bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic Deletion of X-box Binding Protein 1 in Farnesoid X Receptor Null Mice Leads to Enhanced Liver Injury
Authors: Liu Xiaoying , Khalafalla Mahmoud , Chung Chuhan , Gindin Yevgeniy , Hubchak Susan , LeCuyer Brian , Kriegermeier Alyssa , Zhang Danny , Qiu Wei , Ding Xianzhong , Fang Deyu , Green Richard
Published: March 2022

Background & Aims

Farnesoid X receptor (FXR) regulates bile acid metabolism and FXR null (Fxr-/-) mice have elevated bile acid levels and progressive liver injury. The inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP1) pathway is a protective pathway of the unfolded protein response (UPR) that is activated in response to ER stress. In this study we sought to determine the role of the UPR in Fxr-/- mice.

Approach & Results

We examined hepatic UPR gene and protein expression in 10- and 24-week-old wild type (WT) and Fxr-/- mice. Hepatic XBP1 and other UPR pathways were activated in 24-week-old Fxr-/- mice, but not WT mice. To further determine the role of the liver UPR activation in Fxr-/- mice, we generated mice with FXR and liver-specific XBP1 double knockout (DKO, Fxr-/-Xbp1LKO) and Fxr-/-Xbp1fl/fl single knockout (SKO) mice and characterized their phenotypes at different ages. DKO mice demonstrated enhanced liver injury, apoptosis and fibrosis compared with SKO mice. RNA-seq revealed increased gene expression in apoptosis, inflammation and cell proliferation pathways in DKO mice. The proapoptotic C/EBP-homologous protein (CHOP) pathway was activated in DKO mice. At age 60 weeks, all DKO mice and no SKO mice spontaneously developed liver tumors.

Conclusions

The hepatic XBP1 pathway is activated in older Fxr-/- mice and has a protective role. The potential interaction between XBP1 and FXR signaling may be important in modulating the hepatocellular cholestatic stress responses.
Type III interferons induce pyroptosis in gut epithelial cells and delay tissue restitution upon acute intestinal injury
Authors: Sposito Benedetta , Mambu Julien , Gwilt Katlynn Bugda , Spinelli Lionel , Andreeva Natalia , Galland Franck , Naquet Philippe , Mitsialis Vanessa , Thiagarajah Jay R , Snapper Scott B , Broggi Achille , Zanoni Ivan
Published: March 2022

Tissue damage and repair are hallmarks of the inflammatory process. Despite a wealth of information focused on the mechanisms that govern tissue damage, mechanistic insight on how inflammatory immune mediators affect the restitution phase is lacking. Here, we investigated how interferons influence tissue restitution after damage of the intestinal mucosa driven by inflammatory or physical injury. We found that type III, but not type I, interferons serve a central role in the restitution process. Type III interferons induce the upregulation of ZBP1, caspase activation, and cleavage of gasdermin C, and drive epithelial cell death by pyroptosis, thus delaying tissue restitution. We also found that this pathway is transcriptionally regulated in IBD patients. Our findings highlight a new molecular signaling cascade initiated by the immune system that affects the outcome of the immune response by delaying tissue repair and that may have important implications for human inflammatory disorders.
SUMO conjugation regulates the activity of the Integrator complex
Authors: Bragado Laureano , Magalnik Melina , Mammi Pablo , Romero Agustín , Gaioli Nicolás , Pozzi Berta , Srebrow Anabella
Published: March 2022

RNA pol II transcribes snRNA genes in close proximity to Cajal bodies, subnuclear compartments that depend on the SUMO isopeptidase USPL1 for their assembly. We show here that overexpression of USPL1 alters snRNA 3’-end cleavage, a process carried out by the Integrator complex. Beyond its role in snRNA biogenesis, this complex is responsible for regulating the expression of different non-coding and coding transcripts. We validated several subunits of the complex as SUMO conjugation substrates, and found that the SUMOylation of INTS11 subunit is regulated by USPL1. We defined Lys 381, Lys 462 and Lys 475 as bona fide SUMO attachment sites within INTS11 and observed that SUMOylation of this protein is required for efficient Integrator activity. Moreover, while an INTS11 SUMOylation deficient mutant is still capable of interacting with INTS4 and INTS9, its interaction with other subunits of the complex is affected. This mutant also shows a more cytoplasmatic localization than the wild type protein. These findings point to a regulatory role of SUMO conjugation on Integrator activity and suggest the involvement of INTS11 SUMOylation in the assembly of the complex. Furthermore, this work adds the Integrator-dependent RNA processing to the growing list of cellular processes regulated by SUMO conjugation.
Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers
Authors: Wu Meiyun , Wang Yuyang , Zhao Xue , Xin Tianyu , Wu Kun , Liu Haotian , Wu Shinan , Liu Min , Chai Xiaoke , Li Jinhong , Wei Chaogang , Zhu Chaozhe , Liu Yuhe , Zhang Yu-Xuan
Published: March 2022

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children with prelingual deafness provide a unique opportunity to study this developmental stage. Using functional near-infrared spectroscopy, we revealed that the brain of CI children was nearly irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. In addition, speech responses increased linearly in left sylvian parieto-temporal area and right inferior frontal gyrus, and noise responses changed in U shape in right supramarginal gyrus. Such cortical development predicted behavioral improvement. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition in the human brain.

