bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconfigurable pH-Responsive DNA Origami Lattices
Authors: Julin Sofia , Linko Veikko , Kostiainen Mauri A.
Published: February 2023

DNA nanotechnology enables straightforward fabrication of user-defined and nano-meter-precise templates for a cornucopia of different uses. To date, most of these DNA assemblies have been static, but dynamic structures are increasingly coming into view. The programmability of DNA not only allows encoding of the DNA object shape, but it may be equally used in defining the mechanism of action and the type of stimuli-responsiveness of the dynamic structures. However, these "robotic" features of DNA nanostructures are usually demonstrated for only small, discrete and device-like objects rather than for collectively behaving higher-order systems. Here, we show how a large-scale, two-dimensional (2D) and pH-responsive DNA origami -based lattice can be assembled on a mica substrate and further reversibly switched between two distinct states upon the pH change of the surrounding solution. The control over these two configurations is achieved by equipping the arms of the lattice-forming DNA origami units with "pH-latches" that form Hoogsteen-type triplexes at low pH. In a nutshell, we demonstrate how the electrostatic control over the adhesion and mobility of the DNA origami units on the surface can be used both in the large lattice formation (with the help of directed polymerization) and in the conformational switching of the whole lattice on the substrate. To further emphasize the feasibility of the method, we also demonstrate the formation of reconfigurable 2D gold nanoparticle lattices. We believe this work serves as an important milestone in bridging the nanometer-precise DNA origami templates and higher-order large-scale systems with the stimuli-induced dynamicity.
Modulation of transcription burst amplitude underpins dosage compensation in theDrosophilaembryo
Authors: Forbes Beadle Lauren , Zhou Hongpeng , Rattray Magnus , Ashe Hilary L.
Published: February 2023

Dosage compensation, the balancing of X linked gene expression between sexes and to the autosomes, is critical to an organism’s fitness and survival. InDrosophila, dosage compensation involves hypertranscription of the male X chromosome. Here we use quantitative live imaging and modelling at single-cell resolution to determine the mechanism underlying X chromosome dosage compensation inDrosophila. We show that the four X chromosome genes studied undergo transcriptional bursting in male and female embryos. Mechanistically our data reveal that transcriptional upregulation of male X chromosome genes is primarily mediated by a higher RNA polymerase II initiation rate and burst amplitude across the expression domain. In contrast, burst frequency is spatially modulated in nuclei within the expression domain in response to different transcription factor concentrations to tune the transcriptional response. Together, these data show how the local and global regulation of distinct burst parameters establish the complex transcriptional outputs underpinning developmental patterning.
Long-term CRISPR array dynamics and stable host-virus co-existence in subsurface fractured shales
Authors: Amundson Kaela K. , Roux Simon , Shelton Jenna L. , Wilkins Michael J.
Published: February 2023

Viruses are the most ubiquitous biological entities on earth. Even so, elucidating the impact of viruses on microbial communities and associated ecosystem processes often requires identification of strong host-virus linkages – an undeniable challenge in many ecosystems. Subsurface fractured shales present a unique opportunity to first make these strong linkages and subsequently reveal complex long-term host-virus dynamics and trends in CRISPR array size and frequency. Here, we sampled two replicated sets of fractured shale wells for nearly 800 days (Denver-Julesburg Basin, Colorado, USA). We identified a relatively diverse microbial community with widely encoded CRISPR viral defense systems, which facilitated 2,110 CRISPR-based viral linkages across 90 host MAGs representing 25 phyla. Leveraging these linkages with timeseries data across differing well ages, we observed how patterns of host-virus co-existence develop and converge in this closed ecosystem through time. We observed a transition to smaller CRISPR arrays in older, more established wells, potentially reflecting a natural progression where CRISPR arrays harbor fewer, yet more effective spacers that target viral genes with fewer mutations. Together, our findings shed light on the complexities of host-virus temporal dynamics as well as possible drivers of spacer loss and acquisition within CRISPR arrays of diverse microbial populations through time.
Regulation of parvalbumin interneuron plasticity by neuropeptide-encoding genes
Authors: Selten Martijn , Bernard Clémence , Hamid Fursham , Hanusz-Godoy Alicia , Oozeer Fazal , Zimmer Christoph , Marín Oscar
Published: February 2023

Neuronal activity is regulated in a narrow permissive band for the proper operation of neural networks. Changes in synaptic connectivity and network activity, for example, during learning, might disturb this balance, eliciting compensatory mechanisms to maintain network function. In the neocortex, excitatory pyramidal cells and inhibitory interneurons exhibit robust forms of stabilising plasticity. However, while neuronal plasticity has been thoroughly studied in pyramidal cells, little is known about how interneurons adapt to persistent changes in their activity. Here we uncover the critical cellular and molecular mechanisms through which cortical parvalbumin-expressing (PV+) interneurons adapt to changes in their activity levels. We found that changes in the activity of PV+ interneurons drive cell-autonomous, bi-directional compensatory adjustments of the number and strength of inhibitory synapses received by these cells, specifically from other PV+ interneurons. High-throughput profiling of ribosome-associated mRNA revealed that increasing the activity of PV+ interneurons leads to the cell-autonomous upregulation of two genes encoding multiple secreted neuropeptides,VgfandScg2. Functional experiments demonstrated that VGF is critically required for the activity-dependent scaling of inhibitory PV+ synapses onto PV+ interneurons. Our findings reveal an instructive role for neuropeptide-encoding genes in regulating synaptic connections among PV+ interneurons in the adult mouse neocortex.
Developmental and molecular contributions to contextual fear memory emergence in mice
Authors: Lanjewar Alexandra L. , Levitt Pat , Eagleson Kathie L.
Published: February 2023

