bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating CRISPR-based Prime Editing for cancer modeling and CFTR repair in intestinal organoids
Authors: Geurts Maarten H. , de Poel Eyleen , Pleguezuelos-Manzano Cayetano , Carrillo Léo , Andersson-Rolf Amanda , Boretto Matteo , Beekman Jeffrey M. , Clevers Hans 
Published: October 2020

AbstractPrime editing is a recently reported genome editing tool employing a nickase-cas9 fused to a reverse transcriptase that directly synthesizes the desired edit at the target site. The technique holds great promise for clinical application due to its versatility. Here, we explore the use of prime editing in human intestinal organoids. Common TP53 mutations were modeled in human adult stem cell with notable efficiency differences. Next, we functionally repaired the cystic fibrosis CFTR-F508del mutation and compared prime editing to CRISPR/Cas9-mediated homology directed repair and adenine base editing on the CFTR-R785* mutation. Despite encountering varying editing efficiencies and undesired mutations, these results underline the broad applicability of prime editing for modeling oncogenic mutations and showcase the potential clinical application of this technique, pending further optimization.
A novel emaravirus identified in maple with leaf mottle symptoms by deep sequencing
Authors: Rumbou Artemis , Candresse Thierry , von Bargen Susanne , Büttner Carmen 
Published: October 2020

AbstractThe full-length genome of a novelEmaravirushas been identified and characterized from sycamore maple (Acer pseudoplatanus) - a tree species of significant importance in urban and forest areas - showing leaf mottle symptoms. RNA-Seq was performed using RNA preparations from a symptomatic and a symptomless maple tree. Purified double-stranded cDNA from each sample were used for RNA-Seq analysis on the Illumina HiSeq2500system and 14-198 MB data/sample of 100 bp-long paired-end sequence reads were generated. The sequence assembly and analysis revealed the presence of six RNA segments in the symptomatic sample (RNA1: 7,075 nt-long encoding the viral replicase; RNA2: 2,289 nt-long encoding the glycoprotein precursor; RNA3: 1,525 nt-long encoding the nucleocapsid protein; RNA4: 1,533 nt-long encoding the putative movement protein; RNA5: 1,825 nt-long encoding a hypothetical protein P5; RNA6: 1,179 nt-long encoding a hypothetical protein P6). Two independent HTS sequencing runs from the same symptomatic maple tree detected the same genome segments. For one of these sequencing runs the cDNA library was prepared using a primer targeting the conserved genome terminal region, known to be shared between emaraviruses genome segments and a high amount of sequence data was generated. We suggest, therefore, that the six identified genome segments represent the complete genome of a novel emaravirus from maple, which we tentatively name maple mottle-associated virus (MaMaV). RT-PCR assays were performed on symptomatic and non-symptomatic leaves ofA. pseudoplatanustrees coming growing on two different locations in Berlin. MaMaV was only detected from symptomatic trees and all six RNAs were generally simultaneously detected. Non-symptomatic samples were consistently negative for MaMaV. These results suggest that MaMaV might be the symptom inducing virus in the sampled trees. In the present state of the art, this is the first time an Emaravirus is described from maple and is fully genetically characterized.
SMARCAD1 Mediated Active Replication Fork Stability Maintains Genome Integrity
Authors: Yu Lo Calvin Shun , van Toorn Marvin , Gaggioli Vincent , Dias Mariana Paes , Zhu Yifan , Manolika Eleni Maria , Zhao Wei , van der Does Marit , Mukherjee Chirantani , Souto Gonçalves João G S C , van Royen Martin E , French Pim J , Demmers Jeroen , Smal Ihor , Lans Hannes , Wheeler David , Jonkers Jos , Chaudhuri Arnab Ray , Marteijn Jurgen A , Taneja Nitika 
Published: October 2020

ABSTRACTStalled fork protection pathway mediated by BRCA1/2 proteins is critical for replication fork stability that has implications in tumorigenesis. However, it is unclear if additional mechanisms are required to maintain replication fork stability. We describe a novel mechanism by which the chromatin remodeler SMARCAD1 stabilizes active replication forks that is essential for resistance towards replication poisons. We find that loss of SMARCAD1 results in toxic enrichment of 53BP1 at replication forks which mediates untimely dissociation of PCNA via the PCNA-unloader, ATAD5. Faster dissociation of PCNA causes frequent fork stalling, inefficient fork restart and accumulation of single-stranded DNA resulting in genome instability. Although, loss of 53BP1 in SMARCAD1 mutants restore PCNA levels, fork restart efficiency, genome stability and tolerance to replication poisons; this requires BRCA1 mediated fork protection. Interestingly, fork protection challenged BRCA1-deficient naïve- or PARPi-resistant tumors require SMARCAD1 mediated active fork stabilization to maintain unperturbed fork progression and cellular proliferation.
Multimodal 3D atlas of the macaque monkey motor and premotor cortex
Authors: Rapan Lucija , Froudist-Walsh Sean , Niu Meiqi , Xu Ting , Funck Thomas , Zilles Karl , Palomero-Gallagher Nicola 
Published: October 2020

