bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional variation in cardiovascular genes enables a tractable genome editing strategy
Authors: Krysov Vikki A. , Wilson Rachel H. , Ten Nicholas S. , Youlton Nathan , De Jong Hannah N. , Sutton Shirley , Huang Yong , Reuter Chloe , Grove Megan E. , Wheeler Matthew T. , Ashley Euan A. , Parikh Victoria N. 
Published: March 2022

AbstractRecent rise in the number and therapeutic potential of genome engineering technologies has generated excitement in cardiovascular genetics. One significant barrier to their implementation is costly and time consuming reagent development for novel unique variants. Prior data have illuminated the potential for regional clustering of disease-causing genetic variants in known and potential novel functional protein domains. We hypothesized that most cardiovascular disease-relevant genes in ClinVar would display regional variant clustering, and that multiple variants within a regional hotspot could be targeted with limited prime editing reagents. We collated 2,471 high confidence pathogenic or likely pathogenic (P/LP) missense and truncating variants from 111 cardiovascular disease genes. We then defined a regional clustering index (RCI), the percent of P/LP variants in a given gene located within a pre-specified window around each variant. At a window size commensurate with maximally reported prime editing extension length, 78bp, we found that missense variants displayed a higher mean RCI than truncating variants. We next identified genes particularly attractive for pathogenic hotspot-targeted prime editing with at least 20 P/LP variants and observed that the mean RCI in missense variants remained higher than for truncating variants and for rare variants observed in the same genes in gnomAD (Mean±SD RCI78bp: P/LP ClinVar Missense=5.2±5.9%; P/LP ClinVar Truncating=2.1±3.2%, gnomAD Missense=2±3.2%, gnomAD Truncating=1.1±2.4%. p<2.2e-16; ANOVA with post hoc Bonferroni correction). Further, we tested the feasibility of prime editing for multiple variants in a single hotspot in KCNH2, a gene with a high mean missense variant RCI. Sixty variants were induced in this hotspot in HEK293 cells with CRISPR-X. Correction of these variants was attempted with prime editing using two overlapping prime editing guide RNA extensions. The mean prime editing efficiency across CRISPR-X-enriched variants within this hotspot was 57±27%, including 3 P/LP variants. These data underscore the utility of pathogenic variant hotspots in the diagnosis and treatment of inherited cardiovascular disease.
Regional, circuit, and network heterogeneity of brain abnormalities in psychiatric disorders
Authors: Segal Ashlea , Parkes Linden , Aquino Kevin , Kia Seyed Mostafa , Wolfers Thomas , Franke Barbara , Hoogman Martine , Beckmann Christian F. , Westlye Lars T. , Andreassen Ole A. , Zalesky Andrew , Harrison Ben J. , Davey Christopher , Soriano-Mas Carles , Cardoner Narcís , Tiego Jeggan , Yücel Murat , Braganza Leah , Suo Chao , Berk Michael , Cotton Sue , Bellgrove Mark A. , Marquand Andre F. , Fornito Alex 
Published: March 2022

ABSTRACTThe substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy controls. Normative models identified that person-specific deviations from population expectations for regional grey matter volume were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience/ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia, and ADHD. Our findings indicate that while phenotypic differences between cases assigned the same diagnosis may arise from heterogeneity in the location of regional deviations, phenotypic similarities are attributable to dysfunction of common functional circuits and networks.
Female Zebrafish (Danio rerio) Demonstrate Stronger Preference for Established Shoals over Newly-Formed Shoals in the Three-Tank Open-Swim Preference Test
Authors: Velkey Andrew J. , Koon Caroline H. , Danstrom Isabel A. , Wiens Katie M. 
Published: March 2022