Graphic abstract

Highlights

The brain of cochlear implanted toddlers is functionally inferior to neonates

Hearing experiences drive functional development in auditory related cortical areas

Speech and noise processing develop in anti-phasic oscillatory trajectories

Auditory cortical development predicts post-implantation behavioral improvement
Medial septum activation improves strategy switching once strategies are well learned via bidirectional regulation of dopamine neuron population activity
Authors: Bortz D.M. , Feistritzer C.M. , Power C.C. , Grace A.A.
Published: March 2022

Strategy switching is a form of cognitive flexibility that requires inhibiting a previously successful strategy and then switching to a new strategy of a different categorical modality. It is dependent on dopamine (DA) receptor activation and release in ventral striatum and prefrontal cortex, two primary targets of ventral tegmental area (VTA) DA projections. Although the circuitry that underlies strategy switching early in learning has been studied, few studies have examined it after extended discrimination training. This may be important as DA activity and release patterns change across learning, with several studies demonstrating a critical role for substantia nigra pars compacta (SNc) DA activity and release once behaviors are well learned.

Our previous studies demonstrated that medial septum (MS) activation simultaneously increased VTA and decreased SNc DA population activity, as well as improved reversal learning via these actions on DA population activity. We hypothesized that MS activation would improve strategy switching both early in learning and after extended training through its ability to increase VTA DA population activity and decrease SNc DA population activity, respectively. To test this, we activated the MS of male and female rats with designer receptors exclusively activated by designer drugs and measured their performance on an operant-based strategy switching task, following 1, 10, or 15 days of discrimination training. Contrary to our hypothesis, MS activation did not affect strategy switching after 1 day of discrimination training. MS activation improved strategy switching after 10 days of discrimination training, but only in females. MS activation improved strategy switching in both sexes after 15 days of discrimination training. This improvement in strategy switching was attenuated by intra-ventral subiculum bicuculline infusion, which selectively inhibited the MS-mediated decrease in SNc DA population activity, and prevented by infusion of both bicuculline and scopolamine, which inhibited both the MS-mediated decrease in SNc and increase in VTA DA population activity. These data indicate that MS activation improves strategy switching, but only once the original strategy has been sufficiently well learned. They also suggest that the mechanism by which this occurs is likely via the MS’s regulation of DA neuron responsivity, primarily via its ability to down-regulate DA population activity in the SNc.
Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase
Authors: Yang Xiaoli , Ding Zhanyu , Peng Lisi , Song Qiuyue , Cui Fang , Zhang Deyu , Xia Chuanchao , Li Keliang , Yin Hua , Li Shiyu , Li Zhaoshen , Huang Haojie
Published: March 2022

The enteropeptidase (EP) initiates the intestinal digestion by proteolytic processing of trypsinogen, generating catalytic active trypsin. The dysfunction of EP will cause a series of pancreatic diseases, the most severe of which is acute necrotizing pancreatitis. However, the molecular mechanism of EP activation and substrate recognition remain elusive due to the lack of structural information, hampering the structure-based research of EP and even further EP-targeted drug design. Here we report cryo-EM structures of human EP in multiple states, covering the functional cycle spanning from inactive to active state and eventually to the substrate binding state, with the inactive core region reached an atomic 2.7-Å-resolution. The heavy chain of EP exhibits a clamping configuration with the CUB2 domain serving for substrate recognition. The N-terminus of light chain induces the surface loop remodeling from inactive to active conformation, resulting in a highly dynamic and active EP. Then the heavy chain performs like a hinge to ensure the flexibility of light chain for substrate recruitment and subsequent cleavage. Our study provides structural insights of EP remodeling and heavy chain dynamics while performing enzymatic function, facilitating our understanding of the pathogenies of EP-related pancreatitis and the EP-targeted treatment of pancreatitis.
Crystal structure and Hirshfeld surface analysis of tris(acetohydrazide-κ2
N,O)(nitrato-κO)(nitrato-κ2
O,O′)terbium(III) nitrate
Authors: Theppitak Chatphorn , Laksee Sakchai , Chainok Kittipong
Published: March 2022

