bluuebunny/crossref_metadata_2025 huggingface dataset:
Migrant workers in precarious employment
Authors: Zhang Hui , Nardon Luciara , Sears Greg J.
Published: September 2021

Purpose

Various forms of precarious employment create barriers to the integration and inclusion of migrant workers in receiving countries. The purpose of this paper is to review extant research in employment relations and management to identify key factors that contribute to migrant workers' precarious employment and highlight potential avenues for future research.

Design/methodology/approach

The authors conducted a narrative literature review drawing on 38 academic journal articles published between 2005 and 2020.

Findings

The authors’ review suggests that macro- and meso-level factors contribute to the precarious employment conditions of migrant workers. However, there is a limited articulation of successful practices and potential solutions to reduce migrant work precarity and exclusion. The literature on migrant workers' precarious employment experience is primarily focused on low-skilled sector (e.g. agriculture, hospitality, domestic care) jobs. In addition, few studies have explored the role of worker characteristics, such as gender, class, ethnicity, race and migration status, in shaping the experience of migrant workers in precarious employment.

Practical implications

The results of this research highlight the importance of engaging multilevel actors in addressing migrant employment precarity, including policymakers, employers and employment agencies.

Originality/value

This research contributes to a growing conversation of migrant employment precarity by highlighting the heterogeneity of migrant groups and calling for the use of intersectional lenses to understand migrant workers' experiences of precarious employment.
Do we always follow others? The impact of psychological distance on consumers’ observational learning modes
Authors: Gu Chenyan , Zhang Zhe , Hou Yuansi
Published: September 2021

Purpose

To investigate the psychological mechanism of observational learning in the online retailing context, the purpose of this paper is to show how the psychological distance between consumers and products affects modes of observational learning.

Design/methodology/approach

Five experimental studies are conducted to test the hypotheses.

Findings

The findings show that which modes of observational learning are adopted by consumers is affected by consumers’ psychological distance. Specifically, when the psychological distance between consumers and products is proximal, consumers tend to adopt the termed adequate observational learning mode by considering the interaction of information about popularity and the breadth of appeal of a product to make purchase. However, when the psychological distance is distal, consumers would consider information of popularity and breadth of appeal separately without considering the interaction, termed as inadequate observational learning mode. The observed relationship between psychological distance and observational learning mode could be explained by the construal level.

Research limitations/implications

This research advances the observational learning and psychological distance literature by investigating the psychological mechanism behind observational learning modes. Limitations include the use of scenario-based experiments to test the hypotheses, investigation of a single product attribute (i.e. breadth of appeal) and assessment of popularity information by sales volume alone.

Practical implications

The current research provides a deeper understanding of consumer observational learning modes, which can help online retailers to develop effective product strategies and marketing tactics and, finally, achieve stronger competitive positions.

Originality/value

The present research contributes to the literature by examining the psychological mechanism involved in observational learning. This research distinguishes adequate and inadequate observational learning modes from the perspective of psychological distance.
Availability and maintenance modeling of a batch service queuing system
Authors: Agarwal Shweta , Singh S.B.
Published: September 2021

Purpose

The purpose of the paper is to analyze reliability characteristics of batch service queuing system with a single server model that envisages Poisson input process and exponential service times under first come, first served (FCFS) queue discipline.

Design/methodology/approach

With the help of renewal theory and stochastic processes, a model has been designed to discuss the reliability and its characteristics.

Findings

The instantaneous and steady-state availability along with the maintenance model of the systems subject to generalized M/Mb/1 queuing model is derived, and a few particular cases for availability are obtained as well. For supporting the developed model, a case study on electrical distribution system (EDS) has been illustrated, which also includes a comparison for the system subject to M/Mb/1 queuing model and the system without any queue (delay).

Originality/value

It is a quite realistic model that may aid to remove congestion in the system while repairing.
Supplier performance in the public healthcare: internal social capital, logistics capabilities and supply chain risk management capabilities as antecedents in a developing economy
Authors: Tukamuhabwa Benjamin , Mutebi Henry , Isabirye Daniel
Published: September 2021

Purpose

The purpose of this paper is twofold. First, it intends to explore the link between internal social capital, logistics capabilities, supply chain risk management (SCRM) capabilities and supplier performance. Second, the mediating effect of logistics capabilities between internal social capital and SCRM capabilities, and that of SCRM capabilities between logistics capabilities and supplier performance are also examined.

