bluuebunny/crossref_metadata_2025 huggingface dataset:
FoxA1 and FoxA2 regulate growth and cellular identity in NKX2-1-positive lung adenocarcinoma
Authors: Orstad Grace , Fort Gabriela , Parnell Timothy J , Jones Alex , Stubben Chris , Lohman Brian , Gillis Katherine L. , Orellana Walter , Tariq Rushmeen , Klingbeil Olaf , Kaestner Klaus , Vakoc Christopher R. , Spike Benjamin T. , Snyder Eric L.
Published: June 2021

Changes in cellular identity (also known as histologic transformation or lineage plasticity) can drive malignant progression and resistance to therapy in multiple types of cancer, including lung adenocarcinoma (LUAD). The lineage specifying transcription factors FoxA1 and FoxA2 (FoxA1/2) regulate identity in NKX2-1/TTF1-negative LUAD. However, their role in NKX2-1-positive LUAD has not been systematically investigated. We find that Foxa1/2 knockout severely impairs tumorigenesis in KRAS-driven genetically engineered mouse models and human cell lines. Foxa1/2 deletion leads to the collapse of a dual identity state, marked by co-expression of pulmonary and gastrointestinal transcriptional programs, which has been implicated in LUAD progression. Mechanistically, loss of FoxA1/2 leads to aberrant NKX2-1 activity and genomic localization, which inhibits tumorigenesis and drives alternative cellular identity programs associated with non-proliferative states. This work demonstrates that FoxA1/2 expression is a novel lineage-specific vulnerability in NKX2-1-positive LUAD and identifies mechanisms of response and resistance to targeting FoxA1/2 in this disease.
GLI transcriptional repression is inert prior to Hedgehog pathway activation
Authors: Lex Rachel K. , Zhou Weiqiang , Ji Zhicheng , Falkenstein Kristin N. , Schuler Kaleigh E. , Windsor Kathryn E. , Kim Joseph D. , Ji Hongkai , Vokes Steven A.
Published: June 2021

In the absence of Hedgehog (HH) signaling, GLI proteins are post-translationally modified within cilia into transcriptional repressors that subsequently prevent sub-threshold activation of HH target genes. GLI repression is presumably important for preventing precocious expression of target genes before the onset of HH pathway activation, a presumption that underlies the pre-patterning model of anterior-posterior limb polarity. Here, we report that GLI3 repressor is abundant and binds to target genes in early limb development. However, contrary to expectations, GLI3 repression neither regulates the activity of GLI enhancers nor expression of HH target genes as it does after HH signaling has been established. Within the cilia, the transition to active GLI repression is accompanied by increases in axonemal GLI3 localization, possibly signifying altered GLI3 processing. Together, our results demonstrate that GLI3 repression does not prevent precocious activation of HH target genes, or have a pre-patterning role in regulating anterior-posterior limb polarity.
Tetrahymena thermophila Granule Lattice Protein 3 Improves Solubility of Sexual Stage Malaria Antigens Expressed in Escherichia coli
Authors: Akkale Cengiz , Cassidy-Hanley Donna Marie , Clark Theodore G.
Published: June 2021

The requirement for low cost manufacturing makes bacterial cells a logical platform for the production of recombinant subunit vaccines for malaria. However, protein solubility has been a major stumbling block with prokaryotic expression systems. Notable examples include the transmission blocking vaccine candidates, Pfs25 and Pfs48/45, which are almost entirely insoluble when expressed as recombinant proteins in Escherichia coli. Various solubility tags have been used with limited success in improving solubility, although recent studies with granule lattice protein 1 (Grl1p) from the ciliated protozoan, Tetrahymena thermophila, have shown promise. Here, we examine a related solubility tag, granule lattice protein 3 (Grl3p) from T. thermophila, and compare it to both Grl1p and the well-studied maltose binding protein (MBP) used to improve the solubility of multiple protein targets. We find that Grl3p performs comparably to Grl1p when linked to Pfs25 but significantly improves solubility when paired with Pfs48/45.
Analyzing Nested Experimental Designs – A User-Friendly Resampling Method to Determine Experimental Significance
Authors: Kulkarni Rishikesh U. , Wang Catherine L. , Bertozzi Carolyn R.
Published: June 2021

We report Hierarch, a Python package to perform hypothesis tests and compute confidence intervals on hierarchical experimental designs. Using a combination of permutation resampling and bootstrap aggregation, Hierarch can be used to perform hypothesis tests that maintain nominal Type I error rates and generate confidence intervals that maintain the nominal coverage probability without making distributional assumptions about the dataset of interest. Hierarch makes use of the Numba JIT compiler to reduce p-value computation times to under one second for typical datasets in biomedical research. Hierarch also enables researchers to construct user-defined resampling plans that take advantage of Hierarch’s Numba-accelerated functions. Hierarch is freely available as a Python package at https://github.com/rishi-kulkarni/hierarch.
The P-selectin ligand PSGL-1 (CD162) is efficiently incorporated by primary HIV-1 isolates and can facilitate trans-infection
Authors: Burnie Jonathan , Persaud Arvin Tejnarine , Thaya Laxshaginee , Liu Qingbo , Miao Huiyi , Grabinsky Stephen , Norouzi Vanessa , Lusso Paolo , Tang Vera A. , Guzzo Christina
Published: June 2021

