based pipelines it was synthesized from, yielding an average indication accuracy of 13.3% at the top10 cutoff (the most stringent), relative to 10.9% and 7.1% for its constituent pipelines, and a random control accuracy of 2.2%. We demonstrate that docking based virtual screening pipelines have unique performance characteristics and that the CANDO shotgun repurposing paradigm is not dependent on a specific docking method. Our results also provide further evidence that multiple CANDO pipelines can be synthesized to enhance drug repurposing predictive capability relative to their constituent pipelines. Overall, this study indicates that pipelines consisting of varied docking based signature generation methods can capture unique and useful signal for accurate comparison of drug-proteome interaction signatures, leading to improvements in the benchmarking and predictive performance of the CANDO shotgun drug repurposing platform.
Gene set enrichment analysis for genome-wide DNA methylation data
Authors: Maksimovic Jovana , Oshlack Alicia , Phipson Belinda 
Published: August 2020

AbstractDNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalisation and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in themissMethylBioconductor R package.
Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease
Authors: Kulkarni Subhash , Saha Monalee , Slosberg Jared , Singh Alpana , Nagaraj Sushma , Becker Laren , Zhang Chengxiu , Bukowski Alicia , Wang Zhuolun , Liu Guosheng , Leser Jenna , Kumar Mithra , Bakhshi Shriya , Anderson Matthew , Lewandoski Mark , Vincent Elizabeth , Goff Loyal A. , Pasricha Pankaj Jay 
Published: August 2020

AbstractThe enteric nervous system (ENS), a collection of neural cells contained in the wall of the gut, is of fundamental importance to gastrointestinal and systemic health. According to the prevailing paradigm, the ENS arises from progenitor cells migrating from the neural crest and remains largely unchanged thereafter. Here, we show that the lineage composition of maturing ENS changes with time, with a decline in the canonical lineage of neural-crest derived neurons and their replacement by a newly identified lineage of mesoderm-derived neurons. Single cell transcriptomics and immunochemical approaches establish a distinct expression profile of mesoderm-derived neurons. The dynamic balance between the proportions of neurons from these two different lineages in the post-natal gut is dependent on the availability of their respective trophic signals, GDNF-RET and HGF-MET. With increasing age, the mesoderm-derived neurons become the dominant form of neurons in the ENS, a change associated with significant functional effects on intestinal motility which can be reversed by GDNF supplementation. Transcriptomic analyses of human gut tissues show reduced GDNF-RET signaling in patients with intestinal dysmotility which is associated with reduction in neural crest-derived neuronal markers and concomitant increase in transcriptional patterns specific to mesoderm-derived neurons. Normal intestinal function in the adult gastrointestinal tract therefore appears to require an optimal balance between these two distinct lineages within the ENS.
Complete mitogenome of Kashmir musk deer (Moschus cupreus) and its comparative phylogenetic relationships
Authors: Singh Bhim , Gautam Kumudani Bala , Sahoo Subhashree , Kumar Ajit , Gupta Sandeep Kumar 
Published: August 2020

AbstractThe endangered Kashmir musk deer (Moschus cupreus) is native to the high altitudinal region of the Himalayas. In this study, we sequenced, annotated and characterized the complete mitogenome ofM. cupreusto gain insight into the molecular phylogeny and evolution of musk deer. The mitogenome ofM. cupreus, which is 16,354 bp long comprised 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs) and non-coding control region. TheM. cupreusmitogenome composition was highly A+T biased 68.42%, and exhibited a positive AT skew (0.082) and negative GC skew (0.307). The phylogenetic analysis suggested that KMD is the most primitive extant species in the genusMoschuswhereas Alpine musk deer (M. chrysogaster) and Himalayan musk deer (M. leucogaster) are closely related. This result confirmed the placement ofM. cupreuswithin the monotypic family Moschidae of musk deer. This study provides a better understanding of lineage identification and musk deer evolution for further research.
Effect of host-mimicking medium and biofilm growth on the ability of colistin to killPseudomonas aeruginosa
Authors: Sweeney Esther , Sabnis Akshay , Edwards Andrew M. , Harrison Freya 
Published: August 2020

