bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactory rod cells: a rare cell type in the larval zebrafish olfactory epithelium with an actin-rich apical projection
Authors: Cheung King Yee , Jesuthasan Suresh J. , Baxendale Sarah , van Hateren Nicholas J. , Marzo Mar , Hill Christopher J. , Whitfield Tanya T.
Published: November 2020

We report the presence of a rare cell type, the olfactory rod cell, in the developing zebrafish olfactory epithelium. These cells each bear a single actin-rich rod-like apical projection extending about 10 μm from the epithelial surface. Live imaging with a ubiquitous Lifeact-RFP label indicates that the rods can oscillate. Olfactory rods arise within a few hours of the olfactory pit opening, increase in numbers and size during larval stages, and can develop in the absence of olfactory cilia. Olfactory rod cells differ in morphology from the known classes of olfactory sensory neuron, but express reporters driven by neuronal promoters. The cells also differ from secondary sensory cells such as hair cells of the inner ear or lateral line, or sensory cells in the taste bud, as they are not associated with established synaptic terminals. A sub-population of olfactory rod cells expresses a Lifeact-mRFPruby transgene driven by thesox10promoter. Mosaic expression of this transgene reveals that olfactory rod cells have rounded cell bodies located apically in the olfactory epithelium.
A self-exciting point process to study multi-cellular spatial signaling patterns
Authors: Verma Archit , Jena Siddhartha G. , Isakov Danielle R. , Aoki Kazuhiro , Toettcher Jared E. , Engelhardt Barbara E.
Published: November 2020

Multi-cellular organisms rely on spatial signaling among cells to drive their organization, development, and response to stimuli. Several models have been proposed to capture the behavior of spatial signaling in multi-cellular systems, but existing approaches fail to capture both the autonomous behavior of single cells and the interactions of a cell with its neighbors simultaneously. We propose a spatiotemporal model of dynamic cell signaling based on Hawkes processes—self-exciting point processes—that model the signaling processes within a cell and spatial couplings between cells. With this cellular point process (CPP) model, we capture both the single-cell protein bursting rate and the magnitude and duration of signaling between cells relative to spatial locations. Furthermore, our model captures tissues composed of heterogeneous cell types with different bursting rates and signaling behaviors across multiple signaling proteins. We apply our model to epithelial cell systems that exhibit a range of autonomous and spatial signaling behaviors basally and under pharmacological exposure. Our model identifies known drug-induced signaling deficits, characterizes differences in signaling across a wound front, and generalizes to multi-channel observations.
Csf1rbmutation uncouples two waves of microglia development in zebrafish
Authors: Ferrero Giuliano , Miserocchi Magali , Ruggiero Elodie Di , Wittamer Valérie
Published: November 2020

In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. While murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors.Colony-stimulating factor receptor 1 (csf1r)is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish which possess two paralogous genes:csf1raandcsf1rb.While previous work showed invalidation of both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles forcsf1raandcsf1rbin hematopoiesis, and identifiedcsf1rbas an essential regulator of adult microglia development. Notably, we demonstrate thatcsf1rbpositively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microgliain vivo.
The epithelial-mesenchymal transcription factorSNAI1represses transcription of the tumor suppressor miRNAlet-7in cancer
Authors: Wang H , Chirshev E , Hojo N , Suzuki T , Bertucci A , Pierce M , Perry C , Wang R , Zink J , Glackin CA , Ioffe YJ , Unternaehrer JJ
Published: November 2020

We aimed to determine the mechanism of epithelial-mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linkedlet-7repression and acquisition of stemness with the EMT factor,SNAI1. The mechanisms for the loss oflet-7in cancer cells are incompletely understood. In four carcinoma cell lines from breast cancer, pancreatic cancer and ovarian cancer and in ovarian cancer patient-derived cells, we analyzed stem cell phenotype and tumor growth via mRNA, miRNA, and protein expression, spheroid formation, and growth in patient-derived xenografts. We show that treatment with EMT-promoting growth factors orSNAI1overexpression increased stemness and reducedlet-7expression, whileSNAI1knockdown reduced stemness and restoredlet-7expression. Rescue experiments demonstrate that the pro-stemness effects ofSNAI1are mediated vialet-7. In vivo, nanoparticle-delivered siRNA successfully knocked downSNAI1in orthotopic patient-derived xenografts, accompanied by reduced stemness and increasedlet-7expression, and reduced tumor burden. Chromatin immunoprecipitation demonstrated thatSNAI1binds the promoters of variouslet-7family members, and luciferase assays revealed thatSNAI1represseslet-7transcription. In conclusion, theSNAI1/let-7axis is an important component of stemness pathways in cancer cells, and this study provides a rationale for future work examining this axis as a potential target for cancer stem cell-specific therapies.

