bluuebunny/crossref_metadata_2025 huggingface dataset:
Seeking traces of democracy in the workplace: effects on knowledge sharing
Authors: Rezaei Mojtaba , Ferraris Alberto , Busso Donatella , Rizzato Fabio
Published: November 2022

Purpose

This study aims to examine the role of organisational democracy (OD) in facilitating the knowledge sharing (KS) process within companies, thus considering the effect of different OD principles.

Design/methodology/approach

The authors used data collected through a questionnaire on a sample of 254 employees at private universities and colleges to test the relationship between OD and KS. Data were analysed using the structural equation modelling technique.

Findings

Overall, OD has a direct and significant effect on facilitating KS in organisations. Also, the results showed that there are different degrees and intensities among the individual principles (sub-concepts) of OD and KS.

Practical implications

The findings highlight the important role of democracy in an organisation to enhance the organisational climate and employees’ behaviours, thus leading to higher KS outcomes. Also, results, provide an opportunity for managers to consider enhancing democracy in an organisation for improving internal collaboration effectiveness in KS.

Originality/value

This paper sheds light and adds new knowledge to embryonic studies that are directed towards the integration of democracy within the main concept of knowledge management (KM). This emphasises the need to use and stimulate OD and its principles for improving the effectiveness of KM practices with specific attention to KS.
Knowledge sharing behavior among academics: Insights from theory of planned behavior, perceived trust and organizational climate
Authors: Hosen Mosharrof , Ogbeibu Samuel , Lim Weng Marc , Ferraris Alberto , Munim Ziaul Haque , Chong Yee-Lee
Published: November 2022

Purpose

Extant literature on knowledge sharing in higher education institutions (HEIs) concentrates on non-behavioral perspectives and indicates that academics continue to hoard knowledge despite being given incentives to bolster knowledge sharing behavior (KSB). This study aims to examine KSB among academics from a behavioral perspective through the lenses of the theory of planned behavior, perceived trust and organizational climate.

Design/methodology/approach

Self-administered questionnaires were distributed to 12 private universities using the drop-off/pick-up approach, resulting in 405 usable responses, which were analyzed using covariance-based structural equation modeling.

Findings

Academics’ salient beliefs – that is, behavioral beliefs, normative beliefs and control beliefs – significantly influence their attitude, subjective norms and perceived behavioral control (PBC). Attitude, subjective norms, PBC, perceived trust and organizational climate directly influence knowledge sharing intention (KSI), whereas attitude, KSI, subjective norms and PBC directly influence KSB. Noteworthily, KSI is a mediator in the relationships between attitude, subjective norms and PBC with KSB.

Originality/value

This study makes a seminal contribution through the novel conceptualization and theoretical generalizability of the theory of planned behavior by which HEIs can reinforce their competitiveness and global position by enhancing KSB among academics using a profound behavioral strategy.
Exploring the road less travelled: developing the Core4 leader behaviour model by building on the Ohio State studies and comparing it with transformational and transactional leadership
Authors: Mesu Jos , Sanders Karin
Published: November 2022

Purpose

In this study the Core4 model is proposed as a new model of leader behaviour.

Design/methodology/approach

Two independent samples were used to test the construct validity of this model in comparison to a seven-factor transformational/transactional leadership model. Next, convergent and discriminant validity of the Core4 model were examined. The Core4 Leadership Questionnaire was also tested for multigroup invariance. Predictive validity of the Core4 model was compared to that of a transformational/transactional model.

Findings

Results showed that the Core4 model better fitted the data than the transformational/transactional model. A seven-factor transformational/transactional model could not be established. The findings supported convergent and discriminant validity. The Core4 Leadership Questionnaire was not completely invariant across manufacturing and service organisations, but seems appropriate for application in different environments. The Core4 model was more strongly related to the criterion variables than a four-factor transformational/transactional leadership model.

Originality/value

This research shows that the Core4 model offers a valid alternative for the transformational/transactional model of leader behaviour.
Wear and microstructure analysis of aluminium based composite using eggshell and rice husk ash as reinforcement
Authors: Yadav Rajat , Islam Anas , Kumar Dwivedi Vijay
Published: November 2022

Purpose

The purpose of this paper is to study Al-based green composite. To make composite samples of aluminium alloy (AA3105) with different weight percentages of rice husk ash (RHA) and eggshell (ES) particles as reinforcement, stir casting method was used.

Design/methodology/approach

Several other aspects, including the weight percent of reinforcing agent particles, the applied stress and the sliding speed, were taken into consideration. During the course of the wear test, the sliding distance that was recorded varied from a minimum of 1,000 m all the way up to a maximum of 3,135 m (10, 15, 20, 25 and 30 min). The typical range for normal loads is 8–24 N, and their speed is 1.58 m/s.

Findings

With the AA/ES/RHA composite, the wear rates decreases when the grain size of the reinforcing particles enhanced. Scanning electron microscopy images of worn surfaces show that at low speeds, delaminating and ploughing are the main causes of wear. At high speeds, ploughing is major cause of wear. Composites with better wear-resistant properties can be used in wide range of tribological applications, especially in the automotive industry. It was found that hardness increases at the same time as the weight of the reinforcement increases. Tensile and hardness were maximized at 10% reinforcement mix in Al3105.