ABSTRACTIn the present study we reevaluated the parcellation scheme of the macaque frontal agranular cortex by implementing quantitative cytoarchitectonic and multireceptor analyses, with the purpose to integrate and reconcile the discrepancies between previously published maps of this region.We applied an observer-independent and statistically testable approach to determine the position of cytoarchitectonic borders. Analysis of the regional and laminar distribution patterns of 13 different transmitter receptors confirmed the position of cytoarchitectonically identified borders. Receptor densities were extracted from each area and visualized as its “receptor fingerprint”. Hierarchical and principal components analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their fingerprints. Finally, functional connectivity pattern of each identified area was analyzed with areas of prefrontal, cingulate, somatosensory and lateral parietal cortex and the results were depicted as “connectivity fingerprints” and seed-to-vertex connectivity maps.We identified 16 cyto- and receptor architectonically distinct areas, including novel subdivisions of the primary motor area 4 (i.e. 4a, 4p, 4m) and of premotor areas F4 (i.e. F4s, F4d, F4v), F5 (i.e. F5s, F5d, F5v) and F7 (i.e. F7d, F7i, F7s). Multivariate analyses of receptor fingerprints revealed three clusters, which first segregated the subdivisions of area 4 with F4d and F4s from the remaining premotor areas, then separated ventrolateral from dorsolateral and medial premotor areas. The functional connectivity analysis revealed that medial and dorsolateral premotor and motor areas show stronger functional connectivity with areas involved in visual processing, whereas 4p and ventrolateral premotor areas presented a stronger functional connectivity with areas involved in somatomotor responses.For the first time, we provide a 3D atlas integrating cyto- and multi-receptor architectonic features of the macaque motor and premotor cortex. This atlas constitutes a valuable resource for the analysis of functional experiments carried out with non-human primates, for modeling approaches with realistic synaptic dynamics, as well as to provide insights into how brain functions have developed by changes in the underlying microstructure and encoding strategies during evolution.HighlightsMultimodal analysis of macaque motor and premotor cortex reveals novel parcellation3D atlas with cyto- and multireceptor architectonic features of 16 (pre)motor areasPrimary motor area 4 is cyto- and receptor architectonically heterogeneous(Pre)motor areas differ in their functional connectivity fingerprints
In vitroefficacy of Artemisinin-based treatments against SARS-CoV-2
Authors: Gilmore Kerry , Zhou Yuyong , Ramirez Santseharay , Pham Long V. , Fahnøe Ulrik , Feng Shan , Offersgaard Anna , Trimpert Jakob , Bukh Jens , Osterrieder Klaus , Gottwein Judith M. , Seeberger Peter H. 
Published: October 2020

AbstractEffective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We reportin vitroefficacy ofArtemisia annuaextracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs.Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (>179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.
Transcriptomic signatures of sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes
Authors: Kozlova Alena , Butler Robert R , Zhang Siwei , Ujas Thomas , Zhang Hanwen , Steidl Stephan , Sanders Alan R. , Pang Zhiping P. , Vezina Paul , Duan Jubao 
Published: October 2020

AbstractRodents are frequently used to model drug addiction, yet their genetic relevance to human addictive behaviors especially the mounting genome-wide association study (GWAS) findings is poorly understood. Considering a possible gateway drug role of nicotine (NIC), we modeled NIC addiction, specifically NIC sensitization (SST) and self-administration (SA), in F1 progeny of inbred Envigo rats (F344/BN) and conducted integrative genomics analyses. We unexpectedly observed male-specific NIC SST and a parental effect of SA only present in paternal F344 crosses. Transcriptional profiling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) core and shell further revealed sex and brain region-specific transcriptomic signatures of SST and SA. We found that genes associated with SST and SA were enriched for those related to synaptic processes, myelin sheath, and tobacco use disorder or chemdependency. Interestingly, SST-associated genes were often downregulated in male VTA but upregulated in female VTA, and strongly enriched for smoking GWAS risk variants, possibly explaining the male-specific SST. For SA, we found widespread region-specific allelic imbalance of expression (AIE), of which genes showing AIE bias towards paternal F344 alleles in NAc core were strongly enriched for SA-associated genes and for GWAS risk variants of smoking initiation, likely contributing to the parental effect of SA. The transcriptional signatures of sex-specific nicotine SST and SA suggest a mechanistic link between genes underlying these processes and human nicotine addiction, providing a resource for understanding the biology underlying the GWAS findings on human smoking and other addictive phenotypes.
Epidemic characteristics of respiratory viruses in hospitals in a Chinese city during the SARS-CoV-2 epidemic
Authors: Yang Weihua , Chen Jian , Xu Mingjie , Wang Jun , Li Huanjie , Wang Yunshan 
Published: October 2020

