bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-targeting strategy for precise, scarless gene editing with CRISPR/Cas9 and donor ssODNs inChlamydomonas
Authors: Akella Soujanya , Ma Xinrong , Bacova Romana , Harmer Zachary P. , Kolackova Martina , Wen Xiaoxue , Wright David A. , Spalding Martin H. , Weeks Donald P. , Cerutti Heriberto
Published: March 2021

Programmable site-specific nucleases, such as the CRISPR/Cas9 ribonucleoproteins (RNPs), have allowed creation of valuable knockout mutations and targeted gene modifications in Chlamydomonas. However, in walled strains, present methods for editing genes lacking a selectable phenotype involve co-transfection of RNPs and exogenous double-stranded DNA (dsDNA) encoding a selectable marker gene. Repair of the double-stranded DNA breaks induced by the ribonucleoproteins is usually accompanied by genomic insertion of exogenous dsDNA fragments, hindering the recovery of precise, scarless mutations in target genes of interest. In this study, we tested whether co-targeting two genes by electroporation of pairs of CRISPR/Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) would facilitate the recovery of precise edits in a gene of interest (lacking a selectable phenotype) by selection for precise editing of another gene (creating a selectable marker) - in a process completely lacking exogenous dsDNA. We usedPPX1(encoding protoporphyrinogen IX oxidase) as the generated selectable marker, conferring resistance to oxyfluorfen, and identified precisely, scarless editedFTSYorWDTC1genes in ∼1% of the oxyfluorfen resistant colonies. Analysis of the target site sequences in edited mutants suggested that ssODNs were used as templates for DNA synthesis during homology directed repair, a process prone to replicative errors. The Chlamydomonas acetolactate synthase gene could also be efficiently edited to serve as an alternative selectable marker. This transgene-free strategy may allow creation of individual strains containing precise mutations in multiple target genes, to study complex cellular processes, pathways or structures.

One sentence summary

Co-targeting two genes by co-electroporation of CRISPR/Cas9 RNPs and ssODN repair templates allows concomitant genome editing to create a selectable marker gene and to introduce precise modifications in another gene of interest.
Beyond fish eDNA metabarcoding: Field replicates disproportionately improve the detection of stream associated vertebrate species
Authors: Macher Till-Hendrik , Schütz Robin , Arle Jens , Beermann Arne J. , Koschorreck Jan , Leese Florian
Published: March 2021

Fast, reliable, and comprehensive biodiversity monitoring data are needed for environmental decision making and management. Recent work on fish environmental DNA (eDNA) metabarcoding shows that aquatic diversity can be captured fast, reliably, and non-invasively at moderate costs. Because water in a catchment flows to the lowest point in the landscape, often a stream, it can often collect traces of terrestrial species via surface or subsurface runoff along its way or when specimens come into direct contact with water (e.g., for drinking purposes). Thus, fish eDNA metabarcoding data can provide information on fish but also on other vertebrate species that live in riparian habitats. This additional data may offer a much more comprehensive approach for assessing vertebrate diversity at no additional costs. Studies on how the sampling strategy affects species detection especially of stream-associated communities, however, are scarce. We therefore performed an analysis on the effects of biological replication on both fish as well as (semi-)terrestrial species detection. Along a 2 km stretch of the river Mulde (Germany), we collected 18 1-L water samples and analyzed the relation of detected species richness and quantity of biological replicates taken. We detected 58 vertebrate species, of which 25 were fish and lamprey, 18 mammals, and 15 birds, which account for 50%, 24%, and 7% of all native species to the German federal state of Saxony-Anhalt. However, while increasing the number of biological replicates resulted in only 25% more detected fish and lamprey species, mammal, and bird species richness increased disproportionately by 69% and 84%, respectively. Contrary, PCR replicates showed little stochasticity. We thus emphasize to increase the number of biological replicates when the aim is to improve general species detections. This holds especially true, when the focus is on rare aquatic taxa or on (semi-)terrestrial species, the so-called ‘bycatch’. As a clear advantage, this information can be obtained without any additional sampling or laboratory effort when the sampling strategy is chosen carefully. With the increased use of eDNA metabarcoding as part of national fish bioassessment and monitoring programs, the complimentary information provided on bycatch can be used for biodiversity monitoring and conservation on a much broader scale.
Systematic Profiling of Temperature- and Retinal-Sensitive Rhodopsin Variants by Deep Mutational Scanning
Authors: McKee Andrew G. , Kuntz Charles P. , Ortega Joseph T. , Woods Hope , Roushar Francis J. , Meiler Jens , Jastrzebska Beata , Schlebach Jonathan P.
Published: March 2021