Novelty and Impact

This study provides new insight into molecular mechanisms by which EMT transcription factorSNAI1exerts its pro-stemness effects in cancer cells, demonstrating its potential as a stem cell-directed target for therapy.In vitroandin vivo, mesoporous silica nanoparticle-mediatedSNAI1knockdown resulted in restoration of let-7 miRNA, inhibiting stemness and reducing tumor burden. Our studies validatein vivonanoparticle-delivered RNAi targeting theSNAI1/let-7axis as a clinically relevant approach.
E-cadherin interacts with EGFR resulting in hyper-activation of ERK in multiple models of breast cancer
Authors: Russo Gabriella C. , Crawford Ashleigh J. , Clark David , Cui Julie , Carney Ryan , Karl Michelle N. , Su Boyang , Starich Bartholomew , Lih Tung-Shing , Kamat Pratik , Zhang Qiming , Wu Pei-Hsun , Lee Meng-Horng , Leong Hon S. , Rebecca Vito W. , Zhang Hui , Wirtz Denis
Published: November 2020

The loss of the intercellular adhesion molecule E-cadherin is a hallmark of the epithelial- mesenchymal transition (EMT), during which tumor cells transition into an invasive phenotype. Accordingly, E-cadherin has long been considered a tumor suppressor gene. Using novel multi-compartment spheroids and multiplein vivomodels, we show that E-cadherin promotes a hyper-proliferative phenotype in breast cancer cells via interaction with the transmembrane receptor EGFR. This interaction results in the activation of the MEK/ERK signaling pathway, leading to a significant increase in proliferation via the activation of transcription factors including c-Fos. Pharmacological inhibition of MEK activity in E-cadherin positive breast cancer cells significantly decreases both tumor growth and macro-metastasisin vivo. This work provides evidence for a novel role of E-cadherin in breast tumor growth and identifies a potential new target to treat hyper-proliferative E-cadherin-positive breast tumors.
Psychological safety, meaningfulness and empowerment as predictors of employee well-being: a mediating role of promotive voice
Authors: Hasan Fouzia , Kashif Muhammad
Published: November 2020

Purpose

The core aim of this study is to explore how psychological safety, psychological meaningfulness and psychological empowerment predict psychological well-being in a mediating role of promotive voice.

Design/methodology/approach

A cross-sectional survey is employed to collect data from 456 front-line employees (FLEs) working in the banking sector of Pakistan. The collected data were analyzed utilizing the structural equation modelling (SEM) technique.

Findings

The relationship between psychological safety and empowerment is significant. The results support the direct and mediating role of promotive voice to predict psychological well-being among frontliners. Interestingly, the mediation of promotive voice to predict the relationship between psychological meaningfulness and psychological well-being is not supported.

Practical implications

The managers should delegate authority to FLEs working at the front end. Moreover, voicing should be a delightful experience for employees. The management should listen to them carefully and also update the staff about the outcomes of suggestions rendered by them. Finally, rewarding employees can encourage promotive voicing among FLEs.

Originality/value

The psychological safety as an antecedent to promotive voice, promotive voice as a predictor of psychological well-being and the collectivist country context of Pakistan are unique products of this study.
Facial expression recognition based on bidirectional gated recurrent units within deep residual network
Authors: Shen Wenjuan , Li Xiaoling
Published: November 2020

Purpose

recent years, facial expression recognition has been widely used in human machine interaction, clinical medicine and safe driving. However, there is a limitation that conventional recurrent neural networks can only learn the time-series characteristics of expressions based on one-way propagation information.

Design/methodology/approach

To solve such limitation, this paper proposes a novel model based on bidirectional gated recurrent unit networks (Bi-GRUs) with two-way propagations, and the theory of identity mapping residuals is adopted to effectively prevent the problem of gradient disappearance caused by the depth of the introduced network. Since the Inception-V3 network model for spatial feature extraction has too many parameters, it is prone to overfitting during training. This paper proposes a novel facial expression recognition model to add two reduction modules to reduce parameters, so as to obtain an Inception-W network with better generalization.

Findings

Finally, the proposed model is pretrained to determine the best settings and selections. Then, the pretrained model is experimented on two facial expression data sets of CK+ and Oulu- CASIA, and the recognition performance and efficiency are compared with the existing methods. The highest recognition rate is 99.6%, which shows that the method has good recognition accuracy in a certain range.

Originality/value

By using the proposed model for the applications of facial expression, the high recognition accuracy and robust recognition results with lower time consumption will help to build more sophisticated applications in real world.
Evaluating ṣukūk investment intentions in Pakistan from a social cognitive perspective
Authors: Khan Safeer Ullah , Khan Ikram Ullah , Khan Ismail , Din Saif Ud , Khan Abid Ullah
Published: November 2020

Purpose

This study aims to evaluate cognitive, personal and environmental factors affecting investors’ behavioral intentions (BI) to invest in ṣukūk (Islamic investment certificates) in Pakistan.

Design/methodology/approach

Data from 462 participants were collected through survey-questionnaires by using the convenient sampling technique. Hypothesized proposed relationships among the constructs were examined by applying the structural equation modeling (SEM) technique through smart partial least squares.

