bluuebunny/crossref_metadata_2025 huggingface dataset:
Intergovernmental organizations in the face of the Covid-19 pandemic: Organizational behaviour in crises and under uncertainty
Authors: Ulybina Olga , Ferrer Laia Pi , Alasuutari Pertti
Published: June 2022

When Covid-19 broke out, many interpreted it as a crisis that would lead to fundamental changes in different areas of life. The article aims to assess whether this also applies to intergovernmental organizations (IGOs). By analysing the websites of a sample of intergovernmental organizations, we ask: How did the Covid-19 pandemic affect the behaviour of intergovernmental organizations? How can one explain this behaviour of intergovernmental organizations in response to such a major exogenous event as the Covid-19 pandemic? How can the Covid-19 pandemic be best conceptualized in terms of its impact on intergovernmental organizations? We show that the responses of intergovernmental organizations to the Covid-19 pandemic had two important features: (a) intergovernmental organizations responded in a synchronized way, and (b) the pandemic triggered wide-spread non-major adaptations to the changed environment, providing opportunities for legitimation work and minor repackaging of existing activities, but has not led to noticeable transformational change in organizations’ activities. We argue that the observed intergovernmental organization’s responses can be explained partly from rational-choice perspective and partly from sociological institutionalist perspective. Given our data, we argue that the pandemic can be conceptualized as an uncertainty shock, in terms of its impact on intergovernmental organizations.
Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain
Authors: Karam Marie , Janbon Hadrien , Malkinson Guy , Brunet Isabelle
Published: June 2022

Brain perivascular macrophages (PVMs) are border-associated macrophages situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, we used LYVE-1 to identify PVMs in the mouse brain using brain-tissue sections and cleared whole-brains to learn about how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in different patterns and proportions depending on vessel diameter or arterio-venous differentiation. LYVE-1+ PVMs relate to blood vessels in a brain-region-dependent manner. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimer’s Disease proportionally to beta-amyloid deposits. In conclusion, our results reveal unexpected heterogeneity and dynamics of LYVE-1+ PVMs, with selective coverage of brain vasculature, compatible with potential unexplored roles for this population of PVMs in postnatal development, and in regulating brain functions in steady-state and disease conditions.
RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses
Authors: Zhang Liyin , Rashad Sherif , Zhou Yuan , Niizuma Kuniyasu , Tominaga Teiji
Published: June 2022

RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.
Dedifferentiated liposarcoma (DDLPS) in the rectum: A case report
Authors: Li Wei , Liu Qi , Mu Yu , Zhang Kai , Liu Tongjun
Published: June 2022

Dedifferentiated liposarcoma (DDLPS) is a rare subtype of liposarcoma with a poor prognosis. This current case report describes a rectal DDLPS in a 68-year-old Chinese male that presented with lower abdominal pain and weight loss. Computed tomography and magnetic resonance imaging were undertaken to evaluate the tumour. The patient underwent radical resection of the rectal tumour, sigmoid colostomy and partial ureterectomy. The tumour was positive for mouse double minute 2 by immunohistochemistry. The patient healed well but refused chemotherapy postoperatively for economic reasons. The tumour recurred and metastasized 4 weeks after the operation. After relevant treatment, the patient's condition deteriorated and he died of shock, metabolic acidosis, hyperlactataemia and acute renal failure. The case report also reviews the literature in terms of the clinical diagnosis, treatment and pathological characteristics of rectal DDLPS with the aim of improving the level of diagnosis and treatment.
Deep Learning Model for Crash Injury Severity Analysis Using Shapley Additive Explanation Values
Authors: Kang Yashu , Khattak Aemal J.
Published: June 2022

Analysis of traffic crash and associated data provides insights and assists with identification of cause-and-effect relationships with crash probabilities and outcomes. This study utilized eight years of police-reported Nebraska crash data using a deep neural network (DNN) to model crash injury severity outcomes. Prediction performances and model interpretability were examined. The developed DNN excelled in prediction accuracy, precision, and recall but was computationally intensive compared with a baseline multinomial logistic regression model. While the lack of interpretability power of deep learning models limits their usage, the adoption of SHapley Additive exPlanation (SHAP) values was an improvement. Conclusions drawn from the DNN model are generally consistent with the estimated baseline model. For instance, the variable total number of pedestrians was found significant in both scenarios of the multinomial logit model indicating a strong relationship with more severe crash injury outcomes. It was also found important in all three sets of parameters in DNN. SHAP values also allow in-depth analysis of prediction results on a single observation, such as the variable crash type (same direction sideswipe) contributing to classifying a single observation as property damage only. These findings are beneficial for making more informed transportation safety-related decisions.
Influence of Demographic Disparities on Seat Belt Compliance in an Urban Area (Washington, DC)
Authors: Arhin Stephen A. , Manandhar Babin , Anderson Melissa
Published: June 2022

