bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of folliculin detection by immunohistochemistry in Birt-Hogg-Dubé associated kidney tumors
Authors: Glykofridis Iris E. , van de Beek Irma , Vos Wim , Kortman Pim C. , van de Valk Paul , Freire Raimundo , Houweling Arjan C. , Wolthuis Rob M.F.
Published: June 2022

Germline inactivating mutations in folliculin (FLCN) cause Birt–Hogg–Dubé (BHD) syndrome, a rare autosomal dominant disorder predisposing to kidney tumors. Kidney tumors associated with BHD typically lack FLCN expression due to loss of heterozygosity. In this study we assessed the potential of four commercial anti-FLCN antibodies for immunohistochemistry, as currently no routine diagnostic FLCN stainings are performed in the clinic. Despite comprehensive testing, we could not identify a commercial anti-FLCN antibody that is reproducibly effective in immunohistochemical analyses of formalin-fixed paraffin-embedded tissue material. We propose that dedicated future efforts are required to develop a suitable antibody for diagnostic immunohistochemical stainings. The inclusion of FLCN expression status as part of standard renal tumor pathology may contribute to better analyses of the molecular pathology of BHD tumors and facilitate identification of BHD patients, improve their (genetic and clinical) counseling, and enable genetic testing of at risk relatives.
Multiomics analysis of the NAD+–PARP1 axis reveals a role for site-specific ADP-ribosylation in splicing in embryonic stem cells
Authors: Jones Aarin , Kraus W. Lee
Published: June 2022

The differentiation of embryonic stem cells (ESCs) into a lineage-committed state is a dynamic process involving changes in cellular metabolism, epigenetic modifications, post-translational modifications, gene expression, and RNA processing. Here we integrated data from metabolomic, proteomic, and transcriptomic assays to characterize how alterations in NAD+ metabolism during the differentiation of mouse ESCs lead to alteration of the PARP1-mediated ADP-ribosylated (ADPRylated) proteome and mRNA isoform specialization. Our metabolomic analyses indicate that mESCs use distinct NAD+ biosynthetic pathways in different cell states: the de novo pathway in the pluripotent state, and the salvage and Preiss–Handler pathways as differentiation progresses. We observed a dramatic induction of PARP1 catalytic activity driven by enhanced nuclear NAD+ biosynthesis during the early stages of mESC differentiation (e.g., within 12 h of LIF removal). PARP1-modified proteins in mESCs are enriched for biological processes related to stem cell maintenance, transcriptional regulation, and RNA processing. The PARP1 substrates include core spliceosome components, such as U2AF35 and U2AF65, whose splicing functions are modulated by PARP1-mediated site-specific ADP-ribosylation. Finally, we observed that splicing is dysregulated genome-wide in Parp1 knockout mESCs. Together, these results demonstrate a role for the NAD+–PARP1 axis in the maintenance of mESC state, specifically in the splicing program during differentiation.
The interplay of IPD and BIM: a systematic literature review
Authors: Karasu Taha , Aaltonen Kirsi , Haapasalo Harri
Published: June 2022

Purpose

Integrated project delivery (IPD) and building information modeling (BIM) have been discussed as prominent collaborative concepts in recent architecture, engineering and construction (AEC) literature, thus recommended for more advanced value creation. However, they have been studied predominantly as discrete even though they are typically highly interrelated. This study aims to enhance collaboration in AEC projects by tracing recent trends in IPD and BIM literature by making sense of trends and by exploring how their interplay has been discussed and conceptualized.

Design/methodology/approach

This systematic literature review draws on Scopus and Web of Science as the primary databases. In total, 120 academic papers and review articles were sourced. Yet, the final sample includes 71 sources from the past decade (2011–2020), focusing on both IPD and BIM.

Findings

This study identifies 11 interrelated and overlapping themes that are indicative of trends in the recent IPD and BIM literature. This research found that among the identified themes, the clusters of sustainability, transformation and increasing the competence level of staff in the AEC industry, in addition to the concept of quality, require more extensive research in the context of IPD and BIM. Additionally, this study identifies four different approaches to the interplay of IPD and BIM, indicating an absence of scholarly consistency.

Originality/value

Based on the systematic analysis of the recent literature, this study indicates that IPD and BIM have several joint fundamental cornerstones. It is evident that both concepts support the implementation of each other. The success of implementing either one is strongly related to the other. Additionally, we have not found earlier systematic literature reviews that examine the interplay between IPD and BIM in the recent AEC literature.
Generation Z domestic food tourists’ experienced restaurant innovativeness toward destination cognitive food image and revisit intention
Authors: Ding Li , Jiang Caifen , Qu Hailin
Published: June 2022

Purpose

This study aims to investigate the impacts of Generation Z (Gen Z) domestic food tourists’ perceived restaurant innovativeness on destination cognitive food image and examine the impacts of destination cognitive food image on destination brand image and tourists’ revisit intention.

Design/methodology/approach

Data were collected through an online survey, and 337 Gen Z domestic food tourists in Guangzhou participated. Partial least squares structural equation modeling was used for the data analysis.

