bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical networks relating to arousal are differentially coupled to neural activity and hemodynamics
Authors: Meyer-Baese Lisa , Morrissette Arthur , Wang Yunmiao , Le Chatelier Brune , Borden Peter , Keilholz Shella , Stanley Garrett , Jaeger Dieter
Published: December 2022

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25 respectively at a time lag of 0 seconds. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies greater than 1Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.

Significance Statement

We leverage wide-field voltage imaging to examine the relation between cortical changes in membrane potential dynamics and hemodynamics. These two signals are then examined with respect to changes in arousal, as measured by pupil diameter, in awake head fixed mice. Our results show similarities as well as important differences in the correlation of arousal with neuronal population activity dynamics and the hemodynamic signal. Further, the spatial activity correlation maps with arousal depended differentially on the behavioral state of the animal in a frequency dependent manner. Our results indicate that the modulation of brain networks by arousal is dynamically regulated, and only partly overlap between functional networks determined from hemodynamic or voltage activity.
GluN2B-containing NMDA receptors are required for potentiation and depression of responses in ocular dominance plasticity
Authors: Bridi Michelle , Hong Su , Severin Daniel , Kirkwood Alfredo
Published: December 2022

Monocular deprivation (MD) causes an initial decrease in synaptic responses to the deprived eye in juvenile mouse primary visual cortex (V1) through Hebbian long-term depression (LTD). This is followed by a homeostatic increase, which has been attributed to synaptic scaling. However, homeostasis during other forms of visual deprivation is caused by sliding the threshold for Hebbian long-term potentiation (LTP) rather than scaling. We therefore asked whether the homeostatic increase during MD requires GluN2B-containing NMDA receptor activity, which is required to slide the plasticity threshold but not for synaptic scaling. Selective GluN2B blockade from 2-6d after monocular lid suture prevented the homeostatic increase in miniature excitatory postsynaptic current (mEPSC) amplitude in monocular V1 of acute slices and prevented the increase in visually evoked responses in binocular V1in vivo. The decrease in mEPSC amplitude and visually evoked responses during the first 2d of MD also required GluN2B activity. Together, these results indicate that GluN2B-containing NMDA receptors first play a role in LTD immediately following eye closure, and then promote homeostasis during prolonged MD by sliding the plasticity threshold in favor of LTP.
Impact of ERP usage on service differentiation: role of mediating effect of organizational agility
Authors: Shajrawi Afnan , Aburub Faisal
Published: December 2022

Purpose

Several different factors have an influence on the hotel sector in Jordan. Due to the different circumstances and the turbulence in this region, hotels face a competitive and dynamic economic environment, which causes these hotels to seek differentiation. Consequently, hotels need different strategies and support from information technology to achieve a competitive advantage. The purpose of this study is to investigate the extent to which enterprise resource planning ERP system usage affects service differentiation in the hotel sector in Jordan and examine the mediating effect of organizational agility on the aforementioned relationship.

Design/methodology/approach

Questionnaires were used to collect data from the hotel sector in Jordan. The response percentage was 75.41%.

Findings

The result showed that there is a significant effect of ERP system usage on service differentiation in Jordanian hotels, and this relationship was mediated by organizational agility. Organizational agility and its dimensions have a partial mediating role on the relationship between ERP system usage and service differentiation except for responsiveness which has a full mediating role. So, being an agile hotel will increase the ability to achieve service differentiation by using ERP systems.

Practical implications

This research focuses on investigating the mediating role of organizational agility in the relationship between ERP system usage and service differentiation within hotel sector in Jordan. Moreover, this research investigated the applicability of organizational agility on the hotel sector as it is mainly implemented in the manufacturing sector. The results show that organizational agility and its dimensions have a partial mediating role on the relationship between ERP system usage and service differentiation except responsiveness which has a full mediating role. So, being an agile hotel will increase the ability to achieve service differentiation by using ERP systems. Therefore, hotel practitioners in Jordan should focus on applying the required technologies and achieving organizational agility in order to achieve service differentiation. In addition, this study highlights that ERP usage has a positive impact on achieving organizational agility and service differentiation; hence, using these systems will help hotels in Jordan to implement agility capabilities which, in turn, help to achieve service differentiation. However, there are real challenges in hotel sector as implementation of ERP is expensive and time-consuming. The outcomes of this research can have additional reference that could benefit researchers in the future and bring attention of hotel managers in Jordan to the importance and advantages of this research.

Originality/value

A new model has been developed. An empirical investigation was performed on the hotel sector in Jordan to test the new model.
Mobile shopping decision comfort using augmented reality: the effects of perceived augmentation and haptic imagery
Authors: Ivanov Alex , Head Milena , Biela Cosima
Published: December 2022

Purpose

Virtual try-on apps (VTOs) allow consumers to examine fashion and furniture items in usage context without going to a physical store. But the adoption of such apps has varied across product categories, and research on user acceptance of AR marketing has been fragmented. The current study aims to develop and test a general model that explains the formation of decision comfort (DC) in the majority of AR try-on experiences for mobile shopping.