AbstractThe SARS-CoV-2 virus first broke out in China in early 2020. The early symptoms of COVID-19 are similar to those of influenza. Therefore, during the epidemic, patients with similar symptoms will be tested for multiple pathogens at the same time. In order to control the spread of SARS-CoV-2, China has taken many measures. Under this special situation, have the types and epidemic characteristics of respiratory viruses changed? The nucleic acid test results of influenza A virus, influenza B virus and respiratory syncytial virus, as well as the antibody test results of 8 common respiratory viruses of Jinan Central Hospital were collected before and after the occurrence of SARS-CoV-2, and age distribution and time distribution characteristics were statisticed. Furthermore the epidemiological characteristics of this new virus before and after the SARS-CoV-2 epidemic was compared. In the early stage of the SARS-CoV-2 epidemic, influenza A, influenza B and respiratory syncytial virus nucleic acid test samples were large, and the positive rate of the three viruses was high. After that, the sample size and positive rate decreased significantly. No co-infection of SARS-CoV-2 and other viruses was found in our hospital. The sample size before the SARS-CoV-2 outbreak was larger than that after the outbreak, but the positive rate of the outbreak was lower than that after the outbreak. And the infection rate of children decreased in the middle and late stages of the epidemic. This is because since January 23, in order to prevent the spread of the new crown epidemic, my country has adopted measures such as wearing masks, not gathering together, and quarantining at home. This not only prevents the spread of the new crown virus, but also prevents the common respiratory tract. The spread of the virus has reduced the incidence of residents.
Consideration for the asymptomatic transmission of COVID-19: Systematic Review and Meta-Analysis
Authors: Ravindra Khaiwal , Malik Vivek Singh , Padhi Bijaya K , Goel Sonu , Gupta Madhu 
Published: October 2020

AbstractObjectiveWorldwide countries are experiencing viral load in their population, leading to potential infectivity of asymptomatic COVID-19. Current systematic review and meta-analysis aimed to investigate the role of asymptomatic infection worldwide reported in family-cluster, adults, children, health care workers, and travelers.DesignOnline literature search (PubMed, Google Scholar, medRixv, and BioRixv) was accomplished using standard Boolean operators, studies published till 07th June 2020.SettingStudies were included from case reports, short communication, and retrospective to cover sufficient asymptomatic COVID-19 transmission reported.ParticipantsFamilial-clusters, adults, children, health care workers, and travelers.ResultsWe observed asymptomatic transmission among familial-cluster, adults, children, health care workers, and travelers with a proportion of 32% 37%, 26%, 6%, and 32%, respectively. This study observed an overall proportion of 31% (95%CI: 0.19-0.44) with heterogeneity of I2 (97.28%, p=<0.001) among all asymptomatic populations mentioned in this study. Among children and healthcare workers, this study showed no heterogeneity; to overcome the interpretation from a fixed model, the random effect model was also applied to estimate the average distribution across studies included in the meta-analysis.ConclusionWe found and suggest the rigorous epidemiological history, early isolation, social distancing, and increased quarantine period (at least 28 days) after screening asymptomatic cases as well as their close contacts for chest CT scan even after their negative nucleic acid testing to minimize the spread among the community. This systematic review and meta-analysis support asymptomatic COVID-19 transmission between person to person depending on the variation of virus incubation period among individuals. Children especially, school-going aged <18 years, need to be monitored and prevention strategy, e.g., chest CT and social distancing required to prevent the community transmission of COVID-19 in asymptomatic mode.Strengths and limitations of this studyExamine the possibility of asymptomatic COVID-19 transmission in the community at different levels.Supports contact tracing, social distancing, early isolation, and increased quarantine period to minimize the risk of virus spread.Supports chest CT scan and viral nucleic acid testing to identify the asymptomatic cases in the community.Supports rigorous epidemiological history with multiple detection methods.A higher proportion of asymptomatic incidence was seen, suggests monitoring, and maintaining social distancing.
Extending the debate over entrepreneurial education effectiveness: the case of a Saudi university
Authors: Ayed Tahar Lazhar 
Published: October 2020