While P-selectin glycoprotein ligand-1 (PSGL-1/CD162) has been studied extensively for its role in mediating leukocyte rolling through interactions with its receptor, P-selectin, recently, it was identified as a novel HIV-1 host restriction factor. One key mechanism of HIV-1 restriction is the ability of PSGL-1 to be physically incorporated into the external viral envelope, which effectively reduces infectivity by blocking virus attachment through the steric hindrance caused by its large ectodomain. Importantly, a large portion of the literature demonstrating the antiviral activity of PSGL-1 has utilized viruses produced in transfected cells which express high levels of PSGL-1. However, herein we show that virion-incorporated PSGL-1 is far less abundant on the surface of viruses produced via infection of physiologically relevant models (T cell lines and primary cells) compared to transfection (overexpression) models. Unique to this study, we show that PSGL-1 is incorporated in a broad range of HIV-1 and SIV isolates, supporting the physiological relevance of this incorporation. We also report that high levels of virion-incorporated PSGL-1 are detectable in plasma from viremic HIV-1 infected individuals, further corroborating the clinical relevance of PSGL-1 in natural infection. Additionally, we show that PSGL-1 on viruses is functionally active and can bind its cognate receptor, P-selectin, and that virions captured via P-selectin can subsequently be transferred to HIV-permissive bystander cells in a model of trans-infection. Taken together, our data suggest that PSGL-1 may have diverse roles in the physiology of HIV-1 infection, not restricted to the current antiviral paradigm.

IMPORTANCE

PSGL-1 is an HIV-1 host restriction factor which reduces viral infectivity by physically incorporating into the envelope of virions. While the antiviral effects of PSGL-1 in viruses produced by transfection models is profound, HIV-1 continues to remain infectious when produced through natural infection, even when PSGL-1 is incorporated. To study this discordance, we compared the differences in infectivity and PSGL-1 abundance in viruses produced by transfection or infection. Viruses produced via transfection contained unnaturally high levels of incorporated PSGL-1 compared to viruses from primary cells, and were much less infectious. We also found PSGL-1 to be present on a broad range of HIV-1 isolates, including those found in plasma from HIV-infected patients. Remarkably, we show that virion-incorporated PSGL-1 facilitates virus capture and transfer to HIV-permissive host cells via binding to P-selectin. These findings suggest that PSGL-1 may also work to enhance infectionin vivo.
Measuring stereotypes in the banking industry – an application to client relational benefits
Authors: Hobeika Janine
Published: June 2021

Purpose

Despite interest in social stereotypes such as gender, race and age, professional stereotypes of frontline employees is still a new topic that requires measurement in the banking services. The purpose of this paper is to develop and validate a reliable banker stereotype scale that reflects all useful dimensions.

Design/methodology/approach

A multi-dimensional scale is developed using a mixed method in the French context. Qualitative data were collected from two samples (11 private banking clients, 17 retail banking clients). Quantitative data were collected from two diversified samples built by quotas: an exploratory sample (n = 226) and a confirmatory sample (n = 579). Exploratory and confirmatory factor analyses were conducted to test and validate the scale.

Findings

The measurement scale proves to be valid and reliable. The scale is then used in a conceptual model as an explanatory factor of expected relational benefits where relations are analyzed using structural equation modeling. The model successfully provides some explanatory links between the banker stereotypes and the expected relational benefits.

Practical implications

The concept of the professional stereotype can be further used to better understand relationship quality and customer satisfaction through relational benefits, and more widely as a part of the know your customer (KYC) and corporate social responsibility (CSR) procedures.

Originality/value

The scale identifies four behavioral dimensions (partner, paternalistic, subordinate and shark) and one about dress code (formal clothing).
Entrepreneurial learning in extra-curricular start-up programs for students
Authors: Pocek Jasna , Politis Diamanto , Gabrielsson Jonas
Published: June 2021

Purpose

This study focuses on extra-curricular start-up programs for students at higher educational institutions. It explores the social and situated learning experiences of students who participate in start-up programs, as well as how the processes and outcomes of entrepreneurial learning are potentially shaped by this context.

Design/methodology/approach

The study follows multiple cohorts of students who have participated in an extra-curricular start-up program managed by three collaborating universities in Greater Copenhagen. The data have been inductively analyzed using semi-structured interviews with students and project managers during and after the start-up program, complemented with project progress reports, observation notes and survey data.

Findings

The analysis generates a grounded, theoretically informed process model of entrepreneurial learning situated in extra-curricular start-up programs. The model depicts how the immersion, comprehension and co-participation in entrepreneurship as social practice subsequently enables students to expand knowledge structures and develop greater self-confidence in performing entrepreneurship. The model identifies three interconnected components that trigger entrepreneurial learning among students, which allow them to acquire two set of competencies: venture creation competencies and enterprising competencies.