Findings

Compatibility, internal influence, external influence and intrinsic motivation were found to be significant predictors of investors’ BI to invest in ṣukūk. In addition, it was found that the religious aspect not only affects investors’ BI positively but also works as a moderator in the relationships between BI and both internal and external influence.

Practical implications

The results are quite helpful for ṣukūk issuers and regulators to consider cognitive, personal and environmental factors that might enhance the adoption of ṣukūk, especially among Muslim investors.

Originality/value

This study is among the few research studies that shed light on investors’ BI to invest in ṣukūk. Using social cognitive theory, the study investigates the cognitive, personal and environmental factors influencing ṣukūk adoption, which were previously unexplored. In addition, this is the first study that unveils the influential factors of ṣukūk adoption in Pakistan, a Muslim-majority country.
Does PMS influence the strategy pillars: OPP relationship? Evidence from HEIs in Indonesia
Authors: Soewarno Noorlailie , Tjahjadi Bambang , Anmariska Farah
Published: November 2020

Purpose

This study aims to investigate whether strategy pillars have a positive direct effect on organizational productivity performance (OPP) in the Indonesian HEI (Higher Education Institutions) research setting and, if so, whether the effect is mediated by a performance management system (PMS).

Design/methodology/approach

This study used quantitative research employing partial least square structural equation modeling (PLS-SEM) to test the hypotheses. A mediation model of the research framework was developed to investigate the mediating role of PMS.

Findings

Using a sample of 182 Indonesian HEI managers, the results indicate that strategy pillars have a positive effect on OPP. Further analysis shows that PMS partially mediates the strategy pillar–OPP relationship.

Research limitations/implications

This study has limitations. Firstly, the sample size used was relatively small and this may raise the issue of generalization. Secondly, it used a Likert scale and therefore may raise the issue of judgment bias. Lastly, this study is context-specific for Indonesia and caution should be used when generalizing it to other countries.

Practical implications

To enhance the HEIs productivity performance, the HEI managers should develop strong strategy pillars for the purpose of effective strategy formulation and execution.

Social implications

This study provides a model showing how to improve the HEIs productivity performance by employing strategy pillars and a PMS. The better the performance of the HEIs, the better the quality of life of society in the era of the knowledge economy.

Originality/value

Strategy pillars have rarely been researched. This study is therefore one of the few studies on strategy pillars. This study also provides new elements related to measuring strategy pillars, PMS and OPP in the context of HEIs in Indonesia as an emerging economy.
Students’ attitude toward sustainability and humanitarian engineering education using project-based and international field learning pedagogies
Authors: Ngo Truc Thanh , Chase Bradley
Published: November 2020

Purpose

Environmental sustainability and social contexts are becoming increasingly important concepts. The infusion of sustainability and humanitarian engineering (HE) into the academic core curriculum is often challenging. This study aims to provide an understanding of students’ perceptions and attitudes toward the incorporation of active learning of sustainability and humanitarian concepts into engineering education.

Design/methodology/approach

A project-based sustainability course was developed and offered to engineering undergraduates. A HE international field experience was also provided to students as an extracurricular activity. Pre- and post-surveys were conducted to assess students’ perceptions and attitudes toward sustainability and HE project learning experience. An analysis of variance (ANOVA) was performed to determine the statistical significance of the results and demographic influences on students’ experiences.

Findings

Both project-based and international field learning experiences positively influenced the students’ perceptions of sustainable practices, social change and appreciation of the engineering profession. Multidisciplinary learning also helped students become more motivated, engage in sustainability-promoted activities and community work and improve their social interactions. Students gained practical engineering skills that they did not typically receive in traditional classroom settings and recognized the global and social responsibilities that are core to sustainable development education.

Originality/value

The study demonstrates a mixed undergraduate educational model in which students acquired sustainability concepts through a project-based engineering course and practiced social responsibility through international HE projects. The findings help engineering educators understand students’ perceptions toward sustainability and HE, providing insight into effective curriculum design and strategic inclusion of social responsibility in traditional engineering education.
Foreign inflows and economic growth in Pakistan: some new insights
Authors: Tahir Muhammad , Jan Ahmad Ali , Shah Syed Quaid Ali , Alam Md Badrul , Afridi Muhammad Asim , Tariq Yasir Bin , Bashir Malik Fahim
Published: November 2020

Purpose

The purpose of this paper is to explore the contending role of important external inflows on the economic growth of Pakistan economy. The main purpose behind focusing on Pakistan is that it is receiving significant inflows from different international sources such as International Monetary Fund, World Bank and Asian Development Bank.

Design/methodology/approach

The study adopted the autoregressive distributed lag cointegration approach for the purpose of exploring the long-run cointegrating relationship among the variables. As Pakistan Government had been implementing some major liberalization policies during 1990s, data from 1976 to 2018 is used to estimate the specified models to reflect the impact of the surge of foreign inflows occurring from that time. In addition, error correction model is estimated for examining the short-run relationships.