This study evaluated the potential influence of demographic factors on seat belt compliance rates in an urban area. Washington D.C., which is the capital of the United States, is an urban area with mixed and diverse population. The city (and all states) conducts seat belt compliance surveys annually as a requirement of the National Highway Traffic Safety Administration (NHTSA). This article used compliance rates obtained from the field for 2014 through 2020 and matched those with demographic data for the same timeframe. The demographic data for the city was obtained from the United States Census Bureau. Demographic variables including race, educational and income levels for the eight wards in Washington D.C. we extracted for analysis. Overall, seat belt compliance usage in Washington ranged from 93% to 95.7% between 2014 and 2020. Approximately 42.3% of its population are Caucasian while 43.9% are African Americans with the remaining being Asian, Hispanics and other races. In addition, seat belt usage was reported by ward. Using single factor analysis of variance, it was determined that compliance rates in the wards were not statistically influenced by race, educational level, or income level at 5% level of significance. However, when comparing yearly seatbelt compliance from 2014 to 2020, the compliance rates of 2014 versus 2019, and 2014 versus 2020 were determined to be statistically different. Seat belt use should be encouraged for everyone in all jurisdictions. The analysis shows that, in this urban area, the three demographic variables do not have any influence on the compliance rates.
Six Decades of Roadside Encroachment Modeling
Authors: Ray Malcolm H. , Carrigan Christine E.
Published: June 2022

A vehicle encroaches whenever it leaves the lanes of the traveled way and enters the roadside or median. Leaving the traveled way may result in rolling over on roadside terrain or striking a fixed object, so understanding the nature of vehicle encroachments is an important aspect of roadside design. A variety of efforts over the last 60 years have resulted in the collection of data that have been used to model encroachments. This paper summarizes these prior studies, compares the results, and presents recommendations for the best available encroachment models for use in the design of roadsides and medians.
Evaluation of Driving Behavior and Traffic Safety at a Shifting Movements Intersection
Authors: Al-Omari Ma’en Mohammad Ali , Abdel-Aty Mohamed
Published: June 2022

Unconventional intersection designs have been proposed for their theoretical potential to enhance traffic safety and operation simultaneously as a result of reducing the number of conflict points and signal phases. However, this has only been achieved with a very limited range of intersection designs which have a very low number of conflict points and under certain traffic conditions. For example, restricted crossing U-turn (RCUT) intersection, which has the lowest number of conflict points among other proposed intersection designs, has operational advantages at extremely unbalanced traffic volumes. Shifting movements (SM) intersection design, which has the same number of conflict points as the RCUT intersection, has been proposed to replace the RCUT implementation at intersections with medium to high minor traffic volumes. It was proven that SM outperforms an RCUT intersection which has medium to high minor traffic volumes in average delay and throughputs. This study aimed to investigate the safety aspects of this intersection design by utilizing the driving simulator. The effectiveness of using infrastructure-to-vehicle (I2V) communication for mitigating confusion at unconventional intersections was also investigated in the study. The results indicated that RCUT and SM intersections have similar safety performance and crossing them is completed with less risk than crossing the conventional intersection. However, there is a need to improve drivers’ knowledge about the SM intersection, especially with regard to the major left-turn movement. Most participants found that using I2V communication was helpful in understanding unconventional movement patterns.
The Impact of Spirituality and Religious Practice on Senior Living Leader Career Resilience
Authors: Myers Dennis R. , Rogers Robin K. , Garrison Brianna V. , Singletary Jon E. , Groce Haley
Published: June 2022

Experienced senior living leaders (SLLs) report the impact of spirituality and religious practice on SLL role adaptation and continuation. The sample included 18 SLLs in 18 skilled care settings representing public, non-profit, and for-profit types of incorporation, with oversampling of for-profit facilities. The average years of SLL experience was 24 years. In-depth interviews were examined through a thematic analysis approach using Excel software. Seventy-eight percent described how a higher power, religious beliefs, and faith practices were associated with their role. Their narratives revealed three major themes: Frame (calling and pre-dispositional spiritual beliefs and religious practices), Role Performance (how spirituality informed SLL administrative practice), and Benefits (perceived rewards of adherence to spiritual beliefs and practices). Further analysis of the three themes produced codes that added greater specification for each theme. Implications provided for normalizing the spirituality and work-life intersect and infusing ethical integration of spirituality and work-life in SLL educational programs.
Decolonizing children’s agency: Perspectives of children in an Urdu-speaking Bihari camp in Bangladesh
Authors: Afroze Jiniya
Published: June 2022