Originality/value

The findings offer unique insights into how the social and relational environment influence and shape the learning experience of students, hence filling the research void on entrepreneurial learning in the situated context of extra-curricular enterprise activities. The findings also elucidate how individual learning experiences of students are potentially shaped by the immersion, comprehension and co-participation in entrepreneurship as social practice.
The impact of the institutional environment and experience on social entrepreneurship: a multi-group analysis
Authors: Ghazali Ezlika M. , Mutum Dilip S. , Javadi Haleh Hakim
Published: June 2021

Purpose

This study presents a framework for integrating distinct perspectives on social entrepreneurship by combining institutional theory with the social entrepreneurship intention model. The framework assesses the relationships between social support and the perceived feasibility and desirability of social entrepreneurship, the relationships between social support and the institutional environments of social workers, and the moderating role of prior experience of social work and volunteering.

Design/methodology/approach

The model was tested using 266 validated responses from an online and paper-based survey distributed among social workers. Partial least squares structural equation modelling was used to analyse the data, and multi-group analysis was conducted to examine the moderation effects.

Findings

The findings indicate that experience moderates the relationships between the regulatory and cognitive environments, cognitive environments and social support, and social support and perceived feasibility. Experience negatively moderates the relationship between the normative environment and social support.

Practical implications

Active government involvement in the form of incentives and financial support would encourage the creation of social ventures.

Social implications

Educational programmes are also necessary to help raise awareness and increase the familiarity and knowledge of potential social entrepreneurs.

Originality/value

The study analyses the effects of institutional environmental components, recognised as highly influential on the development of social entrepreneurship, as well as the impact of perceived social support on the antecedents of the perceived desirability and feasibility of social entrepreneurship. It also addresses how social work experience modifies these relationships. Contrary to previous studies, the findings suggest that increasing social work experience isolates entrepreneurs from their environment.
Fast-food information, information quality and information gap: a temporal exploration of the notion of information in science communication on climate change
Authors: Graminius Carin
Published: June 2021

Purpose

The purpose of this study is to discuss the concept of information in relation to temporality within the context of climate change communication. Furthermore, the paper aims to highlight the empirical richness of information as a concept by analysing its use in context.

Design/methodology/approach

The discussion is based on 14 semi-structured interviews with initiators and collaborators of 6 open letters on climate change published in 2018–2019. By taking three specific notions the interviewees introduced—fast food information, information quality and information gap–as the analytical point of departure, the study aims for a contextual understanding of information grounded in temporal sensitivity.

Findings

The paper finds that information in the context of open letters is informed by different, and at times contradicting, temporalities and timescapes which align with various material, institutional and discursive practices. Based on this finding, the paper argues that notions of information are intrinsically linked to the act of communicating, and they should be viewed as co-constituting each other.

Originality/value

The paper contributes with an empirically informed discussion regarding the concept of information as it is used in a specific context. It illustrates how “information” is far from being understood in a singular fashion, but is made up of multifaceted and at times contradictory understandings. Ultimately, they correspond to why and how one communicates climate change information.
Lessons learned during Covid-19 concerning cheating in e-examinations by university students
Authors: Krambia Kapardis Maria , Spanoudis George
Published: June 2021

Purpose

The researchers aim to investigate how students can be deterred from cheating, whether legal or ethical policies and procedures are effective and whether there are gender differences.

Design/methodology/approach

Using data on students undertaking midterm and final e-examinations, as well as a control group of students who were caught cheating in an online mid-semester examination, the authors attempt to answer the research questions.

Findings

No differences were found in cheating in terms of students’ gender or whether they were repeating a course or not. However, the study revealed that if there are more internal controls imposed and if before the examination students are made to reinforce their academic integrity, e-examination cheating is reduced.

Originality/value

No other published study was carried out with students who were involved in cheating.
Do socially responsible managers forecast sales more accurately?
Authors: Chronopoulos Panagiotis
Published: June 2021

Purpose

This paper aims to examine whether corporate social responsibility (CSR) is related to management sales forecast accuracy.

Design/methodology/approach

Use KLD measures of corporate responsibility combined with forecast accuracy regression model, including controls for management skills and expertise.

Findings

Socially responsible firms commit forecast errors of lower magnitude and sales forecast accuracy is positively related to the level of CSR.

Research limitations/implications

A strong motive for research on the field of CSR topic under the scope of reporting quality. Future research could focus on alternative measures of CSR; such as announcements included into the financial statements or separately disclosed expenses. Examine the magnitude of confirmed relation, among different economies worldwide.

Practical implications

CSR effect on manager sales forecasting activity, highlight the impact of brand awareness and customer loyalty, as created by implementing CSR strategies, on firm growth and sales expansion.

Social implications

The research enhances the era towards more socially responsible firms, presenting evidence of such an adoption on corporate fundamentals.

