bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol - Ascertaining the career Intentions of UK Medical Students (AIMS) post-graduation: a cross-sectional survey
Authors: Ferreira Tomas , Collins Alexander M. , Horvath Rita 
Published: January 2023

AbstractBackgroundAmong doctors in the United Kingdom, there is growing sentiment regarding delaying specialist training, emigrating to practice medicine abroad, or leaving the profession altogether. This may have significant implications for the future of the profession in the UK. The extent to which this sentiment is also present in the medical student population is unknown.MethodsThe AIMS study is a national, multi-institution, cross-sectional study of all medical students at all medical schools in the United Kingdom. It will be administered via an online questionnaire and disseminated through a collaborative network recruited for this purpose. Our primary outcome is to determine current medical students’ career intentions after graduation and upon completing the Foundation Programme, and to establish the motivations behind these intentions. Secondary outcomes include determining which, if any, demographic factors alter the propensity to pursue different career paths available to a medical graduate, determining which specialties medical students plan on pursuing and understanding current views on the prospect of working in the National Health Service (NHS). Both quantitative analysis and thematic analysis will be used.DiscussionDoctors’ career satisfaction within the NHS is a well-researched topic, however, there is a shortage of high-powered studies able to offer insight into medical students’ outlook on their future careers. It is anticipated that the results from this study will bring clarity to this issue. Identified areas of improvement in medical training or within the NHS could be targeted to improve doctors’ working conditions and help retain medical graduates. Results may also aid future workforce planning efforts.Trial RegistrationNot Applicable.
Covid-19 affects taste independently of smell: results from a combined chemosensory home test and online survey from a global cohort (N=10,953)
Authors: Nguyen Ha , Albayay Javier , Höchenberger Richard , Bhutani Surabhi , Boesveldt Sanne , Busch Niko A. , Croijmans Ilja , Cooper Keiland W. , de Groot Jasper H. B. , Farruggia Michael C. , Fjaeldstad Alexander W. , Hayes John E. , Hummel Thomas , Joseph Paule V. , Laktionova Tatiana K. , Thomas-Danguin Thierry , Veldhuizen Maria G. , Voznessenskaya Vera V. , Parma Valentina , Pepino M. Yanina , Ohla Kathrin 
Published: January 2023

AbstractPeople often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with ten household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 3,356 self-reported a positive and 602 a negative COVID-19 diagnosis (COVID+ and COVID-, respectively); 1,267 were awaiting test results (COVID?). The rest reported no respiratory illness and were grouped by symptoms: sudden smell/taste changes (STC, N=4,445), other symptoms excluding smell or taste loss (OthS, N=832), and no symptoms (NoS, N=416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% Confidence Interval (CI): 15-28%), 47% in smell (95%-CI: 37-56%), and 17% in oral irritation (95%-CI: 10-25%) intensity. In all groups, perceived intensity of smell (r=0.84), taste (r=0.68), and oral irritation (r=0.37) was correlated. Our findings suggest most reports of taste dysfunction with COVID-19 were genuine and not due to misinterpreting smell loss as taste loss (i.e., a classical taste-flavor confusion). Assessing smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and helps to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests.
EEF2-inactivating toxins engage the NLRP1 inflammasome and promote epithelial barrier disruption uponPseudomonasinfection
Authors: Pinilla Miriam , Mazars Raoul , Vergé Romain , Gorse Leana , Santoni Karin , Robinson Kim Samirah , Toh Gee Ann , Prouvensier Laure , LeonIcaza Stephen Adonai , Hessel Audrey , Péricat David , Murris Marlène , Henras Anthony , Buyck Julien , Cougoule Céline , Ravet Emmanuel , Zhong Franklin L. , Planès Rémi , Meunier Etienne 
Published: January 2023