AbstractZebrafish (Danio rerio) share a considerable amount of biological similarity with mammals, including identical or homologous gene expression pathways, neurotransmitters, hormones, and cellular receptors. Zebrafish also display complex social behaviors like shoaling and schooling, making them an attractive model for investigating normal social behavior as well as exploring impaired social function conditions such as autism spectrum disorders. Newly-formed and established shoals exhibit distinct behavior patterns and inter-member interactions that can convey the group’s social stability. We used a three-chamber open-swim preference test to determine whether individual zebrafish show a preference for an established shoal over a newly-formed shoal. Results indicated that both sexes maintained greater proximity to arena zones nearest to the established shoal stimulus. In addition, we report the novel application of Shannon entropy to discover sex differences in systematicity of responses not revealed by unit-based measurements; male subjects spent more time investigating between the two shoals than female subjects. This novel technique using established versus newly-formed shoals can be used in future studies testing transgenics and pharmacological treatments that mimic autism spectrum disorder and other disorders that affect social interaction.
Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial
Authors: Kaabi Nawal Al , Yang Yun Kai , Du Li Fang , Xu Ke , Shao Shuai , Liang Yu , Kang Yun , Su Ji Guo , Zhang Jing , Yang Tian , Hussein Salah , ElDein Mohamed Saif , Yang Sen Sen , Lei Wenwen , Gao Xue Jun , Jiang Zhiwei , Cong Xiangfeng , Tan Yao , Wang Hui , Li Meng , Mekki Hanadi Mekki , Zaher Walid , Mahmoud Sally , Zhang Xue , Qu Chang , Liu Dan Ying , Zhang Jing , Yang Mengjie , Eltantawy Islam , Hou Jun Wei , Lei Ze Hua , Xiao Peng , Wang Zhao Nian , Yin Jin Liang , Mao Xiao Yan , Zhang Jin , Qu Liang , Zhang Yun Tao , Yang Xiao Ming , Wu Guizhen , Li Qi Ming 
Published: March 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.
Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants
Authors: Mijalkov Mite , Veréb Dániel , Jamialahmadi Oveis , Canal-Garcia Anna , Gómez-Ruiz Emiliano , Vidal-Piñeiro Didac , Romeo Stefano , Volpe Giovanni , Pereira Joana B. 
Published: March 2022

AbstractAging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in connectivity between and within resting-state functional networks, however, there is no consensus on the impact of sex on these age-related alterations. Here, in a large cross-sectional sample of 37543 UK Biobank participants, we show that multilayer measures that capture the interaction between positive and negative connections provide crucial information on the impact of sex on age-related changes in network topology, being closely related to cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women. We also provide additional insights into the genetic influences on multilayer connectivity changes that occur during aging. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, opening up new avenues for research into functional brain connectivity in aging.
Interferon regulatory factor 3 upregulates the Treg recruitment factor CCL22 in response to double-stranded DNA in cancer cells
Authors: Kim Jihyun G. , Peña Jocelyn V. , McQueen Hannah P. , Kong Lingwei , Michael Dina , Cook Pamela R. 
Published: March 2022

AbstractCancer immunotherapy holds great promise for the treatment of solid tumors, but its effectiveness is hindered by the recruitment of regulatory T cells (Tregs), which inhibit anti-tumor immune responses. We report here that cytosolic dsDNA, a characteristic of many cancer cells, upregulates expression of the Treg-recruitment chemokine CCL22 in multiple types of malignant epithelial cells. We also identified that interferon regulatory factor 3 (IRF3) is a key regulator of CCL22 in response to dsDNA. Both IRF3 and NF-κB are activated downstream of the stimulator of interferon genes (STING), a primary effector protein responding to multiple cytosolic dsDNA sensors. IRF3 activation by STING triggers robust expression of type I interferons, which can boost anti-tumor immune responses. Thus, STING agonists have been used clinically to activate IRF3 during immunotherapy. However, STING activation in some cases is reported to paradoxically foster a pro-tumor, immunosuppressive environment. Our finding that IRF3 regulates CCL22 in response to dsDNA suggests a possible mechanism contributing to STING-mediated immunosuppression. In addition, we found that cultured cancer cells appear able to evolve mechanisms to co-opt nucleic acid sensing pathways to upregulate CCL22, suggesting that these pathways may contribute to acquired immune evasion in tumors with increased cytosolic dsDNA.
Correlation of biomechanics and cancer cell phenotype by combined Brillouin and Raman spectroscopy of U87-MG glioblastoma cells
Authors: Rix Jan , Uckermann Ortrud , Kirsche Katrin , Schackert Gabriele , Koch Edmund , Kirsch Matthias , Galli Roberta 
Published: March 2022