In the title lanthanide(III) compound, [Tb(NO3)2(C2H6N2O)3]NO3, the asymmetric unit contains one Tb3+ ion, three acetohydrazide (C2H6N2O) ligands, two coordinated nitrate anions, and an isolated nitrate anion. The Tb3+ ion is in a ninefold coordinated distorted tricapped trigonal–prismatic geometry formed by three oxygen atoms and three nitrogen atoms from three different acetohydrazide ligands and three oxygen atoms from two nitrate anions. In the crystal, the complex molecules and the non-coordinated nitrate anions are assembled into a three-dimensional supramolecular architecture through extensive N—H...O hydrogen-bonding interactions between the amine NH groups of the acetohydrazide ligands and the nitrate oxygen atoms. Hirshfeld surface analysis was performed to aid in the visualization of intermolecular contacts.
Hybridity in a hotel chain: designing a package of controls to sustain a hybrid mission
Authors: Bouten Lies , Hoozée Sophie
Published: March 2022

Purpose

While prior control studies typically focus on organizations with an instrumental approach to corporate sustainability, this study concentrates on organizations with an integrative approach, as the latter is needed to address the grand challenge of sustainable development. As such organizations do not single out the financial objective as the dominant one, they pursue a hybrid mission. This study investigates how a control package can be designed that ensures the persistence of such a hybrid mission.

Design/methodology/approach

A case study is undertaken at a luxury hotel chain in which a financial and an environmental objective are continuously balanced. Self-determination theory is used to substantiate insights into how psychological need-supportive controls can be designed at all organizational levels.

Findings

This study highlights how controls are not only needed to direct staff behaviour towards the environmental objective but also to ensure that staff at all organizational levels prioritize the objectives in such way that the hybrid mission can be sustained. Besides structural differentiation and centralization of decision-making, the case organization designed need-supportive controls to foster staff's internalization of the environmental objective and value as well as of the integrative approach.

Social implications

As the need-supportive socialization process fostered staff's integration of the environmental value, this study highlights the transformational potential of controls.

Originality/value

This study provides a unique account of a control package directing staff behaviour towards the balancing of multiple objectives.
Knowledge management capability, entrepreneurial creativity, entrepreneurial intensity and firm performance: the mediating role of ambidexterity
Authors: Garousi Mokhtarzadedeh Nima , Jafarpanah Ismail , Zamani Babgohari Ali
Published: March 2022

Purpose

Literature survey shows that it is not clear how knowledge management capability (KMC) and ambidexterity capability affect entrepreneurial creativity (EC) and entrepreneurial intensity (EI) promotion. While empirical studies have emphasized the importance of these factors in improving business performance, the cumulative effect and self-reinforcing loops of these factors in improving firm performance have not been identified. In this regard, the study seeks to investigate how to increase the entrepreneurial capabilities of KMC, EI, EC and ambidexterity of food firms to improve their performance.

Design/methodology/approach

The method of the present study is applied in terms of purpose and is quantitative in terms of data collection. In order to collect the data, a questionnaire was designed that contained the variables of the conceptual model of the research. This questionnaire was distributed among industrial and academic experts in the Iranian food industry. The method of data collection is an online cross-sectional survey, and the method of data analysis is structural equation modeling using Smart PLS software to analyze the conceptual model.

Findings

The present study is cross-sectional survey research that examines the impact of KMC, EC and EI on firm performance by considering the mediating role of organizational ambidexterity. The research study shows a positive impact of entrepreneurial capabilities as KMC, EI, EC and ambidexterity on performance. Accordingly, if a firm builds KMC and fosters EC, it can achieve ambidextrous innovation and thus enhance its EI and performance in the food industry.

Research limitations/implications

This study highlights the knowledge-based view (KBV) in explaining the role of KMC on innovative capabilities and its influence on performance. Research findings shed light on the importance of KMC as a prerequisite for innovation strategy. The study has also established the mediating role of ambidexterity in entrepreneurial value creation. According to the results, small and medium-sized enterprises (SMEs)' performance is positively influenced by entrepreneurial capabilities as KMC, EI, EC and ambidexterity.

Originality/value

This paper gives insights into how SMEs can improve their performance to gain a competitive advantage by developing knowledge and creative ideas in line with entrepreneurial goals. In this regard, the food industry can adopt new strategies to reduce the impact of these challenges to achieve superior performance and competitive advantage.
Benchmarking Industry 4.0 readiness evaluation using fuzzy approaches
Authors: Wankhede Vishal Ashok , Vinodh S.
Published: March 2022

Purpose

The purpose is to assess Industry 4.0 (I4.0) readiness index using fuzzy logic and multi-grade fuzzy approaches in an automotive component manufacturing organization.

Design/methodology/approach

I4.0 implies fourth industrial revolution that necessitates vital challenges to be dealt with. In this viewpoint, this article presents the evaluation of I4.0 Readiness Index. The evaluation includes two levels with appropriate criteria and factors. Fuzzy logic approach is used for assessment. Furthermore, the results obtained from fuzzy logic have been benchmarked with multi-grade fuzzy approach.

Findings

The proposed assessment model has successfully utilized fuzzy logic approach for assessment of I4.0 readiness index of automotive component manufacturing organization. Based on fuzzy logic approach, readiness index of I4.0 has been found to be (4.74, 6.26, 7.80) which is further benchmarked using multi-grade fuzzy approach. Industry 4.0 readiness index obtained from multi-grade fuzzy approach is 6.258 and thus, validated. Furthermore, 20 weaker areas have been identified and improvement suggestions are provided.