Design/methodology/approach

A theoretical model developed from the extant literature was empirically validated through a cross-sectional survey of 122 respondents in 52 public healthcare facilities in Uganda. The data were analysed using partial least square structural equation modeling (PLS-SEM).

Findings

The study found that internal social capital and SCRM capabilities are significant predictors of supplier performance. Internal social capital is positively and significantly related to logistics capabilities, and logistics capabilities are positively and significantly related to SCRM capabilities. The authors also found non-significant relationships between internal social capital and SCRM capabilities, and between logistics capabilities and supplier performance. Furthermore, it was revealed that logistics capabilities play a partial mediating role in the relationship between internal social capital and SCRM capabilities, while SCRM capabilities fully mediate between logistics capabilities and supplier performance.

Originality/value

Further to providing empirical evidence of the antecedents of supplier performance in the public healthcare in a developing economy, which has been evidently scant, this study provides initial empirical evidence of the mediating role of logistics capabilities in the relationship between internal social capital and SCRM capabilities and that of SCRM capabilities in the relationship between logistics capabilities and supplier performance. This is important for understanding the mechanism through which supplier performance can be enhanced.
Construction project performance: the role of client knowledge and procurement systems
Authors: Windapo Abimbola , Adediran Abdulrauf , Rotimi James Olabode Bamidele , Umeokafor Nnedinma
Published: September 2021

Purpose

This study aims to investigate whether clients’ knowledge about construction procurement systems influence project performance objectives and the role of procurement systems on project performance objectives in South Africa.

Design/methodology/approach

Using a two-round survey, 90 usable questionnaires from construction professionals in South Africa plus 3 expert clients were collected. The data were analysed using descriptive statistics – means, percentages and the analytical hierarchy process to determine the rank of client project performance criteria, while inferential statistics – Pearson product-moment correlation was used in establishing the relationship between the level of clients’ knowledge and project performance.

Findings

It was found that the common procurement systems used are traditional, followed by management-oriented and integrated procurement systems. In addition, it emerged that client’s knowledge of procurement systems shows a positive relationship with the achievement of project performance objectives. Based on these findings, it is concluded that some procurement systems being selected by clients in South Africa are inappropriately selected. This is despite the emergence of more efficient procurement systems. If procurement systems are selected based on the knowledge of the client, it will give better chances of a successful project outcome.

Practical implications

The research suggests the need for clients to seek ways to improve their understanding or increase their knowledge of procurement systems in construction. Policymakers’ responsibilities in driving policies that will place responsibilities on clients to seek a reasonable way to improve their knowledge where possible is implied in the study.

Originality/value

It contributes to improving project performance by examining whether the level of knowledge possessed by a client influences project performance.
Is co-production working well in recovery colleges? Emergent themes from a systematic narrative review
Authors: Bester Karen Louise , McGlade Anne , Darragh Eithne
Published: September 2021

Purpose

“Co-production” is a process in health and social care wherein service users and practitioners work in partnership. Recovery colleges (RCs) are educational establishments offering mental health education; a cornerstone feature is that courses are designed and delivered in parity by both mental health practitioners and “peers” – people with lived experience of mental illness. This paper aims to consider, through the identification of key themes, whether co-production within RCs is operating successfully.

Design/methodology/approach

The paper is a systematic review of qualitative literature. Relevant concept groups were systematically searched using three bibliographic databases: Medline, Social Care Online and Scopus. Articles were quality appraised and then synthesised through inductive thematic analysis and emergent trends identified.

Findings

Synthesis identified three key themes relating to the impact of co-production in RCs: practitioner attitudes, power dynamics between practitioners and service users, and RCs’ relationships with their host organisations. As a result of RC engagement, traditional practitioner/patient hierarchies were found to be eroding. Practitioners felt they were more person-centred. RCs can model good co-productive practices to their host organisations. The review concluded, with some caveats, that RC co-production was of high fidelity.