Originality/value

To the knowledge there is no prior research examining the implications of CSR on sales forecast accuracy.
Health and economic imperatives for households in the context of the anti-Covid-19 strategy in Cameroon. The case of Yaounde
Authors: Ndi Humphrey Ngala , Ndi Roland Akoh , Bang Henry Ngenyam , Mbah Marcellus Forh , Ndzo Judwin Alieh
Published: June 2021

Purpose

This paper aims to explore the responses of households in the informal economic sector to the Cameroon Government strategy against Covid-19 in Yaounde, Cameroon between March and May 2020.

Design/methodology/approach

Given the recency of Covid-19, the exploratory design was used to collect and analyse information for the study. Empirical data was obtained through personal observations and questionnaires, whereas grey data were sourced from official sources in government and international agencies in Yaounde. The mode of the ordinal data generated from the questionnaire was used to characterise the attitudes of respondents to quarantine measures and bar charts were used to illustrate the distribution of responses.

Findings

The government’s strategy against Covid-19 was largely ignored in Yaounde between March and May 2020 because of the influence of the predominantly informal economy on household’s ability to allocate scarce resources between the competing needs of protecting their health on the one hand, and their livelihoods on the other hand. Poor households had to walk a difficult line between shutting down their businesses to protect their health or risking Covid-19 infections to protect their livelihoods. Over 53.1% of respondents thought quarantine measures were unsuccessful as over 63% ignored them. Quarantining and Social distancing were also difficult in informal settlements because of structural congestion.

Research limitations/implications

Perhaps, the greatest limitation of this study was the use of non-probability sampling. As such, sampling error could not be estimated, blurring the ability to ascertain the degree of similarity between the sample and the study population. This made sample generalisability difficult.

Practical implications

There are short-term and long-term policy implications of these findings. Basic comprehensive measures including food and water distribution, as well as rent holidays, must be implemented in informal neighbourhoods to ensure more successful quarantines in future pandemics. In the long run, investments in urban social housing must be carried out to reduce slums, an ever-present risk factor in the rapid propagation of infections.

Originality/value

The originality of this study is first, in its level of analysis which is the household. By measuring household responses to quarantine measures within defined neighbourhoods, the study deviates from most that have adopted a theoretical approach and conducted analysis at country or regional levels. Few studies have attempted to investigate the failure of quarantine measures against Covid-19 from the viewpoint of the occupational characteristics of the populations involved.
Exploring knowledge sharing behavior in healthcare organizations: an integrated perspective of the empowerment theory and self-determination theory
Authors: Wu Su-Ying , Wang Wei-Tsong , Hsieh Yu-Han
Published: June 2021

Purpose

This study examines the role of user psychological empowerment (PE) as a specific type of PE in the context of using health information systems (HIS) and incorporates the contribution of autonomous motivation and knowledge sharing intention (KSI) to the resolution of the key dynamics of interpersonal knowledge sharing behavior (KSB) in healthcare organizations.

Design/methodology/approach

For the data analysis, survey data were collected from 350 employees at three large teaching hospitals in Taiwan. In this study, the partial least squares technique was used with SmartPLS 3.3 software to validate the research model.

Findings

User PE had significant positive effects on autonomous motivation, KSI and KSB. Additionally, autonomous motivation positively affected KSB directly and indirectly via KSI.

Practical implications

Insights into motivation (e.g. user PE and autonomous motivation) play a key role in driving KSI and lead to effective KSB, which aids managers in tailoring their efforts to foster knowledge dissemination and enhance organizational performance.

Originality/value

While finding ways to encourage employees to share knowledge with one another in an organization is an important task, there exists a lack of understanding as to how this task can be accomplished in the context of healthcare organizations. This study is the first to specifically address this issue from a perspective integrating PE and self-determination theory while also incorporating the HIS context with population-specific measures (healthcare organizations) to expand the application of empowerment theory to the information system domain.
The impact of a proactive personality on innovative work behavior: the role of work engagement and transformational leadership
Authors: Mubarak Namra , Khan Jabran , Yasmin Robina , Osmadi Atasya
Published: June 2021

Purpose

Through the lens of social exchange theory, this study aims to assess the relationship between proactive personality and innovative work behavior by incorporating the mediating role of work engagement and moderating role of transformational leadership between proactive personality and work engagement.

Design/methodology/approach

Data were collected from 259 employees working in Pakistani small-medium enterprises (SMEs). The purposive sampling technique was used to collect data. For hypothesis testing, Preacher and Hayes process macro was employed.

Findings

Confirmatory factor analysis verified the distinctiveness of the variables used in this study. The findings show that a proactive personality had a positive influence on innovative work behavior directly and indirectly through work engagement, and transformational leadership positively moderates the relationship between a proactive personality and work engagement in such a way that with high transformational leadership behavior relationship will be strengthened.