Findings

This study found that tourists’ perceptions of restaurant menu, technology-based service and experiential innovativeness played essential roles in enhancing destination cognitive food image. In addition, the destination cognitive food image strengthened the destination brand image and increased tourists’ revisit intentions for the future.

Practical implications

The destination cognitive food image perceived by Gen Z domestic food tourists is affected by the restaurant menu, technology-based service and experiential innovativeness. To build a solid destination food image, restaurant operators and decision-makers should prioritize the allocation of resources to develop their innovation capacity. This study also suggests a path of food tourism destination branding from stakeholders’ perspectives and encourages collaboration with stakeholders. Enhanced food tourism destination competitiveness toward the young tourists’ market will generate an overall win for stakeholders

Originality/value

Food providers’ innovativeness, an important factor attracting young tourists’ attention, has been neglected in the discussion of the food tourism experience. This study fills the research gap, investigates the importance of restaurant innovativeness in building food tourism destination competitiveness and provides valuable suggestions to destination restaurant operators and decision-makers.
Conflict in virtual teams: a bibliometric analysis, systematic review, and research agenda
Authors: Caputo Andrea , Kargina Mariya , Pellegrini Massimiliano Matteo
Published: June 2022

Purpose

The purpose of this study is to map the intellectual structure of the research concerning conflict and conflict management in virtual teams (VT), to contribute to the further integration of knowledge among different streams of research and to develop an interpretative framework to stimulate future research.

Design/methodology/approach

A data set of 107 relevant papers on the topic was retrieved using the Web of Science Core Collection database covering a period ranging from 2001 to 2019. A comparative bibliometric analysis consisting of the integration of results from the citation, co-citation and bibliographic coupling was performed to identify the most influential papers. The systematic literature review complemented the bibliometric results by clustering the most influential papers.

Findings

The results revealed different intellectual structures across several types of analyses. Despite such differences, 41 papers resulted as the most impactful and provided evidence of the emergence of five thematic clusters: trust, performance, cultural diversity, knowledge management and team management.

Research limitations/implications

Based on the bibliometric analyses an interpretative research agenda has been developed that unveils the main future research avenues. The paper also offers important theoretical contributions by systematizing knowledge on conflict in identifying VTs. Managerial contributions in the form of the identification of best practices are also developed to guide conflict management in VTs.

Originality/value

The uniqueness of this paper is related to its effort in studying, mapping and systematizing the knowledge concerning the topic of handling conflicts in VTs. Considering the current contingencies, this research is particularly timely.
Disability of non-academic employees in public universities: an exploration of daily work experiences
Authors: Mousa Mohamed
Published: June 2022

Purpose

Through addressing non-academic disabled employees in seven public universities in Egypt, the author aims to find out the main struggles facing disabled non-academic employees in their work context pre and post Covid-19.

Design/methodology/approach

The author employed a qualitative research method through semi-structured interviews with 28 disabled non-academic employees from seven universities in Egypt. The author subsequently used thematic analysis to determine the main ideas in the transcripts.

Findings

The author of the present paper has discovered the main struggles facing disabled non-academic employees in public universities in Egypt before and after the spread of Covid-19 and grouped them into the following three categories: macro-level struggles (government not serious about adopting a quota system, using disability quotas for political reasons, lack of understanding of the needs of disabled employees, poor infrastructure in work contexts), meso-level struggles (unaware of overqualified disabled employees, underrepresentation of disabled employees at senior administrative positions, assigning disabled employees unfair access to university resources) and micro-level struggles (disabled employees' lack of confidence in accepting promotion, inability of disabled employees to join informal networks and disabled employees' exposure to speech-related harassment).

Originality/value

This paper contributes by filling a gap in HR management and educational leadership, in which empirical studies on the struggles facing disabled non-academic employees in their work contexts have been limited so far.
Animosity, preference conflict and consumption context in an international crisis: a normative influence perspective
Authors: Fong Cher-Min , Chang Hsing-Hua Stella , Han Yu-Lin
Published: June 2022

Purpose

Because of its omission of social influences, conventional animosity research has failed to sufficiently consider consumption context. To address this limitation, this research constitutes two interrelated parts: (a) investigating how normative influences (value-expressive and utilitarian influences) shape consumers’ animosity attitudes and purchase intentions; and (b) building on the normative influence perspective and separating consumption context into purchase (online vs. offline) and usage (private vs. public) contexts. The goal was to examine under the condition of preference conflict, how consumption contexts with different degrees of behavioral exposure affect purchase decisions.

Design/methodology/approach

One pretest, one survey and one experiment were conducted to empirically validate the proposed research model.

Findings

In an international crisis, consumers’ attitudes and behaviors were socially determined. Moreover, the online purchase with private usage (offline purchase with public usage) condition resulted in the highest (lowest) level of purchase intention.