Cognitive impairment is a common phenotype of neurodevelopmental disorders, but how these deficits arise remains elusive. Determining the onset of discrete cognitive capabilities facilitates studies in probing mechanisms underlying their emergence. The present study analyzed the emergence of contextual fear memory persistence (7-day memory retention) and remote memory (30-day memory retention). There was a rapid transition from postnatal day (P) 20 to P21, in which memory persistence emerged in C57Bl/6J male and female mice. Remote memory was present at P23, but expression was not robust compared to pubertal and adult mice. Previous studies reported that following deletion of the MET receptor tyrosine kinase (MET), there are fear memory deficits in adult mice and the timing of critical period plasticity is altered in the developing visual cortex, positioning MET as a regulator for onset of contextual fear memory. SustainingMetpast the normal window of peak cortical expression or deletingMet, however, did not alter the timing of emergence of persistence or remote memory capabilities during development. Fear memory in young adults, however, was disrupted. Remarkably, compared to homecage controls, the number of FOS-expressing infragranular neurons in medial prefrontal cortex (mPFC) did not increase from contextual memory formation recall of fear conditioning at P35 but exhibited enhanced activation at P90 in male and female mice. Additionally, MET-expressing neurons were preferentially recruited at P90 compared to P35 during fear memory expression. The studies demonstrate a developmental profile of contextual fear memory capabilities. Further, developmental disruption ofMetleads to a delayed functional deficit that arises in young adulthood, correlated with an increase of mPFC neuron activation during fear memory recall.
Simulations predict preferred Mg2+coordination in a nonenzymatic primer extension reaction center
Authors: Mittal Shriyaa , Nisler Collin , Szostak Jack W.
Published: February 2023

The mechanism by which genetic information was copied prior to the evolution of ribozymes is of great interest because of its importance to the origin of life. The most effective known process for the nonenzymatic copying of an RNA template is primer extension by a two-step pathway in which 2-aminoimidazole activated nucleotides first react with each other to form an imidazolium-bridged intermediate that subsequently reacts with the primer. Reaction kinetics, structure-activity relationships, and X-ray crystallography have provided insight into the overall reaction mechanism, but many puzzles remain. In particular, high concentrations of Mg2+are required for efficient primer extension, but the mechanism by which Mg2+accelerates primer extension remains unknown. By analogy with the mechanism of DNA and RNA polymerases, a role for Mg2+in facilitating the deprotonation of the primer 3′-hydroxyl is often assumed, but no catalytic metal ion is seen in crystal structures of the primer extension complex. To explore the potential effects of Mg2+binding in the reaction center, we performed atomistic molecular dynamics simulations of a series of modeled complexes in which a Mg2+ion was placed in the reaction center with inner sphere coordination to different sets of functional groups. Our simulations suggest that coordination of a Mg2+ion to both O3′ of the terminal primer nucleotide and the pro-Spnon- bridging oxygen of the reactive phosphate of an imidazolium-bridged dinucleotide would help to preorganize the structure of the primer/template substrate complex to favor the primer-extension reaction. Our results suggest that the catalytic metal ion may play an important role in overcoming electrostatic repulsion between a deprotonated O3′ and the reactive phosphate of the bridged dinucleotide. Our simulations lead to testable predictions of the mode of Mg2+binding that is most relevant to catalysis of primer extension.

STATEMENT OF SIGNIFICANCE

Prior to the evolution of complex enzymes, the replication of genetic material must have relied on nonenzymatic mechanisms. Nonenzymatic RNA template copying can be achieved through the extension of a primer by reaction with a 2-aminoimidazole (2AI) bridged dinucleotide in the presence of Mg2+. Despite progress in understanding the mechanism of this reaction, the catalytic role of Mg2+remains poorly understood. Here, we present a series of molecular dynamics simulations of a model RNA primer-extension complex in different potential reactive conformations. We find that one configuration of both the 2AI moiety and coordination state of the Mg2+promotes a geometry that is most favorable to reaction, suggesting a potential structural role for Mg2+and providing insights to guide future experiments.
The gag-like geneRTL8antagonizes PEG10-mediated virus like particles
Authors: Campodonico Will , Mohan Harihar M. , Black Holly H. , Lau Cristina I. , Paulson Henry L. , Sharkey Lisa M. , Whiteley Alexandra M.
Published: February 2023