Originality/value

In this work, ES and RHA has been used to develop green metal matrix composite to support green revolution as promoted/suggested by United Nations thus reducing the environmental pollution.
How to scale up from animal movement decisions to spatiotemporal patterns: An approach via step selection
Authors: Potts Jonathan R. , Börger Luca
Published: November 2022

Uncovering the mechanisms behind animal space use patterns is of vital importance for predictive ecology, thus conservation and management of ecosystems. Movement is a core driver of those patterns so understanding how movement mechanisms give rise to space use patterns has become an increasingly active area of research.

This study focuses on a particular strand of research in this area, based around step selection analysis (SSA). SSA is a popular way of inferring drivers of movement decisions, but, perhaps less well appreciated, it also parametrises a model of animal movement. Of key interest is that this model can be propagated forwards in time to predict the space use patterns over broader spatial and temporal scales than those that pertain to the proximate movement decisions of animals.

Here, we provide a guide for understanding and using the various existing techniques for scaling up step selection models to predict broad‐scale space use patterns. We give practical guidance on when to use which technique, as well as specific examples together with code in R and Python.

By pulling together various disparate techniques into one place, and providing code and instructions in simple examples, we hope to highlight the importance of these techniques and make them accessible to a wider range of ecologists, ultimately helping expand the usefulness of SSA.
The role of propagule pressure in experimental bark beetle invasions
Authors: Chase Kevin D. , Kelly Dave , Liebhold Andrew M. , Brockerhoff Eckehard G.
Published: November 2022

Although many non‐native species arrive in novel environments, only a fraction successfully establish. A crucial factor affecting the colonization process of invading species is propagule pressure. The positive association between propagule pressure and colonization probability is driven both by stochastic dynamics and the ‘Allee effect’. Although the role of Allee effects in invading populations is theoretically compelling, they are difficult to quantify in the field because the earliest phases of biological invasions are typically not observed.

We conducted parallel studies using two species of bark beetles, Hylurgus ligniperda in New Zealand and Ips pini in North America, to (i) assess the role of propagule pressure on colonization success, (ii) empirically test for Allee effects and (iii) estimate Allee thresholds. We evaluated each of these factors by experimentally testing the effect of propagule pressure (numbers released) on simulated tree colonization success in two different settings: (1) field conditions where beetles could disperse freely and (2) enclosed cages where dispersal loss was prevented.

Colonization success was positively associated with numbers released (i.e. propagule pressure) for both species, though colonization occurred at lower numbers for H. ligniperda than for I. pini. A demographic Allee effect was only detected in H. ligniperda and the Allee threshold was smaller when beetles were released 1 m from host billets than when they were released 10 m away. Greater colonization success at lower release densities may explain the invasion success of H. ligniperda worldwide. Higher release densities required for successful colonization may explain why I. pini is a poor establisher.

Synthesis and applications. Our results linking invasion failure to small founding population densities generally support the theoretical literature on the role of propagule pressure and Allee effects in biological invasions. Agencies such as the International Plant Protection Committee (IPPC) setting phytosanitary measures such as the International Standards for Phytosanitary Measures No. 15 (ISPM 15) should consider using the colonization thresholds estimated here to limit numbers of colonizing individuals below invasion thresholds. Additionally, agencies conducting trapping efforts at ports‐of‐entry should be aware of these thresholds and widely report when trapping numbers exceed these thresholds.
Occupational therapists' practice with complex trauma: A profile
Authors: Mason Julia , Stagnitti Karen
Published: November 2022

Introduction

Many children in Aotearoa (New Zealand) and Australia experience complex trauma and its developmental impacts. Internationally, occupational therapists work with complex trauma and use sensory‐based, integrative, and functional approaches. The practices of occupational therapists in Aotearoa and Australia with children experiencing complex trauma have not previously been described.

Methods

This article reports the quantitative results of a mixed‐methods study which profiled occupational therapists' practice in Aotearoa and Australia with children aged 0 to 12 years old who experienced complex trauma. Twenty‐five participants completed the survey. The average age of participants was 43 years (SD = 10.65), all were female (n = 25), and most identified as New Zealand European (n = 11) or Australian European (n = 9). A survey was distributed via Occupational Therapy New Zealand – Whakaora Ngangahau Aotearoa and Occupational Therapy Australia.

Results

The majority of participants had a bachelor's degree (64%) and worked in community settings (76%). Fourteen participants (56%) used sensory approaches. The most common assessments used were those of sensory processing (n = 12, 48%) and observation (n = 12, 48%). The Sensory Profile was the most popular standardised assessment (n = 8, 32%). The most common interventions used with children experiencing complex trauma were sensory (n = 13, 52%) and play based (n = 13, 52%). Most participants reported not adapting their practices for Māori or Aboriginal children. Most participants felt somewhat prepared (n = 15) for working with complex trauma, with most reporting a lack of experience in this area (n = 10). Supervision was suggested by 92% (n = 23) of the participants.