Originality/value

This study has addressed three research questions that have been left unanswered in the literature. The initial research question is “how proactive personality enhances innovative work behavior?” This study found that proactive personality enhanced innovative work behavior. The second research question is “what are the suggested mechanisms for proactive personality to promote innovative work behavior?” This study has proven that a proactive personality enhanced innovative work behavior through an important mediating mechanism, namely work engagement. Finally, the third question of the study is “does transformational leadership moderate the relationship between proactive personality and work engagement? The study shows that transformational leadership positively moderates between proactive personality and work engagement.
Small–medium enterprise formation and Nigerian economic growth
Authors: Adeosun Oluyemi Theophilus , Shittu Ayodele Ibrahim
Published: June 2021

Purpose

This study examines the nexus between entrepreneurship through small–medium enterprise (SME) business formation and the growth of the Nigerian economy. Furthermore, this paper seeks to explore the link between small enterprise development and econo.

Design/methodology/approach

The paper focused on secondary data for the period 1990–2016 for macro parameters including, registered small and medium scale enterprise, nominal gross domestic product, employment, total labor force and population. Forecasting technique was applied to obtain data for missing trends. Quantitative analytical techniques used include the dynamic method of the error correction model (ECM) and Johansen co-integration test for a long-run correlation.

Findings

The result shows an increasing number of SME formation which has also led to the growth of the economy. However, an increase in the amount of micro-small and medium scale enterprises did not contribute to the development of the economy more than existing businesses. The employment elasticity is positive and significant and shows that the contribution of entrepreneurship regarding employment is the most essential factor that advances economic growth and reduction of unemployment.

Originality/value

The paper examines how the persistent increase in small and medium enterprise formation improves the growth and development of the Nigerian economy, employing the ECM approach.
A stable and sensitive enzyme‐linked immunosorbent assay (ELISA) for the determination of metsulfuron‐methyl residues in foods
Authors: Liu Bing , Qin Yue , Cao Meirong , Shi Haipeng , Li Shijie , Sheng Wei , Wang Shuo
Published: June 2021

A hapten of metsulfuron‐methyl was successfully designed and synthesized from 2‐methylester‐phenylsulfonamide and succinic anhydride, and the polyclonal antibody against metsulfuron‐methyl was prepared by immunization procedure with the hapten–bovine serum albumin conjugate. A stable and sensitive direct competitive enzyme‐linked immunosorbent assay (dcELISA) method had been developed under the optimal conditions. The sensitivity (IC50) was 37.03 ± 1.87 µg/L, and the detection line (IC15) was 1.57 ± 0.11 µg/L. Rice, wheat, oat, flaxseed, milk, and water were chosen to study the recovery test and the recovery rates were 83.11%–117.44% . The matrix effect was eliminated by a simple dilution of the sample extracts. The results from dcELISA were well agreement with the results from HPLC–MS. It was indicated that the developed method had good accuracy and stability. It could be applied for the detection of metsulfuron‐methyl residues. It was worth mentioning that the antibody could recognize metsulfuron‐methyl and tribenuron‐methyl with cross‐reactivities of 100% and 49.72%, respectively. In order to understand the cross‐reactivity, molecular modeling including molecular alignment and electrostatic potential surfaces were introduced. It was found that the special group of metsulfuron‐methyl played an important role, especially on C3 position of the phenyl group.

Practical Application

A stable, sensitive, and low‐cost dc ELISA method had been developed with good accuracy and applied in the determination of metsulfuron‐methyl in foods. Molecular simulation was introduced to understand the specificity between the antibody and the analyst. It was a good method to study the cross‐reactivity between the antibody and the analyst or analogue.
The Effects of Information Acquisition Effort, Psychological Ownership, and Reporting Context on Opportunistic Managerial Reporting*
Authors: Haesebrouck Katlijn
Published: June 2021

Within the context of managerial reporting, the tasks of acquiring and reporting information are logically connected. Although the accounting literature acknowledges their importance, it often treats these tasks as distinct processes. I investigate how the effort exerted to acquire information influences managers' reporting. Managers' information acquisition effort can induce psychological ownership that can lead to a sense of deservingness that increases opportunistic reporting or to a sense of responsibility that reduces opportunism. I predict that the reporting context determines the ultimate effect of information acquisition effort on reporting behavior. I test this prediction with a 2×2 budget reporting experiment. Managers are either endowed with information to report or required to exert effort to earn it, with the latter expected to generate more psychological ownership. In addition, I manipulate the saliency of honesty in the reporting context by framing reporting in terms of a business dilemma (less salient honesty) or an ethical dilemma (more salient honesty). I find that when honesty is less salient, managers build more slack into their report under earned information than endowed information. In contrast, more salient honesty alleviates the effect of earned information on slack. In a supplemental experiment, I find similar results when all managers are endowed with information to report but psychological ownership is manipulated via different firm messaging. These results have important implications for theory and practice. For example, in a less salient honesty context, technological investments that reduce managers' effort needed to acquire information can also help decrease opportunistic reporting.
Medication‐related hospital admissions in aged care residents
Authors: Kalisch Ellett Lisa M. , Kassie Gizat M. , Caughey Gillian E. , Pratt Nicole L. , Ramsay Emmae N. , Roughead Elizabeth E.
Published: June 2021

Objective

To determine the prevalence of medication‐related hospitalisations preceded by potentially suboptimal processes of care in aged care residents.