AbstractThe elucidation of biomechanics furthers understanding of brain tumor biology. Brillouin spectroscopy is a new optical method that addresses viscoelastic properties down to subcellular resolution in contact-free manner. Moreover, it can be combined with Raman spectroscopy to obtain co-localized biochemical information. Here, we applied co-registered Brillouin and Raman spectroscopy to U87-MG human glioblastoma cells in vitro. Using 2D and 3D cultures, we related biomechanical properties with local biochemical composition at subcellular level, as well as cell phenotype. Brillouin and Raman mapping of adherent cells showed that the nucleus and nucleoli are stiffer than the perinuclear region and the cytoplasm. The biomechanics of cell cytoplasm is affected by culturing conditions, i.e. cells grown as spheroids being stiffer than adherent cells. Inside the spheroids, the presence of lipid droplets as assessed by Raman spectroscopy reveals higher Brillouin shifts which is not related to local stiffness increase, but due to a higher refractive index combined with a lower mass density. This highlights the importance of locally defined biochemical reference data for a correct interpretation of the Brillouin shift of cells and tissue in future studies investigating the biomechanics of brain tumor models by Brillouin spectroscopy.
MOSAIC: A Unified Trait Database to Complement Structured Population Models
Authors: Bernard Connor , Santos Gabriel Silva , Deere Jacques A. , Rodriguez-Caro Roberto , Capdevila Pol , Kusch Erik , Gascoigne Samuel J L , Jackson John , Salguero-Gómez Roberto 
Published: March 2022

AbstractThe ecological sciences have joined the big data revolution. However, despite exponential growth in data availability, broader interoperability amongst datasets is still needed to unlock the potential of open access. The interface of demography and functional traits is well-positioned to benefit from said interoperability. Trait-based ecological approaches have been criticised because of their inability to predict fitness components, the core of demography; likewise, demographic approaches are data-hungry, and so using traits as ecological shortcuts to understanding and forecasting population viability could offer great value.Here, we introduce MOSAIC, an open-access trait database that unlocks the demographic potential stored in the COMADRE, COMPADRE, and PADRINO open-access databases. MOSAIC data have been digitised and curated through a combination of existing datasets and additional taxonomic and/or trait records sourced from primary literature. In its first release, MOSAIC (v. 1.0.0) includes 14 trait fields for 300 animal and plant species: biomass, height, growth determination, regeneration, sexual dimorphism, mating system, hermaphrodism, sequential hermaphrodism, dispersal capacity, type of dispersal, mode of dispersal, dispersal classes, volancy, and aquatic habitat dependency. MOSAIC also includes species-level phylogenies for 1,359 species and population-specific climate data where locations are recorded.Using MOSAIC, we highlight a taxonomic mismatch of widely used trait databases with existing structured population models. Despite millions of trait records available in open-access databases, taxonomic overlap between open-access demographic and trait databases is <5%. We identify where traits of interest to ecologists can benefit from database integration and start to quantify traits that are poorly quantified (e.g., growth determination, modularity).The MOSAIC database evidences the importance of improving interoperability in open-access efforts in ecology as well as the need for complementary digitisation to fill targeted taxonomic gaps. In addition, MOSAIC highlights emerging challenges associated with the disparity between locations where different trait records are sourced.
Primary school children's responses to food waste at school
Authors: Yen Dorothy A. , Cappellini Benedetta , Dovey Terry 
Published: March 2022

PurposeThis paper seeks to understand children’s responses to food waste in school by exploring children’s views on food waste and empowering them to discuss and develop their own solutions.Design/methodology/approachUsing creative problem-solving approach and photovoice technique, the authors conducted focus group discussions with 28 primary school children in the UK.FindingsChildren have a clear understanding of the consequences of food waste for individuals, society and the environment. They displayed negative emotions concerning food waste and responded positively to the possibility of food recycling. Their solutions to reduce food waste will require multiple stakeholder engagement, including self-regulation, peer-monitoring, teacher supervision and family support. However, rather than relying on intervention schemes that require significant adult involvement, children placed a heavy emphasis on self-regulation, playing an active role in addressing food waste in school.Originality/valueThis research extends previous understanding, by showing children as agentic consumers who can shape food waste solutions in school. These findings are of use to primary teachers and local education authorities, to aid children in developing their own solutions to reduce food waste in their own schools.
Considerations for creating equitable and inclusive communication campaigns associated with ShakeAlert, the earthquake early warning system for the West Coast of the USA
Authors: Jenkins Mariah R. , McBride Sara K. , Morgoch Meredith , Smith Hollie 
Published: March 2022