Conclusion

Sensory‐based practices were most common among occupational therapists in Aotearoa and Australia who worked with children experiencing complex trauma. The participants suggested supervision, social support, and practical training when working with complex trauma. Advocacy and research are required within this subspecialty, and further professional engagement in the application of culturally safe practice.
Equal Tax for Equal Alcohol? Beverage Types and Antisocial and Unlawful Behaviours*
Authors: Srivastava Preety , Yang Ou , Zhao Xueyan
Published: November 2022

Alcohol taxation is an important policy instrument for correcting for market failures associated with excessive alcohol consumption. This paper examines the beverage‐specific negative externalities by providing empirical evidence linking ten alcoholic beverage types to drink‐driving and hazardous, disturbing or abusive behaviours when intoxicated, using data from six waves of an Australian recreational drug survey. We find that regular‐strength beer and pre‐mixed spirits in a can rank the highest in their links to negative behaviours, followed by mid‐strength beer, cask wine, and bottled spirits. Conversely, drinking low‐strength beer or fortified wine reduces the probability of these risky and unlawful behaviours. Bottled wine is shown to be associated with an elevated chance of drink‐driving but a reduced chance of other negative behaviours. In contrast to the existing volumetric tax rates for per litre of alcohol, of all harmful beverage types, cask wine appears to be significantly undertaxed relative to its external costs to society. We also note that regular‐ and mid‐strength beer are comparable to pre‐mixed drinks in terms of external costs, and yet there is a significant disparity across their tax rates.
Protein hydrolysates derived from aquaculture and marine byproducts through autolytic hydrolysis
Authors: Nikoo Mehdi , Benjakul Soottawat , Ahmadi Gavlighi Hassan
Published: November 2022

Autolysis technology has shown potential for protein hydrolysates production from marine and aquaculture byproducts. Viscera are a source of cheap proteolytic enzymes for producing protein hydrolysates from the whole fish or processing byproducts of the most valuable commercial species by applying autolysis technology. The use of autolysis allows economical production of protein hydrolysate and provides an opportunity to valorize downstream fish and shellfish processing byproducts at a lower cost. As a result, production and application of marine byproduct autolysates is increasing in the global protein hydrolysates market. Nevertheless, several restrictions occur with autolysis, including lipid and protein oxidation mediated by the heterogeneous composition of byproducts. The generally poor storage and handling of byproducts may increase the formation of undesirable metabolites during autolysis, which can be harmful. The formation of nitrogenous compounds (i.e., biogenic amines), loss of freshness, and process of autolysis in the byproducts could increase the rate of quality and safety loss and lead to more significant concern about the use of autolysates for human food applications. The current review focuses on the autolysis process, which is applied for the hydrolysis of aquaculture and marine discards to obtain peptides as functional or nutritive ingredients. It further addresses the latest findings on the mechanisms and factors contributing the deterioration of byproducts and possible ways to control oxidation and other food quality and safety issues in raw materials and protein hydrolysates.
“Fast money” around Federal Statistics Releases
Authors: Huang Joshua , Serra Teresa , Garcia Philip
Published: November 2022

Many public statistics are closely followed by the public as they provide valuable information for decision making. Although economic theory suggests that low‐latency traders (LLTs) can earn excess arbitrage profits from trading on public statistics releases due to their speed advantage, the empirical literature fails to find meaningful LLTs' stock market profits when trading on macroeconomic statistical releases. Here we confirm previous findings with improved techniques, but also show that excess profits can be earned quickly in agricultural commodity futures markets around United States Department of Agriculture (USDA) statistical releases. We attribute differences in the magnitude of the profits to the straightforward nature of the information and to the direct relevance of the reports to traders for the markets considered. Motivated by market concerns, USDA and the United States Department of Labor recently changed their news media prerelease lockup policy to mitigate LLTs' speed advantage. However, we find the policy change had little effect on the speed advantage as no significant reduction in LLTs' profits occurred. Implications of the research are relevant for government agencies concerned with mitigating LLT speed advantages particularly during the release of public statistical information.
Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID‐19 vaccines: A systematic review and meta‐analysis
Authors: Greenhawt Matthew , Shaker Marcus , Golden David B. K. , Abrams Elissa M. , Blumenthal Kimberly G. , Wolfson Anna R. , Stone Cosby A. , Krantz Matthew S. , Chu Derek K. , Dwamena Ben A.
Published: November 2022