PurposeThis study aims to assess the effectiveness of entrepreneurial education (EE) through its impact on the predictor of behavior, which is entrepreneurial intention (EI), by studying the context of a Saudi university, in this case, Umm Al Qura University (UQU). The research theorizes a relationship between EE, innovativeness (INN) as a dimension of personality traits (PTs), and EI, mediated by entrepreneurial motivation (EM). Additionally, in this study, INN played a mediator role between EE and EI.Design/methodology/approachAll direct and indirect effects were tested using a quantitative approach. A sample of 240 undergraduate UQU students from different specialties was applied. UQU is witnessing an unprecedented movement that seeks to spread entrepreneurial culture throughout the educational system as a whole, following the recommendations of the Kingdom's 2030 vision.FindingsThe results indicate that EE and INN significantly predicted EI, though in an uneven manner. However, EM played a significant mediator role only between INN and EI. INN is a significant mediator in the relationship between EE and EI.Practical implicationsFuture entrepreneurs must learn how to think, communicate, solve problems, deal with failure and exploit new opportunities. However, the debate over the contribution of EE to entrepreneurs is continuing. All educators, government officials, members of society and others are involved in encouraging entrepreneurial initiative. They should consider and understand how to affect entrepreneurial feasibility and desirability.Originality/valueVariables included in the research model are not original; however, rarely in recent research works have psychological variables such as EM and INN been integrated into one model to explain the intention to enterprise business. This study provides a well-supported explanation of intention as a good predictor of entrepreneurial behavior that will be useful to all involved in encouraging potential entrepreneurs to succeed.
Probable maximum loss of a pipe network due to earthquakes: a case study in Iloilo city, Philippines
Authors: Jarder Samantha Louise N. , Garciano Lessandro Estelito O. , Maruyama Osamu 
Published: October 2020

Purpose
Buried structures like pipeline systems or water distribution networks (WDN) are vulnerable to seismic activities and the risk of damages increases when there is liquefaction. This paper aims to propose a methodology on how to determine the probable maximum loss (PML) on pipeline systems when earthquakes and liquefaction occur in future scenarios.

Design/methodology/approach
The paper used historical data and presents a case study on how the methodology to estimate the PML was used. The estimation is analytic and relied on simulations to determine the seismic and liquefaction hazard in the study area. Statistical and numerical analysis was used to estimate the damages and losses.

Findings
The output shows the PML of a WDN at different earthquake scenarios. It also shows a comparison between the damages and losses of diameter sizes of the pipes.

Research limitations/implications
In this paper, the damages behaved independently in one area, and correlation was not considered.

Practical implications
This PML methodology can aid in pre-disaster planning to prepare for seismic countermeasures risk transfer such as insurance to reduce the loss.

Originality/value
This paper shows a methodology and example on how to estimate the damages and PMLs of an existing WDN of a projected earthquake and liquefaction hazard based on historical data.
Looking behind eye-catching design: an eye-tracking study on wine bottle design preference
Authors: Merdian Peter , Piroth Philipp , Rueger-Muck Edith , Raab Gerhard 
Published: October 2020

Purpose
The purpose of this study is to find out how unconscious perception and conscious reactions differ when it comes to evaluate wine bottles in a shopping shelf. It was evaluated how attention is related to subjective evaluations of interest and value in the perception of wine bottle design choices.

Design/methodology/approach
The experiment combined implicit eye-tracking observations and a quantitative measurement on the assessment on wine bottle designs. In total, 37 participants rated eight different wine bottle designs based on their interest and assumed value, without any given information about the wines’ original price classification.

Findings
There is a significant difference between the perception of wine bottle designs. Eye-catchy designs do not automatically transform into a higher perception of value and interest towards the product. The unconscious perception of bottles and the conscious reaction differentiate.

Research limitations/implications
The greatest limitation, as with many other implicit studies, is the limited number of subjects and the associated limited validity. In addition, eight bottles in four categories were studied, which is adequate, but does not fully reflect the complexity of the wine market supply.

Practical implications
Manufacturers and wine label designers should challenge existing pre-disposition towards certain wine bottle design choices.

Originality/value
To the best of the authors’ knowledge, this is the first German consumer study that focusses on unconscious perception (measured by implicit eye movement behaviour) and conscious reactions in the context of explicit value and interest evaluation.