Findings

The findings revealed the significant role played by different inflows in accelerating the economic growth. According to results, in the long run, all inflows, for example, Foreign direct investment (FDI), debt, official developdment assistance and remittances, have influenced significantly and positively the economic growth. The two control variables such as inflation and employment level included in the model have also played their expected role in the growth process. In the short run, some of the variables such as remittances, FDI and inflation rate have lost their significance level while for debt, aid and employment level, the signs of their coefficients become reversed.

Practical implications

Based on the findings, the study suggests the policymakers of Pakistan economy to liberalize the economy and attract more inflows from the external sources to accelerate economic growth.

Originality/value

To the best of the authors’ knowledge, this is the first comprehensive empirical study on the role of foreign inflows in the process of economic growth in the context of Pakistan economy.
Being an entrepreneur post-COVID-19 – resilience in times of crisis: a systematic literature review
Authors: Portuguez Castro May , Gómez Zermeño Marcela Georgina
Published: November 2020

Purpose

The COVID-19 pandemic has had an uncertain impact on the global economy, especially for entrepreneurs and small and medium-sized enterprises that have suffered significant consequences. However, resilience has emerged as an entrepreneurial skill that allows companies to adapt and grow stronger in the face of challenges. Therefore, this paper conducted a literature review to identify the factors that comprise resilience to strengthen training programs for entrepreneurial skills. This study aims to lead to future empirical studies that will provide more understanding and equip professionals with the skills to adapt to crises.

Design/methodology/approach

A systematic literature review was performed, analyzing studies related to entrepreneurship, resilience and crises. In total, 30 empirical studies were analyzed to determine the facts of the crises, the methodologies used and the actions taken to address them.

Findings

The review identified resilience factors such as attitudes adopted toward the crisis, the characteristics of the business and the entrepreneur, the relationships with institutions, human and social capital and strategic management. These factors can be considered in training programs for resilient entrepreneurs and by the different actors in the entrepreneurial ecosystem, including the universities and public policymakers, who support them.

Originality/value

This study provides a literature review that focuses on identifying the resilience factors of entrepreneurs who confronted past crises to know how to apply them to overcome the current situation and contribute to post-COVID-19 entrepreneurship. This paper hopes that the findings motivate others to conduct further empirical studies on entrepreneurship and resilience in times of crisis, especially in developing countries and emerging economies.
Transformational leadership and employee outcomes: the mediating role of psychological empowerment
Authors: Saira Saira , Mansoor Sadia , Ali Muhammad
Published: November 2020

Purpose

The purpose of this study is to empirically test the mediating effect of psychological empowerment in the relationship between transformational leadership and two employee outcomes: organizational citizenship behavior and turnover intention.

Design/methodology/approach

The data were collected from 316 employees working in the textile industry to empirically test the proposed model.

Findings

The findings of this study indicate that psychological empowerment mediates the relationship between transformational leadership and both employee outcomes of organizational citizenship behavior and turnover intention.

Research limitations/implications

This study suggests that organizations aiming to minimize turnover intention among employees should develop a transformational leadership style at the managerial level to enhance psychological empowerment among employees, which, in turn, will also improve organizational citizenship behavior.

Originality/value

This study proposes and tests the indirect effect of transformational leadership on organizational citizenship behavior and turnover intention via psychological empowerment.
What matters to ownership structure? Evidence from pre- and post-global financial crisis in an emerging market
Authors: Panda Brahmadev , Kumar Gaurav
Published: November 2020

Purpose

The purpose of this paper is to ascertain determining factors of ownership concentration and institutional portfolio ownership in the listed firms of an emerging market during pre-crisis and post-crisis periods and find variations in determining factors between the two varying market conditions.

Design/methodology/approach

This paper considers 316 listed firms for the pre-crisis period and 408 firms for the post-crisis period, from the NIFTY-500. Pre-crisis period ranges from FY2000-01 to FY2007-08 and post-crisis period ranges from FY2009-10 to FY2016-17. Two-step GMM is utilized to test the hypotheses by controlling the unobserved heterogeneity and endogeneity issues.

Findings

Higher investment and stock market growth leads to ownership dispersion in both the market conditions. Industry information asymmetry leads to dispersion in pre-crisis, while improves concentration in post-crisis phase. Firm size, legal environment and economic growth are found to be a positive determinant of institutional ownership irrespective of market conditions. Institutional investment proliferates with higher stock liquidity and PE ratio, while declines with augmented firm risk, current ratio and stock market turnover during post-crisis phase.

Practical implications

Policymakers should construct a robust legal environment and focus to improve economic conditions to boost institutional ownership. Corporate executives should concentrate to increase stock liquidity and earnings of the firms, and lower market risk to draw more institutional portfolio investments.

Originality/value

This study would enrich emerging governance literature since studies on the determining factors of ownership holdings are limited in the emerging world. It adds novelty by capturing two different market conditions such as pre-crisis and post-crisis phases to obtain the time-dependent and time-independent determinants. It adds uniqueness by considering the determinants of institutional ownership, which is scarce in ownership studies.
A systematic review of current approaches to managing demand and waitlists for mental health services
Authors: Thomas Kerry A. , Schroder Annelise M. , Rickwood Debra J.
Published: November 2020

Purpose

Timely access to effective treatment is a primary goal for mental health services; however, when demand exceeds available resources, services may place clients on a waitlist or restrict services. This paper aims to identify approaches used by mental health services to manage service demand and waitlists.