Design/methodology/approach

After reviewing 30 VTOs available on the iOS app store, the authors chose the Wanna Kicks sneaker shopping VTO as the most representative to test their hypotheses for AR try-on in general. Overall, 178 online consumers performed a sneaker shopping task on their mobile devices, and their responses were analyzed with the partial least squares method.

Findings

The study confirmed the key role of perceived augmentation in leading to DC via a utilitarian and a hedonic path. These effects were attenuated for younger users, and haptic imagery only had a utilitarian impact. Scholars should pay more attention to the variable of age, while managers should act quickly to enhance the basic AR affordances of mobile try-on apps.

Originality/value

This is the first study of a VTO in the footwear category and with a model that tests age as a moderating variable between antecedents and consumer responses.
An assessment of prevalence of poor sleep quality among construction workers in Southern India
Authors: Sathvik S. , Krishnaraj L. , Awuzie Bankole Osita
Published: December 2022

Purpose

Sleep quality has been associated with health and safety issues influencing construction labour productivity in developing countries. Despite its significantly adverse contribution to these facets if left unattended to, limited studies have sought to establish its prevalence and causal factors in labour-intensive contexts. This study aims to bridge the gap between the prevalence and casual factors of poor sleep quality among construction workers.

Design/methodology/approach

Adopting a case study research design, data were collected from a randomly selected sample of construction workers (n = 475) recruited from four construction-based corporations in Southern India. Self-administered questionnaires comprising a Pittsburgh Sleep Quality Index (PSQI) scale was used to measure sleep quality among respondents alongside demographic characteristics, lifestyle preferences and work-habits data. Data were analysed using multivariate logistic regression analysis and descriptive statistical techniques.

Findings

Slightly more than a third of the construction workers (n = 33.9%) surveyed experienced poor sleep quality based on a PSQI method score of = 5. Also, the nexus between demographic characteristics, lifestyle preferences and work habits on the incidence of poor sleep quality among construction workers was confirmed.

Practical implications

The study contributes to the contemporary discourse on improving sleep health of construction workers to enhance their well-being thereby enabling their contribution towards achieving improved construction labour productivity.

Originality/value

This study makes an original contribution to the extent that it seeks to not only determine the prevalence of sleep quality within the construction industry and associated causal factors but to explore its implications on construction labour productivity.
Towards a holistic customer value approach in managing public health care services: a developers' view
Authors: Komulainen Hanna , Nätti Satu , Saraniemi Saila , Ulkuniemi Pauliina
Published: December 2022

Purpose

Recent literature within public service logic has called for more explicit conceptualisation of customer value in public services. This study aims to fill this gap by examining how the customer value approach can be applied in the management of public health care services.

Design/methodology/approach

This study is a qualitative case study of management of public health care services in Finland. The authors interviewed 17 regional health care service developers and analyzed the interview data using thematic analysis.

Findings

The study suggests five propositions for applying customer value approach from the marketing literature in public health care service management. The study enables a deeper understanding of customer value creation in this context and improvement of public health care services.

Originality/value

This study contributes to the public management research in general and public service logic research in particular by suggesting what constitutes customer value in public health care services.
Evaluation of a leadership development impact assessment toolkit: a comparative case study of experts’ perspectives in three Canadian provinces
Authors: Karimi-Dehkordi Mehri , Dickson Graham , Grimes Kelly , Schell Suzanne , Bourgeault Ivy
Published: December 2022

Purpose

This paper aims to explore users' perceptions of whether the Leadership Development Impact Assessment (LDI) Toolkit is valid, reliable, simple to use and cost-effective as a guide to its quality improvement.

Design/methodology/approach

The Canadian Health Leadership Network codesigned and codeveloped the LDI Toolkit as a theory-driven and evidence-informed resource that aims to assist health-care organizational development practitioners to evaluate various programs at five levels of impact: reaction, learning, application, impact and return on investment (ROI) and intangible benefits. A comparative evaluative case study was conducted using online questionnaires and semistructured telephone interviews with three health organizations where robust leadership development programs were in place. A total of seven leadership consultants and specialists participated from three Canadian provinces. Data were analyzed sequentially in two stages involving descriptive statistical analysis augmented with a qualitative content analysis of key themes.

Findings

Users perceived the toolkit as cost-effective in terms of direct costs, indirect costs and intangibles; they found it easy-to-use in terms of clarity, logic and structure, ease of navigation with a coherent layout; and they assessed the sources of the evidence-informed tools and guides as appropriate. Users rated the toolkit highly on their perceptions of its validity and reliability. The analysis also informed the refinement of the toolkit.

Originality/value

The refined LDI Toolkit is a comprehensive online collection of various tools to support health organizations to evaluate the leadership development investments effectively and efficiently at five impact levels including ROI.
Don't talk the talk, but walk the walk: the role of authentic CSR in fostering beneficial employee outcomes
Authors: Servaes Marie , Nguyen Thi Thu Huong , Kluijtmans Tom , Crucke Saskia
Published: December 2022

Purpose

Organizations implement corporate social responsibility (CSR) to act, or present themselves as, sustainable. Yet, CSR efforts by organizations can be negatively received by stakeholders. The increased skepticism by stakeholders toward organizations' CSR programs has led to a growing interest in the influence of CSR authenticity. The purpose of this study is to provide valuable insights into the complex role CSR authenticity plays in stimulating desirable employee attitudes and behaviors.

