bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of somatic variant detection workflows for whole genome sequencing experiments
Authors: Jaksik Roman , Rosiak Jacek , Zawadzki Paweł , Sztromwasser Paweł 
Published: June 2021

AbstractWhole genome sequencing (WGS) becomes increasingly important for advancing personalized cancer care, driving not only basic science studies but also entering into clinical applications. Translating raw WGS data into the right clinical decision requires high accuracy of somatic variant detection, therefore novel data analysis methods have to be carefully evaluated.In this work we tested the performance of well-established somatic variant detection workflows: GATK, CPG-WGS, DRAGEN and Strelka2. By utilizing both real data, with well-defined mutations, and synthetic mutations spiked-in into real data, we were able to assess sensitivity and precision of each workflow, for various coverage and tumor purity levels.Individual tools excelled in different evaluation approaches, however the results demonstrated that DRAGEN has the highest overall performance when sensitivity is preferred over precision, and the opposite is true for CGP-WGS. The differences in results obtained using synthetic and real datasets, indicate that benchmarks based only on a single reference set may provide an incomplete picture.
Epitome: Predicting epigenetic events in novel cell types with multi-cell deep ensemble learning
Authors: Morrow Alyssa Kramer , Hughes John Weston , Singh Jahnavi , Joseph Anthony Douglas , Yosef Nir 
Published: June 2021

AbstractThe accumulation of large epigenomics data consortiums provides us with the opportunity to extrapolate existing knowledge to new cell types and conditions. We propose Epitome, a deep neural network that learns similarities of chromatin accessibility between well characterized reference cell types and a query cellular context, and copies over signal of transcription factor binding and modification of histones from reference cell types when chromatin profiles are similar to the query. Epitome achieves state-of-the-art accuracy when predicting transcription factor binding sites on novel cellular contexts, and can further improve predictions as more epigenetic signals are collected from both reference cell types and the query cellular context of interest.
Geometric Network Analysis Provides Prognostic Information in Patients with High Grade Serous Carcinoma of the Ovary Treated with Immune Checkpoint Inhibitors
Authors: Elkin Rena , Oh Jung Hun , Liu Ying L. , Selenica Pier , Weigelt Britta , Reis-Filho Jorge S. , Zamarin Dmitriy , Deasy Joseph O. , Norton Larry , Levine Arnold J. , Tannenbaum Allen R. 
Published: June 2021

AbstractPurposeNetwork analysis methods can potentially quantify cancer disturbances in gene networks without introducing fitted parameters or variable selection. A new network curvature-based method is introduced to provide an integrated measure of variability within cancer gene networks. The method is applied to high grade serous ovarian cancers (HGSOCs) to predict response to immune checkpoint inhibitors (ICIs), and to rank key genes associated with prognosis.MethodsCopy number alterations (CNAs) from targeted and whole exome sequencing data were extracted for HGSOC patients (n= 45) treated with ICIs. CNAs at a gene level were represented on a protein-protein interaction network to define patient-specific networks with a fixed topology. A version of Ollivier-Ricci curvature was used to identify genes that play a potentially key role in response to immunotherapy and further to stratify patients at high risk of mortality. Overall survival (OS) was defined as the time from the start of ICI treatment to either death or last follow-up. Kaplan-Meier analysis with log-rank test was performed to assess OS between the high and low curvature classified groups.ResultsThe network curvature analysis stratified patients at high risk of mortality with p=0.00047 in Kaplan-Meier analysis. Genes with high curvature were in accordance with CNAs relevant to ovarian cancer.ConclusionNetwork curvature using CNAs has the potential to be a novel predictor for OS in HGSOC patients treated with immunotherapy.
Low numbers of cytokine transcripts drive inflammatory skin diseases by initiating amplification cascades in localized epidermal clusters
Authors: Schäbitz A. , Hillig C. , Farnoud A. , Jargosch M. , Scala E. , Pilz A.C. , Bhalla N. , Mubarak M. , Thomas J. , Stahle M. , Biedermann T. , Schmidt-Weber C.B. , Theis F. , Garzorz-Stark N. , Eyerich K K. , Menden M.P. , Eyerich S. 
Published: June 2021

AbstractAbundant polyclonal T cells infiltrate chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-driving from bystander immune cells. Here, we investigated 52,000 human cutaneous transcriptomes of non-communicable inflammatory skin diseases (ncISD) using spatial transcriptomics. Despite the expected T cell infiltration, we observed only 1-10 pathogenic T cell cytokine per skin section. Cytokine expression was limited to lesional skin and presented in a disease-specific pattern. In fact, we identified responder signatures in direct proximity of cytokines, and showed that single cytokine transcripts initiate amplification cascades of thousands of specific responder transcripts forming localized epidermal clusters. Thus, within the abundant and polyclonal T cell infiltrates of ncISD, only a few T cells drive disease by initiating an inflammatory amplification cascade in their local microenvironment.
Oxaliplatin kills cells via liquid-liquid demixing of nucleoli
Authors: Schmidt H. Broder , Jaafar Zane A. , Rodencal Jason J. , Leonetti Manuel D. , Dixon Scott J. , Rohatgi Rajat , Brandman Onn 
Published: June 2021