Design/methodology/approach

A review of research literature between 2009 and 2019 was conducted using the Medline, PsycINFO, CINAHL, Embase and Cochrane databases. Articles were screened and assessed against inclusion criteria and the methodological quality of included studies was assessed using the Mixed Methods Appraisal Tool.

Findings

In total, 20 articles were located that met the inclusion criteria. Five demand management approaches were identified, namely, walk-in models, triage processes, multi-disciplinary care, patient-led approaches and service delivery changes.

Research limitations/implications

This review identifies effective approaches that services can consider adapting to their local setting; however, further research is needed to demonstrate the clinical effectiveness of services provided under these models.

Originality/value

This review makes a valuable contribution to mental health care service delivery by detailing the strategies that services have adopted to manage demand and, where available, comparative outcomes with traditional service delivery models.
Recovery of the microstructural changes of different duplex stainless steel alloys
Authors: Khoshnaw Fuad , Delaunois Fabienne , Vitry Veronique
Published: November 2020

Purpose

To find out the optimum heat treatments to recover the microstructural changes of stainless steel alloys.

Design/methodology/approach

A total of four alloys were used in this study: two duplex stainless steel (DSS) alloys type 2304 and 2205, super DSS (SDSS) type 2507 and austenitic stainless steel alloy type 316 L. The alloys were heated to different temperatures, 750, 850, 950 and 1,050°C, for three different times, 10 min, 1 and 4 h.

Findings

The microstructural investigations showed that 2205 and 2507 behaved similarly in recovering their microstructures, especially in terms of the ferrite:austenite ratio within specific heat treatments and changing the hardness values. The results indicated that the microstructure of both alloys started to change above 750°C, the largest changes were shown at 850 and 950°C as the lowest ferrite content (FC%) was recorded at 850°C for both alloys. However, the microstructures of both alloys started to recover at 1,050°C. The reduction in the hardness values was attributed to the formation of new ferrite grains, free of residual stresses. On the other hand, the microstructure of the alloy type 2304 was stable and did not show large changes due to the applied heat treatments, similarly for austenitic alloy except showing chromium (Cr) carbide precipitation.

Originality/value

Finding the exact heat treatments, temperature and time to recover the microstructural changes of DSS alloys.
Anthropological understanding of culture – the key for designing Romani housing
Authors: Grbić Milena , Dulić Olivera , Aladžić Viktorija
Published: November 2020

Purpose

This paper aims to demonstrate a possible way in which cultural elements of minorities, in the specific case of the Romani, can be researched and operationalized in certain guidelines for designing housing intended for these groups. The paper was inspired by a constant failure of the present practice of solving the socially vulnerable Romani housing problems, namely, previous attempts have only achieved a negative outcome that, besides the partial satisfaction of urgent housing needs, does not respect the specificities of the Romani culture and lifestyle. The negative result has once again displaced this subject outside of the designing expertise and demands new examinations of strategical principles that precede the solving of the Romani housing question.

Design/methodology/approach

The authors create a methodological turn from the humanistic determination of the term culture towards the anthropological one, forming a clear methodological position of accessing the Romani culture. To test this approach on Romani settlements in Belgrade, this study used on-site observations of everyday life and informal interviews with residents.

Findings

As a practical result, this paper presents an operational knowledge base about Romani housing with design recommendations. In the social sense, this knowledge contributes to the scientific description and explanation of the characteristics of Roma housing. In a wider sense, this paper has the potential to shed light on similar problems of minorities that are present outside of the national borders of Serbia.

Originality/value

The topic of Romani housing is insufficiently researched, especially in the region of the Western Balkans. For this reason, the present study and the obtained results represent a significant contribution to scientific knowledge in this field.
Chronic hepatitis C virus infection impairs natural killer cells–dendritic cells cross‐talk: Anin vitroculture study
Authors: Ragab Dina , Samaha Dalia , Mohamed Nesrine , Rafik Mona , Abdel Hady Walid
Published: November 2020