Membrane protein variants with diminished conformational stability often exhibit enhanced cellular expression at reduced growth temperatures. The expression of “temperature-sensitive” variants is also typically sensitive to corrector molecules that bind and stabilize the native conformation. In this work, we employ deep mutational scanning to compare the effects of reduced growth temperature and an investigational corrector (9-cis-retinal) on the plasma membrane expression of 700 rhodopsin variants in HEK293T cells. We find that the change in expression at reduced growth temperatures is correlated with the response to retinal among variants bearing mutations within a hydrophobic transmembrane domain (TM2). The most sensitive variants within this helix appear to disrupt a network of hydrogen bonds that stabilizes a native helical kink. By comparison, mutants that alter a polar transmembrane domain (TM7) exhibit weaker responses to temperature and retinal that are poorly correlated. Statistical analyses suggest this insensitivity primarily arises from an abundance of mutations that enhance its membrane integration, stabilize its native conformation, and/ or perturb the retinal binding pocket. Finally, we show that the characteristics of purified temperature- and retinal-sensitive variants suggest that the proteostatic effects of retinal may be manifested during translation and cotranslational folding. Together, our findings elucidate various factors that mediate the sensitivity of genetic variants to temperature and to small molecule correctors.
Functional selectivity for social interaction perception in the human superior temporal sulcus during natural viewing
Authors: Lee Masson Haemy , Isik Leyla
Published: March 2021

Recognizing others’ social interactions is a crucial human ability. Using simple stimuli, previous studies have shown that social interactions are selectively processed in the superior temporal sulcus (STS), but prior work with movies has suggested that social interactions are processed in the medial prefrontal cortex (mPFC), part of the theory of mind network. It remains unknown to what extent social interaction selectivity is observed in real world stimuli when controlling for other covarying perceptual and social information, such as faces, voices, and theory of mind. The current study utilizes a functional magnetic resonance imaging (fMRI) movie paradigm and advanced machine learning methods to uncover the brain mechanisms uniquely underlying naturalistic social interaction perception. We analyzed two publicly available fMRI datasets, collected while both male and female human participants (n = 17 and 18) watched two different commercial movies in the MRI scanner. By performing voxel-wise encoding and variance partitioning analyses, we found that broad social-affective features predict neural responses in social brain regions, including the STS and mPFC. However, only the STS showed robust and unique selectivity specifically to social interactions, independent from other covarying features. This selectivity was observed across two separate fMRI datasets. These findings suggest that naturalistic social interaction perception recruits dedicated neural circuity in the STS, separate from the theory of mind network, and is a critical dimension of human social understanding.

Significance Statement

Social interaction perception guides our daily behavior, yet it is unknown how our brain processes real-world social interaction scenes. Here, we demonstrate that social brain areas, including the superior temporal sulcus (STS) and medial prefrontal cortex (mPFC), are sensitive to broad social-affective information in naturalistic movies, replicating prior results with controlled paradigms. We show for the first time however, that the STS, but not mPFC, selectively processes social interactions in natural movies, independent of other co-occurring perceptual and social features, including motion, presence of faces, speech, and mentalizing about others. Our results suggest that social interaction perception is a crucial dimension of social understanding represented in the human brain.
Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants
Authors: Zhang Yi-Nan , Paynter Jennifer , Sou Cindy , Fourfouris Tatiana , Wang Ying , Abraham Ciril , Ngo Timothy , Zhang Yi , He Linling , Zhu Jiang
Published: March 2021

Vaccines that induce potent neutralizing antibody (NAb) responses against emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for combating the coronavirus disease 2019 (COVID-19) pandemic. We demonstrated that mouse plasma induced by self-assembling protein nanoparticles (SApNPs) that present 20 rationally designed S2GΔHR2 spikes of the ancestral Wuhan-Hu-1 strain can neutralize the B.1.1.7, B.1.351, P.1, and B.1.617 variants with the same potency. The adjuvant effect on vaccine-induced immunity was investigated by testing 16 formulations for the multilayered I3-01v9 SApNP. Using single-cell sorting, monoclonal antibodies (mAbs) with diverse neutralization breadth and potency were isolated from mice immunized with the receptor binding domain (RBD), S2GΔHR2 spike, and SApNP vaccines. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble spike, the I3-01v9 SApNP showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold stronger germinal center reactions in lymph node follicles.

ONE-SENTENCE SUMMARY

With a well-defined mechanism, spike nanoparticle vaccines can effectively counter SARS-CoV-2 variants.
Governance mechanism alignment at the top and operating levels of alliance hierarchy: reconciling two competing schools of thought
Authors: Bai Xuan , Sheng Shibin , Li Julie Juan
Published: March 2021

Purpose

This paper aims to examine alliance governance at different hierarchical levels.

Design/methodology/approach

The data is collected from both top-level and operating-level managers in 286 strategic alliances in China (a total of 572 managers). Hierarchical moderated regression models are adopted to test the hypotheses and two-stage regression analyzes are used to correct for endogeneity.

Findings

This paper finds that relational governance has a greater impact on alliance performance than contract utilization at the top level. Furthermore, the simultaneous use of relational governance at the top and operating levels have a detrimental impact on alliance performance. Finally, top-level contract utilization has a negative interaction with operating-level relational governance but a positive interaction with operating-level contract utilization.