PEG10is a retroelement-derivedMart-family gene that is necessary for placentation and has been implicated in neurological disease. PEG10 resembles both retrotransposon and retroviral proteins and forms virus-like particles (VLPs) that can be purified using iodixanol ultracentrifugation. It is hypothesized that formation of VLPs is crucial to the biological roles of PEG10 in reproduction and neurological health. Here, we describe the regulation of PEG10 VLP formation and release in human cells with a role for the relatedMartgeneRTL8. RTL8 resembles a truncated form of PEG10 that shares homology with the N-terminal gag-like capsid domain. Alone, RTL8 is unable to form VLPs, but was incorporated into PEG10-derived particles. RTL8 co-expression decreased the abundance of PEG10 VLPs and increased intracellular levels of PEG10, suggesting a model where RTL8 inhibits PEG10 VLP formation or release. Consistent with this model, RTL8 bound to the N-terminal domain of PEG10 capsid, and modulation of RTL8 influenced PEG10-derived VLP abundance in naturally producing cells. RTL8 is broadly expressed in many of the same tissues as PEG10, including in human brain. Taken together, these results describe a novel antagonistic relationship between two human retroelement-derived genes and have implications for our understanding of PEG10 biology and disease.
Optogenetic recruitment of hypothalamic corticotrophin-releasing-hormone (CRH) neurons reduces motivational drive
Authors: Mitchell Caitlin S , Campbell Erin J , Fisher Simon D , Stanton Laura M , Burton Nicholas J , Pearl Amy J , McNally Gavan P , Bains Jaideep S , Füzesi Tamás , Graham Brett A , Manning Elizabeth E , Dayas Christopher V
Published: February 2023

Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocrine system, via corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN; PVNCRH), initiates a hormonal cascade resulting in glucocorticoid release, and that excessive glucocorticoids change brain circuit function to produce depression-related symptoms. Another, mostly unexplored hypothesis is that the direct activity of PVNCRHneurons and their input to other stress- and reward-related brain regions drives these behaviours. To further understand the direct involvement of PVNCRHneurons in motivation, we used optogenetic stimulation to activate these neurons one hour/day for 5 consecutive days and showed increased acute stress-related behaviours and long-lasting deficits in the motivational drive for sucrose. This was associated with increased Fos-protein expression in the lateral hypothalamus (LH). Direct stimulation of the PVNCRHinputs in the LH produced a similar pattern of effects on sucrose motivation. Together, these data suggest that PVNCRHneuronal activity may be directly responsible for changes in motivational drive and that these behavioural changes may, in part, be driven by PVNCRHsynaptic projections to the LH.
Lean leadership: a bibliometric analysis
Authors: Santos Bruno B. , Sigahi Tiago F. A. C. , Rampasso Izabela Simon , Moraes Gustavo Hermínio Salati Marcondes De , Leal Filho Walter , Anholon Rosley
Published: February 2023

Purpose

The present research aims to understand how the literature on lean leadership is currently structured. For this, the thematic subdivisions within the subject (thematic clusters) are analyzed as well as the networks between authors and the authors' countries and the chronological co-occurrence of terms over the years.

Design/methodology/approach

The research strategy chosen was a bibliometric analysis conducted with documents collected from the Scopus scientific database. After screening, 192 documents were analyzed using the Vosviewer software.

Findings

The main result is related to identifying four thematic clusters. The first cluster is connected to the manufacturing and supply chain industry, and this showed an increasing concern with sustainability, agile manufacturing and digitalization. The second is related to small and medium-sized companies in which Lean concepts, often associated with Six Sigma ideas, present as differentials for competitive advantage. The third one is associated with the civil construction segment, in which there is a great need for cultural and organizational change. The fourth cluster focuses on health organizations. In all clusters, leadership plays a key role.

Practical implications

Besides the contributions to the literature on the theme, this study provides interesting insights for managers regarding the path the managers' sectors are taking in the Lean leadership context.

Originality/value

There are no studies that critically examine Lean leadership literature. This research identifies clusters on the theme, showing how Lean leadership is being addressed by international research.
Large displacement analysis of two-layer beam-columns taking into account slip and uplift
Authors: Oeng Thaileng , Keo Pisey , Guezouli Samy , Hjiaj Mohammed
Published: February 2023

Purpose

This article presents a geometrically non-linear finite element formulation for the analysis of planar two-layer beam-columns taking into account the inter-layer slip and uplift.

Design/methodology/approach

The co-rotational method is adopted, in which the motion of the element is decomposed into a rigid body motion and a small deformational one. The geometrically linear formulation can be used in the local frame and automatically be transformed into a geometrically nonlinear one. In co-rotational frame, both layers are assumed to be discretely connected at the element ends. Slips and uplifts are assumed to be small. Consequently, the condition of non interpenetration between the layers can be treated using a node-to-node contact algorithm. The resolution methods such as penalty (PM) and augmented Lagrangian method (ALM) with Uzawa updating scheme can be used.

Findings

The non-penetration condition between the layers of composite beams can be formulated by using contact law. It is found that despite a low convergence rate of augmented Lagrangian method compared to penalty method, the former prevents the unrealistic penetration. Besides, it is shown that the buckling load of the composite beam-column is largely affected by the uplift stiffness of the connectors.