Drawing on nine months of ethnographic fieldwork with children and adults in an Urdu-speaking Bihari camp in Bangladesh, this paper critically explores the ambiguities, nuances, and messiness of children’s everyday lives and the complex ways in which children negotiate and exercise their agency. With a critical and reflexive analysis of children’s experiences in everyday lives, this paper aims to make a meaningful contribution to the knowledge of childhood and children’s everyday lives in the majority world context by focusing on an under-researched minority within Bangladesh.
Homomercracia. The commodification of sexual and gender diversity in Chilean democracy
Authors: León-Donoso Abelardo
Published: June 2022

The approval of the anti-discrimination law in 2012 and the Civil Union Agreement in 2015 in Chile offer a sharp contrast to a society that has historically repressed LGBTQ people. However, it is not clear why and how public discourse shifted within this conventional heteronormative context. To understand this, I analyze samples taken from the Chilean print and digital media using Critical Discourse Analysis. I propose the concept of Homomercracia: a portmanteau from the Spanish words for homosexuality, market, and democracy, which describes the instrumentalization of political rhetoric related to sexual and gender diversity. I conclude that social and political changes in Chilean society have helped to catalyze these recent advances.
Operationalising ‘toxicity’ in the manosphere: Automation, platform governance and community health
Authors: Trott Verity , Beckett Jennifer , Paech Venessa
Published: June 2022

Social media platforms have been struggling to moderate at scale. In an effort to better cope with content moderation discussion has turned to the role that automated machine-learning (ML) tools might play. The development of automated systems by social media platforms is a notoriously opaque process and public values that pertain to the common good are at stake within these often-obscured processes. One site in which social values are being negotiated is in the framing of what is considered ‘toxic’ by platforms in the development of automated moderation processes. This study takes into consideration differing notions of toxicity – community, platform and societal by examining three measures of toxicity and community health (the ML tool Perspective API; Reddit’s 2020 Content Policy; and the Sense of Community Index-2) and how they are operationalised in the context of r/MGTOW – an antifeminist group known for its misogyny. Several stages of content analysis were conducted on the top posts and comments in r/MGTOW to examine how these different measures of toxicity operate. This paper provides insight into the logics and technicalities of automated moderation tools, platform governance structures, and frameworks for understanding community metrics to interrogate existing uses of ‘toxicity’ as applied to cultural or social subcommunities online. We make a distinction between two used terms: civility and toxicity. Our analysis points to a tension between current social framings and operationalised notions of ‘toxicity’. We argue that there is a clear distinction between civility and toxicity – incivility is a measure of internal perceptions of harm within a community, whereas toxicity is a measure of the capacity for social harms outside of the bounds of the community. This nuanced understanding will enable more targeted interventions to be developed to destabilise the internal conditions that make groups like r/MGTOW internally ‘healthy’ yet externally toxic.
A systematic review of the experiences of autistic young people enrolled in mainstream second-level (post-primary) schools
Authors: Horgan Finbar , Kenny Neil , Flynn Paula
Published: June 2022

Internationally, there is a growing trend towards the inclusion of autistic pupils within mainstream schools. However, concerns have been expressed regarding this policy roll-out preceding empirical evidence demonstrating effective outcomes for autistic students. Concerns have also been expressed regarding the absence of the voices of autistic pupils themselves within research and policy literature. This review seeks to synthesise evidence from qualitative studies relating to the experiences and perspectives of autistic young people enrolled in mainstream second-level or post-primary education. Searches were carried out on three bibliographic databases: Education Research Complete, Education Resources Information Centre and PsychInfo. One thousand sixty-three studies were identified through a combination of database and hand searches of which 33 met the inclusion criteria for the review. Data were synthesised using ‘thematic synthesis’ and the validity of included studies was assessed using the ‘Critical Appraisal Skills Programme’ (CASP) checklist. Thematic synthesis resulted in the development of three analytical themes: ‘Demands of mainstream placements’, ‘Social participation’ and ‘Impacts on the student’. Our analysis revealed that for many autistic young people, mainstream school is a complex and demanding social environment. Further research conducted in partnership with this cohort is essential as inclusive policy and practice continues to develop.