Research limitations/implication

First, the cross-sectional nature of the data collection approach provides only a snapshot of how each type of governance mechanism and its interactions affect alliance performance. Second, the sample is limited to firms located in emerging markets.

Practical implications

Managers should realize that the effectiveness of contract and relational governance mechanisms varies across different management levels and they should be cautious about the cross-level governance mechanism alignment.

Originality/value

This study advances the interfirm governance literature in that this paper examined alliance governance at different hierarchical levels and provides new insights into the ongoing debate on whether the contract and relational governance mechanisms function as complements or substitutes by exploring the governance alignment across different alliance hierarchies.
Gender differences in predictors of technology threat avoidance
Authors: Gillam Andrew R. , Waite Alina M.
Published: March 2021

Purpose

The purpose of this paper is to examine gender differences in predictors of technology threat avoidance motivation and behavior among working US adults. Implications were considered in regard to cybersecurity awareness training motivation and perceptions of need for protective cybersecurity behavior in the workplace.

Design/methodology/approach

A single-shot regression-based study used ordinal regression supported by K-means clustering to evaluate the moderating effects of gender on predictors of technology threat avoidance motivation and behavior on a sample ofn = 206 US adult workers.

Findings

The regression model explained 47.5% of variance in avoidance motivation and 39% of avoidance behavior variance. Gender moderated predictive associations between several independent variables and avoidance motivation: perceived susceptibility, perceived effectiveness, perceived cost and self-efficacy. Gender also moderated the association between avoidance motivation and avoidance behavior.

Research limitations/implications

The predictive impact of gender extends beyond the main effects in technology threat avoidance. Data frequency distributions and inter-variable relationships should be routinely considered in threat avoidance studies, especially if sample variables exhibit non-normal frequency distributions and nonlinear associations.

Practical implications

Gender was significantly associated with threat avoidance motivation and avoidance behavior and exhibited notable associations with antecedents of avoidance motivation. Related insights can inform the design and delivery of training content relating to technology threat avoidance as organizations strive to more effectively leverage information technology end-users as protective assets for the enterprise.

Originality/value

The uniqueness of this study derives from its focus and findings regarding the moderating effects of gender on technology threat avoidance factors and techniques used to measure and evaluate the associations between them.
Users’ attitude on perceived security of enterprise systems mobility: an empirical study
Authors: Palanisamy Ramaraj , Wu Yang
Published: March 2021

Purpose

This study/ paper aims to empirically examine the user attitude on perceived security of enterprise systems (ES) mobility. Organizations are adopting mobile technologies for various business applications including ES to increase the flexibility and to gain sustainable competitive advantage. At the same time, end-users are exposed to security issues when using mobile technologies. The ES have seen breaches and malicious intrusions thereby more sophisticated recreational and commercial cybercrimes have been witnessed. ES have seen data breaches and malicious intrusions leading to more sophisticated cybercrimes. Considering the significance of security in ES mobility, the research questions in this study are: What are the security issues of ES mobility? What are the influences of users’ attitude towards those security issues? What is the impact of users’ attitude towards security issues on perceived security of ES mobility?

Design/methodology/approach

These questions are addressed by empirically testing a security model of mobile ES by collecting data from users of ES mobile systems. Hypotheses were evolved and tested by data collected through a survey questionnaire. The questionnaire survey was administered to 331 users from Chinese small and medium-sized enterprises (SME). The data was statistically analysed by tools such as correlation, factor analysis, regression and the study built a structural equation model (SEM) to examine the interactions between the variables.

Findings

The study results have identified the following security issues: users’ attitude towards mobile device security issues; users’ attitude towards wireless network security issues; users’ attitude towards cloud computing security issues; users’ attitude towards application-level security issues; users’ attitude towards data (access) level security issues; and users’ attitude towards enterprise-level security issues.

Research limitations/implications

The study results are based on a sample of users from Chinese SMEs. The findings may lack generalizability. Therefore, researchers are encouraged to examine the model in a different context. The issues requiring further investigation are the role of gender and type of device on perceived security of ES mobile systems.

Practical implications

The results show that the key security issues are related to a mobile device, wireless network, cloud computing, applications, data and enterprise. By understanding these issues and the best practices, organizations can maintain a high level of security of their mobile ES.

Social implications

Apart from understanding the best practices and the key issues, the authors suggest management and end-users to work collaboratively to achieve a high level of security of the mobile ES.

Originality/value

This is an empirical study conducted from the users’ perspective for validating the set of research hypotheses related to key security issues on the perceived security of mobile ES.
Integrating professional sustainability literacy into the master of public administration curriculum
Authors: Kinzer Kirsten
Published: March 2021

Purpose

Public administration, or the implementation of public policies by civil servants, will be central to implementing the Agenda 2030 Sustainable Development Goals. And yet, few American master of public administration (MPA) programs explicitly focus on sustainable development or sustainability literacy. This study asks whether it is possible to build professional sustainability literacy within a general MPA course, specifically in a course on quantitative methods.