Originality/value

This research pioneers in the animosity literature to identify the possibility of preference conflict in a situational international crisis, and to more delicately separate the conventional consumption context into purchase and usage contexts.
Healthcare provider selection for elderly patients suffering from NCD's: an analysis with the combined approach of DEMATEL and AHP
Authors: Singh Ankit , Jha Ajeya , Purbey Shankar , Ravi Priya
Published: June 2022

Purpose

Elderly patients suffering from non-communicable disease face a dilemma in the selection of healthcare providers. This study attempts to identify the key variables playing a crucial role and identify the appropriate healthcare destination with the help of a combination of Decision-making Trial and Evaluation Laboratory (DEMATEL) and analytic hierarchy process (AHP) techniques. The primary objective is to introduce the DEMATEL and AHP as efficient decision-making methods to choose the right healthcare provider for elderly patients suffering from non-communicable diseases.

Design/methodology/approach

An integrative approach utilizing DEMATEL and AHP is used to reach the ideal solution for healthcare provider selection decisions. The DEMATEL approach is used to segregate the cause and effect variables. Similarly, the AHP is used to identify the weights of the top five cause-inducing variables, and the paired comparison method is used to select the healthcare provider.

Findings

The variables such as dependency on family members, easily accessible services, and patient autonomy play a vital role in the selection decision of healthcare providers in elderly patients suffering from non-communicable diseases.

Practical implications

In terms of priority, home healthcare should be considered the preferred provider for elderly patients suffering from non-communicable diseases followed by neighbourhood registered medical practitioners and hospitals.

Originality/value

This is the first of its kind study which has attempted to solve the healthcare provider selection decision with the combined approach of DEMATEL and AHP.
Giving and taking ownership of a destination brand: mechanisms of stakeholder engagement
Authors: Tøttenborg Alberte , Ooi Can-Seng , Hardy Anne
Published: June 2022

Purpose

This paper aims to explore the complexities of engaging with local stakeholders in destination branding. As the main creators and drivers of the destination brand, many brand authorities metaphorically “give ownership” of the brand to local stakeholders, for them to “take ownership” of it. This paper examines the inherent challenges of this process. In the Tasmanian destination branding process presented here, the Tasmanian authorities used best practices to generate a sense of ownership of the destination brand among local tourism businesses. Some players engaged, but many did not. The study shows the necessity to understand the dynamics between giving ownership of the brand and the various local tourism business stakeholders actually taking ownership.

Design/methodology/approach

This study looks at an Australian destination branding experience, namely, Tasmania’s “Go Behind the Scenery”. Primary data were gathered through 14 in-depth interviews with tourism operators, selected through a purposive sampling approach, based on their various levels of participation in the branding processes. The interviews aimed to understand how they variously engaged with the brand and processes of ownership.

Findings

This study shows that a relatively open interpretation of the brand can welcome wider engagement and generate a sense of ownership through the local businesses’ own interpretations. But there are also barriers for these stakeholders in developing an even stronger sense of ownership. They need more support in addressing their individual circumstance before the brand can align with their business.

Originality/value

This paper accentuates an ownership gap, understood as the gap between giving ownership (mechanisms to transfer ownership from brand authorities to stakeholders) and taking ownership (stakeholders assume responsibility for and manifest the brand). In identifying a gap between these two aspects of engagement, this paper initiates a more nuanced discussion on the mechanisms of stakeholder engagement in the branding process.
Tourist scams, moral emotions and behaviors: impacts on moral emotions, dissatisfaction, revisit intention and negative word of mouth
Authors: Ma Jianan , Li Fangxuan (Sam) , Shang Yuanyuan
Published: June 2022

Purpose

Drawing upon affective events theory (AET), this study aims to explore the relationship between tourists’ perceived deception and moral emotions, dissatisfaction, revisit intention and negative word of mouth.

Design/methodology/approach

Online data from Questionnaire Star were used to examine the proposed research model. A total of 437 valid questionnaires were collected.

Findings

The results suggest that tourist scams as “affective events” could trigger tourists’ moral emotions and dissatisfaction, thereby decreasing their revisit intention and generating negative word of mouth. Additionally, moral emotions were found to act as a mediator between perceived deception and dissatisfaction.

Research limitations/implications

The insights uncovered in this study reveal the mechanisms behind tourists’ reactions to scams and provide implications for tourism destinations, suggesting ways to alleviate the adverse impact of tourist scams.

Originality/value

To the best of the authors’ knowledge, this is the very first study to investigate tourists’ reactions to tourist scams.
Dihydroartemisinin protects blood–brain barrier permeability during sepsis by inhibiting the transcription factor SNAI1
Authors: Liu Fuhong , Liu Jing , Xiang Hongjie , Sun Zongguo , Li Yan , Li Xiao , Liu Yanjun , Liu Ju
Published: June 2022