ABSTRACTThe intracellular inflammasome complex have been implicated in the maladaptive tissue damage and inflammation observed in chronicPseudomonas aeruginosainfection. Human airway and corneal epithelial cells, which are critically altered during chronic infections mediated byP. aeruginosa, specifically express the inflammasome sensor NLRP1. Here, together with a companion study, we report that the NLRP1 inflammasome detects Exotoxin A (EXOA), a ribotoxin released byP. aeruginosaType 2 Secretion System (T2SS) during chronic infection. Mechanistically, EXOA-driven Eukaryotic Elongation Factor 2 (EEF2) ribosylation and covalent inactivation promotes ribotoxic stress and subsequent NLRP1 inflammasome activation, a process shared with other EEF2-inactivating toxins, Diphtheria Toxin and Cholix Toxin. Biochemically, irreversible EEF2 inactivation triggers ribosome stress-associated kinases ZAKα- and P38-dependent NLRP1 phosphorylation and subsequent proteasome-driven functional degradation. Finally, Cystic Fibrosis cells from patients exhibit exacerbated P38 activity and hypersensitivity to EXOA-induced ribotoxic stress-dependent NLRP1 inflammasome activation, a process inhibited by the use of ZAKα inhibitors. Altogether, our results show the importance ofP. aeruginosavirulence factor EXOA at promoting NLRP1-dependent epithelial damage and identify ZAKα as a critical sensor of virulence-inactivated EEF2.KEY POINTSP. aeruginosainduces NLRP1-dependent pyroptosis in human corneal and nasal epithelial cellsP. aeruginosaExotoxin A (EXOA) and other EEF2-inactivating bacterial exotoxins activate the human NLRP1 inflammasomeEEF2 inactivation promotes ribotoxic stress response and ZAKα kinase-dependent NLRP1 inflammasome activation.Bronchial epithelial cells from Cystic Fibrosis patients show extreme sensitivity to ribotoxic stress-dependent NLRP1 inflammasome activation in response to Exotoxin AP38 and ZAKα inhibition protects Cystic Fibrosis epithelial cell from EXOA-induced pyroptosis
Conditional, tissue-specific CRISPR/Cas9 vector system in zebrafish reveal the role of neuropilin-1b in heart regeneration
Authors: Angom Ramcharan Singh , Wang Ying , Wang Enfeng , Dutta Shamit , Mukhopadhyay Debabrata 
Published: January 2023

AbstractCRISPR/Cas9 technology-mediated genome editing has significantly improved the targeted inactivation of genesin vitroandin vivoin many organisms. In this study, we have reported a novel CRISPR-based vector system for conditional tissue-specific gene ablation in zebrafish. Specifically, the cardiac-specificcardiac myosins light chain 2 (cmlc2) promoter drives Cas9 expression to silence theneuropilin-1(nrp1) gene in cardiomyocytes in a heat-shock inducible manner. This vector system establishes a unique tool to regulate the gene knockout in both the developmental and adult stages and hence, widens the possibility of loss-of-function studies in zebrafish at different stages of development and adulthood. Using this approach, we investigated the role of neuropilin isoformsnrp1aandnrp1bin response to cardiac injury and regeneration in adult zebrafish hearts. We observed that both the isoforms (nrp1aandnrp1b) are upregulated after the cryoinjury. Interestingly, thenrp1b-knockout significantly altered heart regeneration and impaired cardiac function in the adult zebrafish, demonstrated by reduced heart rate (ECG), ejection fractions, and fractional shortening. In addition, we show that the knockdown ofnrp1bbut notnrp1ainduces activation of the cardiac remodeling genes in response to cryoinjury. To our knowledge, this is the first study where we have reported a heat shock-mediated conditional knockdown ofnrp1aandnrp1bisoforms using CRISPR/Cas9 technology in the cardiomyocyte in zebrafish, and furthermore have identified a crucial role fornrp1bisoform in zebrafish cardiac remodeling and eventually heart function in response to injury.
Coordinated multiple cellular processes in tongue development
Authors: Kawasaki Maiko , Kawasaki Katsushige , Sari Finsa Tisna , Kudo Takehisa , Nihara Jun , Kitamura Madoka , Nagai Takahiro , Utama Vanessa , Ishida Yoko , Meguro Fumiya , Nishimura Takayuki , Kogure Yuan , Maruyama Satoshi , Tanuma Jun-ichi , Kakihara Yoshito , Maeda Takeyasu , Ghafoor Sarah , Khonsari Roman H. , Corre Pierre , Sharpe Paul T. , Cobourne Martyn T. , Franco Brunella , Ohazama Atsushi 
Published: January 2023

AbstractDysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested migration of other mesoderm-derived cells and CNCC. Some aberrant CNCC abnormally differentiated into osteoblasts due to the lack of Hh signal, which migrated into tongue to form ectopic bone. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations in CNCC to disturb cellular processes which were disrupted in mutant mice. Thus, tongue development requires coordinated multiple cellular processes (cell-cell contact, migration and differentiation). Our results provide hints for possible future treatment in ciliopathies.
Dissecting the basis for differential substrate specificity of ADAR1 and ADAR2
Authors: Zambrano-Mila Marlon S. , Witzenberger Monika , Uzonyi Anna , Nir Ronit , Ben-Aroya Shay , Levanon Erez Y. , Schwartz Schraga 
Published: January 2023