Originality/value

The proposed finite element model is capable of simulating accurately the geometrically non-linear behavior of planar two-layer beam-columns taking into account the inter-layer slip and uplift. Regarding uplift, the non-penetration condition is strictly enforced by considering rigorous contact conditions at the interface. The constraint problem is solved using the penalty method or the augmented Lagrangian method with the Uzawa updating scheme.
Dependent self-employed individuals: are they different from paid employees?
Authors: Dvouletý Ondřej , Nikulin Dagmara
Published: February 2023

Purpose

This study focusses on dependent self-employment, which covers a situation where a person works for the same employer as a typical worker whilst on a self-employment contractual basis, i.e. without a traditional employment contract and without certain rights granted to “regular” employees.

Design/methodology/approach

The research exploits the individual-level dataset of 35 European countries extracted from the 2017 edition of the European Labour Force Survey (EU LFS) and compares the characteristics of employees and dependent self-employed individuals. Methodologically, the study relies on the estimation of a multivariate logistic regression model.

Findings

The main hypothesis assuming that dependent self-employed work most often in low-skilled occupations was empirically supported. There was also a non-linear (u-shaped) relationship between the years of accumulated experience (with a turning point at 35 years) and the likelihood of being dependent self-employed. Other results showed that dependent self-employed are less likely to be women and the dependent self-employed are more likely born outside of the countries where the dependent self-employed participate in the labour markets.

Originality/value

The study contributes to the field by adopting a comparable definition of dependent self-employment and exploiting the recent theoretical support of The Work Precarity Framework. The phenomenon should still be addressed by policymakers and labour office representatives, aiming to protect, primarily, vulnerable lower-skilled workers. The ongoing research should study the longitudinal dimension of dependent self-employment with a focus on motivational aspects.
Curricular flexibility: a comparative case study of homeschooling curriculum adjusting in the USA and China
Authors: Wang Qiu , Langager Mark W.
Published: February 2023

Purpose

Given the less mature homeschooling ecosystem in China, together with the similarity of purpose, the current study examined the lived experiences of curricular choice making in the USA and China and categories of respective families (homeschools), as a way of understanding curricular flexibility. In addressing these features, based on an updated model of curricular flexibility as it applies to homeschooling, the authors examined the aspects of who, what, when, where and how to see if this context offers new light. The authors then consider ways in which the model can be further updated for greater analytical clarity and accuracy. The purpose of this paper is to address these issues.

Design/methodology/approach

A descriptive case study was conducted in the Xi'an city of China and the Seattle metropolitan area of the USA. A survey and two rounds of semi-structured interview data were collected from ten homeschooling families in both contexts.

Findings

The study found families’ adjusted curricula for different motives, as they navigated differing societal contexts, and curricular flexibility in homeschooling contexts was theorized as standardization and structuring strategies and social dimensions, and family preference patterns were identified. Chinese homeschooling families had comparatively less variety of available resources and freedom to homeschools compared to American counterparts, and they operated with the awareness of a standard national curriculum and its social implications.

Originality/value

This study elaborates on a little-discussed topic – the overall curriculum of each homeschool and motives influencing changing curricular choices during the process of homeschooling. And it is the first paper to use the model to explicitly define curricular flexibility in the homeschooling context, thus extending the existing theoretical discussion of curricular flexibility.
The flexible HRM and firm performance nexus: can empowering leadership play any contingent role?
Authors: Pahi Munwar Hussain , Ahmed Umair , Imroz Sohel M. , Shah Syed Mir Muhammad , Yong Irene Seok-Ching
Published: February 2023

Purpose

The purpose of this empirical research was to investigate the individual effects of three dimensions of flexible human resource management (HRM) practices – skill flexibility, behavioral flexibility and human practice flexibility on firm performance and to what extent these relationships are strengthened/weakened when there was the moderation of empowering leadership in small- and medium-sized enterprises (SMEs) of the Kingdom of Bahrain.

Design/methodology/approach

The data were collected from chief executive officers (CEOs) through a questionnaire survey method to test the hypothesized relationships. A final dataset of 315 valid responses was utilized for data analysis, and results were analyzed using the Smart partial least squares structural equation modeling (PLS-SEM) technique.

Findings

The findings revealed positive effects of skill flexibility, behavioral flexibility and human practice flexibility on firm performance. The moderating role of empowering leadership further strengthened the effects of employee skill flexibility and employee behavioral flexibility had on firm performance. However, empowering leadership did not pose any moderating effect on human practice flexibility and firm performance relationship.

Research limitations/implications

This paper offers implications for theories on HRM and leadership. It also provides valuable insights for organizations and leaders seeking to boost firm performance across SMEs.

Practical implications

This paper offers implications for theories on HRM and leadership and also contributes in the understanding of the modern managers.

