bluuebunny/crossref_metadata_2025 huggingface dataset:
The PCI domains are “winged” HEAT domains
Authors: Paul Eleanor Elise , Marintchev Assen
Published: May 2022

The HEAT domains are a family of helical hairpin repeat domains, composed of four or more hairpins. HEAT is derived from the names of four family members: huntingtin, eukaryotic translation elongation factor 3 (eEF3), protein phosphatase 2 regulatory A subunit (PP2A), and mechanistic target of rapamycin (mTOR). HEAT domain-containing proteins play roles in a wide range of cellular processes, such as protein synthesis, nuclear transport and metabolism, and cell signaling. The PCI domains are a related group of helical hairpin domains, with a “winged-helix” (WH) subdomain at their C-terminus, which is responsible for multi-subunit complex formation with other PCI domains. The name is derived from the complexes, where these domains are found: the Proteasome “lid” regulatory subcomplex, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). We noted that in structure homology searches using HEAT domains, sometimes PCI domains appeared in the search results ahead of other HEAT domains, which indicated that the PCI domains could be members of the HEAT domain family, and not a related but separate group. Here, we report extensive structure homology analysis of HEAT and PCI domains, both within and between the two groups of proteins. We present evidence that the PCI domains as a group have greater structural homology with individual groups of HEAT domains than some of the HEAT domain groups have among each other. Therefore, our results indicate that the PCI domains have evolved from a HEAT domain that acquired a WH subdomain. The WH subdomain in turn mediated selfassociation into a multi-subunit complex, which eventually evolved into the common ancestor of the Proteasome lid/CSN/eIF3.
RORβ modulates a gene program that is protective against articular cartilage damage
Authors: Chang Mi Ra , Griffin Patrick R.
Published: May 2022

Osteoarthritis (OA) is the most prevalent chronic joint disease which increases in frequency with age eventually impacting most people over the age of 65. OA is the leading cause of disability and impaired mobility, yet the pathogenesis of OA remains unclear. Treatments have focused mainly on pain relief and reducing joint swelling. Currently there are no effective treatments to slow the progression of the disease and to prevent irreversible loss of cartilage. Here we demonstrate that stable expression of RORβ in cultured cells results in alteration of a gene program that is supportive of chondrogenesis and is protective against development of OA. Specifically, we determined that RORβ regulates the balance of FGFRs signaling on FGFR1/FGFR3 that ERK1/2-MAPK signaling was suppressed by FGFR1(cartilage destruction) and AKT signaling was enhanced by FGFR3 (cartilage protection). These results suggest a critical role for RORβ in chondrogenesis and suggest that identification of mechanisms that control the expression of RORβ in chondrocytes could lead to the development of disease modifying therapies for the treatment of OA.
ORF6 protein of SARS-CoV-2 inhibits TRIM25 mediated RIG-I ubiquitination to mitigate type I IFN induction
Authors: Khatun Oyahida , Sharma Mansi , Narayan Rohan , Tripathi Shashank
Published: May 2022

Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection confers a profound replication advantage on the virus and contributes to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host innate immune system and found that the ORF6 protein mitigated type-I IFN (interferon) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by inhibiting K-63 linked ubiquitination of RIG-I by the E3 Ligase TRIM25. This involves ORF6-mediated targeting of TRIM25 for degradation, also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how the SARS-CoV-2 ORF6 protein inhibits type I-IFN induction and signaling through distinct mechanisms.
Metalation calculators forE. colistrain JM109 (DE3): Aerobic, anaerobic and hydrogen peroxide exposed cells cultured in LB media
Authors: Foster Andrew W. , Clough Sophie E. , Aki Zeynep , Young Tessa R. , Clarke Alison R. , Robinson Nigel J.
Published: May 2022

Three web-based calculators, and three analogous spreadsheets, have been generated that predictin vivometal occupancies of proteins based on known metal affinities. The calculations exploit estimates of the availabilities of the labile buffered pools of different metals inside a cell. Here, metal availabilities have been estimated for a strain ofE. colithat is commonly used in molecular biology and biochemistry research, for example in the production of recombinant proteins. Metal availabilities have been examined for cells grown in LB medium aerobically, anaerobically and in response to H2O2by monitoring the abundance of a selected set of metal-responsive transcripts by qPCR. The selected genes are regulated by DNA-binding metal sensors that have been thermodynamically characterised in related bacterial cells enabling gene expression to be read-out as a function of intracellular metal availabilities expressed as free energies for forming metal complexes. The calculators compare these values with the free energies for forming complexes with the protein of interest, derived from metal affinities, to estimate how effectively the protein can compete with exchangeable binding sites in the intracellular milieu. The calculators then inter-compete the different metals, limiting total occupancy of the site to a maximum stoichiometry of 1, to output percentage occupancies with each metal. In addition to making these new and conditional calculators available, an original purpose of this article was to provide a tutorial which discusses constraints of this approach and presents ways in which such calculators might be exploited in basic and applied research, and in next-generation manufacturing.
Obesity medication lorcaserin requires brainstem GLP-1 neurons to reduce food intake in mice
Authors: Wagner Stefan , Brierley Daniel I. , Leeson-Payne Alasdair , Jiang Wanqing , Chianese Raffaella , Lam Brian Y. H. , Dowsett Georgina K. C. , Cristiano Claudia , Lyons David , Reimann Frank , Gribble Fiona M. , Yeo Giles S.H. , Trapp Stefan , Heisler Lora K.
Published: May 2022