Blood–brain barrier (BBB) injury is involved in the pathogenesis of sepsis‐associated encephalopathy. In this study, we used dihydroartemisinin (DHA), a derivative of artemisinin, to treat a cecal ligation and puncture (CLP)‐induced mouse sepsis model and a tumour necrosis factor α (TNF‐α)‐stimulated human cerebral microvessel endothelial cells (hCMEC)/D3 cell line. We found that DHA decreased BBB permeability and increased the expression of the tight junction protein occludin (OCLN) in the CLP model. In hCMEC/D3 cells, DHA decreased TNF‐α‐induced hyperpermeability and increased the expression of OCLN. DHA also repressed SNAI1 expression in the CLP mouse model and in TNF‐α‐stimulated hCMEC/D3 cells. These data suggest that DHA protects BBB permeability during sepsis by stimulating the expression of OCLN, by downregulating the expression of the SNAI1 transcription factor.
A high‐fat diet changes astrocytic metabolism to promote synaptic plasticity and behavior
Authors: Popov Alexander , Brazhe Nadezda , Fedotova Anna , Tiaglik Alisa , Bychkov Maxim , Morozova Kseniia , Brazhe Alexey , Aronov Dmitry , Lyukmanova Ekaterina , Lazareva Natalia , Li Li , Ponimaskin Evgeni , Verkhratsky Alexei , Semyanov Alexey
Published: June 2022

Aim

A high‐fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognition. Nonetheless, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. We tested how HFD affects astrocyte metabolism, morphology, and physiology.

Methods

We used Raman microspectroscopy to assess the redox state of mitochondria and lipid content in astrocytes and neurons in hippocampal slices of mice subjected to HFD. Astrocytes were loaded with fluorescent dye through patch pipette for morphological analysis. Whole‐cell voltage‐clamp recordings were performed to measure transporter and potassium currents. Western blot analysis quantified the expression of astrocyte‐specific proteins. Field potential recordings measured the magnitude of long‐term potentiation (LTP). Open filed test was performed to evaluate the effect of HFD on animal behavior.

Results

We found that exposure of young mice to 1 month of HFD increases lipid content and relative amount of reduced cytochromes in astrocytes but not in neurons. Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets. Astrocyte remodeling was associated with an increase in expression of ezrin and with no changes in glial fibrillary acidic protein (GFAP), glutamate transporter‐1 (GLT‐1), and glutamine synthetase (GS). Such physiological (non‐reactive) enlargement of astrocytes in the brain active milieu promoted glutamate clearance and LTP and translated into behavioral changes.

Conclusion

Dietary fat intake is not invariably harmful and might exert beneficial effects depending on the biological context.
AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval
Authors: Rekić Dinko , Azarov Ivan , Knöchel Jane , Sokolov Victor , Nilsson Catarina , Wernevik Linda , Han David , Rydén‐Bergsten Tina , Ebrahimi Ahmad , Dota Corina , Carlsson Björn
Published: June 2022

Aims

AZD8233 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide under development for treatment of hypercholesterolaemia. A prespecified concentration‐QT analysis was performed based on data from a single ascending dose study that was prospectively designed to act as a TQT study substitute.

Methods

Subcutaneous single doses ranging from 4 to 120 mg were evaluated in 73 adult healthy male subjects. Time‐matched 12‐lead digital ECG and plasma concentrations (n = 15) were measured at baseline and up to 48 hours after dose in each subject. The analysis was performed using a linear mixed effect model, where change from baseline QTc (ΔQTc) was a dependent variable and time‐matched AZD8233 concentration was an independent variable.

Results

The high clinical exposure scenario was defined as 1.7‐fold the expected Cmax following an assumed therapeutic dose of 60 mg, which corresponds to AZD8233 plasma concentration of 1.39 μg/mL. Estimated placebo‐corrected and baseline‐adjusted QTcF interval (ΔΔQTcF) at this concentration was −2.2 ms (90% CI: −4.11, −0.28). Furthermore, the upper 90% ΔΔQTcF confidence interval was estimated to be below 10 ms at all observed concentrations.

Conclusion

As the effect on ΔΔQTcF is below the threshold for regulatory concern (10 ms), it can be concluded that AZD8233 does not induce QTcF prolongation at the high clinical exposure scenario.
Phenological trajectories of Caribbean very dry tropical forests diverge under different geologic formations
Authors: Restrepo Carla , Delgado Diana , Debrot Adolphe O. , de Vries Albert J. , Houtepen Erik , de Freitas John A.
Published: June 2022

Tropical dry forests experience pronounced seasonal changes in precipitation manifested in varied plant phenologies. At landscape scales, geologic substrate—one of the least understood abiotic factors interacting with precipitation—may modulate phenological responses in these forests through a combination of mechanisms regulating water and nutrient use. We leveraged a phenological dataset from the semiarid island of Curaçao to examine the extent to which plant phenology at multiple levels of biological organization diverge under different geologies. Monthly observations over a 30‐month period of leaves, flowers, and fruits of 69 plant species of different life forms at three nearby sites differing in their underlaying geology were used to examine intra‐ and inter‐annual plant responses at species, community, and system levels. The integration of leaf, flower, and fruit observations at intra‐annual scales revealed diverse phenological strategies among species, broad associations with geologic substrate, and the extent of intra‐specific variation as a function of geology. The community‐ and system‐level analyses at inter‐annual scales showed a reduction in mean leaf scores during the 30‐month period, a weak and strong leafless period in 1993 and 1994, respectively, and differences among geologic substrates. Finally, we observed significant and positive relationships between precipitation and the phenophase scores; the strength of the relationships varied with phenophase and geologic substrate. Results of this work emphasize the importance of geologic substrate, and more broadly speaking landscape heterogeneity, in modulating plant phenological responses in tropical dry forests. Ultimately, this information will become important to understand and mitigate global climate change impacts.