ABSTRACTPlatinum (Pt) compounds such as oxaliplatin are amongst the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here, we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically-relevant concentrations by interfering with the interaction networks that organize nucleoli. This biophysical defect leads to cell cycle arrest, impaired rRNA processing and shutdown of PolI-mediated transcription, ultimately resulting in cell death. We propose that the mechanism of action of oxaliplatin provides a blueprint for the therapeutic targeting of the increasing number of cellular processes being linked to biomolecular condensates.
Diverse routes of Club cell evolution in lung adenocarcinoma
Authors: Chen Yuanyuan , Toth Reka , Chocarro Sara , Weichenhan Dieter , Hey Joschka , Lutsik Pavlo , Sawall Stefan , Stathopoulos Georgios T. , Plass Christoph , Sotillo Rocio 
Published: June 2021

SummaryThe high plasticity of lung epithelial cells, has for many years, confounded the correct identification of the cell-of-origin of lung adenocarcinoma (LUAD), one of the deadliest malignancies worldwide. Here, we address the cell-of-origin of LUAD, by employing lineage-tracing mouse models combined with a CRISPR/Cas9 system to induce an oncogenic Eml4-Alk rearrangement in virtually all epithelial cell types of the lung. We find that Club cells give rise to lung tumours with a higher frequency than AT2 cells. Based on whole genome methylome, we identified that tumours retain an ‘epigenetic memory’ derived from their originating cell type but also develop a tumour-specific pattern regardless of their origin. Single-cell transcriptomic analyses identified two trajectories of Club cell evolution which are similar to the ones used during lung regeneration, providing a link between lung regeneration and cancer initiation. On both routes, tumours lose their Club cell identity and gain an AT2- like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
MARCO+ lymphatic endothelial cells sequester arboviruses to limit viremia and viral dissemination
Authors: Carpentier Kathryn S. , Sheridan Ryan M. , Lucas Cormac J. , Davenport Bennett J. , Li Frances S. , Lucas Erin D. , McCarthy Mary K. , Reynoso Glennys V. , May Nicolas A. , Tamburini Beth A.J. , Hesselberth Jay R. , Hickman Heather D. , Morrison Thomas E. 
Published: June 2021

AbstractWhile viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared from the circulation by MARCO-expressing Kupffer cells in the liver, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the dLN and liver is an important host defense mechanism as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease is more severe. These findings uncover a previously unrecognized arbovirus scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.
The model diatom Phaeodactylum tricornutum provides insights into the diversity and function of microeukaryotic DNA methyltransferases
Authors: Hoguin Antoine , Yang Feng , Groisillier Agnès , Bowler Chris , Genovesio Auguste , Ait-Mohamed Ouardia , Vieira Fabio Rocha Jimenez , Tirichine Leila 
Published: June 2021

AbstractCytosine methylation is an important epigenetic mark involved in the transcriptional control of transposable elements in mammals, plants and fungi. The Stramenopiles-Alveolate-Rhizaria (SAR) lineages are a major group of ecologically important marine microeukaryotes that include the main phytoplankton groups diatoms and dinoflagellates. However, little is known about their DNA methyltransferase diversity. Here, we performed anin-silicoanalysis of DNA methyltransferases found in marine microeukaryotes and showed that they encode divergent DNMT3, DNMT4, DNMT5 and DNMT6 enzymes. Furthermore, we found three classes of enzymes within the DNMT5 family. Using a CRISPR/Cas9 strategy we demonstrated that the loss of the DNMT5a gene correlates with a global depletion of DNA methylation and overexpression of young transposable elements in the model diatomPhaeodactylum tricornutum. The study provides a pioneering view of the structure and function of a DNMT family in the SAR supergroup using an attractive model species.
How GHRM is related to green creativity? A moderated mediation model of green transformational leadership and green perceived organizational support
Authors: Hameed Zahid , Naeem Rana Muhammad , Hassan Marria , Naeem Muhammad , Nazim Muhammad , Maqbool Adnan 
Published: June 2021