Overweight and obesity are rapidly becoming the “new normal” in developed countries, which promotes a widespread negative impact on human health. Amongst recently developed obesity medications are the serotonin 2C receptor (5-HT2CR) agonist lorcaserin and glucagon-like peptide-1 receptor (GLP-1R) agonists, but the brain circuits employed by these medications to produce their therapeutic effects remain to be fully defined. 5-HT2CRs and GLP-1Rs are widely distributed in the brain, including in the key homeostatic region the nucleus of the solitary tract (NTS) where GLP-1 is produced by preproglucagon (PPGNTS) neurons. PPGNTS cells were profiled using histochemistry and single nucleus RNA sequencing (Nuc-Seq) of mouse brainstem. Transcriptomic analyses revealed 5-HT2CR expression was widespread in PPGNTS clusters. Demonstrating the functional significance of this co-expression, lorcaserin required PPGNTS to reduce food intake. Analysis of second order neurons revealed that local GLP1-R neurons within the NTS are necessary for 5-HT2CRNTS food intake suppression. In contrast, GLP-1RNTS were not required for GLP-1R agonist liraglutide and exendin-4’s short term feeding reduction, suggesting scope for lorcaserin and GLP1-R agonist combination therapy. In support of this, lorcaserin+liraglutide and lorcaserin+exendin-4 produced greater reductions in food intake when administered in combination as compared to monotherapies. These data provide insight into the therapeutic mechanisms of lorcaserin and identify a combination strategy to improve the therapeutic profile of lorcaserin and GLP1-R agonists.
Nucleation and stability of branched versus linear Arp2/3-generated actin filaments
Authors: Cao Luyan , Ghasemi Foad , Way Michael , Jégou Antoine , Romet-Lemonne Guillaume
Published: May 2022

Activation of the Arp2/3 complex by VCA-domain-bearing NPFs results in the formation of ‘daughter’ actin filaments branching off the sides of pre-existing ‘mother filaments.’ Alternatively, when stimulated by SPIN90, Arp2/3 directly nucleates ‘linear’ actin filaments. Uncovering the similarities and differences of these two activation mechanisms is fundamental to understanding the regulation and function of Arp2/3. Analysis of individual filaments reveals that the catalytic VCA domain of WASP, N-WASP and WASH, accelerate the Arp2/3-mediated nucleation of linear filaments by SPIN90, in addition to their known branch-promoting activity. Unexpectedly, these VCA domains also destabilize existing branches, as well as SPIN90-Arp2/3 at filament pointed ends. Furthermore, cortactin and GMF, which respectively stabilize and destabilize Arp2/3 at branch junctions, have a similar impact on SPIN90-activated Arp2/3. However, unlike branch junctions, SPIN90-Arp2/3 at the pointed end of linear filaments is not destabilized by piconewton forces, and does not become less stable with time. It thus appears that linear and branched Arp2/3-generated filaments respond similarly to regulatory proteins, albeit with quantitative differences, and that they differ greatly in their responses to aging and to mechanical stress. These results indicate that SPIN90- and VCA-activated Arp2/3 complexes adopt similar yet non-identical conformations, and that their turnover in cells may be regulated differently.
Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees
Authors: Xue Yidan , Georgakopoulou Theodosia , van der Wijk Anne-Eva , Józsa Tamás I. , van Bavel Ed , Payne Stephen J.
Published: May 2022

The microvasculature plays a key role in oxygen transport in the mammalian brain. Despite the close coupling between cerebral vascular geometry and local oxygen demand, recent experiments have reported that microvascular occlusions can lead to unexpected distant tissue hypoxia and infarction. To better understand the spatial correlation between the hypoxic regions and the occlusion sites, we used both in vivo experiments and in silico simulations to investigate the effects of occlusions in cerebral penetrating arteriole trees on tissue hypoxia. In a rat model of microembolisation, 25 µm microspheres were injected through the carotid artery to occlude penetrating arterioles. In representative models of human cortical columns, the penetrating arterioles were occluded by simulating the transport of microspheres of the same size and the oxygen transport was simulated using a Green’s function method. The locations of microspheres and hypoxic regions were segmented, and two novel distance analyses were implemented to study their spatial correlation. The distant hypoxic regions were found to be present in both experiments and simulations, and mainly due to the hypoperfusion in the region downstream of the occlusion site. Furthermore, a reasonable agreement for the spatial correlation between hypoxic regions and occlusion sites is shown between experiments and simulations, which indicates the good applicability of in silico models in understanding the response of cerebral blood flow and oxygen transport to microemboli.