Method

We conducted a retrospective analysis of administrative claims data from the Australian Government Department of Veterans’ Affairs (DVA). We identified all hospital admissions for aged care residents between 1 July 2014 and 30 June 2019. The proportion of hospital admissions preceded by potentially suboptimal medication‐related processes of care was determined.

Results

A total of 18 874 hospitalisations were included, and 46% were preceded by potentially suboptimal medication‐related care. One‐quarter of fracture admissions occurred in residents at risk of fracture who were not using a medicine to prevent fracture, and 87% occurred in residents using falls‐risk medicines. Thirty per cent of heart failure admissions occurred in patients who were not using an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker.

Conclusion

Nearly half of hospital admissions were preceded by potentially suboptimal medication‐related processes of care. Interventions to improve use of medicines for aged care residents in these areas are warranted.
Free human DNA attenuates the activity of antimicrobial peptides in atopic dermatitis
Authors: Kopfnagel Verena , Dreyer Sylvia , Zeitvogel Jana , Pieper Dietmar H. , Buch Anna , Sodeik Beate , Rademacher Franziska , Harder Jürgen , Werfel Thomas
Published: June 2021

Background

The high susceptibility of AD patients to microbial skin infections has been attributed to a deficient antimicrobial peptide (AMP) expression, which is contradicted by a growing amount of recent studies clearly demonstrating that AMP expression is not impaired in lesional skin of AD patients. The reasons for the high susceptibility of AD patients to microbial infections are still unknown.

Methods

The influence of self‐DNA on the antimicrobial activity of RNase 7, LL‐37, and hBD2 has been investigated using antibacterial and antiviral assays. The amount of self‐DNA on skin has been analyzed by skin rinsings and subsequent quantification using dsDNA assays. DNA source was identified by qPCR.

Results

Complex formation of the AMPs with self‐DNA significantly impaired their antibacterial activity againstStaphylococcus aureusand their antiviral activity againstHSV‐1. The inhibition of the antibacterial activity was dependent on the DNA concentration but not on the length of the DNA molecules. Of note, we detected significant higher amounts of cell‐free self‐DNA in skin rinses taken from lesional AD skin compared to skin rinses from non‐lesional skin and from normal skin of healthy donors. Consequently, rinse solution from AD lesional skin prevented antibacterial activity of LL‐37.

Conclusion

Our study indicates that extracellular self‐DNA is released in considerable amounts in AD skin lesions and AMP‐self‐DNA‐complex formation leads to a significant loss of antibacterial and antiviral activity in atopic dermatitis. Studies on strategies to reduce the amount of extracellular DNA in AD are needed to identify possible methods relevant in clinical settings.
Prolonged QT intervals in mice with cardiomyocyte‐specific deficiency of the molecular clock
Authors: Gottlieb Lisa A. , Larsen Karin , Halade Ganesh V. , Young Martin E. , Thomsen Morten B.
Published: June 2021

Aim

Cardiac arrhythmias and sudden deaths have diurnal rhythms in humans. The underlying mechanisms are unknown. Mice with cardiomyocyte‐specific disruption of the molecular clock genes have lower heart rate than control. Because changes in the QT interval on the electrocardiogram is a clinically used marker of risk of arrhythmias, we sought to test if the biological rhythms of QT intervals are dependent on heart rate and if this dependency is changed when the molecular clock is disrupted.

Methods

We implanted radio transmitters in male mice with cardiomyocyte‐specific Bmal1 knockout (CBK) and in control mice and recorded 24‐h ECGs under diurnal and circadian conditions. We obtained left ventricular monophasic action potentials during pacing in hearts ex vivo.

Results

Both RR and QT intervals were longer in conscious CBK than control mice (RR: 117 ± 7 vs 110 ± 9 ms, P < .05; and QT: 53 ± 4 vs 48 ± 2 ms, P < .05). The prolonged QT interval was independent of the slow heart rate in CBK mice. The QT interval exhibited diurnal and circadian rhythms in both CBK and control mice. The action potential duration was longer in CBK than in control mice, indicating slower repolarization. Action potential alternans occurred at lower pacing rate in hearts from CBK than control mice (12 ± 3 vs 16 ± 2 Hz, respectively, P < .05).

Conclusion

The bradycardic CBK mice have prolonged ventricular repolarization independent of the heart rate. Diurnal and circadian rhythms in repolarization are preserved in CBK mice and are not a consequence of the 24‐h rhythm in heart rate. Arrhythmia vulnerability appears to be increased when the cardiac clock is disrupted.
Measuring goal progress using the goal‐based outcome measure in Jigsaw – A primary care youth mental health service
Authors: O'Reilly Aileen , McKenna Niamh , Fitzgerald Amanda
Published: June 2021

Background

Jigsaw is a primary care youth mental health service designed to increase access to and utilisation of mental health supports for 12‐ to 25‐year‐olds. Effectiveness in community youth mental health services is typically assessed using standardised instruments. The aim of this study was to examine the effectiveness of Jigsaw’s brief intervention model of support using an idiographic tool, the goal‐based outcome (GBO) measure. The study also aimed to explore the type of goals set by young people engaging with this service.