Design/methodology/approach

Through a natural experiment conducted in three sections of the graduate course Quantitative Methods in Public Administration at UNC Wilmington, the study explores the relationship between student growth in professional sustainability literacy and a student’s level of foundational sustainability literacy, pro-environmental behavior, background knowledge in statistics and their interest in sustainable development within public administration.

Findings

The study finds that there is a statistically significant relationship between growth in a student’s professional sustainability literacy and two variables: above average foundational sustainability literacy and a high level of interest in sustainability policies and programs.

Originality/value

This study is the first to consider an embedded approach to sustainability education in the field of public administration.
Vehicle direct yaw moment control system based on the improved linear quadratic regulator
Authors: Xie Xianyi , Jin Lisheng , Baicang Guo , Shi Jian
Published: March 2021

Purpose

This study aims to propose an improved linear quadratic regulator (LQR) based on the adjusting weight coefficient, which is used to improve the performance of the vehicle direct yaw moment control (DYC) system.

Design/methodology/approach

After analyzing the responses of the side-slip angle and the yaw rate of the vehicle when driving under different road adhesion coefficients, the genetic algorithm and fuzzy logic theory were applied to design the parameter regulator for an improved LQR. This parameter regulator works according to the changes in the road adhesion coefficient between the tires and the road. Hardware-in-the-loop (HiL) tests with double-lane changes under low and high road surface adhesion coefficients were carried out.

Findings

The HiL test results demonstrate the proposed controllers’ effectiveness and reasonableness and satisfy the real-time requirement. The effectiveness of the proposed controller was also proven using the vehicle-handling stability objective evaluation method.

Originality/value

The objective evaluation results reveal better performance using the improved LQR DYC controller than a front wheel steering vehicle, especially in reducing driver fatigue, improving vehicle-handling stability and enhancing driving safety.
The role of knowledge, trust, and religiosity in explaining the online cash waqf amongst Muslim millennials
Authors: Kasri Rahmatina Awaliah , Chaerunnisa Syafira Rizma
Published: March 2021

Purpose

This study aims to determine the role of knowledge, trust and religiosity in influencing the intention to donate cash waqf online among Muslim millennials in Indonesia.

Design/methodology/approach

Using a framework based on the theory of planned behavior, primary data was collected from 418 Muslim millennials who domiciled in large cities in Indonesia and subsequently analyzed using the structural equation modeling method.

Findings

The main findings suggest that knowledge, trust and religiosity play a positive role in explaining the intention to donate cash waqf online among Indonesia’s millennials. Religiosity is found to be the most powerful factor in influencing attitude, while knowledge is the least significant factor influencing the attitude, which subsequently influences the intention to engage in online cash waqf. Social norms and perceived behavioral control are also positively influencing such intention.

Practical implications

These results imply that it is important for waqf institutions to reflect strong Islamic values in their cash waqf products and to more strongly communicate religious messages about the benefits of giving cash waqf to the millennials. It is also crucial to increase waqf literacy through appropriate campaigns. Moreover, they need to be more transparent and accountable to establish, maintain and enhance trust in their organizations. Overall, these findings are expected to provide insights enabling waqf institutions to devise effective marketing strategies for raising the level of online cash waqf donation in Indonesia.

Originality/value

This is thought to be one of the first studies to investigate the factors influencing online cash waqf donations among Muslim millennials in Indonesia.
The halal tourism – alternative or mass tourism? Indications of traditional mass tourism on crescent rating guidelines on halal tourism
Authors: Rhama Bhayu
Published: March 2021

Purpose

This study aims to identify whether halal tourism, as advocated by Mastercard-Crescent Rating guidelines on halal tourism can be considered as supporting sustainable tourism.

Design/methodology/approach

Three Mastercard-CrescentRating 2019 Reports which are Global Muslim Travel Index, Indonesia Muslim Travel Index and Halal Travel Frontier were evaluated using a qualitative method supports by NVivo software to analyze text and images. Eight indicators (number of tourists, main motivations, main values, interaction with the community, interaction with the environment, most possible destinations, infrastructure and visitor monitorings) are used to classify halal tourism items into mass tourism (traditional, experiential and sensational) and non-mass (alternative) tourism. The qualitative analysis is supported by correlation analysis of GMTI scores with environmental performance index and the global sustainable competitiveness index scores.

Findings

The results showed that halal tourism has unique characters compared with mass and non-mass tourism types. However, halal tourism advocated by CrescentRating unlikely shows similarity with non-mass tourism. It tends to be traditional mass tourism, especially on the perspective of the type of activity, interactions with the environment and local communities, as well as the main values.

Originality/value

Previous research suggested the needs of halal tourism and its relations to sustainability. This research fills the gap by showing the halal tourism, in the perspective of Mastercard-CrescentRating is not prioritized toward sustainable tourism by qualitative and quantitative evidences. This study contributes to the knowledge of sustainability from Islamic perspectives and practices and provides a way to the theory of Islamic sustainable tourism. It also suggests improvements to halal tourism guidelines such as the transparency and guarantees that the profit will be used for social welfare, promotion of sustainability using Qur’anic verses and promotion on environmental and social empowerment activities.
A dynamic performance management approach to frame corruption in public procurement: a case study
Authors: Gnoffo Salvatore
Published: March 2021

Purpose

The purpose of this paper is to frame the causal relationships between corruption in public procurement and performance of local governments.

