bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplification-free long read sequencing reveals unforeseen CRISPR-Cas9 off-target activity
Authors: Höijer Ida , Johansson Josefin , Gudmundsson Sanna , Chin Chen-Shan , Bunikis Ignas , Häggqvist Susana , Emmanouilidou Anastasia , Wilbe Maria , Hoed Marcel den , Bondeson Marie-Louise , Feuk Lars , Gyllensten Ulf , Ameur Adam 
Published: February 2020

AbstractA much-debated concern about CRISPR-Cas9 genome editing is that unspecific guide RNA (gRNA) binding may induce off-target mutations. However, accurate prediction of CRISPR-Cas9 off-target sites and activity is challenging. Here we present SMRT-OTS and Nano-OTS, two amplification-free long-read sequencing protocols for detection of gRNA driven digestion of genomic DNA by Cas9. The methods were assessed using the human cell line HEK293, which was first re-sequenced at 18x coverage using highly accurate (HiFi) SMRT reads to get a detailed view of all on- and off-target binding regions. We then applied SMRT-OTS and Nano-OTS to investigate the specificity of three different gRNAs, resulting in a set of 55 high-confidence gRNA binding sites identified by both methods. Twenty-five (45%) of these sites were not reported by off-target prediction software, either because they contained four or more single nucleotide mismatches or insertion/deletion mismatches, as compared with the human reference. We further discovered that a heterozygous SNP can cause allele-specific gRNA binding. Finally, by performing ade novogenome assembly of the HiFi reads, we were able to re-discover 98.7% of the gRNA binding sites without any prior information about the human reference genome. This suggests that CRISPR-Cas9 off-target sites can be efficiently mapped also in organisms where the genome sequence is unknown. In conclusion, the amplification-free sequencing protocols revealed many gRNA binding sitesin vitrothat would be difficult to predict based on gRNA sequence alignment to a reference. Nevertheless, it is still unknown whetherin vivooff-target editing would occur at these sites.
Functional characterization of thousands of type 2 diabetes-associated and chromatin-modulating variants under steady state and endoplasmic reticulum stress
Authors: Khetan Shubham , Kales Susan , Kursawe Romy , Jillette Alexandria , Reilly Steven K. , Ucar Duygu , Tewhey Ryan , Stitzel Michael L. 
Published: February 2020

AbstractA major goal in functional genomics and complex disease genetics is to identify functionalcis-regulatory elements (CREs) and single nucleotide polymorphisms (SNPs) altering CRE activity in disease-relevant cell types and environmental conditions. We tested >13,000 sequences containing each allele of 6,628 SNPs associated with alteredin vivochromatin accessibility in human islets and/or type 2 diabetes risk (T2D GWAS SNPs) for transcriptional activity in ß cell under steady state and endoplasmic reticulum (ER) stress conditions using the massively parallel reporter assay (MPRA). Approximately 30% (n=1,983) of putative CREs were active in at least one condition. SNP allelic effects onin vitroMPRA activity strongly correlated with their effects onin vivoislet chromatin accessibility (Pearson r=0.52), i.e., alleles associated with increased chromatin accessibility exhibited higher MPRA activity. Importantly, MPRA identified 220/2500 T2D GWAS SNPs, representing 104 distinct association signals, that significantly altered transcriptional activity in ß cells. This study has thus identified functional ß cell transcription-activating sequences within vivorelevance, uncovered regulatory features that modulate transcriptional activity in ß cells under steady state and ER stress conditions, and substantially expanded the set of putative functional variants that modulate transcriptional activity in ß cells from thousands of genetically-linked T2D GWAS SNPs.
Selective Germline Genome Edited Pig Meninges Grafts for the Abdominal Wall Closure in Damage Control Surgery
Authors: Zou Lijin , Zhang Youlai , He Ying , Yu Hui , Chen Jun , Liu Delong , Lin Sixiong , Gao Manman , Zhong Gang , Lei Weicheng , Zhou Guangqian , Zou Xuenong , Li Kai , Yu Yin , Zha Gaofeng , Li Linxian , Zeng Yuanlin , Wang Jianfei , Wang Gang 
Published: February 2020