PurposeThe 2019 Global Assessment Report on Disaster Risk Reduction (GAR) cites earthquakes as the most damaging natural hazard globally, causing billions of dollars of damage and killing thousands of people. Earthquakes have the potential to drastically impact physical, social and economic landscapes; to reduce this risk, earthquake early warning (EEW) systems have been developed. However, these technical EEW systems do not operate in a vacuum; the inequities in social systems, along with the needs of diverse populations, must be considered when developing these systems and their associated communication campaigns.Design/methodology/approachThis article reviews aspects of social vulnerability as they relate to ShakeAlert, the EEW system for the USA. The authors identified two theories (relationship management theory and mute group theory) to inform self-reflective questions for agencies managing campaigns for EEW systems, which can assist in the development of more inclusive communication practices. Finally, the authors suggest this work contributes to important conversations about diversity, equity and inclusion (DEI) issues within early warning systems and earthquake preparedness campaigns in general.FindingsTo increase inclusivity, Macnamara (2012) argues that self-reflective questioning while analyzing perspective, philosophy and approaches for a campaign can help. Specific to EEW campaigns, developers may find self-reflective questions a useful approach to increase inclusion. These questions are guided by two theories and are explored in the paper.Research limitations/implicationsSeveral research limitations exist. First, this work explores two theories to develop a combined theoretical model for self-reflective questions. Further research is required to determine if this approach and the combination of these two theories have adequately informed the development of the reflective questions.Originality/valueThe authors could find little peer-reviewed work examining DEI for EEW systems, and ShakeAlert in particular. While articles on early warning systems exist that explore aspects of this, EEW and ShakeAlert, with its very limited time frames for warnings, creates unique challenges.
Pedestrian evacuation method based on improved cellular automata in emergencies
Authors: Longzhen Zhai , Feng ShaoHong 
Published: March 2022

PurposeThe rapid evacuation of personnel in emergency situations is of great significance to the safety of pedestrians. In order to further improve the evacuation efficiency in emergency situations, this paper proposes a pedestrian evacuation model based on improved cellular automata based on microscopic features.Design/methodology/approachFirst, the space is divided into finer grids, so that a single pedestrian occupies multiple grids to show the microscopic behavior between pedestrians. Second, to simulate the velocity of pedestrian movement under different personnel density, a dynamic grid velocity model is designed to establish a linear correspondence relationship with the density of people in the surrounding environment. Finally, the pedestrian dynamic exit selection mechanism is established to simulate the pedestrian dynamic exit selection process.FindingsThe proposed method is applied to single-exit space evacuation, multi-exit space evacuation, and space evacuation with obstacles, respectively. Average speed and personnel evacuation decisions are analyzed in specific applications. The method proposed in this paper can provide the optimal evacuation plan for pedestrians in multiple exit and obstacle environments.Practical implications/Social implicationsIn fire and emergency situations, the method proposed in this paper can provide a more effective evacuation strategy for pedestrians. The method proposed in this paper can quickly get pedestrians out of the dangerous area and provide a certain reference value for the stable development of society.Originality/valueThis paper proposes a cellular automata pedestrian evacuation method based on a fine grid velocity model. This method can more realistically simulate the microscopic behavior of pedestrians. The proposed model increases the speed of pedestrian movement, allowing pedestrians to dynamically adjust the speed according to the specific situation.
Why do customers want to learn? Antecedents and outcomes of customer learning
Authors: Sun Xiaochi , Eisingerich Andreas Benedikt , Foscht Thomas , Cui Xuebin , Schloffer Judith 
Published: March 2022

Purpose
Customers often want to learn about a product/service, and companies can benefit from such a learning desire. While prior research has shed light on firm-beneficial outcomes of customer learning and explored the motivational factors of business partners’ learning behavior, less is known about the critical antecedents of individual customers’ learning behavior. This study aims to explore the key drivers of individual customers’ learning desires and identified customers with a stronger learning desire.

Design/methodology/approach
This research used both a lab experiment (Study 1, N = 148) and surveys (Study 2, N = 553; Study 3, N = 703) across different participant populations and product contexts.

Findings
This study indicated that both involvement and knowledge-sharing intention drove customer learning desire. Customer expertise further strengthened these main effects. Moreover, a stronger learning desire led to greater customer satisfaction.

Research limitations/implications
This study identified key factors involved in customer learning desire and its potential benefits for companies. Additional research to investigate customer learning in specific environments and forms and regarding specific brands is warranted.

Practical implications
This study emphasizes the importance of supporting customer learning and encourages businesses to manage customer learning proactively. It also provides suggestions for effective learning support for targeted customer groups.

Originality/value
This study contributes to the customer learning literature by exploring key influencing factors of individual customers’ learning desires, based on self-determination theory. It also identified the role of customer expertise in shaping customers’ learning processes. Moreover, this study examined customer learning as a novel way to enhance customer satisfaction.