Originality/value

RC research is growing, but the body of evidence remains relatively small. Most of what exists examine the impact of RCs on individuals’ overall recovery and mental health; there is a limited empirical investigation into whether their flagship feature of parity between peers and practitioners is genuine.
Analysis ofTawarruqcontract in the Islamic profit rate swap (IPRS) implementation in Malaysia
Authors: Ahmad Azlin Alisa , Mohd Dasar Mohd Hafiz , Nik Abdul Ghani Nik Abdul Rahim
Published: September 2021

Purpose

This study aims to analyse the Shariah issues in the implementation oftawarruqcontract in the Islamic profit rate swap (IPRS) instrument in Malaysia.

Design/methodology/approach

This is a qualitative study in applying data analysis and semi-structured interview approaches. Data was collected from various documents including journals, articles and past studies conducted by scholars. To achieve the purpose of this study, the data is analysed based on thematic analysis.

Findings

The study found several Shariah issues regarding the implementation oftawarruqcontract in the IPRS instruments, which have remained a dispute amongst the Islamic financial scholars such as its profit-making purpose, encouragement of debt, impediment of shared risk concept, disputed underlying assets, a deception towards allowing riba and dual agency.

Research limitations/implications

This study recommends several improvements such as the establishment of a neutral agency that does not represent any banking institution to manage thetawarruqcontract commodity purchase from Bursa Suq al-Sila’ (BSAS). In addition, a neutral agency can provide aid in terms of transaction facility or at least consultation service for clients to enable them to conduct the commodity transactions independently.

Practical implications

Moreover, guidelines should be established on the separation of the deadline to sign the agreement of appointment of a bank as the commodity purchase agent and the agreement of appointment of the bank as the commodity sale agent on behalf of clients. All transactions related totawarruqcontract commodity must be done through BSAS. The regulators and industry experts may create a guideline for the IPRS based on the issues and recommendations that have been discussed in this study.

Originality/value

On the basis of the analysis of the criticisms and issues in the implementation oftawarruqcontract in the IPRS instrument, the current study found that an intermediating institution is allowed to gain profits from transactions conducted so long as they are based on Shariah principles of contract in Islam. As there is no parameter specifically for IPRS, thus the suggested parameter can be used by policymakers such as the Central Bank of Malaysia to ensure the industry complies with Shariah principles.
Making the local and the decentralized governable: a study of the implementation of the Chinese Temples Ordinance
Authors: Fung Wan Yin Kimberly
Published: September 2021

Purpose

This paper aims at illustrating how the local and the decentralized temple management bodies were made governable and governed through law.

Design/methodology/approach

This paper examines the implementation of Chinese Temples Ordinances (the Ordinance) and the activities of the Chinese Temples Committee (the Committee) in Hong Kong during colonial times by analyzing official archival records from 1920s to 1970s.

Findings

This paper delineates how the local and decentralized temple management bodies were made governable under the Ordinance. The Ordinance and the Committee translated Chinese temples into financial resources for Chinese charity activities managed by the elite merchant class. Chinese temples were also sometimes translated as obstacles for land development. Though there existed different representations of Chinese temples in practices, the Committee and related officials provided legal reasons under the same legal framework suggested by the Ordinance.

Originality/value

This paper suggests that folk religion as a research topic is not only relevant to studies of religious doctrine, belief and ritual performances. A study of the history of temple management bodies is also highly relevant to the study of colonial governance in Hong Kong. It adds value to the discussion on the trajectory of the development of local communities.
Morphological and behavioural differences facilitate tropical butterfly persistence in variable environments
Authors: Wenda Cheng , Xing Shuang , Nakamura Akihiro , Bonebrake Timothy C.
Published: September 2021

The thermal biology of ectotherms largely determines their abundance and distributions. In general, tropical species inhabiting warm and stable thermal environments tend to have low tolerance to cold and variable environments, which may restrict their expansion into temperate climates. However, the distribution of some tropical species does extend into cooler areas such as tropical borders and high elevation tropical mountains. Behavioural and morphological differences may therefore play important roles in facilitating tropical species to cope with cold and variable climates at tropical edges.

We used field‐validated biophysical models to estimate body temperatures of butterflies across elevational gradients at three sites in southern China and assessed the contribution of behavioural and morphological differences in facilitating their persistence in tropical and temperate climates. We investigated the effects of temperature on the activity of 4,844 individuals of 144 butterfly species along thermal gradients and tested whether species of different climatic affinities—tropical and widespread (distributed in both temperate and tropical regions)—differed in their thermoregulatory strategies (i.e. basking). In addition, we tested whether thermally related morphology or the strength of solar radiation (when butterflies were recorded) was related to such differences.