PurposeThis study aims to examine the relationship between green human resource management (GHRM) practices and green transformational leadership toward inducing employees' green creativity. Specifically, drawing upon the ability, motivation and opportunity theory, the authors tested how green perceived organizational support (green POS) mediates the link between GHRM practices and employees' green creativity. Furthermore, based on the firm's resource-based view, the authors examine the moderating role of green transformational leadership on the relationship between GHRM practice and green POS.Design/methodology/approachUsing a survey questionnaire, this research was conducted with a multi-source sample of 201 supervisors and their 428 subordinates from organizations working in grocery, food and personal care products in Pakistan.FindingsThe findings of structural equation modeling revealed that green POS plays a mediating role between GHRM and employees' green creativity. The study findings also highlighted that green transformational leadership moderates the positive relationship between GHRM practices and green POS.Practical implicationsOrganizations need to implement GHRM practices to achieve environmental performance. Individuals are likely to recognize themselves with organizations that are engaged in green practices, and therefore, organizations can get benefits from implementing GHRM practices.Originality/valueThis research explores green POS and green transformational leadership as novel mechanisms through which GHRM practices influence employees' green creativity in organizations. In addition, the authors empirically examined our theorized relationships in the South Asian context.
Which social media posts generate the most buzz? Evidence from WeChat
Authors: She Jie , Zhang Tao , Chen Qun , Zhang Jianzhang , Fan Weiguo , Wang Hongwei , Chang Qingqing 
Published: June 2021

PurposeFollowing the hierarchy-of-effects model, this study aims to propose a two-step process framework to investigate social media post efficacy via attraction and likes.Design/methodology/approachThe study analyzes 113,785 social media posts from 126 WeChat official accounts to explore how external (headline features and account type) and internal (content features and media type) features impact social media post attractions and likes, respectively.FindingsThe antecedents of post attraction differ from those of post likes. First, headline features (punctuation, length, sentiment and lexical density) and account type significantly influence social media post attraction. Second, content features (depth, tone, domain specificity, lexical density and readability) and media type affect social media post likes.Originality/valueFirst, this study considers online user engagement as a two-step process regarding social media posts and explores different influencing factors. Second, the study constructs new variables (account type and domain specificity) in each stage of the two-step process model.
Impact of novel information technology on IT alignment and sustainable supply chain performance: evidence from Chinese manufacturing industry
Authors: Zhang Shushan , Sun Lei , Sun Qi , Dong Haiying 
Published: June 2021

Purpose
This paper aims to explore how the novel information technology (NIT) [1] affects three dimensions of sustainable supply chain performance (economic performance, environmental performance and social performance) and how two dimensions of IT alignment (IT infrastructure alignment and IT human resources alignment) mediate the relationship between them.

Design/methodology/approach
NIT is defined, the dimension of IT alignment is expanded, the theoretical hypotheses are proposed and are tested using survey data from 394 manufacturing enterprises using NIT in China.

Findings
The results indicate that NIT plays a positive role in improving sustainable supply chain performance, and IT alignment mediates the impact of NIT on sustainable supply chain performance.

Originality/value
This study highlights the impact of NIT on sustainable supply chain performance and demonstrates IT alignment as a mediator between them, it also provides a deeper understanding of how different dimensions of IT alignment affect sustainable supply chain performance
BIM-enabled facilities management (FM): a scrutiny of risks resulting from cyber attacks
Authors: Ghadiminia Nikdokht , Mayouf Mohammad , Cox Sharon , Krasniewicz Jan 
Published: June 2021

Purpose
Building information modelling (BIM) creates a golden thread of information of the facility, which proves useful to those with the malicious intent of breaching the security of the facility. A cyber-attack incurs adverse implications for the facility and its managing organisation. Hence, this paper aims to unravel the impact of a cybersecurity breach, by developing a BIM-facilities management (FM) cybersecurity-risk-matrix to portray what a cybersecurity attack means for various working areas of FM.

Design/methodology/approach
This study commenced with exploring cybersecurity within various stages of a BIM project. This showcased a heightened risk of cybersecurity at the post-occupancy phase. Hence, thematic analysis of two main domains of BIM-FM and cybersecurity in the built environment led to the development of a matrix that illustrated the impact of a cybersecurity attack on a BIM-FM organisation.

Findings
Findings show that the existing approaches to the management of cybersecurity in BIM-FM are technology-dependent, resulting in an over-reliance on technology and a lack of cybersecurity awareness of aspects related to people and processes. This study sheds light on the criticality of cyber-risk at the post-occupancy phase, highlighting the FM areas which will be compromised as a result of a cyber-attack.