Design/methodology/approach

A sample of 482 employees working in the Belgian banking sector allows the authors to test this study’s theoretical model using structural equation modeling (SEM).

Findings

Empirical findings demonstrate that CSR authenticity positively relates to organizational citizenship behavior (OCB). Extending this notion, we find evidence for organizational identification to mediate the relationship between CSR authenticity and OCB. Further, this study highlights that organizational justice mediates the relationship between CSR authenticity and organizational identification. Finally, the importance of ethical leadership is underlined as a boundary condition to the relationship between CSR authenticity and OCB.

Practical implications

For managers, this study provides insights into the importance of CSR authenticity in fostering positive employee outcomes. It offers guidance on how to incorporate CSR authentically, addressing the importance of the organization's core values and supervisors' alignment with these values.

Originality/value

This study distinguishes itself from existing micro-level research, which mainly focuses on employees' evaluation of the organization's attention to CSR, by investigating the outcomes of employees' perceptions of CSR authenticity. Previous research shows that perceptions of CSR authenticity produce positive outcomes among consumers, but that, so far, we know very little about which specific perceptions or behaviors it might elicit among employees. Furthermore, this study provides evidence for interlinkage between leadership, CSR and beneficial outcomes such as OCB, through the integration of ethical leadership behaviors.
Green bonds for sustainability: current pathways and new avenues
Authors: Kedia Nikita , Joshipura Mayank
Published: December 2022

Purpose

The study aims to consolidate knowledge, explore current dynamics, understand knowledge progression, identify primary research streams, present content analysis and provide future research directions for green bonds research.

Design/methodology/approach

The authors reviewed 150 high-quality Scopus-indexed articles on green bonds in two stages. First, they use bibliometric analysis to understand the field's most relevant articles, authors, institutions and journals. Second, they analysed 49 curated articles to identify and analyse primary research streams and offer research directions.

Findings

The authors report the most influential articles, authors, journals and clusters based on article co-citation networks. They identify five green bond research streams: issuance, greenium and its drivers, connectedness, drivers and barriers, and sustainable development.

Research limitations/implications

Using different databases, tools, sample periods or article screening criteria may yield different results. The study's findings are robust to document selection or analytical tools.

Practical implications

The study helps researchers, practitioners, regulators, policymakers, issuers and investors understand green bond issuance, pricing and connectedness research.

Originality/value

This unique study sheds light on publication trends, the most influential articles, authors, journals and the conceptual and intellectual structure of the field. It identifies and elaborates primary research streams, succinctly summarizes the most influential articles and offers future research directions.
Using marketing frameworks to predict the effects of e-cigarette commercials on youth
Authors: Pike James Russell , Miller Stephen , Cappelli Christopher , Tan Nasya , Xie Bin , Stacy Alan W.
Published: December 2022

Purpose

This paper aims to apply the Product Life Cycle (PLC) and Product Evolutionary Cycle (PEC) frameworks to the nicotine and tobacco market to predict the impact of television commercials for electronic cigarettes (e-cigarettes) on youth.

Design/methodology/approach

Surveys were administered over a three-year period to 417 alternative high school students from Southern California who had never used e-cigarettes, cigarettes or cigars at the baseline. Covariate-adjusted logistic regression causal mediation models were used to test competing hypotheses from the PLC and PEC frameworks.

Findings

Results support a refined version of the PEC framework where e-cigarette commercials increase the odds of e-cigarette use, which leads to subsequent use of competing products including cigarettes and cigars.

Practical implications

This investigation demonstrates the utility of frameworks that conceptualize youth-oriented marketing as a two-part process in which potential customers are first convinced to adopt a behavior and then enticed to use a specific product to enact the behavior.

Social implications

Rising rates of nicotine and tobacco product use among youth may be partially attributable to e-cigarette commercials.

Originality/value

Regulations in the USA that permit television commercials for e-cigarettes but restrict the promotion of cigarettes and cigars have created an opportunity to study product adoption among youth consumers when one product has a strategic marketing advantage.
Loss of nitrogen fixing capacity in a montane lichen is linked to increased nitrogen deposition
Authors: Crittenden Peter D. , Ellis Christopher J. , Smith Rognvald I. , Wanek Wolfgang , Thornton Barry
Published: December 2022

The circumboreal/circumpolar N2‐fixing lichenStereocaulon vesuvianumis among the most widespread and abundant fruticose species in montane Britain but has lost the capacity to fix N2over large areas of the country.

To investigate whether loss of N2‐fixation inS. vesuvianumis linked to increased N deposition, we examined thallus morphology, physiology and chemistry at twelve locations representing an N deposition gradient of 3–40 kg ha−1 year−1. Measurements were made in parallel on a non‐N2‐fixing reference species (Parmelia saxatilis). The presence or absence of cephalodia (N2‐fixing nodules containing the cyanobacteriumStigonemasp) was recorded in over 500 herbarium specimens ofS. vesuvianumdating back to 1820.