Lay abstract

Internationally, more autistic pupils are being educated in mainstream schools. Some people have voiced concerns that this policy roll-out is happening before examining the effective outcomes for autistic students. Concerns have also been expressed regarding a lack of the voices of autistic pupils themselves within research and policy. This study was undertaken in order to gather literature that explores the views and experiences of autistic young people in relation to their mainstream school placement at the secondary level. This study aims to summarise the existing literature and provide a new, more complete account of the school experiences of this cohort. After an extensive search, 33 studies were identified by the authors as meeting a set of inclusion criteria. All of the studies included in this review elicited the views and perspectives of at least one autistic young person regarding their mainstream secondary school placement. Upon carefully analysing these studies, the authors developed three key themes as follows: ‘Demands of mainstream placements’, ‘Social participation’ and ‘Impacts on the student’. Our analysis revealed that for many autistic young people, mainstream school is a complex and demanding social environment. Further research that prioritises the voices and perspectives of this cohort is essential as inclusive policy and practice continues to develop.
Accounting for concurrent antihyperglycemic medication changes in dietary and physical activity interventions: A focused literature review
Authors: Campbell Dennis B , Lee Olstad Dana , Donald Teagan , Campbell David JT
Published: June 2022

Aims

To summarize methods used to account for antihyperglycemic medication changes in randomized controlled trials evaluating the effect of dietary and physical activity interventions on glycemia among adults with diabetes.

Methods

Using studies included in two recently published systematic reviews of randomized controlled trials examining the glycemic effects of dietary and physical activity interventions, we evaluated how each study accounted for antihyperglycemic medication changes. Data were analyzed using summary statistics, stratified by the type of intervention studied, and each was assigned a score from 0 to 6 reflecting the strength of medication controls employed.

Results

We evaluated 22 physical activity focused and 27 dietary focused articles. Our scoring system yielded a mean concurrent medication adjustment score of 3.9/6 for the physical activity studies and a score of 1.7/6 ( p < 0.001) for the dietary studies.

Conclusions

We found that randomized controlled trials included in recent systematic reviews of physical activity and dietary interventions did not robustly account or control for changes in antihyperglycemic medications, with physical activity interventions doing so more robustly than dietary interventions. This is a threat to the validity of study findings, as observed glycemic changes may in fact be attributable to imbalances in concurrent medication adjustments between groups.
Identification of circulating lncRNA in chronic kidney disease based on bioinformatics analysis
Authors: Huang Rong , Sun Li-Jing
Published: June 2022

Chronic kidney disease (CKD) is a high mortality disease and generally remains asymptomatic in the early stages. Long non-coding RNA (lncRNA) is defined as a non-protein-coding transcript more than 200 nucleotides which participate in numerous biological processes and have been identified as novel diagnostic markers for many diseases. Detection of circulating lncRNAs is a rapidly evolving, new area of molecular diagnosis. The purpose of our research was to identify circulating lncRNA expression profiles and possible molecular mechanisms involved in CKD. Blood samples were obtained from patients with CKD and healthy volunteers, and high-throughput sequencing was performed to identify differentially expressed (DE) lncRNAs and mRNAs. DE lncRNAs and mRNAs in peripheral blood mononuclear cells (PBMCs) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to ensure the reliability and validity of RNA-seq data. Bioinformatics analysis was used to obtain biological functions and key pathways related to the pathogenesis of CKD. The interaction and co-expression functional networks for DE lncRNAs and mRNAs were also constructed. Our data showed that of the 425 DE lncRNAs detected, 196 lncRNAs were upregulated, while that of 229 lncRNAs were downregulated. A total of 433 DE mRNAs were identified in patients with CKD compared to healthy individuals. GO analysis revealed that DE lncRNAs were highly correlated with binding and pathway regulation. KEGG analysis suggested that DE lncRNAs were obviously enriched in regulatory pathways, such as antigen processing and presentation. We successfully constructed a potential DE lncRNA-mRNA co-expression network and analyzed the target genes of DE lncRNAs to predict cis- and trans-regulation in CKD. 100 lncRNAs that corresponded to 14 transcription factors (TFs) were identified in the TF-lncRNA binary network. Our findings on the lncRNA expression profiles and functional networks may help to interpret the possible molecular mechanisms implied in the pathogenesis of CKD; the results demonstrated that lncRNAs could potentially to be used as diagnostic biomarkers in CKD.
Hybrid Repair of a Persistent Sciatic Artery Aneurysm
Authors: de Boer Madeleine , Joseph Simon , Shiraev Timothy , Boyle Richard , Dubenec Steven
Published: June 2022

Persistent sciatic arteries are rare congenital abnormalities, with an incidence between .01-.6%. Whilst most patients with the pathology are asymptomatic during their younger years, up to 48% of patients will suffer aneurysmal degeneration of the persistent sciatic artery and present with claudication or lower limb ischaemia (from distal embolisation of mural thrombus). Due to the rare nature of persistent sciatic artery aneurysms, optimal management of the pathology is yet to be determined. Both endovascular and open techniques have been described in the management of this pathology, however hybrid management approaches are reported infrequently. The authors present a case of a persistent sciatic artery aneurysm successfully treated in a 69-year-old male utilising a hybrid approach with a femoropopliteal bypass (below knee), Amplatzer plug occlusion of the aneurysm and subsequent resection of the aneurysm.
Social Realism in Red Orchestra 2 (2011)
Authors: Tvorun-Dunn Maxim
Published: June 2022