AbstractIn vivobiofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin byPseudomonas aeruginosawhen grown in cystic fibrosis-mimicking mediumversusstandard medium inin vitrobiofilm assays, and drastically increased tolerance when grown in anex vivoCF model versus thein vitroassay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic intoex vivobiofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix inin vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and R&D pipelines, allowing the assessment of drug entry into biofilms, inin vivo-like conditions, prior to more detailed tests of biofilm killing.
Bacterial single-cell genomics enables phylogenetic analysis and reveals population structures fromin vitroevolutionary studies
Authors: Bawn Matt , Hernandez Johana , Trampari Eleftheria , Thilliez Gaetan , Webber Mark A. , Kingsley Robert A. , Hall Neil , Macaulay Iain C. 
Published: August 2020

AbstractSingle-cell DNA sequencing has the potential to reveal detailed hierarchical structures in evolving populations of cells. Single cell approaches are increasingly used to study clonal evolution in human ageing and cancer, but have not yet been deployed to study evolving microbial populations. Here, we present an approach for single bacterial genomic analysis using FACS isolation of individual bacteria followed by whole-genome amplification and sequencing. We apply this toin vitroexperimental evolution of a hypermutator strain ofSalmonellain response to antibiotic stress (ciprofloxacin). By analysing sequence polymorphisms in individual cells from the population we identified the presence and prevalence of sub-populations which have acquired polymorphisms in genes previously demonstrated to be associated with ciprofloxacin susceptibility. We were also able to identify that the population exposed to antibiotic stress was able to both develop resistance whilst maintaining diversity. This population structure could not be resolved from bulk sequence data, and our results show how high-throughput single-cell sequencing can enhance experimental studies of bacterial evolution.
Breadth of external knowledge search in service sectors
Authors: Radicic Dragana 
Published: August 2020

PurposeThere is a dearth of empirical research on the impact of external knowledge search on innovation performance in different categories of service firms. This study explores the effectiveness of the breadth of external search on product and process innovations in German firms. In particular, the author modelled a non-linear relationship between the breadth of knowledge and product and process innovations.Design/methodology/approachDrawing on the Mannheim Innovation Panel (MIP) data for the German service firms in the period 2014–2016, the author reported findings from a bivariate probit model which took into account mutual interdependence between product and process innovations. Moreover, the model was separately estimated for knowledge-intensive business services (KIBS) and other services. For comparative purposes, the author also estimated the model for manufacturing firms.FindingsEmpirical findings uniformly indicated an invertedU-shaped effect of the breadth of knowledge on both product and process innovations. Furthermore, the results demonstrated that using up to three knowledge sources increases the probability of a joint implementation of product and process innovations. These findings hold for both KIBS firms and other services. However, those service firms that focussed on a single type of innovation experienced diminishing returns to external knowledge when exploiting more than one source of knowledge. These results indicated that a simultaneous introduction of different types of innovation required diverse knowledge sources. In contrast, when focussing on a single type of innovation, service firms experienced diminishing returns when multiple sources were used. However, this finding was only partially found for manufacturing firms. Accordingly, this study’s findings provided support for the demarcation approach, insofar as the breadth of knowledge had a heterogenous impact on innovation in manufacturing relative to service firms.Originality/valuePrevious studies on the breadth of knowledge search mostly examined its influence on innovation performance without separately analysing manufacturing and service firms. The present study focussed on service firms that were further divided into KIBS and other service firms. By investigating potentially non-linear relationships between knowledge breadth and product and process innovations, it illustrated how different innovation strategies were affected by a diverse pool of external knowledge sources.
The value of supply chain integration in the Latin American agri-food industry: trust, commitment and performance outcomes
Authors: Ramirez Manuel Jesus , Roman Ivonne Eliany , Ramos Edgar , Patrucco Andrea Stefano 
Published: August 2020