Author summary

The brain function depends on the continuous oxygen supply through the bloodstream inside the microvasculature. Occlusions in the microvascular network will disturb the oxygen delivery in the brain and result in hypoxic tissues that can lead to infarction and cognitive dysfunction. To aid in understanding the formation of hypoxic tissues caused by micro-occlusions in the penetrating arteriole trees, we use rodent experiments and simulations of human vascular networks to study the spatial correlations between the hypoxic regions and the occlusion locations. Our results suggest that hypoxic regions can form distally from the occlusion site, which agrees with the previous observations in the rat brain. These distant hypoxic regions are primarily due to the lack of blood flow in the brain tissues downstream of the occlusion. Moreover, a reasonable agreement of the spatial relationship is found between the experiments and the simulations, which indicates the applicability of in silico models to study the effects of microemboli on the brain tissue.
Compartment-driven imprinting of intestinal CD4 (regulatory) T cells in inflammatory bowel disease and homeostasis
Authors: Lutter Lisanne , ter Linde José J.M. , Brand Eelco C. , van Konijnenburg David P. Hoytema , Roosenboom Britt , Talabur-Horje Carmen Horjus , Oldenburg Bas , van Wijk Femke
Published: May 2022

Objective

The mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T cell populations. Human CD4 T cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remains incompletely understood.

Design

We performed imaging mass cytometry, flow cytometry, bulk and single-cell RNA-sequencing to profile ileal lamina propria and intraepithelial CD4 T cells (CD4CD8αα, regulatory T cells (Tregs), CD69- and CD69high Trm T cells) in controls and Crohn’s disease (CD) patients (paired non-inflamed and inflamed).

Results

Inflammation results in alterations of the CD4 T cell population with a pronounced increase in Tregs and migrating/infiltrating cells. On a transcriptional level, inflammation within the epithelium induced T cell activation, increased IFNγ responses and effector Treg differentiation. Conversely, few transcriptional changes within the lamina propria were observed. Key regulators including the chromatin remodelers ARID4B and SATB1 were found to drive compartment-specific transcriptional programming of CD4 T(reg) cells.

Conclusion

Inflammation in CD patients primarily induces changes within the epithelium and not the lamina propria. Additionally, there is compartment-specific CD4 T cell imprinting, driven by shared regulators, upon translocation from the lamina propria to the epithelium. The main consequence of epithelial translocation, irrespective of inflammation, seems to be an overall dampening of broad (pro-inflammatory) responses and tight regulation of lifespan. These data suggest differential regulation of the lamina propria and epithelium, with a specific regulatory role in the inflamed epithelium.
The hidden diversity of ancient bornaviral sequences from X and P genes in vertebrate genomes
Authors: Garcia Bea Clarise B. , Mukai Yahiro , Tomonaga Keizo , Horie Masayuki
Published: May 2022

Endogenous bornavirus-like elements (EBLs) are heritable sequences derived from bornaviruses in vertebrate genomes that originate from transcripts of ancient bornaviruses. EBLs have been detected using sequence similarity searches such as tBLASTn, whose technical limitations may hinder the detection of EBLs derived from small and/or rapidly evolving viral X and P genes. Indeed, no EBLs derived from the X and P genes of orthobornaviruses have been detected to date in vertebrate genomes. Here, we aimed to develop a novel strategy to detect such “hidden” EBLs. To this aim, we focused on the 1.9 kb read-through transcript of orthobornaviruses, which encodes a well-conserved N gene and small and rapidly evolving X and P genes. We show a series of evidence supporting the existence of EBLs derived from orthobornaviral X and P genes (EBLX/Ps) in mammalian genomes. Furthermore, we found that an EBLX/P is expressed as a fusion transcript with the cellular gene, ZNF451, which potentially encodes the ZNF451/EBLP fusion protein in miniopterid bat cells. This study contributes to a deeper understanding of ancient bornaviruses and co-evolution between bornaviruses and their hosts. Furthermore, our data suggest that endogenous viral elements detected thus far are just the tip of the iceberg, and further studies are required to understand ancient viruses more accurately.
The LC3B FRET biosensor monitors the modes of action of ATG4B during autophagy in living cells
Authors: Gökerküçük Elif Begüm , Chéron Angélique , Tramier Marc , Bertolin Giulia
Published: May 2022