This research seeks to add to recent critical reevaluations of Alexander Galloway’s seminal “Social Realism in Gaming” through a closer analysis of the texts by Andre Bazin and Gilles Deleuze which inform Galloway’s initial conceptions of social realism. The present work emphasizes social criticism in this esthetic movement and finds the medium specificity of games limits applicability of cinematic terms like neorealism. Procedural rhetoric and effective Brechtian alienation tactics emphasizing player-character subjectivity, can be used to effectively convey the philosophical and ideological tenants of neorealism and broader social realism. This is expanded upon using the World War Two (WWII) game Red Orchestra 2 as a case study. Ultimately this work argues against Galloway’s “congruence requirement” between players real-world contexts and game interactions, rather finding social realism in games as dependent on convergence between a game’s functional and visual rhetoric.
Insights from investigating early childhood ebooks on literacy, cognitive development, and social and emotional learning outcomes
Authors: Farber Matthew , Merchant William
Published: June 2022

Researchers were invited to investigate the effectiveness of bibliotherapeutic electronic books, or ebooks, social and emotional learning (SEL) digital platform in afterschool sites in a large school district situated in the Rocky Mountain region of the United States. This study was not particular to the platform’s efficacy; instead, we sought to explore how bibliotherapeutic ebooks can boost literacy, cognition, and SEL skills in young children. Researchers used a quasi-experimental design with nonequivalent treatment/control groups. Groups were assigned at the site level with individual students as the unit of analysis. Student data on literacy, cognitive ability, and SEL outcomes were collected pre-treatment and post-treatment. The researchers found no significant change in the studied groups. Upon digging deeper into SEL outcomes, researchers uncovered an invisible problem: the school district’s state-mandated measurement suite did not neatly map or align to the constructs within the afterschool curriculum for SEL. Interpretations and implications, including how districts define and assess SEL, are included in the discussion.
Mediatization in Times of Pandemic: How German Grassroots Sports Clubs Employed Digital Media to Overcome Communication Challenges During COVID-19
Authors: Schallhorn Christiana , Nölleke Daniel , Sinner Philip , Seeger Christof , Nieland Jörg-Uwe , Horky Thomas , Mehler Katja
Published: June 2022

The COVID-19 pandemic has had a major impact on all societal domains, including sports. Social distancing measures and the closure of sports facilities posed especially severe challenges for grassroots sports clubs, which thrive on joint activities and member social contact. Drawing on mediatization theory, the study examines the communication challenges faced by grassroots sports clubs and the perceived potential of digital media to overcome these obstacles during and beyond the pandemic. Based on in-depth interviews with 32 club officials of German grassroots sports clubs, the study identified ongoing uncertainty about COVID-19 regulations, preserving members’ sense of belonging during social distancing, and involving everyone in formal processes as the major communication challenges. While most of the interviewees valued the potential of digital media to address these challenges, they acknowledged that the benefits of digital media for individual members would depend on their skill, motivation, and concerns, as well as on the availability of digital infrastructure. For that reason, digital media were not considered a substitute for face-to-face social contact or sporting activity but were seen to extend opportunities for communication and training. More generally, these findings raise new questions about the relationship between mediatization and social cohesion.
Enlarging Post-Traumatic Forehead Mass in Liver Failure: A Case Report and Proposed Algorithm for the Treatment of Pseudoaneurysms of the Superficial Temporal Artery
Authors: Aminzada Amir , McNab Andrea , Ferraro Jennifer J. , Seu Michelle , Tragos Christina
Published: June 2022

Pseudoaneurysms of the superficial temporal artery are an exceedingly rare occurrence, and as such, there is limited data regarding their optimal management. In this paper we describe a case of post-traumatic superficial temporal artery pseudoaneurysm in a patient with alcohol-induced cirrhosis, treated with a combination of interventional radiologic and surgical methods. We also perform a review of the literature to identify the pathophysiology, diagnostic, and current treatment modalities of these entities. Finally, we propose a treatment algorithm for the optimal management of superficial temporal artery pseudoaneurysms under various circumstances.
Evaluation of the putative lymphoma-associated point mutation D427H in the STAT3 transcription factor
Authors: Behrendsen Lena Sophie , Menon Priyanka Rajeev , Khan Muhammad Jawad , Gregus Anke , Wirths Oliver , Meyer Thomas , Staab Julia
Published: June 2022

Background

Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that promotes cell proliferation and immunomodulation in untransformed cells and maintains stemness of transformed cells, facilitating invasion and metastasis. Numerous point mutations in the STAT3 protein have been identified that drive malignancy in various tumor entities. The missense mutation D427H localized in the STAT3 DNA-binding domain has been previously reported in patients with NK/T cell lymphomas. To assess the biological activity of this missense mutation, we compared the STAT3-D427H mutant to wild-type (WT) protein as well as the known hyper-active mutant F174A.