Abstract in Spanish is available with online material.
Recognizing precarity? A comparative analysis of governmental documents in provincial and federal administrations
Authors: Marier Patrik , Grenier Amanda , Kobayashi Karen , Rudman Debbie , Garcia‐Poulin Yoana , Hatzifilalithis Stephanie , Phillipson Chris
Published: June 2022

With an aging population, have federal and provincial governments acknowledged the diversity of the policy needs of older adults? This contribution analyzes administrative and policy documents across ministries to study the frequency and the depth of engagement involving older adults with a disability, older immigrants, and those living in poverty. Precarity received marginal treatment with very limited discussions combining aging in relation to disability, immigration and migration, or poverty. Most documents focused on poverty. Disability and aging are discussed in parallel and rarely in conjunction with aging. These findings suggest a low level of priority for precarity and aging.
Citizen satisfaction with public service delivery: A test of alternative theories
Authors: Reddick Christopher G. , Perlman Bruce J. , Demir Tansu
Published: June 2022

Two prevailing theories explain citizen satisfaction with public services from different levels and sizes of government. Reform theory argues that citizens derive the most satisfaction from larger government units because of economies of scale in service delivery. Political economy theory argues that citizens achieve the most satisfaction from smaller local government units since their voice is more likely to be heard. Both theories have been tested yielding mixed findings. An alternative theory argues that citizens have different levels of satisfaction depending upon the specific services received and directly experienced. These theories are tested using Canadian national public opinion survey data.
Biobanking of human pluripotent stem cells in China
Authors: Stacey Glyn Nigel , Hao Jie
Published: June 2022

In recent years, significant progress has been made internationally in the development of human pluripotent stem cell (hPSC)‐derived products for serious and widespread disorders. Biobanking of the cellular starting materials is a crucial component in the delivery of safe and regulatory compliant cell therapies. In China, key players in these developments have been the recently launched National Stem Cell Resource Center (NSCRC) and its partner organizations in Guangzhou and Shanghai who together, have more than 600 hPSC lines formally recorded in the Chinese Ministry of Science and Technology's stem cell registry. In addition, 47 of these hPSCs have also been registered with the hPSCreg project which means they are independently certified for use in European Commission funded research projects. The NSCRC are currently using their own cell lines to manufacture eight different cell types qualified for clinical use, that are being used in nine clinical studies for different indications. The Institute of Zoology at the Chinese Academy of Sciences (IOZ‐CAS) has worked with NSCRC to establish Chinese and international standards in stem cell research. IOZ‐CAS was also a founding partner in the International Stem Cell Banking Initiative which brings together key stem cell banks to agree minimum standards for the provision of pluripotent stem cells for research and clinical use. Here, we describe recent developments in China in the establishment of hPSCs for use in the manufacture of cell therapies and the significant national and international coordination which has now been established to promote the translation of Chinese hPSC‐based products into clinical use according to national and international standards.
Staufen‐2 functions as a cofactor for enhanced Rev‐mediated nucleocytoplasmic trafficking of HIV‐1 genomic RNA via the CRM1 pathway
Authors: Balakrishnan Kannan , Munusami Punnagai , Mohareer Krishnaveni , Priyakumar U. Deva , Banerjee Atoshi , Luedde Tom , Mande Shekhar C. , Münk Carsten , Banerjee Sharmistha
Published: June 2022

Nucleocytoplasmic shuttling of viral elements, supported by several host factors, is essential for the replication of the human immunodeficiency virus (HIV). HIV‐1 uses a nuclear RNA export pathway mediated by viral protein Rev to transport its Rev response element (RRE)‐containing partially spliced and unspliced transcripts aided by the host nuclear RNA export protein CRM1. The factor(s) interacting with the CRM1‐Rev complex are potential antiretroviral target(s) and could serve as a retroviral model system to study nuclear export machinery adapted by these viruses. We earlier reported that cellular Staufen‐2 interacts with Rev, facilitating viral‐RNA export. Here, we identified the formation of a complex between Staufen‐2, CRM1 and Rev. Molecular docking and simulations mapped the interacting residues in the RNA‐binding Domain 4 of Staufen‐2 as R336 and R337, which were experimentally verified to be critical for interactions among Staufen‐2, CRM1 and Rev by mutational analysis. Staufen‐2 mutants defective in interaction with CRM1 or Rev failed to supplement the Rev‐RNA export activity and viral production, demonstrating the importance of these interactions. Rev‐dependent reporter assays and proviral DNA‐construct transfection‐based studies in Staufen‐2 knockout cells in the presence of leptomycin‐B (LMB) revealed a significant reduction in CRM1‐mediated Rev‐dependent RNA export with decreased virus production as compared to Staufen‐2 knockout background or LMB treatment alone, suggesting the relevance of these interactions in augmenting RNA export activity of Rev. Our observations provide further insights into the mechanistic intricacies of unspliced viral‐RNA export to the cytoplasm and support the notion that abrogating such interactions can reduce HIV‐1 proliferation.
Nitrogen input enhances microbial carbon use efficiency by altering plant–microbe–mineral interactions
Authors: Feng Xuehui , Qin Shuqi , Zhang Dianye , Chen Pengdong , Hu Jie , Wang Guanqin , Liu Yang , Wei Bin , Li Qinlu , Yang Yuanhe , Chen Leiyi
Published: June 2022

