bluuebunny/crossref_metadata_2025 huggingface dataset:
University internship systems and preparation of young people for world of work in the 4th industrial revolution
Authors: Adeosun Oluyemi Theophilus , Shittu Ayodele Ibrahim , Owolabi Temitope J.
Published: June 2021

Purpose

As the 4th industrial revolution (4IR) unfolds, there is an increasing awareness that its implications for workforce transformation and shifts in workforce demand will profoundly impact the future of work. Specifically, the paper seeks to answer the following research questions: i) how does Students’ Industrial Work Experience Scheme (SIWES) equip young people for the real world of work, especially in the era of the third industrial revolution?; ii) does SIWES support the exposure of young people to the world of digitalization?; and iii) what are the effects of the SIWES exposure on the employability of young people? This paper aims to evaluate the University Internship system and preparation of young people for the world of work in the 4th industrial revolution.

Design/methodology/approach

This paper used a mixed method to unravel the objectives of this study, that is, quantitative and qualitative methods. For the former, structured questionnaires were used to elicit a response from 249 young people drawn from tertiary institutions across Lagos State, Nigeria. The latter used an in-depth interview method conducted among 45 respondents (25 employers of labor and 20 lecturers).

Findings

The findings reveal that: SIWES contributes meaningfully to the advancement of knowledge and capacity building among young people; SIWES exposes young people to the world of digitalization, depending on the organization where the internship takes place; and SIWES pays little attention to financial rewards and more attention to the acquisition of skills that are relevant to the world of work. The practical and policy implications of the findings are critically discussed.

Originality/value

This paper critically evaluates the SIWES policy amidst the growing threats of widening skills gap, greater inequality and broader polarization.
Privacy concerns and the prevalence of third-party tracking cookies on ARL library homepages
Authors: Marino Bill
Published: June 2021

Purpose

The integration of third-party resources on library websites may be inadvertently contributing to surveillance technologies without user knowledge. This study set out to determine the prevalence of third-party tracking cookies on Association of Research Libraries (ARL) member homepages, the entities that are tracking users and for what purpose and what control users have over their cookie preferences.

Design/methodology/approach

Homepages from the 124 ARL member libraries were visited. Evidence of a privacy or cookie statement was collected and cookie logs were captured. This data were compared against the Disconnect list of known trackers and analyzed to determine the extent to which third-party tracking cookies were used across ARL sites, who was setting the cookies and for what purpose, and whether this use differed with regards to a library's identifying features.

Findings

It was determined that many ARL libraries do contribute to the ability to track a user's activity across the web, with one-third containing third-party tracking cookies. A user's contact with tracking cookies is influenced by various traits defining the institution. Users are given very little control over the cookies logged on their machines.

Originality/value

This study explores library efforts to protect user privacy, adopting an introspective approach that focuses on library websites. It will provide discussion points for librarians to question not only what third-party tracking cookies are present on their sites and why, but also how to educate their users about privacy issues.
The impact of environmental performance on capital structure and firm performance: the case of Turkey
Authors: Kalash Ismail
Published: June 2021

Purpose

The purpose of this study is to investigate the effect of environmental performance on the capital structure and financial performance of Turkish listed firms.

Design/methodology/approach

This study used data of 49 firms listed on Istanbul Stock Exchange during the period between 2014 and 2019, resulting in 205 firm-year observations. The environmental performance data were drawn from the carbon disclosure project Turkey climate change reports. Ordinary least squares and binary logistic regression models were used to examine whether environmental performance impacts the capital structure and financial performance.

Findings

The findings of this research revealed that environmental performance significantly positively affects the firm leverage. Findings also showed that environmental performance has a significantly positive impact on return on assets, operating profitability and return on equity, but no significant impact on stock returns.

Practical implications

Given the increased borrowing costs for Turkish firms after the 2018 currency crisis in Turkey, the findings of this study are very important as they enable managers of Turkish firms to make better decisions related to capital structure and to understand the role of environmental performance in reducing the cost of debt and enhancing financial performance.

Originality/value

To the author’s knowledge, this research is the first to investigate the effect of environmental performance on capital structure in the Turkish context, and is one of few that explained how environmental performance affects the financial performance of Turkish firms.
Examining the moderating role of HIHRP in the relationship between external integration and productivity
Authors: Tarifa Fernández Jorge , Cespedes-Lorente José , de Burgos Jiménez Jerónimo
Published: June 2021

Purpose

Based on the human resource (HR) and supply chain integration (SCI) literature, this paper aims to argue that high-involvement human resource practices (HIHRP) work as a complementary capability for SCI, and thus, HIHRP moderates the relationship between SCI and firm productivity. This moderating role is analyzed through the following HIHRP dimensions, namely, ability-enhancing, motivation-enhancing and opportunity-enhancing practices framework.