We found that activities of tropical species were restricted (low abundance) at low air temperatures compared to widespread species. Active tropical species were also more likely to bask at cooler body temperatures than widespread species. Heat gain from behavioural thermoregulation was higher for tropical species (when accounting for species abundance), and heat gain correlated with larger thorax widths but not with measured solar radiation.

Our results indicate that physiological intolerance to cold temperatures in tropical species may be compensated through behavioural and morphological responses in thermoregulation in variable subtropical environments. Increasing climatic variability with climate change may render tropical species more vulnerable to cold weather extremes compared to widespread species that are more physiologically suited to variable environments.
Fit for Purpose? BRICS and Inner‐Group Conflicts
Authors: Brosig Malte
Published: September 2021

This contribution argues that BRICS is designed to manage inner‐group tensions indirectly by endorsing a number of pragmatic operating principles. However, these principles seem to work best at smaller scale conflicts but not larger armed confrontation. The article breifly discusses the internal operating procedures of the BRICS group followed by a discussion of their relative value vis‐à‐vis inner group conflict. The article finishes by exploring the role of smaller group members such as South Africa and their ability to dissipate political tensions.
p38 MAPK‐mediated loss of nuclear RNase III enzyme Drosha underlies amyloid beta‐induced neuronal stress in Alzheimer's disease
Authors: Xu Haidong , Liu Xiaolei , Li Wenming , Xi Ye , Su Peng , Meng Bo , Shao Xiaoyun , Tang Beisha , Yang Qian , Mao Zixu
Published: September 2021

MicroRNAs (miRNAs) are small noncoding RNAs ubiquitously expressed in the brain and regulate gene expression at the post‐transcriptional level. The nuclear RNase III enzyme Drosha initiates the maturation process of miRNAs in the nucleus. Strong evidence suggests that dysregulation of miRNAs is involved in many neurological disorders including Alzheimer's disease (AD). Dysfunction of miRNA biogenesis components may be involved in the processes of those diseases. However, the role of Drosha in AD remains unknown. By using immunohistochemistry, biochemistry, and subcellular fractionation methods, we show here that the level of Drosha protein was significantly lower in the postmortem brain of human AD patients as well as in the transgenic rat model of AD. Interestingly, Drosha level was specifically reduced in neurons of the cortex and hippocampus but not in the cerebellum in the AD brain samples. In primary cortical neurons, amyloid‐beta (Aβ) oligomers caused a p38 MAPK‐dependent phosphorylation of Drosha, leading to its redistribution from the nucleus to the cytoplasm and a decrease in its level. This loss of Drosha function preceded Aβ‐induced neuronal death. Importantly, inhibition of p38 MAPK activity or overexpression of Drosha protected neurons from Aβ oligomers‐induced apoptosis. Taken together, these results establish a role for p38 MAPK‐Drosha pathway in modulating neuronal viability under Aβ oligomers stress condition and implicate loss of Drosha as a key molecular change in the pathogenesis of AD.
Clinical management of withdrawal from benzodiazepine anxiolytic and hypnotic medications
Authors: Baldwin David S.
Published: September 2021

Benzodiazepines continue to be prescribed widely in the management of patients with insomnia or anxiety disorders, despite the availability and acceptability of alternative pharmacological and psychological treatments. Many patients will experience adverse effects during treatment and considerable distress when the dosage is reduced and stopped. Management of benzodiazepine withdrawal includes measures to prevent the development of dependence, careful attention to underlying medical conditions, medication consolidation and gradual dosage reduction, accompanying psychological interventions, occasional prescription of concomitant medication, and relapse prevention with on‐going support to address psychosocial stressors. There are needs for easier patient access to services with refined expertise and for further research to optimise strategies for preventing dependence and facilitating withdrawal.
A Genre of Failed Novelists and Poets: Exploring Ethnography through a Narrative Lens
Authors: Fikry Noha
Published: September 2021