Originality/value

This paper investigated the effects of flexible HRM practices on firm performance and the role of empowering leadership across SMEs in Bahrain. It also explored how the performance of SMEs can be improved using flexible HRM practices followed by the presence of empowering leadership.
Terms in journal articles associating with high quality: can qualitative research be world-leading?
Authors: Thelwall Mike , Kousha Kayvan , Abdoli Mahshid , Stuart Emma , Makita Meiko , Wilson Paul , Levitt Jonathan M.
Published: February 2023

Purpose

Scholars often aim to conduct high quality research and their success is judged primarily by peer reviewers. Research quality is difficult for either group to identify, however and misunderstandings can reduce the efficiency of the scientific enterprise. In response, we use a novel term association strategy to seek quantitative evidence of aspects of research that are associated with high or low quality.

Design/methodology/approach

We extracted the words and 2–5-word phrases most strongly associated with different quality scores in each of 34 Units of Assessment (UoAs) in the Research Excellence Framework (REF) 2021. We extracted the terms from 122,331 journal articles 2014–2020 with individual REF2021 quality scores.

Findings

The terms associating with high- or low-quality scores vary between fields but relate to writing styles, methods and topics. We show that the first-person writing style strongly associates with higher quality research in many areas because it is the norm for a set of large prestigious journals. We found methods and topics that associate with both high- and low-quality scores. Worryingly, terms associated with educational and qualitative research attract lower quality scores in multiple areas. REF experts may rarely give high scores to qualitative or educational research because the authors tend to be less competent, because it is harder to do world leading research with these themes, or because they do not value them.

Originality/value

This is the first investigation of journal article terms associating with research quality.
Environmental, social and governance performance: influence on market value in the COVID-19 crisis
Authors: Bodhanwala Shernaz , Bodhanwala Ruzbeh
Published: February 2023

Purpose

The aim of this paper is to study whether adoption of sustainability policies by firms makes their stock market performance resilient to the downside risk during the crisis period.

Design/methodology/approach

The paper empirically examines the relationship between environmental, social and governance (ESG) and stock market performance for Indian companies that have consistently been a part of Refinitiv Eikon ESG database. Further, the study examines whether there exist significant differences in stock market performance of high ESG and low ESG-compliant firms during crisis period. The sample was made up of 70 Indian firms studied over the period 2016–2019 defined as “normal period” as well as for the declared COVID-19 crisis period, i.e. January–March 2020, and full year 2020. The authors used multivariate panel data regression, robust least square multivariate regression, pooled OLS model and two-stage least square regression method.

Findings

The study extends the existing literature by investigating the impact of ESG performance on market value of firms during the crisis period. Based on the stakeholder and “flight to safety” theory, the authors hypothesized that ESG would have significant positive effect on the stock market performance during crisis period; however, the results provide robust evidence that in a well-specified model capturing the effect of accounting-based measures of performance, Size, Growth, Risk and Dividend yield, ESG had no explanatory power over the stock market performance of ESG-compliant firms during crisis period. Furthermore, no significant difference in stock market performance indicators between high and low ESG-compliant firms was observed during the crisis period of 1Q2020 as well as for full year 2020. On contrary, the study finds dividend yield to be statistically significant in determining stock market performance of Indian firms during crisis period. The study extends the existing literature by coining the term, “ESG irrelevance” during crisis period.

Research limitations/implications

The main limitation of this study is its limited sample size because there are very few Indian firms that have secured consistent ESG rating. The study focuses on consistently rated firms to avoid the impact of “greenwashing”. Further, the study is focused on India, which limits the generalizability of our findings to other emerging countries.

Originality/value

To the best of our knowledge, this is among the first few studies that examines sustainability and stock market performance of Indian firms during COVID-19-led crisis period. Our findings highlight no significant difference between stock market performance of high ESG firms and low ESG firms indicating that investors who wish to create wealth by investing in ESG-compliant stocks in India can do so without worrying about the companies’ ESG rating scores.
Corporate governance and cost of equity: the moderating role of ownership concentration levels
Authors: Hashmi Muhammad Arsalan , Istaqlal Urooj , Brahmana Rayenda Khresna
Published: February 2023

Purpose

The study analyzes the influence of corporate governance and ownership concentration levels on the cost of equity. Further, the authors extend the literature by investigating the moderating effect of ownership concentration levels (i.e. at 5%, 10% and 20%) on the relationship between corporate governance and the cost of equity.

Design/methodology/approach

The study applies several robust panel regression techniques to a sample of 114 active non-financial companies listed on the Pakistan Stock Exchange from 2011 to 2016. Corporate governance was measured through a unique index comprising 30 governance attributes. The cost of equity was measured through the capital asset pricing model. Further, the authors construct three variables for ownership concentration levels, i.e. at 5%, 10% and 20%. To address the endogeneity problem, the one-lagged variable model and GMM approaches were also applied.

Findings

The results indicate that better corporate governance reduces the cost of equity, while ownership concentration at high thresholds would increase the cost of equity. Further, the authors find that ownership concentration at the 20% threshold moderates the relationship between corporate governance and the cost of equity. Thus, the authors argue that firms can minimize the risk faced by shareholders by implementing substantive corporate governance mechanisms. In addition, effective corporate governance mechanisms at high ownership concentration levels are imperative for managing the cost of equity.