Although several mechanisms of autophagy have been dissected in the last decade, following this pathway in real time remains challenging. Among the early events leading to its activation, the ATG4B protease primes the key autophagy player LC3B. Given the lack of reporters to follow this event in living cells, we developed a Förster’s Resonance Energy Transfer (FRET) biosensor responding to the priming of LC3B by ATG4B. The biosensor was generated by flanking LC3B within a pH-resistant donor-acceptor FRET pair, Aquamarine/tdLanYFP. We here showed that the biosensor has a dual readout. First, FRET indicates the priming of LC3B by ATG4B and the resolution of the FRET image allows to characterize the spatial heterogeneity of the priming activity. Second, quantifying the number of Aquamarine-LC3B puncta determines the degree of autophagy activation. We then showed that there are pools of unprimed LC3B uponATG4Bdownregulation, and that the priming of the biosensor is abolished inATG4Bknockout cells. The lack of priming can be rescued with the wild-type ATG4B or with the partially active W142A mutant, but not with the catalytically dead C74S mutant. Moreover, we screened for commercially-available ATG4B inhibitors, and we illustrated their differential mode of action by implementing a spatially-resolved, broad-to-sensitive analysis pipeline combining FRET and the quantification of autophagic puncta. Finally, we uncovered the CDK1-dependent regulation of the ATG4B-LC3B axis at mitosis. Therefore, the LC3B FRET biosensor paves the way for a highly-quantitative monitoring of the ATG4B activity in living cells and in real time, with unprecedented spatiotemporal resolution.
Best practices of business process improvement: towards a representation on top of the Quintessence kernel
Authors: Vera Antonio , Zapata Carlos Mario
Published: May 2022

Purpose

Organizational process improvement plays an important role for sustaining business in a competitive environment. Therefore, enterprise leaders are increasingly prone to adopt business process improvement (BPI) practices. However, organizations are unable to implement formal and reusable solutions, representing a gap between academic research and practical use. In addition, companies adopt discipline-dependent solutions, lacking BPI representations of best practices applicable to all organizational divisions. This paper aims to propose some constructs on top of the Quintessence kernel for representing the practice systematic development of the BPI in the BPI lifecycle and we conduct two case studies in a multinational company.

Design/methodology/approach

A quantitative research design was adopted for recognizing gaps in previous approaches and identifying best BPI practices. Subsequently, characterization of practices and activities are represented based on a unified definition model and the Quintessence kernel. Finally, two case studies are developed for applying the solution.

Findings

The formal representation is applicable to multiple disciplines in organizational environments. Besides, the sub-alphas (abstract level progress health attribute) states and the work products resulting from each activity completion criteria evidence the health and progress accomplished during the practice execution.

Originality/value

The practice representation serves as a formal, graphical, reusable and multidiscipline guide compiling activities and tasks for systematically developing BPI during the radical/incremental improvement lifecycle.
Managing supply chains during the Covid-19 crisis: synthesis of academic and practitioner visions and recommendations for the future
Authors: Kohl Markus , Habl Andreas , Kallali Khalil , Puff Jakob , Fottner Johannes , Oger Raphaël , Lauras Matthieu , Li Jiayao
Published: May 2022

Purpose

The Covid-19 pandemic has created an environment of high uncertainty and caused major disruptions in supply chains. The new normal that has emerged during the pandemic is leading to a need to identify new solutions to improve supply chain crisis management in the future. Practitioners require adapted recommendations for solutions to implement. These recommendations are laid out in this paper.

Design/methodology/approach

A combination of a systematic literature review (SLR), qualitative semi-structured interviews and a questionnaire survey of supply chain practitioners is applied. The interviews provide insights into supply chain practitioners' views of their approaches and, together with the solutions proposed in the literature, provide future recommendations for action for supply chain managers.

Findings

During the pandemic, companies experienced disruptions in supply, production and demand, as well as interruptions in transportation and distribution. The majority of the solutions proposed in the literature, coincide with the opinions of practitioners. These include collaborative risk management, real-time monitoring and information sharing, supply network management, scenario planning and “what-if” simulations.

Research limitations/implications

Although the number of interviews conducted and questionnaires completed is limited, they still serve to supplement the SLR with important practical insights and recommendations.

Originality/value

This paper presents a review of recent academic literature focusing on the impact of Covid-19 on supply chains and the existing solutions to mitigate that impact and manage future crises. It has been expanded to include industry perspectives and experiences. The findings of this study present recommended practices and strategies for better managing supply chains during a crisis.
The troubling impact of political interference in Indonesian public sector institutions on ethical leadership credibility
Authors: Eryanto Dedy , van Eeden Jones Iris , Lasthuizen Karin
Published: May 2022

Purpose

This study investigates the impact of political interference on the capacity to combat corruption within Indonesian public sector institutions. It analyses the troubling impact of politicians in strategic leadership positions in public institutions and the impact this has on its ethical leadership credibility.