Guided by Ruth Behar’s provocation to explore how ethnography was born out of the writings of novelists and poets and building on a special issue of Anthropology and Humanism on the art of ethnography published in 2007, I explore the histories, potentials, and boundaries of ethnography as a genre and craft. Relying on narrative theory as a resource that can enrich ethnography, I provide a close reading of several ethnographies, focusing on issues of character, time, and plot. I argue that a focus on narrative helps ethnographers put in conversation multiple selves’ shifting roles in ethnography. Narrative provides tools to put in dynamic dialogue these different selves, animate our texts, and write more accessible and enjoyable ethnographies. On another level, consulting with narrative theory is a reminder to claim all our ancestors and take pride in ethnography as a queer genre whose strength lies in its openings and porous boundaries.
Exploration of real‐world outcomes and treatment patterns in patients treated with anti‐vascular endothelial growth factors for neovascular age‐related macular degeneration in Sweden
Authors: Schroeder Marion , Westborg Inger , Fluur Caroline , Olsen Rasmus , Lövestam‐Adrian Monica
Published: September 2021

Purpose

To analyse and compare the number and interval of anti‐vascular endothelial growth factor (anti‐VEGF) injections in neovascular age‐related macular degeneration (nAMD), as well as the visual development in patients followed up for one to three years in clinical practice and during different index periods.

Methods

This observational study included treatment‐naïve eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017, stratified by different index periods (2007–2010, 2011–2013, 2014–2015 and 2016–2017) and by follow‐up cohorts for each index period of one, two or three years (cohorts 1–3). Their intravitreal anti‐VEGF treatment was assessed by number of injections, injection intervals, visual acuity (VA) and near VA change.

Results

From the earliest index period 2007–2010 to the latest 2016–2017, the number of injections increased for the comparable follow‐up time; 6.2 ± 1.4 versus 8.3 ± 2.0 injections after 1 year of treatment, 4.8 ± 1.6 versus 6.7 ± 2.4 during year 2. The last injection interval was 73 ± 34 days after 1, 71 ± 33 after 2 and 67 ± 32 after 3 years of follow‐up for the index period 2014–2015. For the same period, the percentage of eyes with at least two consecutive 12–16 weeks of injection interval over 1‐, 2‐ and 3‐year follow‐up increased from 5.2%, 15.0%, to 17.5% respectively. Baseline VA for eyes indexed 2016–2017 increased and presented with 62.1 ± 13.4 letters compared with 57.7 ± 13.5 letters in 2007–2010; p < 0.0001.

Conclusions

From the earliest to the latest index periods, the number of injections increased for the comparable follow‐up time. Accordingly, baseline VA and near VA and their outcomes improved continuously.
Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease
Authors: Nakajima Atsushi , Eguchi Yuichiro , Yoneda Masato , Imajo Kento , Tamaki Nobuharu , Suganami Hideki , Nojima Toshiaki , Tanigawa Ryohei , Iizuka Masakazu , Iida Yuki , Loomba Rohit
Published: September 2021

Background

Pemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non‐alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).

Aims

To evaluate the efficacy and safety of Pemafibrate in patients with high‐risk, non‐alcoholic fatty liver disease (NAFLD).

Methods

This double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging‐estimated proton density fat fraction (MRI‐PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI‐PDFF from baseline to week 24. The secondary endpoints included MRE‐based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.

Results

There was no significant difference between the groups in the primary endpoint (−5.3% vs −4.2%; treatment difference −1.0%, P = 0.85). However, MRE‐based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference −5.7%, P = 0.036), and was maintained at week 72 (treatment difference −6.2%, P = 0.024), with significant reduction in ALT and LDL‐C. Adverse events were comparable between the treatment groups and therapy was well tolerated.

Conclusions

Pemafibrate did not decrease liver fat content but had significant reduction in MRE‐based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.
Radiographic and CT appearance of cavitary pulmonary lesions in a lamb
Authors: Kan J , Bauquier J , Tyrrell D , O'Byrne K , Stent AW , Brosnan B
Published: September 2021

Background

Pulmonary abscesses may be cavitary lesions on thoracic radiographs and computed tomography (CT).

Case report

A 26‐day‐old, cross‐breed lamb presented for respiratory distress despite procaine penicillin treatment. Thoracic radiographs revealed several pulmonary ovoid thin‐walled gas and soft tissue opacity structures. CT showed that these gas‐filled structures enclosed mildly contrast enhancing soft tissue attenuating material and surrounded the lobar bronchus to the right middle and caudal lung lobes. Imaging revealed pulmonary cavitary lesions, and chronic pulmonary abscesses was confirmed with histopathology on samples obtained from a right caudal lung lobectomy.