Originality/value

The study reports novel evidence that ownership concentration at a high threshold moderates the effect of corporate governance on the cost of equity.
Practising care in a pandemic: Accounting for everyday life during COVID‐19 among people who inject drugs
Authors: Rance Jake , Bryant Joanne , Caruana Theresa , Brener Loren
Published: February 2023

From the outset of the COVID‐19 pandemic, fears have been raised worldwide regarding the unique challenges facing socially marginalised people such as those who inject drugs. This article draws on in‐depth interviews conducted during the first year of the pandemic with people who inject drugs living in urban and regional Australia. Perhaps the most surprising finding to emerge was the number of participants who reported minimal disruption to their everyday lives, even improved wellbeing in some instances. Attempting to make sense of this unanticipated finding, our analysis draws on the concept of ‘care’, not as a moral disposition or normative code but as something emergent, contingent and realised in practice. Working with Foucault’s ethics and recent feminist insights on the politics of care from the field of Science and Technology Studies, we explore how care was enacted in the everyday lives of our participants. We examine how participants’ daily routines became objects of care and changed practice in response to the pandemic; how their ongoing engagement with harm reduction services afforded not only clinical support but vital forms of social and affective connection; and how for some, care was realised through an ethos and practice of constrained sociality and solitude.
Stigma, mental illness & ethnicity: Time to centre racism and structural stigma
Authors: Kapadia Dharmi
Published: February 2023

This article critically reviews previous research in the field of stigma, mental illness and ‘race’ and ethnicity, and argues for a shift of focus from individual and community blame, as inferred by mental illness stigma, to a more comprehensive view of how stigma operates against a backdrop of structural and institutional racism. Ethnic minority people have poorer mental health outcomes compared with White majority populations. Dominant narratives of greater mental illness stigma in ethnic minority populations, due to religious, spiritual or traditional beliefs and leading to a lower use of services, have taken centre stage in the explanations for these consequent poorer outcomes. This article argues that this ‘fact’ has become taken for granted as knowledge without corresponding comparative research evidence. Research in the field has also failed to robustly consider how racism might operate in conjunction with different forms of mental illness stigma (particularly structural stigma) to exacerbate mental illness and influence pathways to mental health treatment. Future research should centre the role of racism and structural stigma in explaining the poorer mental health outcomes for ethnic minority people.
The influence of Medicare Part D on the list pricing of brand drugs
Authors: Ippolito Benedic N. , Levy Joseph F.
Published: February 2023

Objective

To compare the Medicare Part D market share of brand drugs with their net‐to‐list price ratio.

Data Sources and Study Setting

SSR Health Brand Net Price Tool and Medical Expenditure Panel Survey, 2007–2019.

Study Design

For each drug, we calculated the ratio of net to list price and the percent of users that were Medicare‐eligible. We compared these cross‐sectionally in each year and estimated a difference‐in‐differences model comparing drugs with high or low Medicare market shares (MMS) after following changes to program incentives in 2010.

Data Collection/Extraction Methods

The sample included brand drugs without generic competitors appearing in both datasets.

Principal Findings

Net‐to‐list price ratios were negatively correlated with MMS in the later years of our sample. In 2019, a 10% increase in MMS was associated with a significant 4.6% [95% CI: 2.1%, 7.1%] decrease in net‐to‐list ratio. Difference‐in‐differences showed net‐to‐list price ratios of drugs with above median MMS fell relative to those with below median MMS. By 2019, we observe an absolute reduction of −0.2 [95% CI: −0.29, −0.11], representing 28% reduction relative to the average ratio in 2010.

Conclusions

Greater exposure to the Medicare Part D market was associated with larger differences between net and list prices of drugs.
Unlocking the strength of inducible promoters in Gram‐negative bacteria
Authors: Carrillo Rincón Andrés Felipe , Farny Natalie G.
Published: February 2023

Inducible bacterial promoters are ubiquitous biotechnology tools that have a consistent architecture including two key elements: the operator region recognized by the transcriptional regulatory proteins, and the −10 and −35 consensus sequences required to recruit the sigma (σ) 70 subunits of RNA polymerase to initiate transcription. Despite their widespread use, leaky transcription in the OFF state remains a challenge. We have updated the architecture of the lac and tet promoters to improve their strength, control and portability by the adaptation of the consensus −10 and −35 sequence boxes strongly targeted by σ70, incorporation of a strong ribosome binding site recognized broadly by Gram‐negative bacteria, and independent control of the transcriptional regulators by constitutive promoters. To test the promoters, we use the far‐red fluorescent protein mCardinal, which significantly improves the signal‐to‐background ratio of promoter measurements over widely utilized green fluorescent proteins. We validate the improvement in OFF state control and inducibility by demonstrating production of the toxic and aggregate‐prone cocaine esterase enzyme CocE. We further demonstrate portability of the promoters to additional Gram‐negative species Pseudomonas putida and Vibrio natriegens. Our results represent a significant improvement over existing protein expression systems that will enable advances in protein production for various biotechnology applications.
Combination of echocardiography and pulmonary function tests could predict no complication of pulmonary hypertension during 5 years in patients with systemic sclerosis
Authors: Yoneda Katsuhiko , Takahashi Soshi , Nakayama Kazuhiko , Iwahashi Masanori , Emoto Noriaki , Kumagai Shunichi
Published: February 2023

Objective

To determine whether complications of pulmonary hypertension (PH) can be predicted by noninvasive screening tests in systemic sclerosis (SSc).