Cephalodium abundance inS. vesuvianum, and15N concentration inS. vesuvianumandP. saxatilis, were strongly negatively correlated with N deposition and particularly with dry deposited N; cephalodia do not form at total N deposition rates ≥8–9 kg ha−1 year−1. Other morphological oddities inS. vesuvianumat N‐polluted sites include increased apothecium (fungal reproductive structure) production and green algal biofilm development. Biofilm covered thalli without cephalodia lacked nitrogenase activity and cephalodia at sites where they rarely develop had nitrogenase activities typical for this species. The presence or absence of cephalodia in herbarium specimens ofS. vesuvianumsuggest that the present‐day N‐deposition linked gradient in N2‐fixing capacity did not exist in the 19th century and largely developed between 1900–1940.

Synthesis.We provide clear evidence that N2‐fixing capacity inS. vesuvianumhas been lost in regions subjected to many decades of enhanced atmospheric N deposition. This loss is consistent with established models of diazotrophy, which identify supply of combined N as an inhibitor of N2‐fixation. Progressive depletion of thallus15N with increasing N deposition is in line with available data indicating that much atmospheric N pollution is15N‐depleted. Rates of nitrogenase activity inS. vesuvianumare low compared to other symbiotic systems and perhaps more likely supplanted by elevated N deposition. We suggest that other ecosystem compartments with low rates of fixation (e.g. soils) might also be susceptible to N pollution and merit investigation.
Exploring Sovereignty in Scotland
Authors: McCrone David , Keating Michael
Published: December 2022

It is often said that sovereignty is ever less meaningful in the modern world. Yet, sovereignty claims continue to proliferate. There are two elements: the subject of self‐determination (sovereignty) claims and the object. Scottish independence and Brexit are two examples, yet they differ in important ways. Brexit postulates that the British people are the subject and complete sovereignty is the object. The Scottish independence movement claims the Scottish people is the subject but now places the object (independence) in a European context of shared sovereignty. Analysis of questions placed in the Scottish Social Attitudes Survey (2021) shows that, in spite of Scottish politics being polarised around the issue of independence vs. union, voters show flexibility about what each of these actually means.
What Does Ecological Farming Mean for Farm Labour?
Authors: Davidova Sophia , Hostiou Nathalie , Alebaki Maria , Bailey Alastair , Bakucs Zoltan , Duval Julie , Gouta Penelope , Henderson Stuart , Jacquot Anne‐Lise , Jeanneaux Philippe , Jendrzejewski Błażej , Kilcline Kevin , Konstantidelli Vasilia , Kostov Philip , Latruffe Laure , Schaller Lena , Van Ruymbeke Kato , Védrine Lionel , Veslot Jacques , Vranken Liesbet , Walder Peter
Published: December 2022

Ecological farming, such as organic and low‐input farming, is gaining popularity in the public discourse. One question is how this type of farming may impact farm labour from a socio‐economic point of view. The article first discusses how low‐input farming practices (i.e. with lower reliance on inputs derived from fossil fuels) may affect the economic returns to labour, measured as the farm’s revenue per hour of labour input, on data from the Farm Accountancy Data Network (FADN) in 2004‐‐2015 for four European countries. Returns to labour appear to be highest at the two extremes – very low‐input farms and highly intensive farms. Farms in the low‐input end of the spectrum are in the minority, while the overwhelming majority of farms are intensive and have internal economic incentives to intensify further. The article also analyses how working conditions differ between organic and conventional dairy farms in two European countries based on interviews with farmers in 2019. Results show that all dimensions of working conditions are affected by being an organic farm or not, but this is not the only factor. There are many influences on working conditions, such as the production context and workforce composition.
COVID‐19 complications among patients with opioid use disorder: a retrospective cohort study across five major NYC hospital systems
Authors: Krawczyk Noa , Rivera Bianca D. , Basaraba Cale , Corbeil Thomas , Allen Bennett , Schultebraucks Katharina , Henry Brandy F. , Pincus Harold A. , Levin Frances R. , Martinez Diana
Published: December 2022

Background and Aims

Individuals with opioid use disorder (OUD) suffer disproportionately from COVID‐19. To inform clinical management of OUD patients, research is needed to identify characteristics associated with COVID‐19 progression and death among this population. We aimed to investigate the role of OUD and specific comorbidities on COVID‐19 progression among hospitalized OUD patients.

Design

Retrospective cohort study of merged electronic health records (EHR) from five large private health systems.

Setting

New York City, New York, USA, 2011–21.

Participants

Adults with a COVID‐19 encounter and OUD or opioid overdose diagnosis between March 2020 and February 2021.

Measurements

Primary exposure included diagnosis of OUD/opioid overdose. Risk factors included age, sex, race/ethnicity and common medical, substance use and psychiatric comorbidities known to be associated with COVID‐19 severity. Outcomes included COVID‐19 hospitalization and subsequent intubation, acute kidney failure, severe sepsis and death.