To examine the cross‐talk between NK cells and DCs in hepatitis C virus (HCV) infection, we isolated monocytes and NK cells from 20 chronic HCV patients and 20 healthy controls. Monocytes were used to generate immature DCs which were pulsed with HCV peptides (core, NS3–NS4, and NS5). Four different cocultures were carried out: E1, both DCs and NK cells were from a chronic HCV patient; E2, NK cells from a healthy control cocultured with DCs from a chronic HCV patient; E3, NK cells from a chronic HCV patient cocultured with DCs from a healthy control; and E4, both DCs and NK cells were from a healthy control. Using flow cytometry, we assessed the effect of these different cocultures on levels of maturation markers on DCs and levels of activation/inhibition markers on NK cells. Results showed that peptide‐pulsed HCV DCs showed a maturation defect in the form of decreased HLA‐DR, decreased CD86, and increased CD83 expression especially when cocultured with HCV NK. This was mainly due to core peptide pulsing and to a lesser extent due to NS5 pulsing, whereas there was no effect with NS3–NS4 pulsing. Alternatively, HCV NK cells upregulated both activation and inhibition markers especially when cocultured with healthy DCs. Compared with E2, E1 resulted in higher apoptosis of both NK cells and DCs with the percentage of NK apoptosis higher than that of DCs. Taken together, the data indicate that HCV infection impairs NK–DC cross‐talk which may be a leading cause in viral persistence and chronicity.
The burden of ischemic heart disease and type 2 diabetes mellitus attributable to diet high in sugar‐sweetened beverages in China: An analysis for the Global Burden of Disease Study 2017
Authors: Li Man , Li Xiaojie , Zhao Yanfang , Zhang Lu , Yang Jing , Zhou Maigeng , Wang Zhuoqun
Published: November 2020

Background

The aim of this study was to estimate the burden of ischemic heart disease (IHD) and type 2 diabetes mellitus (T2DM) attributable to a diet high in sugar‐sweetened beverages (SSBs) in China from 1990 to 2017.

Methods

Data from the Global Burden of Disease Study 2017 were used to assess all‐age and age‐standardized, risk‐attributable mortality, years of life lost (YLL), years of life with disability (YLD), and disability‐adjusted life years (DALYs) by age, sex, year, province, and sociodemographic index (SDI).

Results

For total noncommunicable diseases (NCDs), 12 523 (95% uncertainty interval 776‐27 631) deaths, 305 288 (18 611‐661 847) YLL, 142 051 (64 530‐257 468) YLD, and 447 339 (132 677‐858 838) DALYs were attributable to diet high in SSBs in 2017, particularly among males. Age‐standardized, risk‐attributable mortality, YLL, YLD, and DALY rates increased distinctly by 507.3%, 410.3%, 571.0%, and 453.3% from 1990 to 2017 respectively. Age‐sex–specific, risk‐attributable mortality and YLL rates for IHD in older adults (over 65 years) were higher than in young (between 25 and 39 years) and middle‐aged adults (between 40 and 64 years) in 2017; however, the YLD and DALY rates for T2DM were higher in young and middle‐aged males than in older males. The age‐standardized, risk‐attributable DALY rates for total NCDs increased substantially in high‐SDI and high‐middle–SDI provinces during the period.

Conclusions

China has a huge and growing burden of IHD and T2DM attributable to diet high in SSBs, particularly among young and middle‐aged male adults in wealthier provinces. Evidence‐based public health policies at the provincial levels to reduce the consumption of SSBs should be prioritized in China.
The chromosome‐level genome sequence and karyotypic evolution of Megadenia pygmaea (Brassicaceae)
Authors: Yang Wenjie , Zhang Lei , Mandáková Terezie , Huang Li , Li Ting , Jiang Jiebei , Yang Yongzhi , Lysak Martin A. , Liu Jianquan , Hu Quanjun
Published: November 2020

Karyotypic changes in chromosome number and structure are drivers in the divergent evolution of diverse plant species and lineages. This study aimed to reveal the origins of the unique karyotype (2n = 12) and phylogenetic relationships of the genus Megadenia (Brassicaceae). A high‐quality chromosome‐scale genome was assembled for Megadenia pygmaea using Nanopore long reads and high‐throughput chromosome conformation capture (Hi‐C). The assembled genome is 215.2 Mb and is anchored on six pseudochromosomes. We annotated a total of 25,607 high‐confidence protein‐coding genes and corroborated the phylogenetic affinity of Megadenia with the Brassicaceae expanded lineage II, containing numerous agricultural crops. We dated the divergence of Megadenia from its closest relatives to 27.04 (19.11–36.60) million years ago. A reconstruction of the chromosomal composition of the species was performed based on the de novo assembled genome and comparative chromosome painting analysis. The karyotype structure of M. pygmaea is very similar to the previously inferred proto‐Calepineae karyotype (PCK; n = 7) of the lineage II. However, an end‐to‐end translocation between two ancestral chromosomes reduced the chromosome number from n = 7 to n = 6 in Megadenia. Our reference genome provides fundamental information for karyotypic evolution and evolutionary study of this genus.
The association of telomere length with substance use disorders: a systematic review and meta‐analysis of observational studies
Authors: Navarro‐Mateu Fernando , Husky Mathilde , Cayuela‐Fuentes Pedro , Álvarez Francisco‐Javier , Roca‐Vega Agustín , Rubio‐Aparicio María , Chirlaque María Dolores , Cayuela María Luisa , Martínez Salvador , Sánchez‐Meca Julio
Published: November 2020

Background and Aims

Several recent studies have investigated the relationship between telomere length and substance use disorders with inconsistent results. We aimed to assess this association and to identify moderators of the relationship.