Methods

Forty‐seven of 113 SSc patients underwent right heart catheterization (RHC) during 2011–2014. Clinical data, hemodynamic features, echocardiography, and pulmonary function tests had been followed up from the first RHC until 5 years later.

Results

At the first RHC, out of 44 patients, 8 were diagnosed with pre‐capillary PH (mean pulmonary arterial pressure [mPAP] > 20 mm Hg), and 36 patients were defined as no‐PH (mPAP ≤ 20 mm Hg). Three patients with >15 mm Hg of pulmonary artery wedge pressure were excluded. Receiver operating characteristic analyses for pre‐capillary PH using estimated systolic PAP (esPAP) revealed an area under the curve (AUC) of 0.736, with a sensitivity and specificity of 62.5% and 86.1%, respectively, at a cutoff level of 35.0 mm Hg. The predicted percentage diffusing lung capacity for carbon monoxide (DLCO%) revealed an AUC of 0.840, with a sensitivity and specificity of 85.7% and 80.0%, respectively, at a cutoff level of 70.0%. Six pre‐capillary PH patients, including one who died from PH 14 months after the first RHC, indicated exacerbations of mPAP or esPAP within 5 years. When esPAP < 35.0 mm Hg and DLCO% > 70% were met as the cutoff, none had been newly diagnosed with PH over 5 years.

Conclusions

The conventional screening tests may be useful for detecting pre‐capillary PH with SSc, and both esPAP < 35.0 mm Hg and DLCO% > 70% indicated a lower risk of developing PH for at least 5 years.
Smoking, but not use of complementary and alternative medicine predicts residual functional disability in patients with inflammatory arthritis on biologic disease‐modifying anti‐rheumatic drugs: Results from the Singapore National Biologics Register
Authors: Seet Dominic , Yeo Siaw Ing , Aw Man Hua , Dhanasekaran Preeti , Mui‐San Lim Rosa , Koh Li Wearn , Lahiri Manjari
Published: February 2023

Aims

To describe inflammatory arthritis (IA) patients initiating biologic disease‐modifying anti‐rheumatic drugs (bDMARDs) who use complementary and alternative medicine (CAM), and determine the impact of CAM on predicting modified Health Assessment Questionnaire (mHAQ) at 6 months.

Methods

This was a prospective inception cohort study of patients ≥21 years old initiating a bDMARD for IA after July 2016. Data were obtained via questionnaires and abstraction from medical records. Baseline characteristics between ever‐CAM and CAM non‐users were compared. CAM as a predictor of mHAQ ≥1 at 6 months after bDMARD initiation was analyzed using multivariate logistic regression, adjusting for other baseline characteristics.

Results

We recruited 299 patients (36.2% male, mean age 49.0 years). There were 45.8% who had rheumatoid arthritis, 54.2% had a spondyloarthropathy, median disease duration of 1.1 years and median mHAQ of 0.4. Compared to CAM non‐users, ever‐CAM users had a lower mean body mass index, were less likely to speak English, and more likely to smoke and drink alcohol. There was no association of CAM use with high mHAQ and no interaction with smoking. Smoking (odds ratio [OR] 938.9; 95% CI 3.20–275 884.1), baseline mHAQ (OR 252.2; 95% CI 5.34–11 899.2) and Charlson's Comorbidity Index score ≥4 (OR 237.4; 95% CI 1.22–46 184.4) independently predicted high mHAQ at 6 months.

Conclusions

CAM use was not associated with high mHAQ at 6 months. Smoking was an independent predictor of residual functional disability at 6 months, even after adjusting for age, comorbidity and baseline mHAQ. Greater emphasis on smoking cessation may improve long‐term functional outcomes in IA patients on bDMARDs.
Identifying frailty and its associated factors in patients with axial spondyloarthritis
Authors: Öztürk Özgül , Feyzioğlu Özlem , Sarıtaş Fatih
Published: February 2023

Background and Aim

Frailty is an elderly people phenomenon; however, younger adults with comorbidities may show a higher trajectory of frailty toward older age. The frailty status of middle‐aged patients with axial spondyloarthritis (axSpA) remains little researched. We aimed to identify frailty status and to investigate the association of clinical, sociodemographic, and psychosocial factors with frailty.

Methods

This study included 114 patients aged between 40 and 65 years. The patients were classified as frail, pre‐frail, and robust according to Fried's phenotype and the Kihon Checklist (KCL). Physical function, quality of life, depression, anxiety, and disease‐related factors were assessed. Between‐group comparisons and multinomial logistic regression analysis were performed.