AbstractMillions of adenosines are deaminated throughout the transcriptome by ADAR1 and ADAR2, modulating double-stranded RNA (dsRNA) immunogenicity and recoding mRNA. The high variability in the susceptibility of different adenosines to editing begs the question of what are the determinants of substrate specificity. Here, we systematically monitor how secondary structure modulates ADAR2 vs ADAR1 substrate selectivity, on the basis of systematic probing of thousands of synthetic sequences transfected into ADAR1-deleted cell lines exogenously expressing either ADAR2 or ADAR1. In both cases, structural disruptions gave rise to symmetric, strand-specific induced editing at a fixed offset, but of varying length: -26 nt for ADAR2, and -35 nt for ADAR1. We dissect the basis for the differences in offset between ADAR1 and ADAR2 via diverse mutants, domain-swaps, and ADAR evolutionary homologs, and reveal that it is encoded by the differential RNA binding domain architecture. We demonstrate that this offset-enhanced editing can allow an improved design of ADAR2-recruiting therapeutics, with proof-of-concept experiments suggestive of increased on-target and potentially decreased off-target editing. Our findings provide novel insight into the determinants guiding ADAR2 substrate selectivity and into the roles of the RNA binding domains of ADAR1 and ADAR2 in mediating differential targeting, and should facilitate the design of improved ADAR-recruiting therapeutics.
Microtubule-associated proteins MAP7 and MAP7D1 promote DNA double strand break repair in the G1 cell cycle phase
Authors: Dullovi Arlinda , Ozgencil Meryem , Rajvee Vinothini , Tse Wai Yiu , Cutillas Pedro R , Martin Sarah A , Hořejší Zuzana 
Published: January 2023

SummaryThe DNA-damage response is a complex signalling network that guards genomic integrity. The microtubule cytoskeleton is involved in the repair of DNA double-strand breaks; however, little is known about which cytoskeleton-related proteins are involved in DNA repair and how. Using quantitative proteomics, we discovered that microtubule associated proteins MAP7 and MAP7D1 interact with several DNA repair proteins including DNA double-strand break repair proteins RAD50, BRCA1 and 53BP1. We observed that downregulation of MAP7 and MAP7D1 leads to increased phosphorylation of p53 after γ- irradiation. Moreover, we determined that the downregulation of MAP7D1 leads to a strong G1 arrest and that the downregulation of MAP7 and MAP7D1 in cells arrested in G1 negatively affects DNA repair, recruitment of RAD50 to chromatin and localisation of 53BP1 to the sites of damage. These findings describe for the first time a novel function of MAP7 and MAP7D1 in cell cycle regulation and cellular response to DNA double-strand breaks.
Early root phenotyping in sweetpotato (Ipomoea batatasL.) uncovers insights into root system architecture variability
Authors: Duque Luis O. 
Published: January 2023

AbstractBackgroundWe developed a novel, non-destructive, expandable, ebb and flow soilless phenotyping system to deliver a capable way to study early root system architectural traits in stem derived adventitious roots of sweetpotato (Ipomoea batatasL.). The platform was designed to accommodate up to 12 stems in a relatively small area for root screening. This platform was designed with inexpensive materials and equipped with an automatic watering system.MethodsTo test this platform, we designed a screening experiment for root traits using two contrasting sweetpotato genotypes, ‘Covington’ and ‘NC10-275’. We monitored and imaged root growth, architecture, and branching patterns every five days up to 20 days.ResultsWe observed significant differences in both architectural and morphological root traits for both genotypes tested. After 10 days, root length, surface root area, and root volume were higher in ‘NC10-275’ compared to ‘Covington’. However, average root diameter and root branching density were higher in ‘Covington’.ConclusionThese results validated the effective and efficient use of this novel root phenotyping platforming for screening root traits in early stem-derived adventitious roots. This platform allowed for monitoring and 2D imaging root growth over time with minimal disturbance and no destructive root sampling. This platform can be easily tailored for abiotic stress experiments, permit root growth mapping and temporal and dynamic root measurements of primary and secondary adventitious roots. This phenotyping platform can be a suitable tool for examining root system architecture and traits of clonally propagated material for a large set of replicates in a relatively small space.SubjectsPlant Science, Agricultural Science
Understanding networking dynamics in born global firms’ internationalization: balancing the mix of physical and virtual networking in B2B markets
Authors: Tobiassen Anita Ellen , Pettersen Inger Beate 
Published: January 2023

Purpose
This paper aims to explore how born global firms (BGs) in business to business (B2B) markets balance the mix of physical and virtual networking through social media to gain access to resources throughout their internationalization process. Further, the research seeks to understand these firms’ network dynamics in their continual adaptation to changing resource requirements throughout the internationalization process.

Design/methodology/approach
This research adopts a multiple case study approach based on in-depth interviews with founders and key informants in BGs in the software industry, supplemented with extensive secondary data.

Findings
Results reveal that networking through social media is efficient and can be used to access vital resources and to build trusting relationships in a B2B context, yet in combination with physical networking. This research found several boundary conditions related to the mix of physical and virtual networking, i.e. the relationship culture in the industry, strategic importance of partner/customer, type of product complexity and managers’ perceptions of the usefulness of social media in a B2B context. These conditions could evolve over time.