For persons with immediate allergic reactions to mRNA COVID‐19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all‐severity immediate allergic reactions upon re‐vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception‐Oct 4, 2021) for studies addressing immediate (≤4 h post‐vaccination) all‐severity allergic reactions to 2nd mRNA COVID‐19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta‐analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS‐2 assessed risk of bias. Among 20 studies of mRNA COVID‐19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re‐vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01–0.52) and specificity 0.97 (95%CrI 0.9–1). PEG test sensitivity was 0.02 (95%CrI 0.00–0.07) and specificity 0.99 (95%CrI 0.96–1). PS test sensitivity was 0.03 (95%CrI 0.00–0.0.11) and specificity 0.97 (95%CrI 0.91–1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00–0.08) and specificity was 0.98 (95%CrI 0.95–1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all‐severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID‐19 vaccines. mRNA COVID‐19 vaccine or excipient ST has limited risk assessment utility.
Intestinal ultrasound detects an increased diameter and submucosal layer thickness in the appendix of patients with ulcerative colitis compared to healthy controls – a prospective cohort study
Authors: Reijntjes Maud A. , de Voogd Floris A. E. , Bemelman Willem A. , Hompes Roel , d'Haens Geert , Buskens Christianne J. , Gecse Krisztina B.
Published: November 2022

Background

Increasing evidence suggests that appendicectomy as alternative treatment for ulcerative colitis (UC), especially in patients with histopathological appendiceal inflammation. Intestinal ultrasound (IUS) is a non‐invasive diagnostic modality to characterise appendiceal inflammation.

Aims

To assess appendiceal IUS characteristics in UC patients and compare findings to healthy controls (HC).

Methods

In this prospective study, appendiceal IUS was performed in consecutive UC patients with active (A; n = 35) or quiescent (Q; n = 30) disease and in HC (n = 30). Transverse appendiceal diameter (TAD) and additional IUS parameters (bowel wall thickness, submucosal layer thickness and colour Doppler signal) were assessed.

Results

The appendix was visualised in 41/65 UC patients (63.1%; A vs. Q: 23/35 vs. 18/30, p = 0.67) and 18/30 (60%) HC. UC patients had a higher TAD (A: 5.5 mm, Q: 5.0 mm, HC: 4.3 mm; A‐HC p < 0.01; Q‐HC p = 0.01, A‐Q p = ns) and submucosal layer thickness (A: 1.0 mm, Q: 1.0 mm, HC: 0.7 mm; A‐HC p < 0.01, Q‐HC: p = 0.01, A‐Q: p = ns) when compared to HC. A TAD ≥6 mm corresponding to an ultrasonographic suspicion of acute appendicitis was mainly reported in A‐UC patients (A: 43%; Q: 6%; HC: 0%, p = 0.01) and occurred irrespective of disease extent. However, none of the patients had a clinical suspicion of acute appendicitis.

Conclusion

A TAD ≥6 mm was predominantly seen in A‐UC. TAD was higher in UC patients compared to HC irrespective of disease activity and was characterised by an increased submucosal layer thickness. IUS therefore has the potential to identify UC patients with appendiceal inflammation.
Potential cerebrovascular accident signal for risankizumab: A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS)
Authors: Woods Richard H.
Published: November 2022

Aims

The interleukin‐23 (IL‐23) inhibitor risankizumab was recently approved for the treatment of moderate‐to‐severe plaque psoriasis in the United States. Low rates of cerebrovascular accident (CVA) were observed in risankizumab‐treated patients during clinical trials. The aim of this study was to determine whether risankizumab may be associated with CVA in a real‐world setting.

Methods

A retrospective disproportionality analysis was conducted utilizing postmarketing adverse event reports submitted to the US Food and Drug Administration Adverse Event Reporting System (FAERS) through the fourth quarter of 2021. A custom query consisting of 22 CVA‐related Medical Dictionary for Regulatory Activities (MedDRA) preferred terms previously reported in clinical trials of plaque psoriasis medications was used to identify cases. Disproportionality was measured by calculating reporting odds ratios (ROR) and 95% confidence intervals (CI), whereby the lower limit of a 95% CI >1.0 and ≥ three cases was considered a signal.

Results

Risankizumab was associated with significantly disproportionate CVA reporting compared to all other drugs in FAERS (ROR 2.48; 95% CI 2.14–2.88) as well as 11 alternative plaque psoriasis therapeutics across five pharmacologic classes. The largest disproportionality signals for risankizumab were identified relative to apremilast (ROR 9.07; 95% CI 7.56–10.89), ixekizumab (ROR 6.75; 95% CI 5.14–8.86), guselkumab (ROR 6.74; 95% CI 4.68–9.71), certolizumab (ROR 5.70; 95% CI 4.74–6.85) and etanercept (ROR 4.91; 95% CI 4.21–5.73).