Method

The study sample consisted of a secondary dataset of 4839 young people aged 12–25 years (63.5% female, 36.5% male) who engaged with one of Jigsaw’s 13 brief intervention services. Overall, 7366 goals set using the GBO were examined. Inductive thematic analysis was conducted to examine the type of goals set by young people, and inferential analyses were used to examine statistical and reliable changes in goal progress.

Results

The goals young people set focused on developing coping mechanisms and personal growth and managing interpersonal difficulties. Mean scores for progress towards goals improved significantly from pre‐ to postintervention. The reliable change index (RCI) indicated that change greater than 2.82 points represents reliable change on the GBO, with 78.6% of young people showing reliable improvement. Demographic characteristics did not impact goal progress.

Conclusion

These findings suggest Jigsaw’s brief intervention model of support is effective in assisting young people reach their goals and that the GBO is a suitable measure for young people attending a community‐based youth mental health service.
T‐cell infiltration, contribution and regulation in the central nervous system post‐traumatic injury
Authors: Xu Lvwan , Ye Xin , Wang Qingyi , Xu Bihan , Zhong Jinjie , Chen Ying‐ying , Wang Lin‐lin
Published: June 2021

T cells participate in the repair process and immune response in the CNS post‐traumatic injury and play both a beneficial and harmful role. Together with nerve cells and other immune cells, they form a microenvironment in the CNS post‐traumatic injury. The repair of traumatic CNS injury is a long‐term process. T cells contribute to the repair of the injury site to influence the recovery. Recently, with the advance of new techniques, such as mass spectrometry‐based flow cytometry, modern live‐cell imaging, etc, research focusing on T cells is becoming one of the valuable directions for the future therapy of traumatic CNS injury. In this review, we summarized the infiltration, contribution and regulation of T cells in post‐traumatic injury, discussed the clinical significance and predicted the future research direction.
Impact of pregnancy on the trajectories of cardiovascular risk factors in women with and without gestational diabetes
Authors: Retnakaran Ravi , Shah Baiju R.
Published: June 2021

Aims

The elevated lifetime risk of cardiovascular disease in women who develop gestational diabetes mellitus (GDM) has been attributed to adverse life‐course trajectories of cardiovascular risk factors that arise before pregnancy and continue thereafter. We hypothesized that pregnancy may differentially affect these trajectories in women who develop GDM and those who do not.

Materials and methods

With population‐based administrative databases, we identified all nulliparous women in Ontario, Canada, who had singleton pregnancies between January 2011 and December 2016 and ≥2 measurements of the following analytes both before and after pregnancy: glycated haemoglobin (HbA1c), glucose, lipids and transaminases. In total, 39 581 women (4373 with GDM) had 3.9 ± 3.4 tests before and 4.6 ± 5.4 tests after pregnancy.

Results

Both before and after pregnancy, women who developed GDM had higher HbA1c, fasting glucose, low‐density lipoprotein (LDL)‐cholesterol and triglycerides than their peers, with lower high‐density lipoprotein (HDL)‐cholesterol (all p < .0001). Before pregnancy, women who went on to GDM had higher annual increases than their peers did in HbA1c, fasting glucose and triglycerides (all p ≤ .01); lesser annual decrease in LDL (p = .0003); and greater annual decrease in HDL (p = .0006). Compared with pre‐pregnancy, the postpartum differences in annual rates of change in HbA1c and fasting glucose were 6.9‐ and 3.3‐fold higher, respectively, in women with GDM. Conversely, the respective postpartum differences in annual rates of change in triglycerides, LDL and HDL were 1.2, 1.6 and 0.3 times lower than before pregnancy.

Conclusion

After pregnancy, differences in pregravid trajectories of glycaemic measures are amplified between women with GDM and their peers. In contrast, pregravid differences in lipid measures persist but do not differentially worsen after pregnancy.
Healthcare costs of post‐stroke oropharyngeal dysphagia and its complications: malnutrition and respiratory infections
Authors: Marin Sergio , Serra‐Prat Mateu , Ortega Omar , Audouard Fericgla Monica , Valls Jordi , Palomera Elisabet , Cunillera Ramon , Palomeras Ernest , Ibàñez Josep Maria , Clavé Pere
Published: June 2021

Background and purpose

The healthcare economic costs of post‐stroke oropharyngeal dysphagia (OD) are not fully understood. The purpose of this study was to assess the acute, subacute and long‐term costs related to post‐stroke OD and its main complications (malnutrition and respiratory infections).

Methods

A cost of illness study of patients admitted to Mataró Hospital (Catalonia, Spain) from May 2010 to September 2014 with a stroke diagnosis was performed. OD, malnutrition and respiratory infections were assessed during hospitalization and follow‐up (3 and 12 months). Hospitalization and long‐term costs were measured from hospital and healthcare system perspectives. Multivariate linear regression analysis was performed to assess the independent effect of OD, malnutrition and respiratory infections on healthcare costs during hospitalization, and at 3 and 12 months’ follow‐up.