Design/methodology/approach

A qualitative multi-method approach was followed. Firstly, media publications were analysed to describe typical cases of corruption by political and public leaders and to evaluate the current state of the country. Secondly, the authors studied the selection and appointment processes for strategic leadership in two types of leading Indonesian public sector institutions based on laws and regulations and critical (media) publications to assess the problem of political interference. Lastly, the authors used insights from 42 face-to-face interviews within one leading public institution to understand the problem of political interference and its impact on ethical leadership credibility in Indonesia.

Findings

When politicians are appointed in strategic leadership positions of public institutions, including CEOs, the board of directors and commissioners, the downside is that such political support causes a conflict of interest that seriously threatens the independent functioning of public institutions and the ethical reputation of the public sector as a whole. The influence of specific Indonesian cultural values and norms only reinforces these ethical challenges in building public sector integrity.

Originality/value

Most empirical studies on ethical leadership focus on middle managers and the impact of ethical leadership on organisational outcomes. In addition, little is yet known about the effectiveness of ethical leadership in developing countries. This study attempts to address this gap and analyses the troubling role of politicians in strategic leadership positions in Indonesia's public institutions and the impact this has on its ethical leadership credibility.
Labor shortages during the COVID-19 and labor supply based on minimizing effort to achieve a target utility level: confounding economic policies
Authors: Cebula Richard , Foley Maggie
Published: May 2022

Purpose

The purpose of this analysis is to explain why labor shortages may have appeared during this pandemic. Interestingly, in this COVID-19 pandemic period, the labor supply shortage could very well become more easily explained than under the traditional portrayal of consumer economic behavior. The matter seemingly lends itself to provocative empirical inquiry.

Design/methodology/approach

From this model, it can be shown that the consumer’s labor supply curve is negatively sloped and, indeed, could even assume the form of a rectangular hyperbola. Applying this model in the labor market could explain the labor shortage in the USA during the COVID-19 pandemic.

Findings

Arguably, rational consumer behavior can take the form, under a variety of circumstances (including cultural), for consumers/households that have achieved a “comfortable” standing of living/utility level, involve the minimization of work effort to achieve that utility level. In other words, constrained utility maximization is not the only rational form of consumer economic behavior. When the former behavior prevails over the latter, there are myriad implications. These do include an inverse relationship between work effort and wage rate, i.e. a negatively sloped labor supply curve.

Originality/value

This paper departs from the conventional treatment of deriving the supply curve of labor based on constrained utility maximization. Instead, it acknowledges that consumers may have a target standard of living and seek to minimize the cost of achieving that given living standard.
The role of recommender systems in fostering consumers' long-term platform engagement
Authors: Maslowska Ewa , Malthouse Edward C. , Hollebeek Linda D.
Published: May 2022

Purpose

Recommender systems (RS) are designed to communicate with users and drive consumers' engagement with the platform. However, little is known about the strength of this relationship and how RS can create stronger consumer engagement (CE) with the platform brand. Addressing this gap, this paper examines the role of RS in converting consumers' short-term engagement with the RS to their longer-term platform engagement.

Design/methodology/approach

To explore these issues, the authors review key literature in the areas of CE and RS, from which they develop a conceptual framework.

Findings

The proposed framework suggests RS design as an important precursor to consumers' RS use, which is expected to affect their platform engagement/disengagement, in turn impacting the firm's long-term outcomes. The authors also identify key managerial tactics, strategies and challenges to aid the conversion of consumers' RS to CE.

Research limitations/implications

This research raises pertinent implications for research on the RS/CE interface, as synthesized in a proposed research agenda.

Practical implications

Based on the attained insight, authors outline implications for managing, facilitating and leveraging the proposed RS to CE conversion process. Correspondingly, authors argue that, to optimize RS effectiveness, RS designers should understand the nature of CE.

Originality/value

By exploring the effect of consumers' RS on their longer-term CE with the platform, the analyses offer pioneering managerial insight into RS effectiveness from a CE perspective.
An XGBoost-based multivariate deep learning framework for stock index futures price forecasting
Authors: Wang Jujie , Cheng Qian , Dong Ying
Published: May 2022

Purpose

With the rapid development of the financial market, stock index futures have been the one of important financial instruments. Predicting stock index futures accurately can bring considerable benefits for investors. However, traditional models do not perform well in stock index futures forecasting. This study put forward a novel hybrid model to improve the predictive accuracy of stock index futures.

Design/methodology/approach

This study put forward a multivariate deep learning framework based on extreme gradient boosting (XGBoost) for stock index futures price forecasting. First, the original sequences were decomposed into several sub-sequences by variational mode decomposition (VMD), and these sub-sequences were reconstructed by sample entropy (SE). Second, the gradient boosting decision tree (GBDT) was used to rank the feature importance of influential factors, and the top influential factors were chosen for further prediction. Next, reconstructed sequence and the multiple factors screened were input into the bidirectional gate recurring unit (BiGRU) for modeling. Finally, XGBoost was used to integrate the modeling results.