Research limitations/implications

The assessment module include two levels (Six Criteria and 50 Factors). The assessment model could be expanded based on advancements in industrial developments. Therefore, future researchers could utilize findings of the readiness model to further develop multi-level assessment module for Industry 4.0 readiness in organization. The developed readiness model helped researchers in understanding the methodology to assess I4.0 readiness of organization.

Practical implications

The model has been tested with reference to automotive component manufacturing organization and hence the inferences derived have practical relevance. Furthermore, the benchmarking strategy adopted in the present study is simple to understand that makes the model unique and could be applied to other organizations. The results obtained from the study reveal that fuzzy logic-based readiness model is efficient to assess I4.0 readiness of industry.

Originality/value

The development of model for I4.0 readiness assessment and further analysis is the original contribution of the authors. The developed fuzzy logic based I4.0 readiness model indicated the readiness level of an organization using I4RI. Also, the model provided weaker areas based on FPII values which is essential to improve the readiness of organization that already began with the adoption of I4.0 concepts. Further modification in the readiness model would help in enhancing I4.0 readiness of organization. Moreover, the benchmarking strategy adopted in the study i.e. MGF would help to validate the computed I4.0 readiness.
Do corporate social responsibility reduce crash risk of stock price: evidence from China
Authors: Su Kun , Zhou Ziting
Published: March 2022

Purpose

The 2008 global financial crisis stimulated the research interest in stock price crash risk. However, the determinants of stock price crash risk remain unclear, especially in transitional economies. The purpose of this paper is to investigate the association between corporate social responsibility (CSR) and stock price crash risk, as well as the moderating effects under different contexts.

Design/methodology/approach

Using firm-level data of listed firms in China from 2010 to 2019, this paper estimates with correlation analysis and multiple regression analysis.

Findings

This paper’s empirical results show that the constraint of CSR on bad news hoarding behavior can reduce stock price crash risk. Further research shows that internal CSR has a significant effect on crash risks, while external CSR has not. Additionally, CSR has a relatively weak impact on crash risk in state-owned enterprises, enterprises with higher internal control quality and enterprises with better regional financial development.

Originality/value

This paper contributes to the stock price crash risks literature by examining the CSR-stock price crash risk linkage in a Chinese context, revealing collective explanations under different contexts with important implications for the application of CSR in business practice.
Evaluating megaprojects from a sustainability perspective: a case of China-Pakistan economic corridor (CPEC)
Authors: Hassan Masoodul , Mahmood Zeeshan , Janjua Saleem , Asif Numra
Published: March 2022

Purpose

This paper aims to examine the impact of various economic, social and environmental issues on the sustainable development of Pakistan, both directly and indirectly through the sustainability dimensions of China–Pakistan Economic Corridor (CPEC), a multi-billion-dollar megaproject.

Design/methodology/approach

Using a quantitative (deductive) methodological approach, data were collected using a strategy of an online questionnaire survey from diverse stakeholders of CPEC in Pakistan. Partial least squares-based structural equation modeling technique was used to test the relationship between observed and latent variables.

Findings

The results confirmed the positive impact of various economic, social and environmental issues on the sustainable development of Pakistan directly and indirectly through the partial mediation of sustainability dimensions of CPEC.

Practical implications

Sustainability perceptions of stakeholders about CPEC and its relationship with sustainable development are critical issues for governments and policymakers. This paper suggest how economic, social and environmental dimensions of CPEC can enhance the positive perception which is necessary for stakeholder involvement and support for megaprojects such as CPEC.

Originality/value

This study evaluated the megaprojects of CPEC from a sustainability perspective through stakeholders’ perceptions by proposing and testing a parsimonious research model that has never been examined in the existing literature.
Impact of working capital management on profitability: evidence from listed companies in Qatar
Authors: Aldubhani Maad A. Q. , Wang Jitian , Gong Tingting , Maudhah Ramzi Ali
Published: March 2022

Purpose

This study aimed to find out whether working capital management policies affect the profitability of manufacturing companies listed on the Qatar Stock Exchange.

Design/methodology/approach

To assess the working capital management and profitability relationship, the authors applied a multiple regression analysis methodology in all manufacturing companies listed on the Qatar Stock Exchange (ten firms) between 2015 and 2019. Average collection period, inventory turnover, average payment period and cash conversion cycle were adopted as proxies for working capital management, and profitability was measured by operating profit margin (OPM), return on assets (ROA), return on capital employed (ROCE) and return on equity (ROE).

Findings

The study found that companies with shorter receivables collection periods and cash conversion cycles are more profitable. Longer inventory turnover periods and accounts payable payment periods are related to higher profitability of the firms.