Findings

Of 110 917 COVID‐19+ adults, 1.17% were ever diagnosed with OUD/opioid overdose. OUD patients had higher risk of COVID‐19 hospitalization [adjusted risk ratio (aRR) = 1.40, 95% confidence interval (CI) = 1.33, 1.47], intubation [adjusted odds ratio (aOR) = 2.05, 95% CI = 1.74, 2.42], kidney failure (aRR = 1.51, 95% CI = 1.34, 1.70), sepsis (aRR = 2.30, 95% CI = 1.88, 2.81) and death (aRR = 2.10, 95% CI = 1.84, 2.40). Among hospitalized OUD patients, risks for worse COVID‐19 outcomes included being male; older; of a race/ethnicity other than white, black or Hispanic; and having comorbid chronic kidney disease, diabetes, obesity or cancer. Protective factors included having asthma, hepatitis‐C and chronic pain.

Conclusions

Opioid use disorder patients appear to have a substantial risk for COVID‐19‐associated morbidity and mortality, with particular comorbidities and treatments moderating this risk.
The Effect of the Financial Structure Decision and Governance Mechanism on Shareholders' Wealth: Nonlinearity Evidence from a Petroleum‐based Economy
Authors: Shaddady Ali
Published: December 2022

This study was designed to determine the nature of the association between the financial structure decision and shareholders' wealth—dividend payments—of firms listed on one of the largest stock markets in oil‐based economies, the Saudi stock market. The study used panel data for all nonfinancial firms listed in Saudi Arabia's primary stock market (TASI) during the period from 2000 to 2018. The pooled ordinary least squares, quantile, generalized method of moments and U‐tests were conducted to evaluate the association between the financial structure decision and dividend payment. The preliminary findings revealed a positive effect of financial leverage on dividend payments using a linear model. However, when a nonlinear model was used, the study found a nonlinear relation between the financial structure decision and dividend payouts, which exhibited an inverted U‐shaped curve driven by levels of debt. This nonlinear relation verifies the tenets of the trade‐off theory of optimum debt level based on the costs and benefits of the debt. Further, the study found a negative influence of firm performance, size, and age on dividend payments. The outcomes of this study may provide useful insights for policymakers, managers, and lenders into the optimal level of financial leverage and efficient dividend policies.
Estrogen receptor 1 appears essential for fetal viability in a murine model of premature birth
Authors: Schmiedecke Stacey S. , Thagard Andrew S. , Edwards Sarah M. , Talley Rebecca L. , Dornisch Elisabeth M. , Damicis Jennifer R. , McLane Michael , Burd Irina , Napolitano Peter G. , Ieronimakis Nicholas
Published: December 2022

Problem

Protective effects for adult neurological disorders have been attributed to sex hormones. Using a murine model of prematurity, we evaluated the role of estrogen signaling in the process of perinatal brain injury following exposure to intrauterine inflammation.

Method of study

Intrauterine lipopolysaccharide (LPS) was used to invoke preterm labor and fetal neuroinflammation. Fetal brains were analyzed for changes in Esr1, Esr2 and Cyp19. Dams heterozygous for the Esr1 knockout allele were also given intrauterine LPS to compare delivery and offspring viability to wild type controls.

Results

The upregulation in inflammatory cytokines was accompanied by an increase in Esr1 and Esr2 transcripts, though protein levels declined. Cyp19 did not differ by mRNA or protein abundance. Offspring from Esr1 mutants were larger, had a longer gestation and significantly greater mortality.

Conclusions

Estrogen signaling is altered in the fetal brains of preterm offspring exposed to neuroinflammatory injury. The reduction of Esr1 and Esr2 proteins with LPS suggests that these proteins are degraded. It is possible that transcriptional upregulation of Esr1 and Esr2 occurs to compensate for the loss of these proteins. Alternatively, the translation of Esr1 and Esr2 mRNAs may be disrupted with LPS while a feedback mechanism upregulates transcription. Intact Esr1 signaling is also associated with early preterm delivery following exposure to intrauterine LPS. A loss of one Esr1 allele delays this process, but appears to do so at the cost of fetal viability. These results suggest estrogen signaling plays opposing roles between maternal and fetal responses to preterm birth.
Translation of hyaluronic acid–based vitreous substitutes towards current regulations for medical devices
Authors: Schulz André , Germann Anja , Heinz Werner R. , Engelhard Melanie , Menz Helge , Rickmann Annekatrin , Meiser Ina , Wien Sascha , Wagner Sylvia , Januschowski Kai , Szurman Peter
Published: December 2022

Purpose

Hydrogel‐based vitreous substitutes have the potential to overcome the limitations of current clinically used endotamponades. With the goal of entering clinical trials, the present study aimed to (I) transfer the material synthesis of hyaluronic acid–based hydrogels into a routine, pharmaceutical‐appropriate production and (II) evaluate the properties of the vitreous substitutes in terms of the current regulations for medical devices (MDR/ISO standards).