Originality/value
This study seeks to shift focus to the people and process aspects of cybersecurity in BIM-FM. Through discussing the interconnections between the physical and digital assets of a built facility, this study develops a cyber-risk matrix, which acts as a foundation for empirical investigations of the matter in future research.
Teaching as a part of academics' professionalization: the case of Czech educational sciences
Authors: Poláchová Vašt'atková Jana , Dopita Miroslav 
Published: June 2021

PurposeThe article explores the current as well as the future concepts of university teaching by the academics/the “leaders of educational sciences” in the context of the changes of the academia that have affected the academic professionalization.Design/methodology/approachThe Delphi method was implemented to answer a research question dealing with the possible change in academics' concept of teaching as part of their current and future work. In this study, the experienced academics in the area of educational science are seen as the “leaders” since through their intensive teaching activities on all three levels (bachelor, master and doctoral) as well as through the high-quality research, they “lead” the concept of a particular science as well as the educational policy. Four rounds were used for consensus building among “leaders” based on a multiple interaction in an anonymous setting.FindingsThe research points out that academic professionalization in research is at its maximum. The currently perceived concept of teaching is content-oriented. However, the results also indicate the need for a gradual change in training Czech academics, should they accept their role also as university teachers in the future and be able to highlight the predicted change of teaching to support learning. Whether the strategy of a particular university will or will not accept all the academics' diverse roles seems to become the crucial factor.Research limitations/implicationsSeveral rounds with the same group of experts, which is the principle of Delphi method, is at the same time a limitation of the study, as in most of the research based on this method. The participation in the expert panel dropped throughout the rounds; however, geographic (in terms of university) dispersion of participating experts remained. The final fourth round confirmed the collective judgments of academics.Practical implicationsThe article broadens the understanding of changes in the content of academics' professionalization with respect to changes in the academia. It emphasizes the role of an academic as an educator and concludes with the need of institutional reform in the context of a single university in a decentralized system.Social implicationsThe article questions the trends of (national) educational policy in the sense that academics at universities are not only scientists but also teachers. However, the study also shows that the acceptance of their teaching abilities remains mainly on the organizational level.Originality/valueA less common method of data collection among rather rarely involved group of experts in educational sciences brings a different view of the profession of academics, who (not only in the Czech context) are seen mainly as researchers and not as teachers. Humboldt's ideal regarding the unity of diverse roles is, thus, threatened due to narrower focus on academics' professionalization.
Employee performance appraisal system development in the National Library and Archives of Iran (NLAI): soft operational research approach
Authors: Zendehdel Nobari Babak , Gholipour Aryan , Ebrahimi Elham , Shoja Ali 
Published: June 2021

PurposeThe performance evaluation process is a key step in any management system and constitutes the basis for continuous improvement. Resistance to change is considered as a critical factor in any change management project; so, development of employee performance appraisal systems like all of the change management projects has always faced many challenges. This study seeks to illustrate the two-year experience (2018–2020) and lessons learned by developing an employee performance appraisal system in the National Library and Archives of Iran (NLAI) as a cultural public sector organization.Design/methodology/approachThis study was carried out by using soft operational research (OR) approaches, using a novel combination of two methods, soft system methodology (SSM) and importance performance analysis (IPA). For this purpose, at the beginning, with the help of the SSM approach, the challenges of implementation was identified, then, using the opinions and experiences of the system's stakeholders, improvement actions were defined and prioritized using the IPA method.FindingsThe research findings showed that “coaching development,” “optimizing the forced distribution rating system (FDRS)” and “customizing the system” are the most important improvement actions.Originality/valueThe research has bridged the gap between research and practice in the field of employee performance appraisal system in national libraries.
Lipid transfer protein syndrome due to wild grape juice and various vegetables: A life‐threatening food allergen
Authors: Hanada Miho , Nakagawa Michiyo , Hamabata Akemi , Amano Hiroo 
Published: June 2021

AbstractWe report a 16‐year‐old Japanese male with mugwort pollinosis in whom ingestion of wild grape juice and various vegetables caused recurrent general urticaria, abdominal pain, dyspnea, and loss of consciousness. A skin prick test demonstrated positive reactions to a wide variety of both non‐heated and heated vegetables and fruits such as wild grape, bell pepper, onion, Chinese cabbage, tomato, eggplant, and broccoli. The serum immunoglobulin E levels (ImmunoCAP ISAC®) for Art v 3, Pla a 3, Pru p 3, and Jug r 3, which are lipid transfer protein (LTP) homologs, were positive but those for Bet v 1 and Bet v 2 were negative. We diagnosed the patient as having LTP syndrome, a condition in which additional factors such as exercise, non‐steroidal anti‐inflammatory drugs, or alcohol may trigger an allergic reaction. Wild grapes contain a large amount of salicylic acid, and in our patient ingestion of wild grape juice led to immediate loss of consciousness in the absence of exercise. This suggests that salicylic acid contained in fruits and vegetables may act as an important cofactor in LTP syndrome. Although sensitization to LTP is rarely reported in Asia, LTP are considered to be potentially life‐threatening food allergens, and therefore warrant attention.