Conclusion

This study detected a previously unreported signal of disproportionate CVA reporting with the real‐world use of risankizumab. Further long‐term observational data will be necessary to better characterize this unconfirmed potential safety signal.
Isoflurane impairs GluN2B‐containing NMDA receptors trafficking and cognition via decreasing histone acetylation and EphB2 expression in aged hippocampal neurons
Authors: Hao Jing‐Ru , Hu Qiu‐Mei , Yang Xiu , Wei Pan , Wang Hu‐Yi , Sun Nan , Gao Can
Published: November 2022

Perioperative neurocognitive disorders (PND) is a common complication that occurs among elderly patients in the perioperative course. Current clinical evidence has shown that isoflurane exposure could cause cognitive decline, but the exact molecular mechanisms remain unclear. As both NMDARs‐dependent synaptic plasticity and histone acetylation play vital roles in processing learning and memory, we postulated that these alternations might occur in the isoflurane‐associated PND. Here, we found that isoflurane impaired fear memory in aged mice, decreased GluN2B‐containing NMDA receptors phosphorylation and trafficking, as well as the expression of EphB2, a key regulator of synaptic localization of NMDA receptors. We also identified that isoflurane could increase the expression of HDAC2, which was significantly enriched at the ephb2 gene promoter and regulated the transcription of ephb2. Furthermore, we showed that suberoylanilide hydroxamic acid (SAHA), a nonselective HDAC inhibitor or knocking‐down HDAC2 rescued the cognitive dysfunction in isoflurane‐treated aged mice via increasing acetylation of H3Ac, expression of EphB2 and promoting NMDA receptor trafficking. Collectively, our study highlighted the crucial role of histone posttranslational modifications for EphB2‐GluN2B signals in isoflurane‐associated PND, and modulating HDAC2 might be a new therapeutic strategy for isoflurane‐associated PND.
Latent Multinomial Models for Extended Batch-Mark Data
Authors: Zhang Wei , Bonner Simon J. , McCrea Rachel S.
Published: November 2022

Batch marking is common and useful for many capture–recapture studies where individual marks cannot be applied due to various constraints such as timing, cost, or marking difficulty. When batch marks are used, observed data are not individual capture histories but a set of counts including the numbers of individuals first marked, marked individuals that are recaptured, and individuals captured but released without being marked (applicable to some studies) on each capture occasion. Fitting traditional capture–recapture models to such data requires one to identify all possible sets of capture–recapture histories that may lead to the observed data, which is computationally infeasible even for a small number of capture occasions. In this paper, we propose a latent multinomial model to deal with such data, where the observed vector of counts is a non-invertible linear transformation of a latent vector that follows a multinomial distribution depending on model parameters. The latent multinomial model can be fitted efficiently through a saddlepoint approximation based maximum likelihood approach. The model framework is very flexible and can be applied to data collected with different study designs. Simulation studies indicate that reliable estimation results are obtained for all parameters of the proposed model. We apply the model to analysis of golden mantella data collected using batch marks in Central Madagascar.
CHCHD2 p.Thr61Ile knock‐in mice exhibit motor defects and neuropathological features of Parkinson's disease
Authors: Fan Liyuan , Zhang Shuo , Li Xinwei , Hu Zhengwei , Yang Jing , Zhang Shuyu , Zheng Huimin , Su Yun , Luo Haiyang , Liu Xinjing , Fan Yu , Sun Huifang , Zhang Zhongxian , Miao Jinxin , Song Bo , Xia Zongping , Shi Changhe , Mao Chengyuan , Xu Yuming
Published: November 2022

The p.Thr61Ile (p.T61I) mutation in coiled‐coil‐helix–coiled‐coil‐helix domain containing 2 (CHCHD2) was deemed a causative factor in Parkinson's disease (PD). However, the pathomechanism of the CHCHD2 p.T61I mutation in PD remains unclear. Few existing mouse models of CHCHD2‐related PD completely reproduce the features of PD, and no transgenic or knock‐in (KI) mouse models of CHCHD2 mutations have been reported. In the present study, we generated a novel CHCHD2 p.T61I KI mouse model, which exhibited accelerated mortality, progressive motor deficits, and dopaminergic (DA) neurons loss with age, accompanied by the accumulation and aggregation of α‐synuclein and p‐α‐synuclein in the brains of the mutant mice. The mitochondria of mouse brains and induced pluripotent stem cells (iPSCs)‐derived DA neurons carrying the CHCHD2 p.T61I mutation exhibited aberrant morphology and impaired function. Mechanistically, proteomic and RNA sequencing analysis revealed that p.T61I mutation induced mitochondrial dysfunction in aged mice likely through repressed insulin‐degrading enzyme (IDE) expression, resulting in the degeneration of the nervous system. Overall, this CHCHD2 p.T61I KI mouse model recapitulated the crucial clinical and neuropathological aspects of patients with PD and provided a novel tool for understanding the pathogenic mechanism and therapeutic interventions of CHCHD2‐related PD.
Selective neurodegeneration generated by intravenous α‐synuclein pre‐formed fibril administration is not associated with endogenous α‐synuclein levels in the rat brain
Authors: Kuan Wei‐Li , Alfaidi Maha , Horne Catherine B. , Vallin Benjamin , Fox Sarah , Fazal Shaline V. , Williams‐Gray Caroline H. , Barker Roger A.
Published: November 2022