Findings

For the sake of examining the robustness of the proposed model, CSI 500 stock index futures, NASDAQ 100 index futures, FTSE 100 index futures and CAC 40 index futures are selected as sample data. The empirical consequences demonstrate that the proposed model can serve as an effective tool for stock index futures prediction. In other words, the proposed model can improve the accuracy of stock index futures.

Originality/value

In this paper, an innovative hybrid model is proposed to enhance the predictive accuracy of stock index futures. Meanwhile, this method can be applied in other financial products prediction to achieve better forecasting results.
Potential blood pressure lowering effect of L-citrulline supplementation in at risk populations: a meta-analysis
Authors: Jafarnejad Sadegh , Tsang Catherine , Amin Negin
Published: May 2022

Purpose

This paper aims to investigate the effect of L-citrulline supplementation on blood pressure (BP) in middle-aged and elderly populations.

Design/methodology/approach

Three electronic databases, namely, Google Scholar, PubMed and Scopus, were searched from 1990 to November 2020. Random effects model analysis was applied for quantitative data synthesis, and 6 trials with 150 participants were identified and included in the analysis.

Findings

Results showed an overall non-significant effect of L-citrulline supplementation on both systolic BP (SBP) and diastolic BP (DBP) in middle-aged and elderly participants. However, stratified analysis indicated a significant reduction in SBP (SMD: −0.41, 95% CI: −0.84, 0.02; p = 0.06, heterogeneity p = 0.41; I2 = 10%) but not in DBP (SMD:−0.15, 95% CI: −0.57, 0.28; p = 0.51, heterogeneity p = 0.60; I2 = 0%), following longer-term (= 8 weeks) supplementation of L-citrulline. Additionally, higher doses of L-citrulline (= 6 grams) showed a marginally significant reduction in DBP (SMD: −0.38, 95% CI: −0.78, 0.02; p = 0.06, heterogeneity p = 0.50; I2 = 0%).

Originality/value

In conclusion, a higher dosage and longer duration of supplementation with L-citrulline may have potential BP lowering effects in populations at an increased risk of hypertension
Luce Irigaray: A philosophy of teaching in ancient and modern perspective
Authors: White Richard
Published: May 2022

Luce Irigaray offers a powerful ‘philosophy of teaching’ that connects with the ancient paradigm. In this paper, I discuss the relationship between teaching and love as this is depicted in Plato, and I look at Irigaray's reading of the Symposium. Then I show how Irigaray's own philosophy can help us to think about the ideal teaching situation and its most essential aspects, including dialogue, difference, inspiration and embodiment. To be clear, this paper does not offer a comprehensive account of Irigaray's thought, but it extrapolates from her work on teaching and related themes such as love; and it sketches the outline of a guiding ideal, and a philosophy of teaching, which can help us in the current educational context.
The International Extension of Denial of Justice
Authors: Hepburn Jarrod
Published: May 2022

Denial of justice arises under customary international law when states prevent foreigners from accessing domestic courts. Certain states, scholars and arbitrators have maintained that an extension of the rule against denial of justice applies when states prevent access to international courts or tribunals. If correct, this extension would impose a significant control on states’ engagement with international adjudication. However, this article contends that the international extension of denial of justice is unsupported on any account of custom. A state's interference with international adjudication might be treated as ineffective, or it might breach the instrument containing the state's consent to the international claim. But this article argues that it does not, and should not, also breach the customary rule on denial of justice. The article therefore aims to clarify both the customary law in this area and the actual and desirable extent of states’ autonomy in their engagement with international adjudication.
The outcomes of margin status after sleeve lobectomy for patients of non–small cell lung cancer
Authors: Ren Jianghao , Zhu Mingyang , Xu Yuanyuan , Liu Ruijun , Ren Ting , Guo Zhiyi , Ren Jiangbin , Wang Kan , Tan Qiang
Published: May 2022

Background

Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy.

Methods

In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence‐free survival (RFS). We performed a subgroup analysis to further our investigation.

Results

After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence‐free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status.

Conclusion

In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.
Romania: Political Developments and Data in 2021
Authors: STAN LAVINIA , ZAHARIA RAZVAN
Published: May 2022

Romania was affected by Cabinet instability, an energy crisis and the Covid‐19 pandemic in 2021, a year when no elections or referenda were held. Its self‐interested political elite, rocked by scandals related to plagiarism and preoccupied almost exclusively with the distribution of positions, was unable to address the oil and gas crisis affecting every household, and unwilling to help an underfunded healthcare system.
The black summer bushfires: impacts and risk factors for livestock bushfire injury in south‐eastern Australia
Authors: Cowled BD , Hillman A , Ward MP , Clutterbuck H , Doyle M , Webb Ware J , Thomas M , Plain K , Barwell R , Laurence M , Pfeiffer C
Published: May 2022

Background

The 2019/2020 Australian bushfires were the largest bushfire event in modern Australian history. While actions to mitigate risk to homes from bushfires are well reported, there is very little research reported on the impacts of bushfires on livestock. With an increasing incidence of bushfires predicted, there is an urgent need to identify how farmers can best protect their livestock.