Design/methodology/approach

An outcome-based dynamic performance management approach is adopted to explore a representative case study of a small Italian municipality. The model is based on three sources: qualitative primary data generated by face-to-face convergent interviews; secondary data retrieved from documents describing legal cases linked to procurement and open-access repositories; and an extensive literature review.

Findings

Emphasizing the role of community civic morality systemically may help to understand some counterintuitive results in the past research and support decision-makers and policymakers in setting effective strategies to curb the associated negative implications.

Social implications

A dynamic approach of performance management aimed at framing corruption in public procurement may guide policymakers and decision-makers in keeping their “cognitive radar” constantly active, in a way to detect emerging corruptive phenomena that could be otherwise ignored by normal diagnostical approaches. It may also help to promote organizational ethical learning and improve community outcomes.

Originality/value

This research provides a causal and systemic framework of relationships involving local government performance and wrongdoings in public procurement, by including performance risk indicators linked to structural and individualistic causes of corruption.
Mobile health (mHealth) application loyalty in young consumers
Authors: Soni Manjari , Jain Kokil , Jajodia Isha
Published: March 2021

Purpose

The emergence of mHealth applications has led to the rise of health-based services delivered over smartphones. Younger people are often found to be more innovative toward technology, especially related to smartphones (Rai et al., 2013). Most mHealth application downloaders are continually shifting between applications because of the hyper-competition making achieving loyal consumers challenging (Racherla et al., 2012). The purpose of this paper is to study the determinants that help increase young consumers mHealth application loyalty. This study integrates self-determination theory (SDT), gamification elements and engagement to examine loyalty.

Design/methodology/approach

A valid sample of 263 college student’s data was obtained for data analysis from a survey conducted in multiple campuses of the Delhi University in India.

Findings

The three psychological needs: need for autonomy, need for competence and need for relatedness, showed a positive impact on intrinsic motivation. From the gamification factors; perceived playfulness, the level of challenge and social interaction, only the first two showed a positive impact on extrinsic motivation. Both motivation factors influence engagement, showing a frequent interaction with the application, leading to loyalty.

Originality/value

Previous studies examined the adoption of mHealth services, this study is one of the first to examine young consumers’ loyalty in using mhealth apps. It sheds light on the existing literature and contributes to research on mHealth applications by determining the factors that lead to loyalty by the young consumers.
Land Does Not Vote. Neither Do Percentages
Authors: Kennedy-Shaffer Lee
Published: March 2021

Mapping election outcomes can be tricky, and the outputs can mislead – especially those that display vote share shifts over time, argues Lee Kennedy-Shaffer
COVID-19 and High School Grades: An Early Case Study
Authors: Schramm Harrison , Rubin Isaac , Schramm Norah
Published: March 2021

Harrison Schramm, Isaac Rubin and Norah Schramm investigate the impact distance learning may have had on the grades of students at a California high school
Thep-value Statement, Five Years On
Authors: Matthews Robert
Published: March 2021

The American Statistical Association's 2016 p-value statement generated debates and disagreements, editorials and symposia, and a plethora of ideas for how science could be changed for the better. Now, five years on, Robert Matthews asks what, if anything, has the statement achieved?
Sound Human, Steer Clear of Jargon, and be Prepared
Authors: McConway Kevin , Spiegelhalter David
Published: March 2021

Kevin McConway and David Spiegelhalter offer tips to statisticians communicating through the media, especially in the time of Covid-19
As Covid Makes Clear, Statistics Education is a Must
Authors: Franklin Christine
Published: March 2021

Christine Franklin introduces a new framework for statistics education, contending that statistical reasoning skills should “no longer be optional” for school-age students
What's the Big Idea? Data Linkage
Authors: Harron Katie
Published: March 2021

Katie Harron explains the statistical concepts that underpin the complex but crucial process of linking records stored in different databases
Review: News, Numbers, and Public Opinion in a Data-Driven World
Authors: King Thomas
Published: March 2021

Book review by Thomas King.
Galactocerebroside biosynthesis pathways of Mycoplasma species: an antigen triggering Guillain–Barré–Stohl syndrome
Authors: Gaspari Erika , Koehorst Jasper J. , Frey Joachim , Martins dos Santos Vitor A.P. , Suarez‐Diez Maria
Published: March 2021