Originality/value

Previous studies have assessed the relationship between working capital management and profitability. However, this study is the first one to use these four variables combined (OPM, ROA, ROCE and ROE) to measure profitability; this is what was limited in previous studies. In comparison, the previous studies were not comprehensive in studying the impact of working capital management on profitability from all aspects of profitability's variables [operational (OPM), economic (ROA), capitalist (ROCE) and financial (ROE)]. However, this study focused on all these aspects to make the results of the study more accurate. Also, it is worth mentioning that this study is the first research performed on Qatar Stock Exchange, although Qatar has achieved remarkable progress in the industrial sector in recent years, making it one of the first industrialized countries in the Middle East.
Money laundering risk judgement by compliance officers at financial institutions in Malaysia: the effects of customer risk determinants and regulatory enforcement
Authors: Jamil Ainul Huda , Mohd-Sanusi Zuraidah , Mat-Isa Yusarina , Yaacob Najihah Marha
Published: March 2022

Purpose

This paper aims to provide an empirical analysis of the effects of regulatory enforcement and customer risk determinants on money laundering risk judgment. The study further explores the moderating impact of regulatory enforcement on compliance officers in the banking and money service business (MSB) sectors. The analysis is conducted to find the important factors that contribute to the issues of risk judgement among compliance officers to establish effective anti-money laundering (AML) and countering financing of terrorism compliance at the financial institutions, as highlighted in the National Risk Assessment Report 2017 by the Central Bank of Malaysia.

Design/methodology/approach

An experimental study with four different scenarios of case studies distributed to 124 compliance officers at the banking and MSB sectors was conducted via online platforms. The paper uses a quantitative approach via structural equation modelling.

Findings

The result shows a significant effect of customer risk determinants and regulatory enforcement on money laundering risk judgement, taking into account competency as the control measure. A further test on the interaction effects of both determinants shows a significant result on the money laundering risk judgement. The empirical evidence indicated that regulatory enforcement influenced compliance officers’ money laundering risk judgement and suspicious transaction report submission. In other words, the banking and MSB sectors’ AML compliance significantly depends on the regulators’ enforcement activity.

Research limitations/implications

This study is limited to two independent variables: regulatory enforcement and customer risk determinants. Future studies may consider other factors affecting compliance officers’ money laundering risk judgement, such as technical competency, knowledge management, digitalization and technology and ethical issues.

Practical implications

This study provides several theoretical and practical implications. Emphasizing the excellent quality of judgement and, eventually, good quality of reporting the suspicious transactions will not be achieved merely from enforcing fines and punishment, but comprehensive measures must be taken. Increasing the competency and training, educating the compliance officers, supporting the industry and practitioners with incentives and digitalization, enhancing the campaign and awareness among the public and standardizing the policy shall be the good initiatives for the regulatory enforcement to establish.

Originality/value

This paper provides a valuable contribution to the body of knowledge and fulfills the significant gaps in the literature on money laundering, not to mention, the integration between behavioural studies and anti-money laundering compliance, which has scarcely been statistically evident from the research studies.
The disproportionate value of ‘weeds’ to pollinators and biodiversity
Authors: Balfour Nicholas J. , Ratnieks Francis L. W.
Published: March 2022

Agricultural intensification has been implicated in global biodiversity declines. In the European Union, agri‐environmental schemes are designed to address this. For pollinating insects, funding has been provided to sow wildflower mixes. However, previous research indicates that a suite of agricultural weeds are also of great importance to pollinators.

Here, we compare the biodiversity associated with the species which are considered harmful to agricultural production and legally deemed as ‘injurious’ by the United Kingdom 1959 Weeds Act (common ragwort Jacobaea vulgaris, creeping thistle Cirsium arvense, spear thistle C. vulgare, curled dock Rumex crispus and broadleaved dock R. obtusifolius), with plant species recommended for pollinator‐targeted agri‐environmental options.

In our field study, the abundance and diversity of pollinators visiting the weed species averaged twice that of the recommended plants and included the main insect orders (Coleoptera, Diptera, Hymenoptera and Lepidoptera). This relationship was also seen in a meta‐analysis of literature data, which indicates that fourfold more flower‐visitor species and fivefold more conservation‐listed species are associated with the weeds. Additionally, the literature shows that twice the number of herbivorous insect species are associated with these plants.

We suggest that several factors are responsible for this pattern. Injurious weed species are widely distributed, their flower morphology allows access to a wide variety of pollinator species, and they produce, on average, four times more nectar sugar than the recommended plant species.

Freedom of information requests to public bodies such as local councils, Natural England and Highways England indicate that c. £10 million per year is spent controlling injurious weeds. Meanwhile, the cost of the four pollinator‐targeted agri‐environmental options in the United Kingdom exceeds £40 m annually.