Selective loss of discrete neuronal populations is a prominent feature of many neurodegenerative conditions, but the molecular basis of this is poorly understood. A central role of α‐synuclein in the selective neurodegeneration of Parkinson's disease has been speculated, as its level of expression critically determines the propensity of this protein to misfold. To investigate whether the propensity of neuronal cell loss is associated with the level of endogenous α‐synuclein expression, non‐transgenic rats were given a single intravenous administration of α‐synuclein pre‐formed fibrils (PFFs) reversibly complexed with the rabies virus glycoprotein peptide (RVG9R). The number of surviving cells in different neuronal populations was systematically quantified using unbiased stereology. Our data demonstrated that a non‐selective, transvascular delivery of α‐synuclein PFFs led to a time‐dependent loss of specific populations of midbrain (but not olfactory) dopaminergic neurons, medullary (but not pontine) cholinergic neurons, and brainstem serotonergic neurons. Contrary to the central role of endogenous α‐synuclein expression in determining the seeding and aggregation propensity of pathological α‐synuclein, we did not observe an association between the levels of α‐synuclein expression in different regions of the rodent brain (although did not ascertain this at the individual cell level) and neurodegenerative propensity. The results from our study highlight the complexity of the neurodegenerative process generated by α‐synuclein seeding. Further investigations are therefore required to elucidate the molecular basis of neurodegeneration driven by exogenous pathogenic α‐synuclein spread.
STAT1‐ and NFAT‐independent amplification of purinoceptor function integrates cellular senescence with interleukin‐6 production in preadipocytes
Authors: Majeed Yasser , Madani Aisha Y. , Altamimi Ahmed I. , Courjaret Raphael , Vakayil Muneera , Fountain Samuel J. , Machaca Khaled , Mazloum Nayef A.
Published: November 2022

Background and Purpose

Senescent preadipocytes promote adipose tissue dysfunction by secreting pro‐inflammatory factors, although little is known about the mechanisms regulating their production. We investigated if up‐regulated purinoceptor function sensitizes senescent preadipocytes to cognate agonists and how such sensitization regulates inflammation.

Experimental Approach

Etoposide was used to trigger senescence in 3T3‐L1 preadipocytes. CRISPR/Cas9 technology or pharmacology allowed studies of transcription factor function. Fura‐2 imaging was used for calcium measurements. Interleukin‐6 levels were quantified using quantitative PCR and ELISA. Specific agonists and antagonists supported studies of purinoceptor coupling to interleukin‐6 production. Experiments in MS1 VEGF angiosarcoma cells and adipose tissue samples from obese mice complemented preadipocyte experiments.

Key Results

DNA damage‐induced senescence up‐regulated purinoceptor expression levels in preadipocytes and MS1 VEGF angiosarcoma cells. ATP‐evoked Ca2+ release was potentiated in senescent preadipocytes. ATP enhanced interleukin‐6 production, an effect mimicked by ADP but not UTP, in a calcium‐independent manner. Senescence‐associated up‐regulation and activation of the adenosine A3 receptor also enhanced interleukin‐6 production. However, nucleotide hydrolysis was not essential because exposure to ATPγS also enhanced interleukin‐6 secretion. Pharmacological experiments suggested coupling of P2X ion channels and P2Y12–P2Y13 receptors to downstream interleukin‐6 production. Interleukin‐6 signalling exacerbated inflammation during senescence and compromised adipogenesis.

Conclusions and Implications

We report a previously uncharacterized link between cellular senescence and purinergic signalling in preadipocytes and endothelial cancer cells, raising the possibility that up‐regulated purinoceptors play key modulatory roles in senescence‐associated conditions like obesity and cancer. There is potential for exploitation of specific purinoceptor antagonists as therapeutics in inflammatory disorders.
Gut microbiota‐derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling
Authors: Liu Li‐Wei , Xie Yu , Li Guan‐Qun , Zhang Tao , Sui Yu‐Hang , Zhao Zhong‐Jie , Zhang Yang‐Yang , Yang Wen‐Bo , Geng Xing‐Long , Xue Dong‐Bo , Chen Hua , Wang Yong‐Wei , Lu Tian‐Qi , Shang Li‐Ren , Li Zhi‐Bo , Li Le , Sun Bei
Published: November 2022

Background and Purpose

Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota‐derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation.

Experimental Approach

AP rat and mouse models were established by administration of caerulein or sodium taurocholate in vivo. Pancreatic acinar cells were exposed to caerulein and lipopolysaccharide in vitro to simulate AP.

Key Results

Normobiotic FMT alleviated AP‐induced gut microbiota dysbiosis and ameliorated the severity of AP, including mitochondrial dysfunction, oxidative damage and inflammation. Normobiotic FMT induced higher levels of NAD+ (nicotinamide adenine dinucleotide)‐associated metabolites, particularly nicotinamide mononucleotide (NMN). NMN administration mitigated AP‐mediated mitochondrial dysfunction, oxidative damage and inflammation by increasing pancreatic NAD+ levels. Similarly, overexpression of the NAD+‐dependent mitochondrial deacetylase sirtuin 3 (SIRT3) alleviated the severity of AP. Furthermore, SIRT3 deacetylated peroxiredoxin 5 (PRDX5) and enhanced PRDX5 protein expression, thereby promoting its antioxidant and anti‐inflammatory activities in AP. Importantly, normobiotic FMT‐mediated NMN metabolism induced SIRT3–PRDX5 pathway activation during AP.