Microbial growth and respiration are at the core of the soil carbon (C) cycle, as these microbial physiological performances ultimately determine the fate of soil C. Microbial C use efficiency (CUE), a critical metric to characterize the partitioning of C between microbial growth and respiration, thus controls the sign and magnitude of soil C‐climate feedback. Despite its importance, the response of CUE to nitrogen (N) input and the relevant regulatory mechanisms remain poorly understood, leading to large uncertainties in predicting soil C dynamics under continuous N input. By combining a multi‐level field N addition experiment with a substrate‐independent 18O‐H2O labelling approach as well as high‐throughput sequencing and mineral analysis, here we elucidated how N‐induced changes in plant–microbial–mineral interactions drove the responses of microbial CUE to N input. We found that microbial CUE increased significantly as a consequence of enhanced microbial growth after 6‐year N addition. In contrast to the prevailing view, the elevated microbial growth and CUE were not mainly driven by the reduced stoichiometric imbalance, but strongly associated with the increased soil C accessibility from weakened mineral protection. Such attenuated organo–mineral association was further linked to the N‐induced changes in the plant community and the increased oxalic acid in the soil. These findings provide empirical evidence for the tight linkage between mineral‐associated C dynamics and microbial physiology, highlighting the need to disentangle the complex plant–microbe–mineral interactions to improve soil C prediction under anthropogenic N input.
Investigating immunoregulatory effects of myeloid cell autophagy in acute and chronic inflammation
Authors: Hasnat Md Abul , Cheang IanIan , Dankers Wendy , Lee Jacinta PW , Truong Lynda M , Pervin Mehnaz , Jones Sarah A , Morand Eric F , Ooi Joshua D , Harris James
Published: June 2022

Studies have highlighted a critical role for autophagy in the regulation of multiple cytokines. Autophagy inhibits the release of interleukin (IL)‐1 family cytokines, including IL‐1α, IL‐1β and IL‐18, by myeloid cells. This, in turn, impacts the release of other cytokines by myeloid cells, as well as other cells of the immune system, including IL‐22, IL‐23, IL‐17 and interferon‐γ. Here, we assessed the impact of genetic depletion of the autophagy gene Atg7 in myeloid cells on acute and chronic inflammation. In a model of acute lipopolysaccharide‐induced endotoxemia, loss of autophagy in myeloid cells resulted in increased release of proinflammatory cytokines, both locally and systemically. By contrast, loss of Atg7 in myeloid cells in the Lyn−/− model of lupus‐like autoimmunity resulted in reduced systemic release of IL‐6 and IL‐10, with no effects on other cytokines observed. In addition, Lyn−/− mice with autophagy‐deficient myeloid cells showed reduced expression of autoantibodies relevant to systemic lupus erythematosus, including anti‐histone and anti‐Smith protein. In vitro, loss of autophagy, through pharmacological inhibition or small interfering RNA against Becn1, inhibited IL‐10 release by human and mouse myeloid cells. This effect was evident at the level of Il10 messenger RNA expression. Our data highlight potentially important differences in the role of myeloid cell autophagy in acute and chronic inflammation and demonstrate a direct role for autophagy in the production and release of IL‐10 by macrophages.
From Hybrid Spaces to In‐between Spaces: A Journey with Contemporary Art and Situated Knowledge
Authors: Jové Glòria , Gutiérrez‐Ujaque Daniel , Bonastra Quim , Simón‐Martín Meritxell
Published: June 2022

Theoretical knowledge taught in the classroom forms the bulk of lectures in Initial Teacher Training today. Persuaded that knowledge constructed in the community ought to permeate Teacher Training, Zeichner has developed the notion of Hybrid Space – a space for reflection, training and educational improvement where the background of academic/professional knowledge merges to create new learning opportunities, and where the voices of all participants emerge inclusively. Drawing on but also nuancing Zeichner’s Hybrid Space, this paper examines how (1) incorporating working with (in, about, through) contemporary art into our teaching, and (2) putting this pedagogical approach into play by means of situated learning contexts that work with and in the community offers the opportunity to create an innovative teaching approach. This innovation takes the form of transdisciplinary and nomadic learning inputs that operate within an in‐between space and result in unique and unrepeatable learning experiences for all the participants involved.
A comparison of clinical outcomes and cost of radiofrequency catheter ablation for atrial fibrillation with monitored anesthesia care versus general anesthesia
Authors: Yokokawa Miki , Chugh Aman , Dubovoy Anna , Engoren Milo , Jongnarangsin Krit , Latchamsetty Rakesh , Ghanbari Hamid , Saeed Mohammed , Cunnane Ryan , Crawford Thomas , Ghannam Michael , Liang Jackson , Keast Robert , Karpenko David , Bogun Frank , Pelosi Frank , Dubovoy Timur , Caldwell Mathew , Morady Fred , Oral Hakan
Published: June 2022

Introduction

Monitored anesthesia care (MAC) or general anesthesia (GA) can be used during catheter ablation (CA) of atrial fibrillation (AF). However, each approach may have advantages and disadvantages with variability in operator preferences. The optimal approach has not been well established. The purpose of this study was to compare procedural efficacy, safety, clinical outcomes, and cost of CA for AF performed with MAC versus GA.