Conclusion

To the authors' knowledge, this is the first radiographic and CT report of cavitary pulmonary lesions in a lamb. The pulmonary abscesses in this case were suspected to be due aspiration pneumonia occurring during bottle feeding, along with the high possibility of failure of passive transfer from its orphan history.
Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain
Authors: Shulman Robert J. , Chumpitazi Bruno P. , Abdel‐Rahman Susan M. , Garg Uttam , Musaad Salma , Kearns Gregory L.
Published: September 2021

Aims

Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.

Methods

Thirty children ages 7–12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice or 180 mg thrice daily) for 1 week during which time the WMC test was repeated.

Results

Evaluable area under the plasma concentration vs. time curve (AUClast) data were available in 29 of 30 participants. A direct linear relationship (apparent dose‐proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half‐life 2.1, 3.5 and 4.6 hours for the 180, 360 and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P = .003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P < .05).

Conclusion

Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose‐proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.
THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Ion channels
Authors: Alexander Stephen P H , Mathie Alistair , Peters John A , Veale Emma L , Striessnig Jörg , Kelly Eamonn , Armstrong Jane F , Faccenda Elena , Harding Simon D , Pawson Adam J , Southan Christopher , Davies Jamie A , Aldrich Richard W. , Attali Bernard , Baggetta Austin M , Becirovic Elvir , Biel Martin , Bill Roslyn M. , Catterall William A. , Conner Alex C. , Davies Paul , Delling Markus , Virgilio Francesco Di , Falzoni Simonetta , Fenske Stefanie , George Chandy , Goldstein Steve A. N. , Grissmer Stephan , Ha Kotdaji , Hammelmann Verena , Hanukoglu Israel , Jarvis Mike , Jensen Anders A. , Kaczmarek Leonard K. , Kellenberger Stephan , Kennedy Charles , King Brian , Kitchen Philip , Lynch Joseph W. , Perez‐Reyes Edward , Plant Leigh D. , Rash Lachlan , Ren Dejian , Salman Mootaz M. , Sivilotti Lucia G. , Smart Trevor G. , Snutch Terrance P. , Tian Jinbin , Trimmer James S. , Van den Eynde Charlotte , Vriens Joris , Wei Aguan D. , Winn Brenda T. , Wulff Heike , Xu Haoxing , Yue Lixia , Zhang Xiaoli , Zhu Michael
Published: September 2021

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found athttp://onlinelibrary.wiley.com/doi/bph.15539. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Targeting α‐synuclein aggregation and its role in mitochondrial dysfunction in Parkinson's disease
Authors: Haque Md Ezazul , Akther Mahbuba , Azam Shofiul , Kim In‐Su , Lin Yuxi , Lee Young‐Ho , Choi Dong‐Kug
Published: September 2021

Lewy bodies that contain aggregated α‐synuclein in dopamine neurons are the main culprit for neurodegeneration in Parkinson's disease. However, mitochondrial dysfunction has a well‐established and prominent role in the pathogenesis of Parkinson's disease. The exact mechanism by which α‐synuclein causes dopamine neuronal loss is unclear. Recent evidence suggests that aggregated α‐synuclein localises in the mitochondria contributes to oxidative stress‐mediated apoptosis in neurons. Therefore, the involvement of aggregated α‐synuclein in mitochondrial dysfunction‐mediated neuronal loss has made it an emerging drug target for the treatment of Parkinson's disease. However, the exact mechanism by which α‐synuclein permeabilises through the mitochondrial membrane and affects the electron transport chain remains under investigation. In the present study, we describe mitochondria–α‐synuclein interactions and how α‐synuclein aggregation modulates mitochondrial homeostasis in Parkinson's disease pathogenesis. We also discuss recent therapeutic interventions targeting α‐synuclein aggregation that may help researchers to design novel therapeutic treatments for Parkinson's disease.
Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
Authors: MaruYama Takashi , Kobayashi Shuhei , Shibata Hiroyuki , Chen WanJun , Owada Yuji
Published: September 2021

Regulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4+ T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors.
The diagnostic trajectory of developmental coordination disorder in the Netherlands: Experiences of mothers
Authors: Lust Jessica M. , Adams Imke L. J. , Reinders‐Messelink Heleen A. , Luijckx Joli , Schoemaker Marina M. , Steenbergen Bert
Published: September 2021

Background

Receiving a diagnosis can have a major impact on the child and its family. Parental satisfaction concerning the diagnostic trajectory is important with regard to acceptance and coping with their child's problems. Our aim was to describe the diagnostic trajectory of developmental coordination disorder (DCD) in the Netherlands and identify factors that are related to parents' satisfaction.