AbstractReconstruction of abdominal wall defects is still a big challenge in surgery, especially where there is insufficient fascia muscular or excessive tension of the defects in emergency and life-threatening scenarios. Indeed, the concept of damage control surgery has been advanced in the management of both traumatic and nontraumatic surgical settings. The strategy requires abridged surgery and quick back to intensive care units (ICU) for aggressive resuscitation. In the damage control laparotomy, patients are left with open abdomen or provisional closure of the abdomen with a planned return to the operating room for definitive surgery. So far, various techniques have been utilized to achieve early temporary abdominal closure, but there is no clear consensus on the ideal method or material for abdominal wall reconstruction. We recently successfully created the selective germline genome-edited pig (SGGEP) and here we aimed to explore the feasibility of in vivo reconstruction of the abdominal wall in a rabbit model with SGGEP meninges grafts (SGGEP-MGs). Our result showed that the SGGEP-MGs could restore the integrity of the defect very well. After 7 weeks of engraftment, there was no sign of herniation observed, the grafts were re-vascularized, and the defects were well repaired. Histologically, the boundary between the graft and the host was very well integrated and there was no strong inflammatory response. Therefore, this kind of closure could help restore the fluid and electrolyte balance and to dampen systemic inflammatory response in damge control surgery while ADM graft failed to establish re-vascularization as the same as the SGGEP-MG. It is concluded that the meninges of SGGEP could serve as a high-quality alternative for restoring the integrity of the abdominal wall, especially for damage control surgery.
Genetic Architecture of Complex Traits and Disease Risk Predictors
Authors: Yong Soke Yuen , Raben Timothy G. , Lello Louis , Hsu Stephen D.H. 
Published: February 2020

AbstractGenomic prediction of complex human traits (e.g., height, cognitive ability, bone density) and disease risks (e.g., breast cancer, diabetes, heart disease, atrial fibrillation) has advanced considerably in recent years. Predictors have been constructed using penalized algorithms that favor sparsity: i.e., which use as few genetic variants as possible. We analyze the specific genetic variants (SNPs) utilized in these predictors, which can vary from dozens to as many as thirty thousand. We find that the fraction of SNPs in or near genic regions varies widely by phenotype. For the majority of disease conditions studied,a large amountof the variance is accounted for by SNPs outside of coding regions. The state of these SNPs cannot be determined from exome-sequencing data. This suggests that exome data alone will miss much of the heritability for these traits – i.e., existing PRS cannot be computed from exome data alone. We also study the fraction of SNPs and of variance that is in common between pairs of predictors. The DNA regions used in disease risk predictors so far constructed seem to be largely disjoint (with a few interesting exceptions), suggesting that individual genetic disease risks are largely uncorrelated. It seems possible in theory for an individual to be a low-risk outlier in all conditions simultaneously.
Intracellular Lipid Droplet Accumulation Occurs Early Following Viral Infection and Is Required for an Efficient Interferon Response
Authors: Monson EA , Crosse KM , Duan M , Chen W , O’Shea RD , Wakim LM , Whelan DR , Helbig KJ 
Published: February 2020

SummaryLipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 hours post viral infection, is transient, and returns to basal levels by 72 hours. This phenomenon occurred following viral infections, bothin vitroandin vivo. Virally driven LD induction was type-I interferon (IFN) independent, however, was dependent on EGFR engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponded with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both HSV-1 and Zika virus (ZIKV). Here, we demonstrate for the first time, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.
When vision lags, motor prediction follows
Authors: Rohde Marieke , Altan Gizem , Ernst Marc O. 
Published: February 2020

AbstractWhen we act, our brains register the visual feedback of the outcome of our actions only approximately 150 ms after sending the motor commands to the muscles. By anticipating the sensory consequences of our actions, temporal prediction mechanisms help us to accurately perform time-critical motor actions, such as catching a ball, and to experience the world as temporally coherent. It remains unclear whether these prediction mechanisms can adapt in a general way to changing sensory feedback delays, as they occur, for instance, when neural processing times increase during development. We here used Augmented Reality to train participants for one hour in a range of everyday life tasks with different levels of artificial visual feedback delay: 0 ms (No Delay), 100 ms (Small Delay) and 250 ms (Large Delay). We tested whether temporal aftereffects (increased motor-anticipation) generalize across different perceptual and motor tasks that participants did not practice during training and that involve different aspects of sensorimotor integration (motor planning, feedback control, sensorimotor time perception). Our results show a consistent temporal aftereffect of 33% across tasks and levels of delay. This suggests that the human sensorimotor system can adapt to the presence of visual feedback delays in a that affects sensorimotor prediction in general.
Unveiling the effects of figurative meanings in manipulated online hotel reviews on consumers' behavioral intentions
Authors: Akhtar Naeem , Akhtar Muhammad Nadeem , Siddiqi Umar Iqbal , Riaz Muhammad , Zhuang Weiqing 
Published: February 2020