Results

In all, 395 patients were included of whom 178 had OD at admission. Patients with OD incurred major total in‐hospital costs (€5357.67 ± €3391.62 vs. €3976.30 ± €1992.58, p < 0.0001), 3‐month costs (€8242.0 ± €5376.0 vs. €5320.0 ± €4053.0, p < 0.0001) and 12‐month costs (€11,617.58 ± €12,033.58 vs. €7242.78 ± €7402.55, p < 0.0001). OD was independently associated with a cost increase of €789.68 (p = 0.011) during hospitalization and of €873.5 (p = 0.084) at 3 months but not at 12 months. However, patients with OD who were at risk of malnutrition or malnourished and suffered respiratory infections incurred major mean costs compared with those patients without OD (€19,817.58 ± €13,724.83 vs. €7242.8 ± €7402.6, p < 0.0004) at 12 months’ follow‐up.

Conclusion

Oropharyngeal dysphagia causes significant high economic costs during hospitalization that strongly and significantly increase with the development of malnutrition and respiratory infections at long‐term follow‐up.
Parental self‐efficacy: Examining its mediating and reciprocally predictive roles in supportive emotion socialization
Authors: Fung Wing Kai , Chung Kevin Kien Hoa , Lam Chun Bun
Published: June 2021

This longitudinal study examined the associations between child negative affect, parental self‐efficacy (PSE), and parents’ approaches to the provision of supportive socialization. It also investigated the bidirectionality between PSE, problem‐focus socialization, and emotion‐focus socialization across two time points separated by one year. Participants were 757 Hong Kong Chinese parents (47.4% fathers) of kindergarten children. At both time 1 and time 2, parents reported their PSE, problem‐focus socialization, and emotion‐focus socialization. Additionally, parents rated their child's negative affect at time 1. Results from the cross‐lagged panel model revealed that, controlling for the effects of school's socioeconomic strata, child gender, parental age, and educational level, PSE at time 1 mediated the indirect links of child negative affect at time 1 with problem‐focus (indirect effect: β = −.02, SE = .02, p < .05) and emotion‐focus (indirect effect: β = −.02, SE = .01, p < .05) socialization at time 2 and that PSE (β = .10, SE = .06, p < .01) and problem‐focus socialization (β = .15, SE = .03, p < .05) were reciprocally associated with each other. Findings underscored the role of PSE in understanding parental provision of supportive socialization and the co‐development of belief about parenting and parenting behaviors.
Buried treasure – the teaching potential of Kodachrome slides brought into the digital age
Authors: Zufall Alina Gertrud , Mark Erica Jaclyn , Pollack Karlyn , Russell Mark
Published: June 2021

Clinical images on Kodachrome slides have been used for decades in dermatologic education. While the technology to view these images is becoming obsolete, many training programs possess high‐quality slides that have educational benefit. The University of Virginia Department of Dermatology possesses a collection of such slides that are currently being digitized and integrated into an educational software program. We present this article as a means of providing a uniform protocol for institutions with large Kodachrome collections to do the same. Our work has proven beneficial for both medical students interested in dermatology, allowing them to gain exposure to a variety of conditions that are not well emphasized in the general curriculum, as well as for dermatology residents, who use the program as a means to hone their diagnostic skills. Not only is there educational benefit to be derived from digitizing these slides but time is of the essence, as these slides can easily become damaged or degraded, and the technology needed to scan them is quickly becoming less available.
Contribution of functional genomics to identify the genetic basis of water‐deficit tolerance in barley and the related molecular mechanisms
Authors: Marok Mohamed Amine , Marok‐Alim Djamila , Rey Pascal
Published: June 2021

Drought, a major environmental constraint, has increasing impact on agricultural production. Genetic improvement for maintaining crop productivity in such adverse conditions is a critical challenge for breeders. Barley exhibits a remarkable genetic diversity associated with a widespread geographical distribution in contrasted climates. This diversity, which resides in regional landraces and wild accessions, has been only recently explored using functional genomics. Here, we review the data gained to identify in the barley germplasm collections, candidate genes participating in mechanisms conferring drought tolerance via signalling and protective mechanisms. We particularly focus on genes, for which QTL determination and association genetic‐based mapping methods validate their likely roles in tolerance. Thus, allelic variants coding for transcription factors, heat shock or late embryogenesis proteins, and actors involved in ABA‐signalling pathways, proline biosynthesis or redox regulation, have been characterized in wild and landrace populations, and constitute a solid basis for improving barley drought tolerance. The huge advance in sequencing technology and mass spectrometry, combined with the power of bioinformatics tools, makes it possible to envisage trials including a large number of genotypes to compare their physiological and biochemical features upon water deficit, and simultaneously determine the genetic basis of their differential behaviour. The implementation of such approaches will be powerful to identify promising loci for breeders for improving barley responses to drought.