Results

Frailty and pre‐frailty prevalences were 20.2% and 49.1% for Fried's phenotype and 36.0% and 33.3% for the KCL. Frail adults had impaired physical function and increased disease activity compared to pre‐frail and robust patients. Adjusted multinomial logistic regression analysis revealed that disease activity (odds ratio [OR] = 1.62, 95% CI = 1.12‐2.34) and Short Physical Performance Battery (OR = 0.32, 95% CI = 0.18‐0.56) were associated with Fried's phenotype‐determined frailty. Disease activity (OR = 1.91, 95% CI = 1.11‐3.26), Bath Ankylosing Spondylitis Functional Index (OR = 2.70, 95% CI = 1.56‐4.67), and depression (OR = 1.55, 95% CI = 1.18‐2.02) were associated with the KCL determined frailty.

Conclusion

Frailty and pre‐frailty are commonly detected in middle‐aged individuals with axSpA. Our findings highlight a possible need for frailty screening and preventive programs targeting middle‐aged axSpA patients.
Circ_0003340 regulates the expression of ENAH to affect the development of esophageal cancer through miR‐874‐3p
Authors: Wang Jingyi , Zhao Ning , Peng Shengzu , Zhang Tao
Published: February 2023

Background

Esophageal cancer is a malignant tumor with a poor prognosis and high incidence. Circular RNAs (circRNAs) have been shown to be involved in the pathogenesis of cancers, including esophageal cancer. Here, we explored the precise role of circ_0003340 in esophageal cancer development.

Methods

The expression levels of circ_0003340, miR‐874‐3p and enabled homolog (ENAH) were detected by quantitative real‐time polymerase chain reaction and western blot. Subcellular localization and RNase R assays were used to characterize circ_0003340. Cell Counting Kit 8, flow cytometry, transwell assays were used to analyze cell proliferation, apoptosis, migration and invasion. The effect of circ_0003340 on tumor growth was assessed by tumor experiments in vivo. Dual‐luciferase reporter assay was used to analyze the relationship between miR‐874‐3p and circ_0003340 or ENAH.

Results

Circ_0003340 was mainly located in the cytoplasm and was upregulated in esophageal cancer tissues and cells. Circ_0003340 knockdown inhibited cell proliferation, migration, invasion, glucose consumption, and lactate production and induced cell apoptosis in esophageal cancer cells. Moreover, circ_0003340 knockdown suppressed tumor growth in vivo. MiR‐874‐3p was reduced in esophageal cancer tissues and cells, and it was a molecular mediator of circ_0003340 function in esophageal cancer cells. ENAH was identified as a direct and functional target of miR‐874‐3p in esophageal cancer cells. The promotion effect of circ_0003340 on ENAH was ameliorated by miR‐874‐3p.

Conclusion

The data demonstrated that circ_0003340 promoted the progression of esophageal cancer through miR‐874‐3p/ENAH axis, which might provide novel therapeutic targets for esophageal cancer intervention.
The impact of COVID‐19 on trends in alcohol use disorder treatment in Veterans Health Administration
Authors: Perumalswami Ponni V. , Kilpatrick Sidonie , Frost Madeline C. , Adams Megan A. , Kim Hyungjin Myra , Zhang Lan , Lin Lewei
Published: February 2023

Background and Aims

The COVID‐19 pandemic disrupted health‐care provision in the United States and prompted increases in telehealth‐delivery of care. This study measured alcohol use disorder (AUD) treatment trends across visit modalities before and during COVID‐19.

Design, Setting, Participants and Measurements

We conducted a national, retrospective cohort study with interrupted time‐series models to estimate the impact of COVID‐19 on AUD treatment in the Veterans Health Administration (VHA) in the United States during pre‐COVID‐19 (March 2019 to February 2020) and COVID‐19 (March 2020 to February 2021) periods. We analyzed monthly trends in telephone, video and in‐person visits for AUD treatment and compared patient and treatment characteristics of patients receiving AUD treatment between the pre‐COVID‐19 and COVID‐19 periods. AUD was defined using International Classification of Diseases, 10th revision (ICD‐10) codes for alcohol abuse (F10.1) and alcohol dependence (F10.2), which have previously been used to study AUD in VHA.

Findings

The predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the beginning of the pre‐COVID period was 13.8% (n = 49 494). The predicted percentage decreased by 4.3% (P = 0.001) immediately at the start of the COVID‐19 period due to a decline in AUD psychotherapy. Despite an increase of 0.3% per month (P = 0.026) following the start of COVID‐19, the predicted percentage of VHA patients with an AUD diagnosis receiving any AUD treatment at the end of the study period remained below the pre‐COVID‐19 period. In February 2021, AUD psychotherapy visits were primarily delivered by video (50%, 58 748), followed by in‐person (36.6%, 43 251) and telephone (13.8%, 16 299), while AUD pharmacotherapy visits were delivered by telephone (38.9%, 3623) followed by in‐person (34.3%, 3193) and video (26.8%, 2498) modalities. Characteristics of VHA patients receiving AUD treatment were largely similar between pre‐COVID‐19 and COVID‐19 periods.

Conclusions

Despite increased telehealth use, the percentage of United States Veterans Health Administration patients with an alcohol use disorder (AUD) diagnosis receiving AUD treatment declined during COVID‐19 (March 2020 to February 2021) mainly due to a decrease in psychotherapy.