PurposeThis paper aims to explore the antecedents and performance outcomes of supply chain integration in the agri-food industry in Latin America, a context that the literature on supply chain management has not extensively addressed. The quinoa supply chain, an industry that has encountered a boost in market demand in the past year, is selected as the unit of analysis. Supply chain integration dynamics are analyzed to provide recommendations about integration strategies and benefits in the agricultural sector.Design/methodology/approachA conceptual model was designed in this study, which includes the drivers (i.e. trust and commitment) and outcomes (i.e. operational and economic performance) of supply chain integration. The relationships were verified through a unique survey, the data of which were collected from 79 respondents operating at different levels of the Peruvian quinoa supply chain (i.e. suppliers, producers and customers). The proposed hypotheses were tested through the partial least squares (PLS) regression.FindingsThe results underscore the relevance of trust and commitment as enablers of supply chain integration initiatives in the agri-food industry. These factors are particularly essential for involving the farmers who are the most upstream actors in the supply chain and characterized by unstructured organizations. A high level of integration in these types of supply chain enhances the capacity to improve operational performance, which in turns positively affects the main economic indicators.Originality/valueThis study contributes to the discussion of supply chain integration in the agri-food industry, which remains unexplored thus far. It relies on a multitier collection of responses, which is extended to all the levels of the quinoa supply chain, thereby providing the study with a unique depth of analysis. Furthermore, this work contributes to the ongoing discourse on the performance impact of supply chain integration, which several SCM scholars have recently questioned.
Green warehousing, logistics optimization, social values and ethics and economic performance: the role of supply chain sustainability
Authors: Agyabeng-Mensah Yaw , Ahenkorah Esther , Afum Ebenezer , Dacosta Essel , Tian Zhongxing 
Published: August 2020

PurposeThis study primarily explores the influence of green warehousing, logistics optimization and social values and ethics on supply chain sustainability and economic performance. The study further examines the mediating role of supply chain sustainability between economic performance and green warehousing, logistics optimization and social values and ethics.Design/methodology/approachThe study employs a quantitative research approach where survey data are collected from 200 managers of manufacturing companies in Ghana. The dataset is analyzed using partial least square structural equation modeling software (PLS-SEM) SmartPLS 3.FindingsThe results show that green warehousing and logistics optimization negatively influence economic performance but improves economic performance through supply chain sustainability. It is further discovered that social values and ethics have a positive influence on supply chain sustainability and economic performance.Originality/valueThis paper proposes and tests a theoretical model that explores the relationships between green warehousing, supply chain sustainability, economic performance, logistics optimization and social values and ethics through the resource dependency theory (RDT) in the manufacturing firms in Ghana.
Mobile technologies for contact tracing and prevention of COVID-19 positive cases: a cross- sectional study
Authors: S. Prabu , Velan Balamurugan , S. Christalin Nelson , F.V. Jayasudha , P. Visu , K. Janarthanan 
Published: August 2020

Purpose
The purpose of this paper is to review the techniques for versatile advancements in contact tracing for the coronavirus disease 2019 (COVID-19) positive cases in this pandemic and to introduce the way of using the mobile location information collected within the country India. As the method, an exploratory review of current measures was conducted for confirmed COVID-19 contact tracing after understanding the current situation of the world. This paper has examined the way of using free locational information in an innovative way to reduce the spread of COVID-19 spread.

Design/methodology/approach
COVID-19 pandemic is the utmost global economic and health challenge of the century. One powerful and consistent procedure to slow down the spread and decrease the effect of COVID-19 is to track the essential and auxiliary contacts of confirmed COVID-19 positive cases by using contact-tracing innovation.

Findings
Although it takes the information from various clients, there are numerous odds in the information. The sincere measures were taken by the authors to avoid the abuse of information by any kind. A portion of the tips for keeping information from getting abused is on the whole, the information ought to be with just higher specialists, and they ought not to have the authorization to impart information to anybody.