Design/methodology/approach

Using empirical data collected from a survey of the agri-food sector (horticultural firms of southern Spain), the moderating effects of HIHRP on the relationship between supply chain external integrations (with customers and suppliers) and productivity are examined. Hierarchical regression analysis is used to test the proposed hypotheses.

Findings

The results support that HIHRP has a moderating effect on the SCI/productivity relationship. However, these results are only significant in the case of supplier integration.

Originality/value

This study analyzes HIHRP as a complementary asset in the context of SCI and makes both theoretical and managerial contributions to the SCI literature by empirically analyzing the role of HR practices in enhancing the relationship between SCI and performance.
Using the social return on investment (SROI) as a measure of the effectiveness of social innovation projects implemented under public policies
Authors: Moroń Dorota , Klimowicz Monika
Published: June 2021

Purpose

This paper aims to contribute to the on-going debate about the best way to measure the economic effectiveness of public policies, as well to explore the possibility of using the social return on investment (SROI) method as one of the indicators.

Design/methodology/approach

This study combines the SROI method with the case study analysis and comparative study. The paper presents the process of economic evaluation with the use of the SROI methodology and its results, along with methodological and evaluation observations.

Findings

This study confirms some assumptions based both on the subject literature, as well as, on own experience related to the implementation of the evaluation, the author also points out dilemmas related to the use of SROI analysis and the possibility of using it to measure the effectiveness of social innovation projects.

Research limitations/implications

The study contains several practical suggestions on the advantages and disadvantages of the SROI method in the evaluation of particular public policy intervention.

Practical implications

The paper includes implications for the use of SROI analysis of social innovation projects implemented in the frames of public policies.

Originality/value

The authors’ ambition is to provide practical suggestions on the advantages and disadvantages of the SROI method in the evaluation of particular public policy intervention and to contribute to the discussion about the possible space for comparing the results of economic evaluation based on the SROI method. Furthermore, it is different than most approaches to SROI analysis as the authors combine this method with the case study analysis and comparative study.
Human resource management-related responses of health organizations to Covid-19
Authors: Tursunbayeva Aizhan
Published: June 2021

Purpose

COVID-19 has been a big reset to human resource (HR) processes. Organizations’ HR functions around the world have been working hard to effect a response that falls under four main headings: jobs and work continuity; physical health and well-being; need for mental health, resilience, family support and dealing with uncertainty; and remote work. Knowledge of whether and how these responses have been adopted by health organizations or their potential impact is scarce.

Design/methodology/approach

This paper discusses some of the HR strategies adopted or recommended for adoption by health systems/organizations with specific reference to the aforementioned HR response categories.

Findings

The evidence available illustrates that the HR responses adopted by health organizations are mostly in line with those adopted by organizations from other sectors, though not without some variances. The findings also suggest that COVID has acted as a “technological catalyst” for HR practices in health organizations.

Research limitations/implications

The background readings that informed this study also helped to identify some literature gaps that could be addressed by future research and practice.

Practical implications

The state of the art presented in this paper may be of value to health leaders and health HR managers in further strengthening their responses to both pre-existing and post-COVID people-related challenges.

Originality/value

This work is timely considering existing literature gaps and the fact that the existing evidence gets outdated quickly as the emergency progresses.
Climate‐specific biosynthetic gene clusters in populations of a lichen‐forming fungus
Authors: Singh Garima , Calchera Anjuli , Schulz Meike , Drechsler Moritz , Bode Helge B. , Schmitt Imke , Dal Grande Francesco
Published: June 2021

Natural products can contribute to abiotic stress tolerance in plants and fungi. We hypothesize that biosynthetic gene clusters (BGCs), the genomic elements that underlie natural product biosynthesis, display structured differences along elevation gradients. We analysed biosynthetic gene variation in natural populations of the lichen‐forming fungus Umbilicaria pustulata. We collected a total of 600 individuals from the Mediterranean and cold‐temperate climates. Population genomic analyses indicate that U. pustulata contains three clusters that are highly differentiated between the Mediterranean and cold‐temperate populations. One entire cluster is exclusively present in cold‐temperate populations, and a second cluster is putatively dysfunctional in all cold‐temperate populations. In the third cluster variation is fixed in all cold‐temperate populations due to hitchhiking. In these two clusters the presence of consistent allele frequency differences among replicate populations/gradients suggests that selection rather than drift is driving the pattern. We advocate that the landscape of fungal biosynthetic genes is shaped by both positive and hitchhiking selection. We demonstrate, for the first time, the presence of climate‐associated BGCs and BGC variations in lichen‐forming fungi. While the associated secondary metabolites of the candidate clusters are presently unknown, our study paves the way for targeted discovery of natural products with ecological significance.
Origin of symbiotic gut spirochetes as key players in the nutrition of termites
Authors: Tokuda Gaku
Published: June 2021