Synthesis and applications. Our results clearly show that weeds have an underappreciated value to biodiversity. Unfortunately, current UK agricultural policy encourages neither land sparing for nor land sharing with weeds. The UK government is, however, currently committed to overhauling agricultural payments to encourage more wildlife‐ and climate‐friendly practices. Thus, the challenge of reconciling the conflicts between agricultural production and these native and biodiverse species should be a renewed priority to land managers, researchers and policymakers.
Accelerated avian invasion into the Mediterranean region endangers biodiversity and mandates international collaboration
Authors: Magory Cohen Tali , Hauber Mark E. , Akriotis Triantaphyllos , Crochet Pierre‐André , Karris Georgios , Kirschel Alexander N. G. , Khoury Fares , Menchetti Mattia , Mori Emiliano , Per Esra , Reino Luís , Saavedra Susana , Santana Joana , Dor Roi
Published: March 2022

Despite posing a serious threat to global biodiversity, national and international management efforts have not been able to limit the spread of most invasive species. In highly dispersive species, local invasions may be followed by regional range expansion that crosses international borders. In such cases, independent management efforts of the invading population may be futile unless international collaboration is practiced.

We focus on the ongoing human‐mediated invasion of the common myna Acridotheres tristis into the Mediterranean basin, a region rich in overall numbers of species and endemic species, where common mynas have been introduced into a handful of countries. Some introductions were followed by subsequent range expansions into neighbouring countries. This species poses major threats to the biodiversity of the Mediterranean which is already susceptible to biodiversity loss as the result of ongoing land use and climate changes. Without action, this species and possibly others similar to it, could have severe consequences for native ecosystems.

Policy implications. Given the regional scope of its invasion in the Mediterranean basin, common myna management requires an international collaboration to successfully prevent additional introductions and range expansions and to avoid accelerating threats to Mediterranean biodiversity, already at risk as a result of ongoing changes in land use and climate. We argue that international reciprocal transfer of information and the development of regional mitigation are essential for the successful management of the invasion of the common myna and other species into the Mediterranean.
Unreasonably Limiting Recourse to the Courts? R (on the application of Haworth) v HMRC
Authors: Blackwell Michael
Published: March 2022

Follower notices, introduced in Finance Act 2014, can in certain avoidance situations be served on a taxpayer by HMRC (the UK revenue authority) where HMRC is of the opinion that the principles or reasoning of a decided case would deny the tax advantage in dispute. Such a taxpayer, who persists with the dispute, is then exposed to a tax‐geared penalty of up to 50 percent and can be required to pay the tax in dispute before the litigation is determined. The follower notice regime was considered by the UK Supreme Court in R (on the application of Haworth) v HMRC. The Supreme Court judgment addresses fundamental issues concerning access to the courts, the doctrine of precedent and balancing taxpayer rights against the public interest in the collection of taxes.
Brexit, food law and the UK's search for a post‐EU identity
Authors: Lydgate Emily , Anthony Chloe
Published: March 2022

Food law has played a central, contested role in defining the UK's post‐Brexit identity as a regulating and trading nation. Mapping reforms to key areas of food law across retained EU law, the UK internal market and UK trade law and policy reveals profound reforms, and an emerging, distinct UK approach to law‐making. We identify three themes: increased conferral of regulatory powers and functions to UK Ministers, coupled with an expansion of so‐called non‐legislative approaches to regulation and policy‐making and increased scope for divergence between UK nations. These reforms have achieved core aims of the UK government: autonomy from the EU, a fully frictionless internal market within Great Britain, and streamlined regulatory reform. However, the achievement of these aims has come at a price. Food law reveals that post‐Brexit legislative processes have been shaped by, but also entrench, unilateral executive decision‐making, lessened transparency and disunity between UK nations.
The paradox of local inequality: Meritocratic beliefs in unequal localities
Authors: Morris Katy , Bühlmann Felix , Sommet Nicolas , Vandecasteele Leen
Published: March 2022

A puzzle has emerged amidst rising inequality: why do people profess high levels of belief in meritocracy even as income gains are increasingly concentrated at the top? In light of contradictory theories and evidence, we undertake the first assessment of the relationship between local income inequality and meritocratic beliefs outside the United States, using data from the UK Household Longitudinal Study. We find that the positive relationship between country‐level income inequality and meritocratic beliefs identified in the recent literature does not translate straightforwardly below country level: there is no robust relationship between local income inequality and meritocratic beliefs in England. However, there is a robust—and somewhat paradoxical—positive association between high local income inequality and meritocratic beliefs among those with the lowest incomes. On average, respondents with annual household incomes of £10,000 are five points more likely (on a 100‐point scale) to believe their hard work will pay off if they live in the most rather than the least unequal places in England. We also show that this applies beyond the specific case of meritocratic beliefs: low‐income respondents in unequal places are also notably more satisfied with their own (low) income than similar respondents in more equal localities. In line with system justification theory, we argue that belief in meritocracy serves as an important tool of psychological resilience for low‐income individuals who regularly come into contact with others more economically fortunate than themselves: though it legitimates their current position at the bottom of the status hierarchy, this belief also offers the promise of future advancement. While this reduces concern about the psychological effects of growing local income inequality on the most economically vulnerable, it also suggests that there is little prospect of demand for systemic economic change emerging from what might have been considered the most likely places.
Low‐ versus high‐concentration intravenous immunoglobulin for children with Kawasaki disease in the acute phase
Authors: Suzuki Takanori , Michihata Nobuaki , Yoshikawa Tetsushi , Saito Kazuyoshi , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: March 2022

Purpose

Few studies have compared the effects of low‐concentration (5%) and high‐concentration (10%) intravenous immunoglobulin (IVIG) preparations for patients with Kawasaki disease (KD) in the acute phase. The purpose of this study was to compare outcomes between low‐ and high‐concentration IVIG preparations in children with KD, using a national inpatient database in Japan.