Infection by Mycoplasma pneumoniae has been identified as a preceding factor of Guillain–Barré–Stohl syndrome. The Guillain–Barré–Stohl syndrome is triggered by an immune reaction against the major glycolipids and it has been postulated that M. pneumoniae infection triggers this syndrome due to bacterial production of galactocerebroside. Here, we present an extensive comparison of 224 genome sequences from 104 Mycoplasma species to characterize the genetic determinants of galactocerebroside biosynthesis. Hidden Markov models were used to analyse glycosil transferases, leading to identification of a functional protein domain, termed M2000535 that appears in about a third of the studied genomes. This domain appears to be associated with a potential UDP‐glucose epimerase, which converts UDP‐glucose into UDP‐galactose, a main substrate for the biosynthesis of galactocerebroside. These findings clarify the pathogenic mechanisms underlining the triggering of Guillain–Barré–Stohl syndrome by M. pneumoniae infections.
An MRI framework for respiratory motion modelling validation
Authors: Meschini Giorgia , Paganelli Chiara , Vai Alessandro , Fontana Giulia , Molinelli Silvia , Pella Andrea , Vitolo Viviana , Barcellini Amelia , Orlandi Ester , Ciocca Mario , Riboldi Marco , Baroni Guido
Published: March 2021

Introduction

Respiratory motion models establish a correspondence between respiratory‐correlated (RC) 4‐dimensional (4D) imaging and respiratory surrogates, to estimate time‐resolved (TR) 3D breathing motion. To evaluate the performance of motion models on real patient data, a validation framework based on magnetic resonance imaging (MRI) is proposed, entailing the use of RC 4DMRI to build the model, and on both (i) TR 2D cine‐MRI and (ii) additional 4DMRI data for testing intra‐/inter‐fraction breathing motion variability.

Methods

Repeated MRI data were acquired in 7 patients with abdominal lesions. The considered model relied on deformable image registration (DIR) for building the model and compensating for inter‐fraction baseline variations. Both 2D and 3D validation were performed, by comparing model estimations with the ground truth 2D cine‐MRI and 4DMRI respiratory phases, respectively.

Results

The median DIR error was comparable to the voxel size (1.33 × 1.33 × 5 mm3), with higher values in the presence of large inter‐fraction motion (median value: 2.97 mm). In the 2D validation, the median estimation error on anatomical landmarks’ position resulted below 4 mm in every scenario, whereas in the 3D validation it was 1.33 mm and 4.21 mm when testing intra‐ and inter‐fraction motion, respectively. The range of motion described in the cine‐MRI was comparable to the motion of the building 4DMRI, being always above the estimation error. Overall, the model performance was dependent on DIR error, presenting reduced accuracy when inter‐fraction baseline variations occurred.

Conclusions

Results suggest the potential of the proposed framework in evaluating global motion models for organ motion management in MRI‐guided radiotherapy.
Granulocyte‐macrophage colony‐stimulating factor initiates amniotic membrane rupture and preterm birth in a mouse model
Authors: Nold Christopher , Esteves Kristyn , Jensen Todd , Vella Anthony T.
Published: March 2021

Objective

Preterm premature rupture of membranes is associated with 30% of all preterm births. The weakening of amniotic membranes is associated with an increase in matrix metallopeptidases (MMPs) along with a decrease in their inhibitors, tissue inhibitor metallopeptidases (TIMPs). Additionally, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) has been shown to weaken fetal membranes in‐vitro. We hypothesize pregnant mice treated with GM‐CSF lead to increased MMPs:TIMPs resulting in membrane rupture and preterm birth.

Study Design

Pregnant CD‐1 mice on gestational day 17 received either an intrauterine injection of GM‐CSF or vehicle control. A second series of mice were administered an intrauterine injection of Lipopolysaccharide along with either anti‐mouse GM‐CSF or control antibody. Mice were evaluated for rupture of membranes and/or preterm birth and the uterus, amniotic fluid, and serum were collected for analysis.

Results

87.5% of GM‐CSF mice exhibited evidence of membrane rupture or preterm birth, compared with 0% in control mice (p < .001). Treatment with GM‐CSF decreased the expression of TNFα (p < .05) while increasing the ratio of MMP2:TIMP1 (p < .05), MMP2:TIMP2 (p < .05), MMP2:TIMP3 (p < .001), MMP9:TIMP1 (p < .01), MMP9:TIMP2 (p < .05), MMP9:TIMP3 (p < .001), and MMP10:TIMP1 (p < .05). Mice treated with LPS and the GM‐CSF antibody resulted in a decrease in the ratio of MMP2:TIMP1 (p < .0001) compared with controls.

Conclusion

These studies demonstrate GM‐CSF will result in membrane rupture and preterm birth by increasing the ratio MMPs:TIMPs in our animal model. By increasing our understanding of the molecular pathways associated with GM‐CSF, we may be able to develop future therapies to prevent preterm birth and reduce neonatal morbidity.
Effect of metastereotypes on female cooperative behaviour and the mediating role of intergroup anxiety
Authors: Ma Yuting , Dang Qingxiu , Zhang Baoshan
Published: March 2021