Methods

Systematic review and meta‐analysis. Selection criteria were observational studies reporting telomere length in people with a substance use disorder compared with a control group. Studies focused solely on nicotine addiction, employing other study designs, and non‐human studies were excluded. Study selection and data extraction were independently conducted by two researchers following a standardized protocol and included studies until December 2019. Standardized mean differences were used as the effect size index [d; 95% confidence interval (CI)] and random‐effects models were used for the meta‐analysis. Cochran's Q‐statistic, I2 index, visual inspection of the forest plot and a 95% prediction interval were applied to verify study heterogeneity. Subgroup analyses and meta‐regressions were conducted to explore heterogeneity. Small study effects were examined using the ‘funnel plot’, the Egger test, Duval & Tweedie's trim‐and‐fill method and the precision‐effect test–precision‐effect estimate with standard error (PET‐PEESE) method. The risk of bias and the quality of evidence were assessed.

Results

Ten studies (12 analysis units with 2671 cases and 4532 controls) met the selection criteria. An overall effect size of moderate magnitude was found (d+ = −0.63; 95% CI = −1.00 and −0.26; P = 0.0008). A potential small study effect was detected, as well as large heterogeneity between studies (Q‐statistic P < 0.001, I2 = 97.3%). Selection of controls, reporting laboratory quality control procedures and total sample size significantly affected the effect size. The quality of the evidence was very low, based on risk of bias analysis and the grading of recommendations assessment, development and evaluation (GRADE) system.

Conclusions

People with substance use disorders appear to have shorter telomere length than controls; however, this finding should be interpreted with caution due to the poor quality of the evidence.
Drug‐specific T‐cell responses in patients with liver injury following treatment with the BACE inhibitor atabecestat
Authors: Thomson Paul J. , Kafu Laila , Meng Xiaoli , Snoeys Jan , De Bondt An , De Maeyer Dries , Wils Hans , Leclercq Laurent , Vinken Petra , Naisbitt Dean J.
Published: November 2020

Background

Atabecestat is an orally administered BACE inhibitor developed to treat Alzheimer's disease. Elevations in hepatic enzymes were detected in a number of in trial patients, which resulted in termination of the drug development programme. Immunohistochemical characterization of liver tissue from an index case of atabecestat‐mediated liver injury revealed an infiltration of T‐lymphocytes in areas of hepatocellular damage. This coupled with the fact that liver injury had a delayed onset suggests that the adaptive immune system may be involved in the pathogenesis. The aim of this study was to generate and characterize atabecestat(metabolite)‐responsive T‐cell clones from patients with liver injury.

Methods

Peripheral blood mononuclear cells were cultured with atabecestat and its metabolites (diaminothiazine [DIAT], N‐acetyl DIAT & epoxide) and cloning was attempted in a number of patients. Atabecestat(metabolite)‐responsive clones were analysed in terms of T‐cell phenotype, function, pathways of T‐cell activation and cross‐reactivity with structurally related compounds.

Results

CD4+ T‐cell clones activated with the DIAT metabolite were detected in 5 out of 8 patients (up to 4.5% cloning efficiency). Lower numbers of CD4+ and CD8+ clones displayed reactivity against atabecestat. Clones proliferated and secreted IFN‐γ, IL‐13 and cytolytic molecules following atabecestat or DIAT stimulation. Certain atabecestat and DIAT‐responsive clones cross‐reacted with N‐acetyl DIAT; however, no cross‐reactivity was observed between atabecestat and DIAT. CD4+ clones were activated through a direct, reversible compound‐HLA class II interaction with no requirement for protein processing.

Conclusion

The detection of atabecestat metabolite‐responsive T‐cell clones activated via a pharmacological interactions pathway in patients with liver injury is indicative of an immune‐based mechanism for the observed hepatic enzyme elevations.
Locating the Farmer: Ideologies of Agricultural Labor in Bihar, India
Authors: Kantor Hayden S.
Published: November 2020

Ethnographic fieldwork in Bihar, India, reveals paradoxes at the core of contemporary agriculture. Rural people view growing their own food as a crucial bulwark against the vicissitudes of the market but prioritize off‐farm employment to meet rising household expenses. Landowners who cultivate crops often refer to themselves as unemployed while complaining about a lack of laborers to work the land. They do not always refer to themselves as farmers, while many people who do not call themselves farmers nevertheless perform farm work and rely on agriculture as a livelihood. These paradoxes point to the fuzziness and incoherence surrounding the term “farmer” as both an identity and analytical concept. Ideologies of agricultural labor are shaped by different subject positions and social categories, such as caste, gender, and age. The fractured, fluid, and contingent nature of agriculture, in which people move between different locations and identities, provides the grounds for problematizing scholarly categories of agricultural labor—categories like farmer, landlord, peasant, sharecropper, and laborer. The on‐the‐ground realities of agriculture necessitate reframing the conceptual language to attend to the specificity and materiality of labor in particular sites and moments while also foregrounding the ambivalence, vulnerability, and incompleteness that inheres in agricultural labor.
A poison information centre can provide important assessment and guidance regarding medication errors in nursing homes: A prospective cohort study
Authors: Vinther Siri , Bøgevig Søren , Eriksen Karen Reenberg , Hansen Nete Brandt , Petersen Tonny Studsgaard , Dalhoff Kim Peder , Christensen Mikkel Bring
Published: November 2020