Method

We used the Diagnostic Procedure Combination database to identify patients with KD treated with IVIG from April 2012 to March 2020. We identified those receiving high‐ and low‐concentration IVIG preparations as an initial treatment. The outcomes included the proportions of patients with coronary artery abnormalities (CAAs) and IVIG resistance, length of stay, and medical costs. Propensity score‐matched analyses were conducted to compare the outcomes between the 2 groups. Instrumental variable analyses were performed to confirm the results.

Result

We identified 48 046 patients with KD and created 4:1 propensity score‐matched pairs between the low‐ and high‐concentration IVIG groups. There was a significant difference in the percentage with IVIG resistance between the 2 groups (20.6% vs 24.1%; risk difference, 3.5% [95% confidence interval, 2.3‐4.7]; P < .001). However, there was no significant difference in CAAs (1.6% vs 1.6%; risk difference, 0.013% [95% confidence interval, −0.34 to 0.37]; P = .953). The instrumental variable analyses showed similar results.

Conclusions

The proportion of CAAs did not differ significantly between those receiving low‐ and high‐concentration IVIG. To confirm the results of this study, prospective studies adjusting for duration of IVIG administration and duration of observation are needed.
Biological mechanisms of aging predict age‐related disease co‐occurrence in patients
Authors: Fraser Helen C. , Kuan Valerie , Johnen Ronja , Zwierzyna Magdalena , Hingorani Aroon D. , Beyer Andreas , Partridge Linda
Published: March 2022

Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age‐related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co‐occurrence of age‐related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non‐random associations between age‐related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age‐related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age‐related diseases. Mechanisms of aging hence contribute both together and individually to age‐related disease co‐occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.
Fast and efficient algorithms for sparse semiparametric bifunctional regression
Authors: Novo Silvia , Vieu Philippe , Aneiros Germán
Published: March 2022

A new sparse semiparametric model is proposed, which incorporates the influence of two functional random variables in a scalar response in a flexible and interpretable manner. One of the functional covariates is included through a single‐index structure, while the other is included linearly through the high‐dimensional vector formed by its discretised observations. For this model, two new algorithms are presented for selecting relevant variables in the linear part and estimating the model. Both procedures utilise the functional origin of linear covariates. Finite sample experiments demonstrated the scope of application of both algorithms: the first method is a fast algorithm that provides a solution (without loss in predictive ability) for the significant computational time required by standard variable selection methods for estimating this model, and the second algorithm completes the set of relevant linear covariates provided by the first, thus improving its predictive efficiency. Some asymptotic results theoretically support both procedures. A real data application demonstrated the applicability of the presented methodology from a predictive perspective in terms of the interpretability of outputs and low computational cost.
Recurrent surgery in uterine prolapse: A nationwide register study
Authors: Brunes Malin , Johannesson Ulrika , Drca Anna , Bergman Ida , Söderberg Marie , Warnqvist Anna , Ek Marion
Published: March 2022

Introduction

One in three women with pelvic organ prolapse (POP) undergoing surgery have a relapse. Currently, no optimal surgical treatment has been identified for correcting a uterine prolapse. This population‐based register study aims to compare the relapse rate in patients with uterine prolapse undergoing hysterectomy with suspension or uterine‐sparing surgical procedures.

Material and methods

All women with uterine prolapse undergoing prolapse surgery in Sweden from January 1, 2015 to December 31, 2018, were identified from the Gynecological Operation Register (GynOp). The primary outcome was the number of recurrent POP surgeries up to December 31, 2020.

Results

Sacrospinous hysteropexy (SSHP) without graft and sacrohysteropexy (SHP) were associated with a significantly higher rate of recurrent POP surgery (SSHP without graft: adjusted odds ratio [aOR] 2.6, 95% CI 2.0–3.5; SHP aOR 2.6, 95% CI 1.8–3.7) and patients describing a sense of globe (SSHP without graft, aOR 2.0, 95% CI 1.6–2.6; SHP, aOR 1.8, 95% CI 1.1–3.1) compared with cervical amputation with uterosacral ligament fixation (Manchester procedure). There was no difference in the reoperation rate or sense of a globe between SSHP with graft and Manchester procedure. Patients undergoing SSHP without graft had a higher frequency of 1‐year postoperative complications compared with Manchester procedure (aOR 2.0, 95% CI 1.6–2.6) and SHP (aOR 2.4, 95% CI 1.4–3.9). Moreover, the frequency of 1‐year postoperative complications was higher in SSHP with graft (aOR 1.6, 95% CI 1.1–2.2) than in Manchester procedure.