Conclusion and Implications

Gut microbiota‐derived NMN alleviates the severity of AP by activating the SIRT3–PRDX5 pathway. Normobiotic FMT could be served as a potential strategy for AP treatment.
Wanted: A political sociology of race in Canada
Authors: Livingstone Anne‐Marie
Published: November 2022

The essay discusses the importance of political sociology for the study of race in the settler state of Canada, and proposes directions for future research.
Identification of 5‐(3‐(methylsulfonyl)phenyl)‐3‐(4‐(methylsulfonyl)phenyl)‐3H‐imidazo[4,5‐b]pyridine as novel orally bioavailable and metabolically stable antimalarial compound for further exploration
Authors: Kundu Mrinalkanti , Dutta Aditi , Roy Kuldeep K. , Mal Sajal K. , Karmakar Shouvik , Mandal Aritra , Mondal Susanta K. , Kumar Sanjay , Saha Soumya , Pradhan Subhankar , Sarkar Ratul , Chakrabarti Monali , Malik Pradip K. , Banerjee Manish
Published: November 2022

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin‐based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold‐hopping approach combined with docking studies for putative‐binding interactions with Plasmodium falciparum phosphatidylinositol‐4‐kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5‐(3‐(methylsulfonyl)phenyl)‐3‐(4‐(methylsulfonyl)phenyl)‐3H‐imidazo[4,5‐b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME‐PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC50 = 29 nM) with meager in vitro intrinsic clearance, moderate plasma‐protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies.
Salvageable waste associated with intravitreal injections: A local medical waste management approach
Authors: Rogerson Thomas , Dedina Liana , Goggin Michael , Chan Weng Onn
Published: November 2022

Background

Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single‐use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age‐related macular degeneration and diabetic macular oedema.

Methods

A prospective controlled cohort study was performed over 5 weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real‐time sorting of waste occurred. The number of injections given and waste amounts were recorded.

Results

116 and 286 injections were given at Sites A and B, respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared with 175.1 g at our intervention site. This represents a 62.8% reduction (p < 0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8 kg (67.5%) was salvageable.

Conclusions

This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy among other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real‐world methodology.
One park, two owners—Inconsistencies in forest stewardship
Authors: Křenová Zdenka , Janík Tomáš , Romportl Dušan
Published: November 2022

Appropriate management of European spruce forests in this time of climate change is a significant challenge. Uniform principles of quality forest practice must be applied, essentially in forests that are valuable from a conservation point of view. However, this may be problematic in protected areas with mixed ownership and disparate priorities. Managerial decision‐making is often based on personal knowledge, previous experience, priorities other than conservation, or political influence. Clear management guidelines at the European and national levels are lacking in many protected areas. In this article, we use data from the Šumava NP to elucidate varied management approaches applied by state and private municipal owners in forests of high conservation value. We used high‐resolution aerial photographs to evaluate the effects of forest management practices applied, and compared the status of spruce habitats before and after a major windstorm and large‐scale bark beetle outbreak. We found that follow‐up forest management measures have significantly affected forests in the Šumava NP negatively. However, changes are not equally spread across the area of study, with forest ownership important for the type and intensity of changes. Kašperské Hory Municipality, managed their forests more as a productive commercial forest as contrasted to the state owned forest. We compare our findings with experiences from other Central European national parks with similar forest management challenges. Options for improving and unifying the management of conservation‐valuable forests held in state and private ownership are discussed in the conclusion. Wide political consensus and stability together with long‐term mutual trust and a willingness to collaborate among conservationists, forest managers and forest owners were recognized to be essential for the successful achievement of conservation goals.
Patient Preferences in Hidradenitis Suppurativa (APProach‐HS): a discrete choice experiment
Authors: Faverio Kristin , Peitsch Wiebke K. , Görig Tatiana , Schneider‐Burrus Sylke , Benzel Friderike , Goebeler Matthias , Schummer Patrick , Badran Alaa , Schaarschmidt Marthe‐Lisa , Harth Wolfgang , Mössner Rotraut , Kromer Christian
Published: November 2022

Background and Objectives

Treatment options for moderate‐to‐severe hidradenitis suppurativa (HS) comprise antibiotics, biologics, and different surgical methods. These approaches differ substantially regarding the treatment process, success rates, and adverse events. However, information on patient preferences for HS therapies is hitherto scarce. Our aim was to assess patient preferences for medicamentous and surgical treatment of HS with conjoint analysis.

Patients and Methods

In this cross‐section study, computerized discrete choice experiments were used to quantify patient preferences for HS therapies decomposed into treatment modality (tablets, subcutaneous injections, surgery with secondary‐intention healing or primary closure), probability of sustained therapeutic success, probability of mild or severe adverse events, and duration of treatment or wound healing.