Results

Although previously reported as an activating mutation, the STAT3-D427H mutant neither showed elevated cytokine-induced tyrosine phosphorylation nor altered nuclear accumulation, as compared to the WT protein. However, the D427H mutant displayed enhanced binding to STAT-specific DNA-binding sites but a reduced sequence specificity and dissociation rate from DNA, which was demonstrated by electrophoretic mobility shift assays. This observation is consistent with the phenotype of the homologous E421K mutation in the STAT1 protein, which also displayed enhanced binding to DNA but lacked a corresponding increase in transcriptional activity.

Conclusions

Based on our data, it is unlikely that the D427H missense mutation in the STAT3 protein possesses an oncogenic potential beyond the WT molecule.
The evolution of vitamin C biosynthesis and transport in animals
Authors: Duque Pedro , Vieira Cristina P. , Bastos Bárbara , Vieira Jorge
Published: June 2022

Background

Vitamin C (VC) is an indispensable antioxidant and co-factor for optimal function and development of eukaryotic cells. In animals, VC can be synthesized by the organism, acquired through the diet, or both. In the single VC synthesis pathway described in animals, the penultimate step is catalysed by Regucalcin, and the last step by l-gulonolactone oxidase (GULO). The GULO gene has been implicated in VC synthesis only, while Regucalcin has been shown to have multiple functions in mammals.

Results

Both GULO and Regucalcin can be found in non-bilaterian, protostome and deuterostome species. Regucalcin, as here shown, is involved in multiple functions such as VC synthesis, calcium homeostasis, and the oxidative stress response in both Deuterostomes and Protostomes, and in insects in receptor-mediated uptake of hexamerin storage proteins from haemolymph. In Insecta and Nematoda, however, there is no GULO gene, and in the latter no Regucalcin gene, but species from these lineages are still able to synthesize VC, implying at least one novel synthesis pathway. In vertebrates, SVCT1, a gene that belongs to a family with up to five members, as here shown, is the only gene involved in the uptake of VC in the gut. This specificity is likely the result of a subfunctionalization event that happened at the base of the Craniata subphylum. SVCT-like genes present in non-Vertebrate animals are likely involved in both VC and nucleobase transport. It is also shown that in lineages where GULO has been lost, SVCT1 is now an essential gene, while in lineages where SVCT1 gene has been lost, GULO is now an essential gene.

Conclusions

The simultaneous study, for the first time, of GULO, Regucalcin and SVCTs evolution provides a clear picture of VC synthesis/acquisition and reveals very different selective pressures in different animal taxonomic groups.
Cultivar-specific markers, mutations, and chimerisim of Cavendish banana somaclonal variants resistant to Fusarium oxysporum f. sp. cubense tropical race 4
Authors: Hou Bo-Han , Tsai Yi-Heng , Chiang Ming-Hau , Tsao Shu-Ming , Huang Shih-Hung , Chao Chih-Ping , Chen Ho-Ming
Published: June 2022

Background

The selection of tissue culture–derived somaclonal variants of Giant Cavendish banana (Musa spp., Cavendish sub-group AAA) by the Taiwan Banana Research Institute (TBRI) has resulted in several cultivars resistant to Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), a destructive fungus threatening global banana production. However, the mutations in these somaclonal variants have not yet been determined. We performed an RNA-sequencing (RNA-seq) analysis of three TBRI Foc TR4–resistant cultivars: ‘Tai-Chiao No. 5’ (TC5), ‘Tai-Chiao No. 7’ (TC7), and ‘Formosana’ (FM), as well as their susceptible progenitor ‘Pei-Chiao’ (PC), to investigate the sequence variations among them and develop cultivar-specific markers.

Results

A group of single-nucleotide variants (SNVs) specific to one cultivar were identified from the analysis of RNA-seq data and validated using Sanger sequencing from genomic DNA. Several SNVs were further converted into cleaved amplified polymorphic sequence (CAPS) markers or derived CAPS markers that could identify the three Foc TR4–resistant cultivars among 6 local and 5 international Cavendish cultivars. Compared with PC, the three resistant cultivars showed a loss or alteration of heterozygosity in some chromosomal regions, which appears to be a consequence of single-copy chromosomal deletions. Notably, TC7 and FM shared a common deletion region on chromosome 5; however, different TC7 tissues displayed varying degrees of allele ratios in this region, suggesting the presence of chimerism in TC7.