Methods

The study population consisted of 810 consecutive patients (mean age: 63 ± 10 years, paroxysmal AF: 48%) who underwent a first CA for AF. All patients completed a preprocedural evaluation by the anesthesiologists. Among the 810 patients, MAC was used in 534 (66%) and GA in 276 (34%). Ten patients (1.5%) had to convert to GA during the CA.

Results

Although the total anesthesia care was longer with GA particularly in patients with persistent AF, CA was shorter by 5 min with GA than MAC (p < 0.01). Prevalence of perioperative complications was similar between the two groups (4% vs. 4%, p = 0.89). There was no atrioesophageal fistula with either approach. GA was associated with a small, ~7% increase in total charges due to longer anesthesia care. During 43 ± 17 months of follow‐up after a single ablation procedure, 271/534 patients (51%) in the MAC and 129/276 (47%) patients in the GA groups were in sinus rhythm without concomitant antiarrhythmic drug therapy (p = 0.28).

Conclusion

With the participation of an anesthesiologist, and proper preoperative assessment, CA of AF using GA or MAC has similar efficacy and safety.
Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes
Authors: Ponirakis Georgios , Al‐Janahi Ibrahim , Elgassim Einas , Gad Hoda , Petropoulos Ioannis N , Khan Adnan , Ali Hamda , Siddique Mashhood A , Gul Wajiha , Ferdousi Maryam , Kalteniece Alise , Mohamed Fatima FS , Ahmed Lina HM , Dakroury Youssra , El Shewehy Abeer MM , Al‐Mohamedi Abdulrahman , AlMarri Fatema , Homssi Moayad , Qazi Murtaza , Hadid Nebras H , Al‐Khayat Fatima , Mahfoud Ziyad R , Azmi Shazli , Alam Uazman , Zirie Mahmoud A , Al‐Ansari Yousuf , Jayyousi Amin , Rigby Alan S , Kilpatrick Eric S , Atkin Stephen L , Malik Rayaz A
Published: June 2022

Aims/Introduction

Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years.

Materials and Methods

Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow‐up.

Results

Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05–0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain.

Conclusions

In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.
Cerebrospinal fluid and plasma procalcitonin for the diagnosis of neonatal bacterial meningitis
Authors: Dutta Sourabh , Sachdeva Naresh , Pal Arnab , Ray Pallab
Published: June 2022

Aim

There is a paucity of data on cerebrospinal fluid (CSF) procalcitonin (PCT) to diagnose neonatal meningitis. We evaluated CSF PCT to diagnose bacterial meningitis among neonates with suspected sepsis.

Methods

Neonates undergoing lumbar puncture (LP) as part of sepsis workup were included.

Index Tests: CSF PCT, plasma PCT, CSF:plasma PCT ratio and CSF cytochemistry.

Reference Standards: ‘Definite meningitis’ defined by positive CSF culture and/or gram stain and/or broad‐based primer 16S rDNA polymerase chain reaction. ‘Definite or probable’ meningitis is defined as definite meningitis or abnormal cytochemistry.

Results

Of 216 eligible neonates, 18 had ‘definite meningitis’ and 37 ‘definite or probable meningitis’. Median (Q1, Q3) CSF PCT level was significantly higher in ‘definite meningitis’ compared to ‘no definite meningitis’ (0.429 (0.123, 1.300) vs. 0.181 (0.119, 0.286) ng/mL respectively, P = 0.028). Likewise, it was significantly higher in ‘definite or probable meningitis’ compared to no meningitis (0.245 (0.136, 0.675) vs. 0.170 (0.116, 0.28), P = 0.01). The area under the receiver operator characteristics curve of CSF PCT level for definite meningitis was 0.656 and for ‘definite or probable meningitis’ 0.635. Paired comparisons of area under the receiver operator characteristics curve of CSF PCT with the other index tests showed no significant differences. Based on a priori cut‐off of 0.2 ng/mL, CSF PCT level had a sensitivity (95% confidence interval) of 67% (50, 80), specificity 58% (54, 61), LR+ 1.6 (1.1, 2.0) and LR− 0.6 (0.3, 0.9).