Originality/value
This research contributes to enhanced understanding of how resource-constrained BGs balance the mix of physical and virtual networking through social media in a B2B context, influenced by boundary conditions, achieving a network dynamic to advance internationalization.
Using social media to create real time online networks of school leaders
Authors: Miller Dustin , Tilak Shantanu , Evans Marvin , Glassman Michael 
Published: January 2023

PurposeSchool leaders work in a fast-paced job that requires critical decision-making, often without the luxury of time. Additionally, problems may be new and leave school leaders feeling isolated and ill-equipped to adequately address situations. To that end, this study introduced the use of Reddit, a social media platform, to connect school leaders with colleagues who can provide real time support when pressing issues arise.Design/methodology/approachThis mixed methods study used hierarchical regressions, linguistic analysis of online discussions and qualitative analysis of focus group interviews to understand if online collective efficacy led to higher technology acceptance and principal efficacy for school leaders when discussing work-related and sociocultural issues online.FindingsFindings revealed that (1) school leaders build collective efficacy among their peers and are willing to engage more freely in online communities, (2) school leaders are willing to embrace the use of technology if provided time and exposure to such communities and (3) seasoned school leaders are more likely to interact openly with colleagues in online discussions versus their less-experienced peers on how online communities can support school leaders in challenging, ever-changing aspects of their work.Originality/valueWe recommend both school district and educational leadership professional associations consider creating easily accessible online communities as spaces where school leaders have opportunities to engage confidentially with their colleagues over important work-related issues. Future studies should also continue to investigate the impact of school leader online communities through both quantitative and qualitative methodologies.
The role of narcissism in entrepreneurial activity: a systematic literature review
Authors: Burger Bastian , Kanbach Dominik K. , Kraus Sascha 
Published: January 2023

Purpose
Recent years have seen a meteoric rise in the study of narcissism in entrepreneurship, although little consolidation has occurred in this area. The purpose of this paper is the development of an integrative framework to harmonise the academic discussion and serve as a structured foundation for future research.

Design/methodology/approach
The authors conducted an artificial intelligence-aided, structured literature review focused on content analysis of concepts and contexts to map out current findings and research gaps in startup narcissism research.

Findings
According to the findings of this study, narcissistic tendencies have the potential to positively influence startup success early on in an entrepreneur's journey, but after a certain point in the process, the influence of narcissism on success becomes predominantly negative.

Research limitations/implications
The research field is currently not very harmonised regarding research measures, research subjects and key research terms. Further research must use a standardised approach to add value to the research body.

Practical implications
Narcissism is a two-sided sword for founders. In the early stages of a company, many of the founder’s tasks can benefit from narcissistic tendencies. In the later stages of a company, that might shift to overwhelmingly negative effects of narcissism.

Originality/value
Methodically, this study is the first one to establish an artificial intelligence component to add value to the results of a review paper to the best of the authors’ knowledge. The results of this study provide a clear framework of entrepreneurial intention, entrepreneurial activity and entrepreneurial performance to give researchers the opportunity of a more differentiated way of organising work.
Biologics in pediatric psoriasis
Authors: Wang Wen‐Ming , Jin Hong‐Zhong 
Published: January 2023

AbstractPsoriasis is a chronic inflammatory skin disorder with a chronic relapsing course. Biologics have revolutionized the treatment of adult psoriasis with higher efficacy and favorable safety profile. Recently, more studies have focused on the use of biologics in pediatric psoriasis, and several biologics have been approved for use therein. This review is divided into two sections: the first part focuses on real‐world studies on the use of biologics in pediatric psoriasis and the second part summarizes the findings of other clinical trials related to biologics in pediatric psoriasis. Case reports have been excluded from this review. Several biologics were used for treating pediatric psoriasis and the efficacy is encouraging. According to the studies included in this review, anti‐IL‐12/23 and anti‐IL‐17A for treating pediatric psoriasis might have a better efficacy than anti‐TNF‐α, but more data are needed.
Harry and Meghan Shine a Light on Monarchy, and its Demands
Authors: Hazell Robert 
Published: January 2023

AbstractThe Netflix documentary Harry and Meghan conveys the impression that they have been uniquely victimised. But the difficulties they have faced are shared by all the royal families of Europe. It is monarchy which is unique, in the extraordinary demands which it makes of close members of the royal family. They lack freedoms which ordinary citizens take for granted: privacy; free choice of career; freedom of speech; freedom to marry whom they like; freedom of religion; and freedom to travel. It is not surprising if individual royals wish to escape the gilded cage. But as Harry and Meghan have shown, opting out is easier said than done.