Conclusions

This work demonstrates that reliable SNV markers of tissue culture–derived and propagated banana cultivars with a triploid genome can be developed through RNA-seq data analysis. Moreover, the analysis of sequence heterozygosity can uncover chromosomal deletions and chimerism in banana somaclonal variants. The markers obtained from this study will assist with the identification of TBRI Cavendish somaclonal variants for the quality control of tissue culture propagation, and the protection of breeders’ rights.
Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity
Authors: Zielińska-Bliźniewska Hanna , Paprocka-Zjawiona Milena , Merecz-Sadowska Anna , Zajdel Radosław , Bliźniewska-Kowalska Katarzyna , Malinowska Katarzyna
Published: June 2022

Background

Chronic rhinosinusitis (CRS) is a group of heterogeneous diseases characterized by epithelial inflammation and tissue eosinophilic infiltration. IL-5, POSTN, and IL-33 are important factors that act as chemoattractants for eosinophils, and a tissue-remodeling protein positively correlated with eosinophils in blood and mediators of eosinophilic infiltration. The aim of the study was to determine the expression of IL-5, POSTN and IL-33, at the gene and protein levels, in eosinophilic CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and to correlate this expression with clinical severity.

Materials and methods

The study included 40 CRSwNP patients and 53 CRSsNP patients and 40 control subjects. The expression of IL-5, POSTN and IL-33 mRNA was determined in sinonasal mucosal samples and in nasal polyp tissue by real-time PCR. Protein levels in the serum of CRSwNP patients were measured by ELISA. Computed tomography was evaluated according to Lund–Mackay scores, and visual analog scale scores were assessed.

Results

NP tissue demonstrated significantly higher IL-5 and POSTN mRNA expression than the sinonasal tissue in the CRSsNP and CRSwNP groups. CRS groups demonstrated elevated IL-33 mRNA expression in comparison to controls irrespective of the presence of NP. No correlation was found between IL-5, POSTN and IL-33 mRNA expression and disease severity. CRSwNP group demonstrated significantly higher serum IL-5, POSTN and IL-33 protein levels than controls, and this corresponds to disease severity.

Conclusion

Serum IL-5, POSTN and IL-33 levels may be important markers for classification of eosinophilic CRSwNP patients, along with disease severity.
Comprehensive safety profile evaluation of bivalirudin in Chinese ST-segment elevation myocardial infarction patients receiving percutaneous coronary intervention: a prospective, multicenter, intensive monitoring study
Authors: Zheng Haijun , Wang Zhonghua , Li Qi , Zhao Yingxin , Liu Yin , Chen Aiming , Deng Jianping , Su Guohai
Published: June 2022

Background

This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI).

Methods

In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time.

Results

AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively.

Conclusion

Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure.
Machine learning to predict post-operative acute kidney injury stage 3 after heart transplantation
Authors: Li Tingyu , Yang Yuelong , Huang Jinsong , Chen Rui , Wu Yijin , Li Zhuo , Lin Guisen , Liu Hui , Wu Min
Published: June 2022

Background

Acute kidney injury (AKI) stage 3, one of the most severe complications in patients with heart transplantation (HT), is associated with substantial morbidity and mortality. We aimed to develop a machine learning (ML) model to predict post-transplant AKI stage 3 based on preoperative and perioperative features.

Methods

Data from 107 consecutive HT recipients in the provincial center between 2018 and 2020 were included for analysis. Logistic regression with L2 regularization was used for the ML model building. The predictive performance of the ML model was assessed using the area under the curve (AUC) in tenfold stratified cross-validation and was compared with that of the Cleveland-clinical model.

Results

Post-transplant AKI occurred in 76 (71.0%) patients including 15 (14.0%) stage 1, 18 (16.8%) stage 2, and 43 (40.2%) stage 3 cases. The top six features selected for the ML model to predicate AKI stage 3 were serum cystatin C, estimated glomerular filtration rate (eGFR), right atrial long-axis dimension, left atrial anteroposterior dimension, serum creatinine (SCr) and FVII. The predictive performance of the ML model (AUC: 0.821; 95% confidence interval [CI]: 0.740–0.901) was significantly higher compared with that of the Cleveland-clinical model (AUC: 0.654; 95% [CI]: 0.545–0.763, p < 0.05).