Method

Mothers of 60 children with a DCD diagnosis completed an online survey concerning their experiences during and after the diagnostic trajectory of obtaining this diagnosis.

Results

Forty percent of the mothers rated the diagnostic trajectory towards a DCD diagnosis as stressful and 47% rated the knowledgeability of the first professional they consulted (mostly a general practitioner, paediatric physical therapist, or youth health care physician) as having no or just superficial knowledge about DCD. Around 60% of the mothers described a lack of knowledge and support at their child's school after receiving the diagnosis. Notwithstanding this, the majority of the participating mothers was (very) satisfied with the diagnostic trajectory. Higher appreciation of both the manner of the diagnosing professional and the post‐diagnostic support provided were predictive of higher satisfaction.

Conclusions

Our results underline the importance of improving the knowledgeability in primary schools and primary health care professionals with regard to DCD.
Aspirations and women's empowerment: Evidence from Kyrgyzstan
Authors: Kosec Katrina , Akramov Kamiljon , Mirkasimov Bakhrom , Song Jie , Zhao Hongdi
Published: September 2021

There is an enormous interest in development interventions aimed at reducing behavioural poverty traps, including by raising women's and girls' aspirations, or future‐oriented goals. However, little is known about how women's aspirations influence their gender attitudes, the marriages into which they select and their involvement in intra‐household decision‐making. We find that women in Kyrgyzstan with higher aspirations are more likely to espouse egalitarian gender attitudes, as are their husbands, and their husbands have higher aspirations. They also live in households in which women play a greater role in decision‐making, and in which spouses are more likely to agree about women's roles in decision‐making.
The effects of cerebral amyloidopathy on regional glucose metabolism in older adults with depression and mild cognitive impairment while performing memory tasks
Authors: Lee Eun Seong , Youn HyunChul , Hyung Won Seok William , Suh Sangil , Han Cheol E. , Eo Jae Seon , Jeong Hyun‐Ghang
Published: September 2021

Co‐occurring depression and mild cognitive impairment (MCI) in older adults are important because they have a high risk of conversion to dementia. In the present study, task‐related F‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) was used to analyse older adults with concomitant depression and MCI. We recruited 20 older adults with simultaneous depression and MCI and 10 older adults with normal cognition (NC). The Verbal Paired Associates test and digit span test were used for the task‐related FDG‐PET. The 20 older adults with depression and MCI were classified into two groups based on the F‐18 florbetaben PET results: depressed MCI patients with (LLD‐MCI‐A[+]; n = 11) and without amyloid accumulation (LLD‐MCI‐A[−]; n = 9). Reduced regional cerebral glucose metabolism (rCMglc) in the left superior frontal region was observed in the LLD‐MCI‐A(−) group compared with the NC group. Analyses of the NC and LLD‐MCI‐A(+) groups showed significantly decreased rCMglc in the right inferior parietal and left middle frontal regions in the LLD‐MCI‐A(+) group. rCMglc in the left precuneus was lower in the LLD‐MCI‐A(+) group than in the LLD‐MCI‐A(−) group. Significant correlations between the rCMglc in the right inferior parietal/left precuneus regions and memory task scores were observed based on correlation analyses of NC and LLD‐MCI‐A(+) groups. The findings in the present study indicate the presence of amyloid accumulation influences glucose metabolism in depressed elderly subjects with MCI while performing cognitive tasks. Task‐related FDG‐PET examinations may help differentiate MCI associated with depression from comorbid depression in patients with prodromal Alzheimer's disease.
Do immortals need an eject button? Sartre and the importance of always having an exit
Authors: Buben Adam
Published: September 2021