Objectives

Compare bushfire affected farms with and without injured livestock to identify associations between risk factors and bushfire injury. Infer management approaches that can be used to reduce bushfire injury in livestock.

Method

A case‐control study using a structured interview questionnaire, delivered in late 2020 to cattle and sheep farmers in south‐eastern Australia (New South Wales and Victoria) whose farmland was burnt in the 2019/2020 Australian bushfires. Case farms were farms with bushfires injured or killed livestock. Control farms were farms that had no bushfire injured livestock but that still had fire present on the farm. Interview responses were summarised and information theoretical approaches were used to identify potential risk factors for livestock bushfire injury and protective actions that could inform future fire‐preparation recommendations.

Results and discussion

Of 46 farms in the case‐control study, 21 (46%) reported bushfire injured or killed livestock. Apparent protective factors identified included: preparation (having a bushfire plan and more than two farm bushfire fighting units), backburning and receiving assistance from fire authorities. Combined beef and sheep grazing enterprises appeared to have an increased risk of bushfire injury to livestock.
Using intra‐task flexibility on an intelligent tutoring system to promote arithmetic problem‐solving proficiency
Authors: del Olmo‐Muñoz Javier , González‐Calero José Antonio , Diago Pascual D. , Arnau David , Arevalillo‐Herráez Miguel
Published: May 2022

Problem solving is often regarded as one of the most essential cognitive functions in our daily lives, and, for that reason, educational theorists have long stressed the need for its development. As cognitive flexibility is a fundamental characteristic necessary throughout the problem‐solving process, the purpose of this study is to analyse students' problem‐solving performance after following intra‐task flexibility‐based training mediated by an intelligent tutoring system. With this aim, 110 fifth and sixth grade students took part in a quasi‐experimental study that included six forty‐five‐minute flexibility‐based training sessions preceded and followed by test sessions in order to evaluate eventual problem‐solving proficiency improvements. The findings show that intra‐task flexibility training enhances students' ability to solve arithmetic word problems, especially when flexibility‐related activities are completed sequentially in the same session and not in different sessions. Furthermore, the proposed instruction is particularly helpful in improving girls' problem‐solving competence, which can minimize eventual gender gaps and strengthen their STEM vocation.

Practitioner notes

What is already known about this topic

Cognitive flexibility is beneficial in finding appropriate problem‐solving strategies.

Exposing students to a variety of problem‐solving methods or strategies can improve their cognitive flexibility.

Boys are more likely than girls to flexibly apply multiple solution paths while solving problems, which leads to gender differences in mathematics.

By contrast, girls are more prone to take advantage of instructional advice when using intelligent tutoring systems (ITS).

What this paper adds

Prompting students to apply multiple resolution strategies within the same problem (intra‐task flexibility instruction) is comparatively more efficient than standard instruction in promoting problem‐solving performance.

It is more effective in terms of problem‐solving proficiency to ask students to find different resolutions for a problem sequentially in the same session than to do so in separate sessions.

Effectiveness of ITS‐mediated flexibility‐based training leads to the promotion of problem‐solving proficiency, particularly in the case of female students.

Implications for practice and/or policy

The use of the ITS HINTS has the potential to promote the use of multiple solutions in problem solving by monitoring the resolution paths of the student, which can be difficult in a traditional classroom setting.

ITS‐mediated flexibility‐based training is especially effective in improving girls' problem‐solving competence, which can minimize eventual gender gaps and strengthen their STEM vocation.
Fifty years of the British journal of learning disabilities: The power of the past
Authors: Davies Ian , Iriate Edurne Garcia , Jarrett Simon , Johnson Kelley , Stainton Tim , Tilley Liz , Walmsley Jan
Published: May 2022

Accessible summary

This special issue of the journal celebrates the 50th birthday of the British Journal of Learning Disabilities (BJLD). The stories in this special issue are about the history of learning disability from around the world.

It is important that people know about the history of learning disability, because people with learning disabilities have been kept in the dark for too long. Ian Davies says “why should we be forgotten? We're as much a part of society as everyone else”.

Over the years BJLD has included stories about learning disability history, but many of these stories were written by people who do not have learning disabilities.

In the past few years, people with learning disabilities have been doing important history projects. In this special issue, we have included stories about history that have been written by people with learning disabilities.