PurposeThe present study develops a conceptual model that shows how the manipulation attributes of word choice, sentence fluency, convention of meaning, and organization of sentence structure in online hotel reviews are connected to linguistic errors, such as spelling and grammar and argument errors, how such errors intensify the likelihood that messages will be misunderstood, and how these misunderstandings affect customers' responses.Design/methodology/approachA structured questionnaire was employed to collect data from 591 inbound tourists in Beijing, China. Data analysis was conducted using SPSS 25.0 and Amos Graphics 23.0. Descriptive analysis was performed to explain the sociodemographic characteristic of respondents. Structural equation modeling was performed to examine hypothesized relationships.FindingsResults demonstrate that manipulation attributes increase linguistic errors, and two linguistic errors have profound positive effects on customers' understanding of meaning, which influence their responses in the form of negative online ratings and low purchase intentions.Originality/valueThe study's findings contribute to the literature on hospitality, linguistics, and consumer behavior, and have managerial implications for online review websites, online travel agents, and hotel management. Research limitations lead to suggestions for future research for hospitality scholars.
Debt types and burdens by family structures
Authors: Xiao Jing Jian , Yao Rui 
Published: February 2020

PurposeThe purpose of this study was to examine family structure differences in debt types and burdens of American families.Design/methodology/approachData was from the 2016 Survey of Consumer Finances. Eight types of family structures, five specific debts, and two debt burden indicators are examined with multivariate logistic regressions.FindingsAfter controlling for several socioeconomic variables, multivariate logistic regression results show that married with children families are more likely than five other family types to have any debt. In terms of specific debt, married with children families are more likely than six other types of families to have mortgages, four other types to have credit card loans, five other types to have to vehicle loans, three other types to have education loans, and one other type to have purchase loans. Married with children families are more likely than three other types of families (childless married couples, single males, and single females) to be late in debt payment for 60 or more days.Research limitations/implicationsThe data is limited to one-year cross-sectional data. To gain more insights on this topic, panel data could be used.Practical implicationsThe findings can be used for financial service professionals to identify loan demand and risk associated with various family structures and develop effective marketing strategies to serve these clients.Social implicationsThe findings are informative for public policymakers to develop family friendly economic policies and for consumer educators who help consumers make effective financial decisions when borrowing various types of loans.Originality/valueFirst, this study uses an innovative definition of family structure that counts several nontraditional family structures. Second, this study examines family structure differences in holdings of five specific debts together.
Toward a description framework of information encountering experiences
Authors: Jiang Tingting , Fu Shiting , Song Enmei 
Published: February 2020

PurposeOne of the primary challenges of conducting information encountering (IE) research is the difficulty in capturing people's IE experiences. The purpose of this paper is to develop a general description framework of IE experiences as guidance for participants to record diary entries in diary studies of IE.Design/methodology/approach340 descriptions of IE incidents were collected from 18 previous IE studies as secondary data. A thematic analysis of the secondary data engendered a general description framework of IE experiences composed of 9 main themes and 31 sub-themes. The framework was then applied in a diary study to investigate Generation Z's online IE behavior.FindingsThe nine main themes of the framework, including “environment”, “foreground activity”, “stimulus noticed”, “reaction to stimulus”, “content examined”, “interaction with encountered information”, “value of experience”, “pre-encountering emotional state”, and “post-encountering emotional state”, were used to create a diary questionnaire for collecting IE incidents. The sub-themes were refined and organized into a coding scheme for the content analysis of the incidents collected. The diary study collected 255 valid IE incidents which were analyzed based on three phases, that is, pre-encountering, encountering, and post-encountering.Originality/valueThe value of this study consists in its methodological contributions. First, it makes creative use of secondary data accumulated in the literature and derives from the thematic analysis a general framework which people follow to describe their IE experiences. Second, it demonstrates the great potential of diaries for data collection in IE research through the successful application of the general description framework of IE experiences in a diary study. Third, the diary questionnaire created based on the framework provides sufficient guidance in eliciting complete and detailed IE incidents.
Effect of mind-power ability among achieving entrepreneurs in South Africa
Authors: van Rensburg Nico , Ogujiuba Kanayo 
Published: February 2020