This study explored the effect of metastereotypes on female cooperative behaviour, and the mediating role of intergroup anxiety. Cooperative behaviour was measured by the ultimatum game, in which a responder decides whether to accept a monetary division offered by a proposer to get the corresponding amount of money or reject it, leaving neither player with anything. Study 1, through a laboratory experiment on 62 Chinese female college students, showed that female participants in a metastereotype activation group showed more intergroup anxiety and less cooperative behaviour than participants in a control group; intergroup anxiety played a mediating role between metastereotypes and female cooperative behaviour. Study 2 (n = 94) used an imagined intergroup contact technique to reduce the level of intergroup anxiety to further verify the mediating role of intergroup anxiety obtained from Study 1. The results showed that experiencing imagined intergroup contact reduced the negative effect of metastereotypes on female cooperative behaviour through mitigating intergroup anxiety. These findings revealed the possible effects of metastereotypes on female cooperative behaviour and the related possible behavioural mechanism, providing new insights into understanding women’s cooperative behaviour and improving teamwork efficiency.
Real‐life impact of COVID‐19 pandemic lockdown on the management of pediatric and adult asthma: A survey by the EAACI Asthma Section
Authors: Eguiluz‐Gracia Ibon , van den Berge Maarten , Boccabella Cristina , Bonini Matteo , Caruso Cristiano , Couto Mariana , Erkekol FerdaOner , Rukhadze Maia , Sanchez‐Garcia Silvia , del Giacco Stefano , Jutel Marek , Agache Ioana
Published: March 2021

Background

The restrictions imposed by the COVID‐19 pandemic impact heavily the management of chronic diseases like asthma. This study aimed to evaluate the management of adults and children with asthma during COVID‐19‐related lockdown.

Methods

A survey was launched by the European Academy of Allergy and Clinical Immunology (EAACI) via e‐mail, website, and social media to EAACI members and members of peer societies.

Results

The survey was completed by 339 healthcare professionals from 52 countries. 79% of follow‐up consultations were replaced by phone calls, whereas 49% of newly referred patients attended the clinic. 62%, 76%, 66%, 76%, and 87% of responders did not conduct spirometry, impulse oscillometry, bronchodilator test, FeNO, or methacholine provocation, respectively, for asthma diagnosis in adults. The numbers were similar for children. 73% of responders based the initial asthma diagnosis and the prescription of inhaled therapy on clinical parameters only. Lung function tests were used in 29% of cases to monitor asthma worsening, and only 56% of participants were recommended to their patients ambulatory peak expiratory flow (PEF) measurements. Using a 1 (not at all) to 5 (very much) scale, the responders considered that the quality of healthcare provided and the patients’ asthma status had deteriorated during the lockdown with 3.2 points and 2.8 points, respectively.

Conclusion

Collectively, these results suggest that all necessary resources should be allocated to ensure the performance of lung function tests for initial diagnosis, whereas digital remote monitoring should be reinforced for the follow‐up of children and adults with asthma.
CytoBas: Precision component‐resolved diagnostics for allergy using flow cytometric staining of basophils with recombinant allergen tetramers
Authors: McKenzie Craig I. , Varese Nirupama , Aui Pei M. , Wines Bruce D. , Hogarth Philip Mark , Thien Francis , Hew Mark , Rolland Jennifer M. , O’Hehir Robyn E. , van Zelm Menno C.
Published: March 2021

Background

Diagnostic tests for allergy rely on detecting allergen‐specific IgE. Component‐resolved diagnostics incorporate multiple defined allergen components to improve the quality of diagnosis and patient care.

Objective

To develop a new approach for determining sensitization to specific allergen components that utilizes fluorescent protein tetramers for direct staining of IgE on blood basophils by flow cytometry.

Methods

Recombinant forms of Lol p 1 and Lol p 5 proteins from ryegrass pollen (RGP) and Api m 1 from honeybee venom (BV) were produced, biotinylated, and tetramerized with streptavidin‐fluorochrome conjugates. Blood samples from 50 RGP‐allergic, 41 BV‐allergic, and 26 controls were incubated with fluorescent protein tetramers for flow cytometric evaluation of basophil allergen binding and activation.

Results

Allergen tetramers bound to and activated basophils from relevant allergic patients but not controls. Direct fluorescence staining of Api m 1 and Lol p 1 tetramers had greater positive predictive values than basophil activation for BV and RGP allergy, respectively, as defined with receiver operator characteristics (ROC) curves. Staining intensities of allergen tetramers correlated with allergen‐specific IgE levels in serum. Inclusion of multiple allergens coupled with distinct fluorochromes in a single‐tube assay enabled rapid detection of sensitization to both Lol p 1 and Lol p 5 in RGP‐allergic patients and discriminated between controls, BV‐allergic, and RGP‐allergic patients.

Conclusion

Our novel flow cytometric assay, termed CytoBas, enables rapid and reliable detection of clinically relevant allergic sensitization. The intensity of fluorescent allergen tetramer staining of basophils has a high positive predictive value for disease, and the assay can be multiplexed for a component‐resolved and differential diagnostic test for allergy.
Risk factors for ventricular tachyarrhythmic events in patients without left bundle branch block who receive cardiac resynchronization therapy
Authors: Younis Arwa , Aktas Mehmet K. , Zareba Wojciech , McNitt Scott , Kutyifa Valentina , Goldenberg Ilan
Published: March 2021

Introduction

Cardiac resynchronization therapy (CRT) may be pro‐arrhythmic in patients with non‐left bundle branch block (non‐LBBB). We hypothesized that combined assessment of risk factors (RF) for ventricular tachyarrhythmias (VTAs) can be used to stratify non‐LBBB patients for CRT implantation.