In the next 50 years, it needs to be easier for people with learning disabilities to write for journals like BJLD. It should also be easier for people with learning disabilities to find out about other people's research in journals like BJLD.
Clinical significance of IDC‐P as predictive factor after intensity‐modulated radiation therapy
Authors: Aizawa Rihito , Tsuzuki Toyonori , Haga Hironori , Nakamura Kiyonao , Ogata Takashi , Inoue Takahiro , Kobayashi Takashi , Akamatsu Shusuke , Goto Takayuki , Ogawa Osamu , Mizowaki Takashi
Published: May 2022

The clinical significance of intraductal carcinoma of the prostate (IDC‐P) in men with nonmetastatic prostate cancer (PCa) treated with high‐dose external‐beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC‐P in men who received intensity‐modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high‐risk (H‐R) and very high–risk (VH‐R) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re‐reviewed biopsy cores for the presence of IDC‐P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6‐month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with H‐R and VH‐R PCa were analyzed. Intraductal carcinoma of the prostate was present in 27.9% (n = 43). The median follow‐up period was 8.4 years. The 10‐year PCa‐specific survival, biochemical failure (BF), clinical failure, and castration‐resistant PCa rates were 90.0%, 47.8%, 27.5%, and 24.5% in patients with IDC‐P, and 96.6%, 32.6%, 10.8%, and 7.0% in those without IDC‐P, respectively (p = 0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC‐P was not identified as an independent predictive factor for BF (p = 0.26). The presence of IDC‐P was correlated with a significantly higher incidence of disease progression in men with H‐R and VH‐R PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC‐P as an independent predictive factor for survival outcomes.
Measuring steroids in hair opens up possibilities to identify congenital adrenal hyperplasia in developing countries
Authors: Waaijers Selma , Utari Agustini , van der Doelen Rick H. A. , Faradz Sultana M. H. , Hensen‐Lodewijk Renate , Olthaar Andre J. , Geutjes Paul J. , Sweep Fred C. , Claahsen‐van der Grinten Hedi L. , van Herwaarden Antonius E.
Published: May 2022

Objective

Patients with congenital adrenal hyperplasia (CAH) in developing countries have limited access to appropriate laboratory facilities for diagnosis and follow‐up. The aim of this study is to evaluate steroid measurement in hair as a diagnostic tool to identify and monitor CAH in these patients.

Design

A method was developed to measure steroids in hair, the stability of steroids in hair was assessed, and the concentration range in healthy volunteers was determined. Hair samples of patients, before and after starting therapy, were transported at ambient temperature to The Netherlands for analysis.

Patients

Twenty‐two Indonesian CAH patients and 84 healthy volunteers participated.

Measurements

Cortisol, 17‐hydroxyprogesterone (17OHP), androstenedione, and testosterone in hair were measured by liquid chromatography with tandem mass spectrometry.

Results

Steroids in hair could be measured and remained stable (<4.9% deviation) for at least 3 weeks at 4°C and 30°C. In each of the untreated patients, hair concentrations of 17OHP (9.43–1135 pmol/g), androstenedione (36.1–432 pmol/g), and testosterone (2.85–69.2 pmol/g) were all above the upper limit of the corresponding range in healthy volunteers; 5.5 pmol/g, 13 pmol/g, and 1.8 pmol/g, respectively. After starting glucocorticoid treatment, the steroid concentrations in the hair of CAH patients decreased significantly for androstenedione (73%) and testosterone (59%) after 6 months.

Conclusions

CAH could be confirmed in Indonesian patients based on the concentration of 17OHP, androstenedione, and testosterone in hair, and a treatment effect was observed. These findings open up opportunities to diagnose and/or monitor CAH in developing countries with a simple noninvasive technique.
Evidence for a Shared Instrument Prototype from English, Dutch, and German
Authors: Rissman Lilia , van Putten Saskia , Majid Asifa
Published: May 2022

At conceptual and linguistic levels of cognition, events are said to be represented in terms of abstract categories, for example, the sentenceJackie cut the bagel with a knifeencodes the categories Agent (i.e.,Jackie) and Patient (i.e.,the bagel). In this paper, we ask whether entities such asthe knifeare also represented in terms of such a category (often labeled “Instrument”) and, if so, whether this category has a prototype structure. We hypothesized the Proto‐instrument is atool: a physical object manipulated by an intentional agent to affect a change in another individual or object. To test this, we asked speakers of English, Dutch, and German to complete an event description task and a sentence acceptability judgment task in which events were viewed with more or less prototypical instruments. We found broad similarities in how English, Dutch, and German partition the semantic space of instrumental events, suggesting there is a shared concept of the Instrument category. However, there was no evidence to support the specific hypothesis that tools are the core of the Instrument category—instead, our results suggest the most prototypical Instrument is the direct extension of an intentional agent. This paper supports theoretical frameworks where thematic roles are analyzed in terms of prototypes and suggests new avenues of research on how instrumental category structure differs across linguistic and conceptual domains.