Conclusions

The Manchester procedure was associated with a low rate of recurrent POP surgery, symptomatic recurrence and low surgical morbidity compared with other surgical methods in women with uterine prolapse.
Effects of dietary supplementation with N‐carbamylglutamate on maternal endometrium and fetal development during early pregnancy in Inner Mongolia white cashmere goats
Authors: Zhang Chong Zhi , Sang Dan , Wu Bao Sheng , Li Sheng Li , Zhang Chun Hua , Jin Lu , Li Jin Xia , Gu Ying , Ga Na Mei Ri , Hua Mei , Sun Hai Zhou
Published: March 2022

This study investigated the effects of dietary supplementation with N‐carbamylglutamate (NCG) on maternal endometrium and fetal development during early pregnancy of Inner Mongolia white cashmere goats. Forty‐eight pregnant Inner Mongolia white cashmere goats (average age 3 years old, average lactation parity 2, and average body weight 43.81 ± 2.66 kg) were randomly allocated to three groups: a basal diet (control group, n = 16), a basal diet plus 0.30‐g NCG/d (NCG1 group, n = 16), and a basal diet plus 0.40‐g NCG/d (NCG2 group, n = 16). All of the does were housed in individual pens and the NCG treatment was conducted from Days 0 to 90 of pregnancy. At Days 17 and 90 of pregnancy, six representative pregnant does in each group were slaughtered. The current study results demonstrated that maternal NCG administration during early pregnancy effectively increased the arginine family of amino acids and the glucogenic amino acids concentrations and promoted the mRNA expression of osteopontin (OPN), αv and β3 integrins, and endometrial development of Inner Mongolia white cashmere goats. The supplementation improved the fetal brown adipose tissue (BAT) stores and the mRNA expression of UCP‐1 and BMP7, thereby helping to the fetal early development.
Spatial+: A novel approach to spatial confounding
Authors: Dupont Emiko , Wood Simon N. , Augustin Nicole H.
Published: March 2022

In spatial regression models, collinearity between covariates and spatial effects can lead to significant bias in effect estimates. This problem, known as spatial confounding, is encountered modeling forestry data to assess the effect of temperature on tree health. Reliable inference is difficult as results depend on whether or not spatial effects are included in the model. We propose a novel approach, spatial+, for dealing with spatial confounding when the covariate of interest is spatially dependent but not fully determined by spatial location. Using a thin plate spline model formulation we see that, in this case, the bias in covariate effect estimates is a direct result of spatial smoothing. Spatial+ reduces the sensitivity of the estimates to smoothing by replacing the covariates by their residuals after spatial dependence has been regressed away. Through asymptotic analysis we show that spatial+ avoids the bias problems of the spatial model. This is also demonstrated in a simulation study. Spatial+ is straightforward to implement using existing software and, as the response variable is the same as that of the spatial model, standard model selection criteria can be used for comparisons. A major advantage of the method is also that it extends to models with non‐Gaussian response distributions. Finally, while our results are derived in a thin plate spline setting, the spatial+ methodology transfers easily to other spatial model formulations.
Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS)
Authors: Garg Akanksha , Patel Bijal , Abbara Ali , Dhillo Waljit S.
Published: March 2022

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the leading cause of anovulatory subfertility. Increased gonadotrophin releasing hormone (GnRH) pulsatility in the hypothalamus results in preferential luteinizing hormone (LH) secretion from the pituitary gland, leading to ovarian hyperandrogenism and oligo/anovulation. The resultant hyperandrogenism reduces negative feedback from sex steroids such as oestradiol and progesterone to the hypothalamus, and thus perpetuates the increase in GnRH pulsatility. GnRH neurons do not have receptors for oestrogen, progesterone, or androgens, and thus the disrupted feedback is hypothesized to occur via upstream neurons. Likely candidates for these upstream regulators of GnRH neuronal pulsatility are Kisspeptin, Neurokinin B (NKB), and Dynorphin neurons (termed KNDy neurons). Growing insight into the neuroendocrine dysfunction underpinning the heightened GnRH pulsatility seen in PCOS has led to research on the use of pharmaceutical agents that specifically target the activity of these KNDy neurons to attenuate symptoms of PCOS. This review aims to highlight the neuroendocrine abnormalities that lead to increased GnRH pulsatility in PCOS, and outline data on recent therapeutic advancements that could potentially be used to treat PCOS. Emerging evidence has investigated the use of neurokinin 3 receptor (NK3R) antagonists as a method of reducing GnRH pulsatility and alleviating features of PCOS such as hyperandrogenism. We also consider other potential mechanisms by which increased GnRH pulsatility is controlled, which could form the basis of future avenues of research.