Methods

The multistep manufacturing process of the vitreous substitutes, including the modification of hyaluronic acid with glycidyl methacrylate, photocopolymerization with N‐vinylpyrrolidone, and successive hydrogel purification, was developed under laboratory conditions, characterized using 1H‐NMR, FT‐IR and UV/Vis spectroscopies and HPLC, and transferred towards a pharmaceutical production environment considering GMP standards. The optical and viscoelastic characteristics of the hyaluronic acid–based hydrogels were compared with those of extracted human vitreous and silicone oil. The effect of the hydrogels on the metabolic activity, proliferation and apoptosis of fibroblast (MRC‐5, BJ, L929), retinal pigment epithelial (ARPE‐19, hiPSC‐derived RPE) and photoreceptor cells (661W) was studied as well as their mucosal tolerance via a HET‐CAM assay.

Results

Hyaluronic acid–based hydrogels having a suitable purity, sterility, high transparency (>90%), appropriate refractive index (1.3365) and viscoelasticity (G′ > G″) were prepared in a standardized manner under controlled process conditions. The metabolic activity, proliferation and apoptosis of various cell types as well as egg choroid were unaffected by the hyaluronic acid–based vitreous substitutes, demonstrating their biocompatibility.

Conclusions

The present study demonstrates the successful transferability of the crucial synthesis steps of hyaluronic acid–based hydrogels into a routine, GMP‐compliant production process while achieving the optical and viscoelastic properties, biocompatibility and purity required for their clinical use as vitreous substitutes.
A subset of VEGFR‐TKIs activates AMPK in LKB1‐mutant lung cancer
Authors: Yang Lujie , Zhang Qin , Xiong Yanli , Dang Zhaoqian , Xiao He , Chen Qian , Dai Xiaoyan , Zhang Lei , Zhu Jianwu , Wang Dong , Li Mengxia
Published: December 2022

The mutation of tumor suppressor gene liver kinase B1 (LKB1) has a prevalence of about 20% in non–small cell lung cancer (NSCLC). LKB1‐mutant lung cancer is characterized by enhanced aggressiveness and immune escape and is associated with poor prognosis. Therefore, it is urgent to develop effective therapeutic methods for LKB1‐mutant NSCLC. Recently, apatinib, a VEGFR‐TKI, was found to significantly improve the outcome of LKB1‐mutant NSCLC, but the mechanism is not completely clear. In this study, AMP‐activated protein kinase (AMPK), the crucial downstream kinase of LKB1 was excavated as the potential target of apatinib. Biochemical experiments verified that apatinib is a direct AMPK activator. Moreover, clinically available VEGFR‐TKIs were found to regulate AMPK differently: Apatinib and anlotinib can directly activate AMPK, while axitinib and sunitinib can directly inhibit AMPK. Activation of AMPK by apatinib leads to the phosphorylation of acetyl‐CoA carboxylase (ACC) and inhibition of de novo fatty acid synthesis (FAsyn), which is upregulated in LKB1‐null cancers. Moreover, the killing effect of apatinib was obviously enhanced under delipidated condition, and the combination of exogenous FA restriction with apatinib treatment can be a promising method for treating LKB1‐mutant NSCLC. This study discovered AMPK as an important off‐target of apatinib and elucidated different effects of this cluster of VEGFR‐TKIs on AMPK. This finding can be the basis for the accurate and combined application of these drugs in clinic and highlights that the subset of VEGFR‐TKIs including apatinib and anlotinib are potentially valuable in the treatment of LKB1‐mutant NSCLC.
When to cryopreserve ovarian tissue: Determining the effects of chemotherapy on the ovarian reserve by studying follicular density and apoptosis
Authors: Labrune Elsa , Bianchetti Serge , Lepinasse Odile , Soignon Gaelle , Salle Bruno , Lornage Jacqueline
Published: December 2022

Objectives

Patients scheduled to receive chemotherapy should be counselled on fertility preservation. Known gonadotoxic chemotherapies such as alkylating agents have a high risk of altering ovarian reserve. In some cases, the urgency of treatment requires the use of chemotherapy before fertility preservation, which will be carried out at a later stage. Usually the ovarian tissue is cryopreserved. The aim of our study is to investigate the impact of chemotherapies on follicular density and the apoptosis of reserve follicles.

Methods

We included 140 patients: 63 patients, mean age 18.8 years, were included in the group “no chemotherapy” (group A) and 77 patients, mean age 17.1 years, in the group “received chemotherapy before ovarian conservation” (group B). None of the patients had had pelvic radiotherapy prior to ovarian cryopreservation. The histological parameters studied were follicular density and the presence of malignant cells. We selected 12 patients from group A and 15 patients from group B, comparable in age and pathology, for whom we evaluated follicle apoptosis by immunostaining cleaved caspase‐3.

Results

We demonstrated an inverse relationship between follicular density and age (p < 0.0001), as well as a lack of effect of chemotherapy on follicular density (p = 0.87). We showed the impact of various chemotherapies, especially with alkylating agents, on the apoptosis of ovarian follicles (p < 0.0001). Three patients had ovarian tissue infiltration, two of which were malignant.