Results

Averaged over the cohort (n  =  216 patients with HS), sustained therapeutic success was considered as most important (Relative Importance Score [RIS]: 36.2), followed by the treatment modality (RIS: 24.0), and duration of treatment/wound healing (RIS: 19.9), whereas mild or severe adverse events (RIS: 10.7 or 9.3) were regarded as less relevant. Patients preferred tablets, followed by subcutaneous injections, and disliked surgery with primary closure. Preferences differed significantly dependent on age and affected body regions.

Conclusions

Awareness of patient preferences is essential for patient‐centered care in HS.
A tale of two Martins: Is Luther to blame for Heidegger's destruction of ontotheology?
Authors: Bielfeldt Dennis
Published: November 2022

Much has been written about Heidegger's indebtedness to Luther in developing Being and Time. Recently Duane Armitage has claimed that since Heidegger is the “root to all continental philosophy of religion and postmodern theology,” and since his “disdain for onto‐theology is rooted in Luther, . . . essentially all postmodern theological thinking is fundamentally Lutheran.” Clearly, both Martins de‐emphasize theology's penchant for abstract metaphysics and look instead to recover the facticity of concrete lived Christian existence. But surface similarities should not occlude what profoundly differentiates the two, for the Martins depart radically in what they thought thinking did and what the truth‐conditions of their respective discourses were. Luther who assumed theological realism was concerned with how human beings really stand in relation to God, while Heidegger brackets such questions in favor of a description of the phenomenological shape of the Christian life. I employ elementary model theory in order to provide greater precision and accuracy in evaluating the stark semantic differences between their respective approaches.
Christian theology as comparative theology: Towards a radical change of “Method”
Authors: Kärkkäinen Veli‐Matti
Published: November 2022

This essay makes a recommendation for an expansion in the approach and “method” of Christian theology: it proposes Christian theology as comparative theology. In the religiously pluralistic world, it is not sufficient merely to engage other faith traditions as an “auxiliary task.” Rather, the comparative task should belong to the “normal” way of doing “basic” Christian theological work. While Christian theology is not subsumed under comparative theology, as it were, the essay argues that without the comparative task, Christian theology may fail its calling in the third millennium.
Evaluation of left atrial and left ventricular functions in patients with Wolff‐Parkinson‐White syndrome before and after radiofrequency catheter ablation using three‐dimensional speckle tracking echocardiography
Authors: Dogdus Mustafa , Dindas Ferhat , Turan Oguzhan Ekrem , Yilancioglu Resit Yigit , Ozgul Ufuk , Inevi Umut Dursun , Ozcan Emin Evren
Published: November 2022

Background

Wolff‐Parkinson‐White (WPW) syndrome is one of the most common congenital cardiac abnormalities among ventricular pre‐excitation syndromes. Radiofrequency catheter ablation (RFCA) treatment of accessory pathways (APs) in WPW patients is an established curative therapy restoring normal atrioventricular conduction. We have not encountered any studies evaluating both the LA and LV functions of these patients before and after RFCA with three dimensional‐speckle tracking echocardiography (3D‐speckle tracking echocardiography (STE)).

Aim

The purpose of the current study was to assess the LA and LV functions in patients with WPW syndrome before and after RFCA using 3D‐STE.

Methods

A total of 21 patients with WPW syndrome who had been scheduled for RFCA were prospectively recruited for this study. 3D‐STE examinations of the patients were performed 12–24 h before ablation and 1 month after ablation.

Results

The LV‐global longitudinal strain (LV‐GLS) and LV‐global circumferential strain (LV‐GCS) were significantly depressed in the pre‐RFCA WPW group than in the control group (−14.3 ± 2.1 vs. −21.5 ± 2.2, p < .001; −12.6 ± 1.8 vs. −20.4 ± 1.8, p < .001, respectively). The left atrial strain‐reservoir (LAS‐r) and LAS‐active were significantly decreased in the pre‐RFCA WPW group than in the control group (31.9 ± 2.4 vs. 48.8 ± 2.6, p < .001; 11.7 ± 2 vs. 26.5 ± 2.1, p < .001, respectively). The LV‐GLS, LV‐GCS, LAS‐r, and LAS‐active values improved after RFCA compared to before.

Conclusion

The results of our study indicated that there are subclinical impairments in LV and LA myocardial dynamics in the apparently healthy WPW patients, and these deteriorations improve after RFCA of AP.
Economic uncertainty: Mispricing and ambiguity premium
Authors: Cai Charlie X. , Fu Xi , Kerestecioglu Semih
Published: November 2022

We uncover two channels of effect in the financial market when investors face macroeconomic uncertainty. Conditional on a common mispricing index, we find that economic uncertainty exposure (EUE) induces disagreement, which amplifies mispricing. The highest EUE quintile produces an annualised mispricing alpha of 9.96%, more than double the unconditional mispricing effect. An ambiguity premium of 3.84% alpha is documented in the “non‐mispricing” quintile. The EUE‐induced mispricing effect is different from the existing limits of arbitrage explanations. The ambiguity premium is predictably observed during the unfolding of shocks of COVID‐19 to the market.