Conclusions

Higher values of CSF PCT are associated with neonatal bacterial meningitis. However, the diagnostic performance of CSF PCT is modest and not significantly different from standard tests.
Obsidian and mafic volcanic glasses from the Philippines and Vietnam found in the Paris Museum Australasian tektite collection
Authors: Rochette P. , Bezaeva N. S. , Beck P. , Debaille V. , Folco L. , Gattacceca J. , Gounelle M. , Masotta M.
Published: June 2022

During the systematic magnetic susceptibility survey of the Paris Museum Australasian tektite collection, we identified three previously overlooked occurrences of volcanic glass that resembles tektites, based on anomalous magnetic properties, high water content, the presence of microcrystals, and anomalous chemical composition. These occurrences are from the Phu Yen province in south‐central Vietnam (two rhyolitic glass fragments) and from the Philippines: one from northern Luzon Island (a basaltic rounded etched glass), one from Santa Mesa near Manilla (a dozen small rounded rhyolitic gravels). The two occurrences in the Philippines are quite similar to previously described volcanic glasses from the nearby Pagudpod and Nagcarlan localities, respectively. The rhyolitic glass specimens from the Phu Yen province are the first documentation of a geological occurrence of obsidian in Vietnam. This work is a warning note that glass samples with anomalous properties found among tektite collections may correspond to volcanic pseudotektites instead of real tektites with anomalous composition. The basaltic glass sample from the Philippines locally shows microcrystalline quench textures previously unknown in natural samples. These findings may also be of interest for archeologists involved in glass artifacts sourcing.
Did U.S. Governments Violate Individual Human Rights? A Thomistic Response to COVID-19 Government Mandates
Authors: Moats Nathaniel A.
Published: June 2022

In response to the COVID-19 pandemic, some Americans have claimed that U.S. governments have superseded their jurisdiction and violated individuals’ human rights in the use of government mandates. Many citizens and politicians have also claimed that governments are utilizing the pandemic as a smoke screen to take individual rights away from citizens to gain further power. In light of such claims, I provide a Thomistic response to argue that state and local political authorities’ use of public health mandates were other-regarding in seeking to protect the common good in an unprecedented health crisis. Further, I argue that the characterization of individual rights atomized from community has led to an improper understanding of political authorities, individual rights, and our duties to our communities. Rejecting the reductive, skeptical, individualistic, and atomistic views that many Americans have engendered, I provide a Thomistic political orientation that more adequately helps us think about political authorities’ and citizens’ responsibilities within our political communities.
Thiamine metabolism genes in diatoms are not regulated by thiamine despite the presence of predicted riboswitches
Authors: Llavero‐Pasquina Marcel , Geisler Katrin , Holzer Andre , Mehrshahi Payam , Mendoza‐Ochoa Gonzalo I. , Newsad Shelby A. , Davey Matthew P. , Smith Alison G.
Published: June 2022

Thiamine pyrophosphate (TPP), an essential co‐factor for all species, is biosynthesised through a metabolically expensive pathway regulated by TPP riboswitches in bacteria, fungi, plants and green algae. Diatoms are microalgae responsible for c. 20% of global primary production. They have been predicted to contain TPP aptamers in the 3′UTR of some thiamine metabolism‐related genes, but little information is known about their function and regulation.

We used bioinformatics, antimetabolite growth assays, RT‐qPCR, targeted mutagenesis and reporter constructs to test whether the predicted TPP riboswitches respond to thiamine supplementation in diatoms. Gene editing was used to investigate the functions of the genes with associated TPP riboswitches in Phaeodactylum tricornutum.

We found that thiamine‐related genes with putative TPP aptamers are not responsive to supplementation with thiamine or its precursor 4‐amino‐5‐hydroxymethyl‐2‐methylpyrimidine (HMP), and targeted mutation of the TPP aptamer in the THIC gene encoding HMP‐P synthase does not deregulate thiamine biosynthesis in P. tricornutum. Through genome editing we established that PtTHIC is essential for thiamine biosynthesis and another gene, PtSSSP, is necessary for thiamine uptake.

Our results highlight the importance of experimentally testing bioinformatic aptamer predictions and provide new insights into the thiamine metabolism shaping the structure of marine microbial communities with global biogeochemical importance.
RE‐SURVEY OF THE ANCHORAGE AT MARONITSAROUKKAS, CYPRUS: DEFINING AND VIEWING A LATE BRONZE AGE COASTSCAPE
Authors: Atkins Carrie E. , Manning Sturt W.
Published: June 2022

Directly offshore from the Late Cypriot (LC) site of MaroniTsaroukkason the south‐central coast of Cyprus lie the remains of an anchorage with stone anchors, LC ceramics, and stone blocks. Initially surveyed in 1995–96, the anchorage was re‐surveyed from 2017–19 to investigate and document fully the underwater site and to develop accurate underwater survey recording methodologies for defining this coastscape interaction zone. The site was surveyed by measuring finds into an established grid and using a computer‐controlled camera system for photogrammetry. The results expand the known extent of the anchorage, include newly documented archaeological remains, and challenge us to re‐conceptualize the area. In addition to anchors and pottery representative of maritime use, the presence of unfinished anchors and LC IA ceramic assemblages in the western part of the site indicates a LC coastal region likely once terrestrial that is now submerged, forming part of a newly identified coastscape locale.