Conclusion

This work underlines the fact that conservation of ovarian tissue after chemotherapy remains possible.
Work as affective care: Visiting parents’ experiences of paid work abroad
Authors: Sampaio Dora
Published: December 2022

This article offers the concept of ‘work as affective care’ to explore the entanglement between financial and affective in transnational life. This is discussed in relation to practices of paid work by nonmigrant older parents during visits to their adult children abroad, an understudied dimension in the visiting friends and relatives, transnational family, and ageing scholarship. Drawing on ethnographic research with Brazilian transnational families, the article makes two distinct contributions. First, it emphasizes the broader repertoire of activities performed during visits, namely paid work outside the family household. Second, it underscores a temporal dimension to visits, namely prolonged stays. The discussion reveals a financial dimension to care where paid work acts as a form of affective care across places and generations. While often described positively, the intersections between financial and affective goals are not always harmonious, and material and affective needs can prove difficult to reconcile.
Compliant citizens, defiant rebels or neither? Exploring change and complexity in COVID‐19 vaccine attitudes and decisions in Bradford, UK: Findings from a follow‐up qualitative study
Authors: Lockyer Bridget , Moss Rachael H. , Endacott Charlotte , Islam Shahid , Sheard Laura ,   the Bradford Institute for Health Research Covid‐19 Scientific Advisory Group
Published: December 2022

Background

COVID‐19 vaccines have been the central pillar of the public health response to the pandemic, intended to enable us to ‘live with Covid’. It is important to understand change and complexity of COVID‐19 vaccines attitudes and decisions to maximize uptake through an empathetic lens.

Objective

To explore the factors that influenced people's COVID‐19 vaccines decisions and how their complex attitudes towards the vaccines had changed in an eventful year.

Design and Participants

This is a follow‐up study that took place in Bradford, UK between October 2021 and January 2022, 1 year after the original study. In‐depth phone interviews were conducted with 12 (of the 20 originally interviewed) people from different ethnic groups and areas of Bradford. Reflexive thematic analysis was conducted.

Results

Eleven of the 12 participants interviewed had received both doses of the COVID‐19 vaccine and most intended to have a booster dose. Participants described a variety of reasons why they had decided to have the vaccines, including the following: feeling at increased risk at work; protecting family and others in their communities; unrestricted travel and being influenced by the vaccine decisions of family, friends and colleagues. All participants discussed ongoing interaction with COVID‐19 misinformation and for some, this meant they were uneasy about their decision to have the vaccine. They described feeling overloaded by and disengaged from COVID‐19 information, which they often found contradictory and some felt mistrustful of the UK Government's motives and decisions during the pandemic.

Conclusions

The majority of participants had managed to navigate an overwhelming amount of circulating COVID‐19 misinformation and chosen to have two or more COVID‐19 vaccines, even if they had been previously said they were unsure. However, these decisions were complicated, demonstrating the continuum of vaccine hesitancy and acceptance. This follow‐up study underlines that vaccine attitudes are changeable and contextual.

Patient or Public Contribution

The original study was developed through a rapid community and stakeholder engagement process in 2020. Discussion with the Bradford Council Public Health team and the public through the Bradford COVID‐19 Community Insights Group was undertaken in 2021 to identify important priorities for this follow‐up study.
Defining an abnormal p53 immunohistochemical stain in Barrett's oesophagus‐related dysplasia: a single‐positive crypt is a sensitive and specific marker of dysplasia
Authors: Tomaszewski Kristen J , Neyaz Azfar , Sauder Kenan , Rickelt Steffen , Zhang M. Lisa , Yilmaz Omer , Crotty Rory , Shroff Stuti , Odze Robert , Mattia Anthony , Patil Deepa T , Deshpande Vikram
Published: December 2022

Aims

p53 is an independent risk stratification marker in Barrett's oesophagus (BE), but no universally accepted definition exists for abnormal p53 staining. Herein, we assess p53 stains in two cohorts to: (1) define abnormal p53 staining in BE‐related dysplasia (BERD) and (2) assess the specificity and sensitivity of this cut‐point for the diagnosis of dysplasia.

Methods

Cohort 1 (n = 313) included (1) dysplastic BE biopsies, (2) prior non‐dysplastic BE (NDBE) biopsies from the same patients and (3) NDBE biopsies from patients who never progressed to dysplasia. Cohort 2 (n = 191) consisted of BE biopsies in which p53 staining aided in diagnosing dysplasia. Automated p53 staining quantification was performed on cohort 1. A semiquantitative p53 analysis, performed on both cohorts, included: (1) number of strongly positive glands, (2) strong glandular surface staining, (3) percentage of strongly positive glands and (4) null phenotype.

Results

NDBE biopsies from cohort 1 patients who progressed to dysplasia were more likely to show p53 positivity than non‐progressors (16.9 versus 0.6%) (P = 0.0001). The optimal quantitative cut‐point for distinguishing dysplastic from never‐dysplasia biopsies was 10 strongly positive cells. By semiquantitative analysis, a single strongly p53‐positive gland distinguished dysplastic from never‐dysplasia BE (sensitivity 98.6%, specificity 99.4%). The semiquantitative and quantitative analyses correlated (P = 0.0001). In cohort 2, the sensitivity and specificity for BERD of ≥ 1 strongly positive p53 gland were 86.0 and 88.6%.