Originality/value
This paper helps to track the COVID-19 positive cases as of now by using the field information assortment and outbreak examination stages. At the same time, mobile location information used inside the current guideline, rules for information handlers must incorporate measures to reduce the abusing of information.
Aesthetics and conviviality as key factors in a successful wine tourism experience
Authors: Haller Coralie , Hess-Misslin Isabelle , Mereaux Jean-Paul 
Published: August 2020

Purpose
Several studies in management science have called for a better understanding of the experience economy approach to develop wine tourism. Few studies, however, have analysed experiential dimensions in the context of French wine-growing regions. The purpose of this paper is to focus on the difference between what wine tourism providers consider relevant in their market offer and what customers expect from their wine tourism experience. A new categorisation of wine tourists’ expectations based on Pine and Gilmore’s (1998) four realms model and Quadri-Felliti and Fiore’s model (2012) are developed.

Design/methodology/approach
A mixed methodology, qualitatively analysing 17 semi-structural interviews with the main wine tourism stakeholders in the Alsace region in north-east France and quantitatively analysing 233 questionnaires on wine tourists’ expectations and behaviours are adopted.

Findings
The study reveals a difference between experiential offers predicated on an educational approach and the explicit expectations of wine tourists (combining aesthetics, conviviality and authenticity, whose central focus is an encounter with the winemaker). Overall, the findings point to a need for greater inclusion of the experiential aspect in the offer designed for wine tourists.

Originality/value
The study identifies a gap between the educational dimension that professionals tend to promote in their offers and the real expectations of wine tourists who express more interest in the aesthetic dimension provided by an attractive visit environment and an enjoyable experience. At the heart of the authentic experience for wine tourists is meeting the winegrower, making authenticity a major factor.
Influence of micro-scale velocity slip on the dynamic characteristics of aerostatic slider
Authors: Chen Dongju , Kong Shuai , Liu Jingfang , Fan Jinwei 
Published: August 2020

Purpose
The purpose of this paper is to propose the pressure fluctuation to further evaluate and predict the dynamic and static characteristics of the aerostatic slider and improve the calculation accuracy of the aerostatic slider.

Design/methodology/approach
First-order velocity slip is introduced into the traditional gas-film fluid equation, and the numerical analysis method is used to solve the static performance of the aerostatic slider. The finite element analysis method is used to solve its dynamic characteristics.

Findings
It can be concluded from the simulation and experimental results that the model considering the velocity slip in the gas film flow is more accurate. The errors between the modal detection results and the vibration detection results (0.8%–5.8%) under speed slip are smaller than the traditional cases (23.7%–210%), which also verifies the correctness of the above conclusions.

Originality/value
In this paper, the method of simulation and experiment is used to prove that the first-order velocity slip model is more suitable to predict the dynamic response of the aerostatic slider than the condition without slip.

Peer review
The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-02-2020-0059/
Social audit, accountability and accounting – an Indian perspective
Authors: Chawla Akhila 
Published: August 2020

PurposeThe purpose of this case study is to investigate the role of a governmental social audit (SA) practice in enabling emancipation, and changing patterns in the balance of power, position and understandings between dominant micro actors and disenfranchised rural citizens.Design/methodology/approachEnlisting Bourdieu's practice theory concepts of field, habitus, capitals and symbolic violence, the case study is informed by semi-structured interviews at central, state, district, block and village levels as well field observations and secondary data. This study is a part of a larger critical accounting research project conducted in India over four months, covering eight annual implementation cycles.FindingsThe study demonstrates that despite entrenched hegemonic micro forces and public sector corruption, SA's accounting and accountability practices have altered the rules of the game in this field. This emancipatory perspective has redefined deep-seated, generational patterns of power relations and domination, impacting the distribution of capitals and habitus in the daily life of rural citizens.Research limitations/implicationsThis study provides an alternative perspective to understanding governmental SA formats in developing nation contexts at the micro level. In line with Celerier and Botey's (2015) focus on inclusionary and democratic participation, this study challenges the dominant perspective of accounting as strengthening power asymmetries and focuses on its potential as an emancipatory agent.Originality/valueThe paper provides a site of effective implementation of a participative accountability practice in developing nation contexts that offer suggestions to states, countries and policy-makers. This paper also adds to critical accounting literature in the field of SA and social services at a micro level. Drawing upon Bourdieu in this underexplored field, it shines a light on relational elements of change through accounting and accountability practices for researchers and practitioners.