Methods

The study comprised 412 non‐LBBB patients from MADIT‐CRT randomized to CRT‐D (n = 215) versus ICD only (n = 197). Best‐subset regression analysis was performed to identify RF associated with increased VTA risk in CRT‐D patients without LBBB. The primary end point was first occurrence of sustained VTA during follow‐up. Secondary end points included VTA/death and appropriate shock.

Results

Four RFs were associated with increased VTA risk: blood urea nitrogen >25mg/dl, ejection fraction <20%, prior nonsustained VT, and female gender. Among CRT‐D patients, 114 (53%) had no RF, while 101 (47%) had ≥1 RF. The 4‐year cumulative probability of VTA was higher among those with ≥1 RF compared with those without RF (40% vs. 14%, p < .001). Multivariate analysis showed that in patients without RF, treatment with CRT‐D was associated with a 61% reduction in VTA compared with ICD‐only therapy (p = .002), whereas among patients with ≥1 RF, treatment with CRT‐D was associated with a corresponding 73% (p = .025) risk increase. Consistent results were observed when the secondary end points of VTA/death and appropriate ICD shocks were assessed.

Conclusion

Combined assessment of factors associated with increased risk for VTA can be used for improved selection of non‐LBBB patients for CRT‐D.
Reimagining the global food regimes for relational spaces
Authors: Wang Kuan‐Chi
Published: March 2021

As the food regime approach was originally built on the influential world‐system analytical framework, it is worth highlighting human geographers’ efforts to transcend world‐system theory (and the food regime approach) to emphasise how different types of political‐economic processes operate relationally and differentially across regions in the capitalist world. Meanwhile, other geographical perspectives and approaches, such as “critical GIS,” have contributed to the re‐imagination of regions relationally at a range of geographical scales, operating as distinct pathways for commodities over time. Accordingly, drawing on the more‐than‐qualitative relational approach supported by critical GIS and the regional and political geography literature, this paper applies centrality analysis – a quantitative social network analysis – and time‐series analysis to explore and visualise the transformation of the trade networks of high‐value crops in Asia. The paper argues that applying a more‐than‐qualitative relational approach to food regime scholarship can advance our understanding of the emerging regional dynamics in the global food system. Particularly, the findings of this paper show that the rise of China in the global food system has been accompanied by the emergence of Thailand and Vietnam as central actors. Such a multipolar food regime is applicable to address a regional food system, as its regional centrality is defined by clusters of states with more diffuse centrality.
On integrative social contracts theory and corporate decision‐making in a polarized political economy
Authors: Baird Catharyn , Mayer Don
Published: March 2021

The priority rules in Donaldson and Dunfee's Integrative Social Contracts Theory (ISCT) provide a useful tool for firms facing polarizing social issues in the United States. ISCT and its priority rules are applied here to divisive social issues such as contraception, gun control, and LGBTQ rights. The ISCT process also benefits firms that serve parts of the world where norms are evolving, and can help firms clarify and communicate their own values.
Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta‐analysis
Authors: Wang Zixuan , Brauer Ruth , Man Kenneth K. C. , Alfageh Basmah , Mongkhon Pajaree , Wong Ian C. K.
Published: March 2021

Objective

To evaluate the association between antipsychotic use in pregnancy and the risk of congenital malformations in children.

Data sources

Searches of PubMed, EMBASE, PsycINFO and Cochrane Library were conducted from inception to 06 January 2020 using keywords: antipsychotics, pregnancy, pregnancy complication and congenital abnormalities.

Study selection

Of 38 reports initially identified as being of potential interest, 13 studies met our inclusion criteria: English observational studies that examined the association between gestational antipsychotic use and congenital malformations in children.

Data extraction

Data were extracted independently by 2 investigators including the publication year, study site, study period, data source, study design, sample size, medication exposure, exposure period and pregnancy definition, exposure as well as outcome ascertainment, selection of study and comparison group, confounding adjustment, statistical analysis, and method of linkage between mother and children. Risk estimates were pooled using a random‐effect model and the I2 statistic was used to evaluate the degree of heterogeneity.

Results

Thirteen studies met our systematic review inclusion criteria. Six studies with a total of 2 515 272 pregnancy episodes were included in our meta‐analysis, which provided a pooled adjusted risk ratio of 1.23, 95% confidence interval: 0.96–1.58. The I2 result showed moderate heterogeneity between studies (I2 = 35.2%, P = .173).

Conclusion

We did not find strong evidence of an association between prenatal exposure to antipsychotic medications and the risk of congenital malformations in children. We recommend further studies investigate this association, focusing on specific medication classes and dose responses, which would help clinicians decide whether to prescribe certain antipsychotics during pregnancy.