Conclusions

A single strongly positive p53 gland is sensitive and specific for BERD. Automated p53 analysis may reduce subjectivity associated with the diagnosis of BERD.
Tolerated, threatening and celebrated: How Canadian news media frames temporary migrant workers
Authors: Tungohan Ethel , Careless Jon
Published: December 2022

Immigration scholars have long observed that migrant workers are paradoxically both welcomed and deemed threatening within the nation state. In this paper, we investigate the extent to which mainstream media outlets reinforce these perceptions. Using critical discourse analysis, we analysed 561 articles in three mainstream newspapers to ascertain the various discourses used to describe migrant workers and migrant work. Our analysis specifically found that a cluster of ‘hiring scandals’ led to an increase in coverage on migrant work, and affected the types of discourses used in reference to migrant workers. Prior to these scandals, migrant work generated minimal media coverage. Ultimately, we find that migrant workers are deemed tolerable to the nation‐state at certain time periods, deemed as threats in other time periods, and, in the current moment of the global health crisis, are deemed absolutely essential. Migrant workers are thus only 'conditionally included' in the state.
SARS‐CoV‐2 infection‐induced immunity and the duration of viral shedding: Results from a Nicaraguan household cohort study
Authors: Maier Hannah E. , Plazaola Miguel , Lopez Roger , Sanchez Nery , Saborio Saira , Ojeda Sergio , Barilla Carlos , Kuan Guillermina , Balmaseda Angel , Gordon Aubree
Published: December 2022

Background

Much of the world's population has been infected with SARS‐CoV‐2. Thus, immunity from prior infection will play a critical role in future SARS‐CoV‐2 transmission. We investigated the impact of infection‐induced immunity on viral shedding duration and viral load.

Methods

We conducted a household cohort study in Managua, Nicaragua, with an embedded transmission study that closely monitors participants regardless of symptoms. Real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity, respectively. Blood samples were collected twice annually and surrounding household intensive monitoring periods. We used accelerated failure time models to compare shedding times. Participants vaccinated ≥14 days prior to infection were excluded from primary analyses.

Results

There were 600 RT‐PCR‐confirmed SARS‐CoV‐2 infections in unvaccinated participants between May 1, 2020, and March 10, 2022, with prior ELISA data. Prior infection was associated with 48% shorter shedding times (event time ratio [ETR] 0.52, 95% CI: 0.39–0.69, mean shedding: 13.7 vs. 26.4 days). A fourfold higher anti‐SARS‐CoV‐2 spike titer was associated with 17% shorter shedding (ETR 0.83, 95% CI: 0.78–0.90). Similarly, maximum viral loads (lowest cycle threshold [CT]) were lower for previously infected individuals (mean CT 29.8 vs. 28.0, p = 4.02 × 10−3), for adults and children ≥10 years, but not for children 0–9 years; there was little difference in CT levels for previously infected versus naïve adults aged above 60 years.

Conclusions

Prior infection‐induced immunity was associated with shorter viral shedding and lower viral loads, which may be important in the transition from pandemic to endemicity.
Tailoring the efficient laser‐absorption‐melting behavior of Bi2O3‐B2O3‐ZnO‐Nd2O3 glass for the OLED encapsulation
Authors: Leng Yue , Chen Yaoyi , Yang Yanguo , Si Yunxiang , Xie Tianyi , Wang Huaizhi , Meng Fancheng , Ren Haishen , Lin Huixing
Published: December 2022

The efficient 810 nm laser energy conversion of glass frit had been proven to be the key to the long‐term hermetic encapsulation of Organic Light Emitting Display (OLED). A direct laser energy conversion laser‐assisted Bi2O3‐B2O3‐ZnO‐Nd2O3 sealing glass material without extra laser absorbent such as carbon black, was designed and systematically investigated. The addition of Nd2O3, as glass modifiers with higher cationic field strength, could be conducive to enhancing the polymerization of glass network structure, manifesting that the glass‐transition temperature Tg, onset‐crystallization temperature Tc and thermal stability ΔT (ΔT = Tc‐Tg) increased, while thermal expansion coefficient CTE dropped to 9.72×10−6/°C and advantageously matched with the glass substrate (8±1×10−6/°C). More importantly, the absorption rate of BBZ‐Nd glass was more than 50 % between 800∼810 nm owing to the 4f‐4f electron transition of Nd3+ ions, and yet the reflectivity and transmittance of the wavelength at 800–810 nm were lower. As optimal compositions, the addition of 3.0 wt% Nd2O3 in Bi2O3‐B2O3‐ZnO‐Nd2O3 glass frit with higher absorption coefficients (80 %) led to instantaneous bonding encapsulation between glass substrates without interfacial cracks or pores with the 808 nm wavelength of the laser at 20 W and 2.4 mm/s.