Conclusions

The ML model, which achieved an effective predictive performance for post-transplant AKI stage 3, may be helpful for timely intervention to improve the patient’s prognosis.
Effect of single ventricular premature contractions on response to cardiac resynchronization therapy
Authors: Merkel Eperke Dóra , Boros András Mihaly , Schwertner Walter Richárd , Behon Anett , Kovács Attila , Lakatos Bálint Károly , Gellér László , Kosztin Annamária , Merkely Béla
Published: June 2022

Background

We lack data on the effect of single premature ventricular contractions (PVCs) on the clinical and echocardiographic response after cardiac resynchronization therapy (CRT) device implantation. We aimed to assess the predictive value of PVCs at early, 1 month-follow up on echocardiographic response and all-cause mortality.

Methods

In our prospective, single-center study, 125 heart failure patients underwent CRT implantation based on the current guidelines. Echocardiographic reverse remodeling was defined as a ≥ 15% improvement in left ventricular ejection fraction (LVEF), end-systolic volume (LVESV), or left atrial volume (LAV) measured 6 months after CRT implantation. All-cause mortality was investigated by Wilcoxon analysis.

Results

The median number of PVCs was 11,401 in those 67 patients who attended the 1-month follow-up. Regarding echocardiographic endpoints, patients with less PVCs develop significantly larger LAV reverse remodeling compared to those with high number of PVCs. During the mean follow-up time of 2.1 years, 26 (21%) patients died. Patients with a higher number of PVCs than our median cut-off value showed a higher risk of early all-cause mortality (HR 0.97; 95% CI 0.38–2.48; P = 0.04). However, when patients were followed up to 9 years, its significance diminished (HR 0.78; 95% CI 0.42–1.46; P = 0.15).

Conclusions

In patients undergoing CRT implantation, lower number of PVCs predicted atrial remodeling and showed a trend for a better mortality outcome. Our results suggest the importance of the early assessment of PVCs in cardiac resynchronization therapy and warrant further investigations.
The gut microbiota composition in patients with right- and left-sided colorectal cancer and after curative colectomy, as analyzed by 16S rRNA gene amplicon sequencing
Authors: Suga Daisuke , Mizutani Hiroki , Fukui Shunsuke , Kobayashi Mayu , Shimada Yasuaki , Nakazawa Yuuichi , Nishiura Yuuki , Kawasaki Yuuya , Moritani Isao , Yamanaka Yutaka , Inoue Hidekazu , Ojima Eiki , Mohri Yasuhiko , Nakagawa Hayato , Dohi Kaoru , Takaba Kei , Wada Hideo , Shiraki Katsuya
Published: June 2022

Background

Gut pathological microbial imbalance or dysbiosis is closely associated with colorectal cancer. Although there are observable differences in molecular and clinical characteristics between patients with right- and left-sided colon cancer, differences in their gut microbiomes have not been thoroughly investigated. Furthermore, subsequent changes in microbiota status after partial colectomy remain unknown. We examined the human gut microbiota composition to determine its relationship with colon cancer and partial colon resection according to location.

Methods

Stool samples from forty-one subjects (10 in the control group, 10 in the right-sided colon cancer [RCC] group, 6 in the sigmoid colon cancer [SCC] group, 9 in the right colon resection [RCR] group and 6 in the sigmoid colon resection [SCR] group) were collected, and DNA was extracted. After terminal restriction fragment length polymorphism (T-RFLP) analysis, the samples were subjected to 16S rRNA gene amplicon sequencing, and the metabolic function of the microbiota was predicted using PICRUSt2.

Results

T-RFLP analysis showed a reduced ratio of clostridial cluster XIVa in the SCC patients and clostridial cluster IX in the RCC patients, although these changes were not evident in the RCR or SCR patients. 16S rRNA gene amplicon sequencing demonstrated that the diversity of the gut microbiota in the RCC group was higher than that in the control group, and the diversity in the SCR group was significantly higher than that in the RCR group. Principal coordinate analysis (PCoA) revealed significant differences according to the group. Analyses of the microbiota revealed that Firmicutes was significantly dominant in the RCC group and that the SCC group had a higher abundance of Verrucomicrobia. At the genus level, linear discriminant analysis effect size (LEfSe) revealed several bacteria, such as Ruminococcaceae, Streptococcaceae, Clostridiaceae, Gemellaceae, and Desulfovibrio, in the RCC group and several oral microbiomes in the SCC group. Metabolic function prediction revealed that cholesterol transport- and metabolism-related enzymes were specifically upregulated in the RCC group and that cobalamin metabolism-related enzymes were downregulated in the SCC group.

Conclusion

Gut microbial properties differ between RCC and SCC patients and between right hemicolectomy and sigmoidectomy patients and may contribute to clinical manifestations.