Sartre directly addresses some of the core issues involved in the contemporary debate about the desirability of immortality. He thinks mortality can never be the source of life's meaning because death cuts us off before meaning can be determined, and because any meaning that survives is no longer our own. These claims already put Sartre at odds with immortality nay‐sayers who believe the limitations provided by our chronological finitude are essential to meaning, but he takes it further by arguing that the actual meaning‐generating limitations of our temporal situation would remain intact even if our lives never ended. Thus, Sartre seems like an obvious resource for anyone defending immortality. However, he does suggest one major reason to be wary. The possibility of ending up in a perpetually miserable situation makes truly indestructible immortality less attractive, and this diminished attractiveness suggests that we should not take the ability to die too lightly. With all of this in mind, I argue for a form of immortality involving indefinite life‐extension with the possibility to opt out in case existence becomes irreparably intolerable.
Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease
Authors: Jokinen Hanna , Laakso Hanna M. , Ahlström Matti , Arola Anne , Lempiäinen Juha , Pitkänen Johanna , Paajanen Teemu , Sikkes Sietske A. M. , Koikkalainen Juha , Lötjönen Jyrki , Korvenoja Antti , Erkinjuntti Timo , Melkas Susanna
Published: September 2021

Background

Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH).

Methods

Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation.

Results

Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single‐leg stance, timed up‐and‐go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant‐evaluated IADL, but not on self‐evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up‐and‐go performance.

Conclusion

The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.
Adult‐onset idiopathic dystonia: A national data‐linkage study to determine epidemiological, social deprivation, and mortality characteristics
Authors: Bailey Grace A. , Rawlings Anna , Torabi Fatemeh , Pickrell Owen , Peall Kathryn J.
Published: September 2021

Background and purpose

Accurate epidemiological information is essential for the improved understanding of dystonia syndromes, as well as better provisioning of clinical services and providing context for diagnostic decision‐making. Here, we determine epidemiological, social deprivation, and mortality characteristics of adult‐onset idiopathic dystonia in the Welsh population.

Methods

A retrospective population‐based cohort study using anonymized electronic health care data in Wales was conducted to identify individuals with dystonia between 1 January 1994 and 31 December 2017. We developed a case‐ascertainment algorithm to determine dystonia incidence and prevalence, as well as characterization of the dystonia cohort, based on social deprivation and mortality.

Results

The case‐ascertainment algorithm (79% sensitivity) identified 54,966 cases; of these cases, 41,660 had adult‐onset idiopathic dystonia (≥20 years). Amongst the adult‐onset form, the median age at diagnosis was 41 years, with males significantly older at time of diagnosis compared to females. Prevalence rates ranged from 0.02% in 1994 to 1.2% in 2017. The average annual incidence was 87.7/100,000/year, increasing from 49.9/100,000/year (1994) to 96.21/100,000/year (2017). In 2017, people with dystonia had a similar life expectancy to the Welsh population.

Conclusions

We have developed a case‐ascertainment algorithm, supported by the introduction of a neurologist‐reviewed validation cohort, providing a platform for future population‐based dystonia studies. We have established robust population‐level prevalence and incidence values for adult‐onset idiopathic forms of dystonia, with this reflecting increasing clinical recognition and identification of causal genes. Underlying causes of death mirrored those of the general population, including circulatory disorders, respiratory disorders, cancers, and dementia.
We are not all the same: The importance of perceived difference in racial ideology and Afrocentricity for African American relationships
Authors: Parsons Aleja , Scott Shelby B. , Knopp Kayla , Nguyen Phuong Linh L. , Markman Howard J. , Stanley Scott M.
Published: September 2021

A large body of existing research on African American relationships perpetuates a deficit model that assumes Eurocentric norms and emphasizes between‐group differences (e.g., cross‐racial comparisons with the majority group—European Americans). The current study examined within‐group variability and the influence of culturally unique factors, Afrocentricity, racial ideology, and perceived discrepancy between self and partner on African American relationship processes. Data were collected from 137 self‐identified African American adults in same‐race, cross‐gender relationships. Consistent with the literature on protective values of Afrocentricity, there was an association between reported relationship quality and high levels of one's own and perceived partner's Afrocentricity. Discrepancies between self and partner Afrocentricity were not associated with relationship processes, but higher perceived discrepancies across all four subscales of racial ideology were associated with lower relationship dedication. Higher perceived discrepancies on the humanist and assimilationist subscales were also related to higher levels of conflict. These findings have important clinical implications and demonstrate a need for further research into the nuances of individual factors and dyadic processes that are unique to African American couples.