PurposeThis paper aims to identify how mind-power ability and its underlying elements, acting as drivers, impact managerial, and individual performance levels among achieving entrepreneurs in South Africa.Design/methodology/approachThe study adopted a qualitative approach and included 15 male entrepreneurs who were purposively selected based on the study’s requirements. The primary data was collected through semi-structured one-on-one interviews, and interpretative phenomenological analysis served as the primary method of data analysis.FindingsFindings from this study suggest that mind-power ability as an accustomed performance factor does indeed exist – and consists of a unique group of accustomed underlying elements – that significantly affects and contributes to both the managerial and individual performance levels of achieving entrepreneurs in South Africa.Research limitations/implicationsThe strategic implementation of mind-power ability as a performance enhancer serves as a valuable aspect in the arsenal of achieving entrepreneurs. However, this study was limited to the opinion of a small sample of participants in a specific field. Also, the phenomenological nature of this study requires the researcher’s interpretation of results to be viewed as the truth.Practical implicationsThe study provides a new perspective and validates how the strategic implementation of mind-power techniques can boost entrepreneurial performance all-round. The study also proves new insights into the relationship between mind-power ability and cognitive and motivational processes, and further contributes beyond existing theory.Originality/valueThe study is novel and provides new insight into the strategic implementation and powerful effects of mind-power ability in entrepreneurship.
Disentangling the reputation – performance paradox: Indian evidence
Authors: Kaur Amanpreet , Singh Balwinder 
Published: February 2020

PurposeThe purpose of this study is to examine the existence of bi-directional relation between corporate reputation and financial performance in developing nation like India.Design/methodology/approachThe study conducts panel regression analysis on data collected from annual reports of Indian companies constituting BSE 500 index over a period of 10 years (1 April, 2002 to 31 March, 2012).FindingsThe results of the study point towards the existence of strong positive bi-directional liaison between reputation and performance in India, thereby confirming the presence of “vicious circle” in context of emerging economy like India. The results are in line with the findings of Roberts and Dowling (2002) and Eberl and Schwaiger (2005), who asserted existence of reputational “vicious circle” in developed nations.Research limitations/implicationsThe current study measures the performance of companies through accounting-based measures only. However, incorporating market-based measures could have provided better insights into the relationship between corporate reputation and financial performance. The period of study pertains to the pre-mandatory regime, wherein changes brought about by the enactment of companies act, 2013 is out of the scope of the present research.Practical implicationsIt is argued that in actual practice managers should realise the ingenuity of intangible resources and incorporate them into their strategical plans. It is high time that corporate managers of developing nations give impetus to reputation building activities and uphold a good reputation to improve their financial outcomes. Thus, where good financial performance seems indispensable to build a good reputation, at the same time having the resource (good reputation) is not sufficient, its nurturing, management and effective use is all the more crucial if it is to improve financial performance.Originality/valueThere exists hardly any study comprehensively examining the relationship between corporate reputation and financial performance in the Indian context. This is the first known study to empirically test the lag relation between corporate reputation and financial performance in the Indian market. The study is unique as it follows a different approach in measuring corporate reputation. It is the first longitudinal study to analyse the bi-directional reputation-performance liaison in an emerging economy like India.
Digital inclusion for visually impaired students through assistive technologies in academic libraries
Authors: Alabi Adefunke O. , Mutula Stephen M. 
Published: February 2020

Purpose
The purpose of this paper is to determine the state-of-the-art assistive technologies (ATs) developed for people living with visual disability and those that are used in academic libraries around the world as a way of proffering solution to the challenges faced by visually impaired students in accessing information.

Design/methodology/approach
The data used for this paper were derived from website of companies that specialize in ATs for people living with disability and the library website of the top 14 universities in the world based on the 2020 QS world ranking of universities.

Findings
This study found that foremost academic libraries in the UK and the USA have integrated various ATs into library services as information access mechanism for students living with visual impairment. The study found that the most commonly used screen reader software is the Job Access With Speech (JAWS). The study also found that one of the institutions has a mission statement on their website, clearly stating support for people living with disability.

Research limitations/implications
This study was conducted using only the 2020 QS world ranking of universities. It would be interesting to see results of academic libraries from Africa based on their ranking.

Practical implications
The paper provides highlights on trends that may inform academic libraries in the quest to providing ATs for students living with visual impairments. This paper may assist academics libraries who are at the brink of decision-making on use of ATs as information access mechanism to the visually impaired students.

Originality/value
This paper is the first to provide librarians with ideas and innovations on specific ATs used by leading academic libraries in the world.