The Danish Poison Information Centre (DPIC) regularly receives inquiries about nursing home residents who have been exposed to a medication error. The aim of this prospective cohort study was to describe and discuss the types and consequences of these errors. Data were collected from 1 March 2018 to 31 March 2019. Registered data included characteristics of caller and resident, data related to the suspected medication error, risk assessment and recommendation. Consequences and clinical outcomes were assessed by follow‐up telephone calls. Over the study period, the DPIC was consulted about 145 medication errors occurring at Danish nursing homes. The median number of substances administered by error was two (interquartile range 1‐5). Hospitalization was recommended in 21% of cases. In one‐third of the cases where consultation with the DPIC was done with the resident either on his/her way to or in hospital, hospitalization was found unnecessary, and the resident could have stayed in accustomed surroundings for observation. Follow‐up demonstrated that very few medication errors had a severe outcome. This prospective study illustrates that consulting with a poison information centre can qualify risk assessment and potentially reduce hospital admissions following medication errors in a nursing home setting.
The Experiences of Social Assistance Recipients on the Ontario Basic Income Pilot
Authors: McDowell Tom , Ferdosi Mohammad
Published: November 2020

This article attempts to fill part of the research void created by the premature cancellation of the Ontario Basic Income Pilot (OBIP), reporting the results of former Ontario Works and Ontario Disability Support Program service users who received basic income in the Hamilton region through a comparison of their experiences related to physical and mental health, food and housing security, financial security, and social and family relations. It shows that basic income led to improvements on a variety of indicators, proving transformational for some. The evidence suggests that when compared to existing income support systems, a basic income modeled similar to OBIP can significantly improve recipients’ lives, while at the same time providing a more humane approach to service delivery.
The Division of Domestic Labor before and during the COVID‐19 Pandemic in Canada: Stagnation versus Shifts in Fathers’ Contributions
Authors: Shafer Kevin , Scheibling Casey , Milkie Melissa A.
Published: November 2020

The COVID‐19 pandemic created rapid, wide‐ranging, and significant disruptions to work and family life. Accordingly, these dramatic changes may have reshaped parents’ gendered division of labor in the short term. Using data from 1,234 Canadian parents in different‐sex relationships, we compare retrospective reports of perceived sharing in how housework and childcare tasks were split prior to the declaration of the pandemic to assessments of equality afterward. Further, we describe perceptions of changes in fathers’ engagement in these tasks overall, by respondent gender, and by employment arrangements before and during the pandemic. Results indicate small shifts toward a more equal division of labor in the early “lockdown” months, with increased participation in housework and childcare by fathers, supporting the needs exposure hypothesis. We conclude by discussing gender differences in parents’ reports and potential implications for longer term gender equality.
Outcomes following local excision of early anal squamous cell carcinomas of the anal canal and perianal margin
Authors: Maccabe Tom A. , Parwaiz Iram , Longman Robert J. , Thomas Michael G. , Messenger David E.
Published: November 2020

Aim

There is a paucity of data on outcomes from local excision (LE) of early anal squamous cell carcinomas (ASCCs). This study aimed to assess survival outcomes according to tumour location, perianal (PAT) or anal canal (ACT), and to determine factors associated with R1 excision and outcomes according to T‐category.

Methods

This was a retrospective cohort study of consecutive patients with early ASCC treated by LE from 2007 to 2019. Data were collected on baseline demographics, tumour location, staging, excision histology, adjuvant treatment, site and timing of recurrence. The main outcome measures were R1 resection, locoregional recurrence (LRR), disease‐free survival and overall survival.

Results

Of 367 patients treated for ASCC, 39 (10.6%) patients with complete follow‐up data underwent LE: 15 ACTs and 24 PATs. R1 resections were obtained in 27 patients (69.2%) and occurred more frequently in ACTs than PATs (93.3% vs. 54.2%, P = 0.006). Eighteen of 27 patients (66.7%) received adjuvant therapy (chemoradiotherapy [n = 11], radiotherapy alone [n = 7]) for R1 excision or re‐excision, following which LRR developed in one of 10 (10.0%) patients in the ACT cohort and one of eight (12.5%) patients in the PAT cohort. There was no difference in 5‐year LRR‐free survival (82.0% vs. 70.1%, P = 0.252), disease‐free survival (58.2% vs. 78.4%, P = 0.200) or overall survival (86.2% vs. 95.7%, P = 0.607) between the ACT and PAT cohorts.

Conclusions

LE is a feasible treatment option for early ASCCs of the perianal margin but not the anal canal. Acceptable long‐term outcomes can still be achieved with adjuvant therapy in the presence of a positive margin. Larger prospective studies to assess LE as a treatment strategy, such as the ACT3 trial, are warranted.