Termites harbour symbiotic spirochetes in their hindguts, which have long been considered treponemes, although they represent separate lines of descent from known species of Treponema. ‘Termite gut treponemes’ have a mutualistic relationship with the host termites with their physiological properties including CO2‐reductive acetogenesis, from which the resulting acetate fulfils most of the respiratory requirement of the host. Song and co‐workers showed that a spirochetal isolate (strain RmG30) from a Madeira cockroach represents the earliest branching lineage of extremely diverse termite (Treponema) cluster I and was a simple homolactic fermenter, suggesting that CO2‐reductive acetogenesis exhibited by some members of termite cluster I originated via horizontal gene transfer. Phylogenomic and 16S rRNA sequence‐based phylogenetic analyses indicated a deeply‐branched sister clade containing termite cluster I was distinguishable as a family‐level lineage. In this context, a new family, ‘Termitinemataceae’ has been proposed for this clade. Strain RmG30 has been designated as the type strain of Breznakiella homolactica gen. nov. sp. nov. named after John A. Breznak, an American microbiologist distinguished in termite gut microbiology. The study has posed important questions for the future, including the actual roles of the termite spirochetes in each termite lineage and the evolutionary process of their physiological properties.
Acceptance of oat‐based beverages tailored for patients with cancer
Authors: Enriquez Fernandez Blanca E. , Klassen Pamela , Mazurak Vera , Chen Lingyun , Prado Carla M. , Wismer Wendy V.
Published: June 2021

Oat‐based beverages are a nutritious product with the potential to support increased nutrient intake of patients with cancer. The aim of this research was to evaluate the sensory acceptance of oat‐based beverages and perceptions of oats among patients with cancer as future vehicles for nutrient delivery. In study 1, three flavors of oat‐beverages were well accepted without significant difference in liking among flavors or serving temperature, or between patients with cancer and healthy participants. Patients with cancer more frequently rated the beverages as too sweet compared to healthy participants; flavor intensity was just about right for all participants. In the second study, one of two formulations fortified with protein and fish oil was not different in liking compared to the unfortified chocolate product. Patients associated oat food products with specific oat‐based food products and oat health benefits in a free‐word association task in the third study. Together, sensory acceptance and the perceived health benefits of oats indicate the potential for oats to be incorporated in fortified and unfortified products tailored for patients with cancer.

Practical Application

The three studies presented here to assess the sensory acceptance of oat‐based beverages and perceptions of oats among patients with cancer demonstrate that oats can be incorporated in fortified and unfortified products tailored for patients with cancer. Inadequate nutrition is highly prevalent among oncology patients and there is a lack of available products targeted to improve their nutritional intake. These findings can support product developers and sensory scientists in the development and evaluation of food products acceptable to this population.
Disentangling adaptation from drift in bottlenecked and reintroduced populations of Alpine ibex
Authors: Leigh Deborah M. , Lischer Heidi E. L. , Guillaume Frédéric , Grossen Christine , Günther Torsten
Published: June 2021

Identifying local adaptation in bottlenecked species is essential for conservation management. Selection detection methods have an important role in species management plans, assessments of adaptive capacity, and looking for responses to climate change. Yet, the allele frequency changes exploited in selection detection methods are similar to those caused by the strong neutral genetic drift expected during a bottleneck. Consequently, it is often unclear what accuracy selection detection methods have across bottlenecked populations. In this study, simulations were used to explore if signals of selection could be confidently distinguished from genetic drift across 23 bottlenecked and reintroduced populations of Alpine ibex (Capra ibex). The meticulously recorded demographic history of the Alpine ibex was used to generate comprehensive simulated SNP data. The simulated SNPs were then used to benchmark the confidence we could place in outliers identified in empirical Alpine ibex RADseq derived SNP data. Within the simulated data set, the false positive rates were high for all selection detection methods (FST outlier scans and Genetic‐Environment Association analyses) but fell substantially when two or more methods were combined. True positive rates were consistently low and became negligible with increased stringency. Despite finding many outlier loci in the empirical Alpine ibex SNPs, none could be distinguished from genetic drift‐driven false positives. Unfortunately, the low true positive rate also prevents the exclusion of recent local adaptation within the Alpine ibex. The baselines and stringent approach outlined here should be applied to other bottlenecked species to ensure the risk of false positive, or negative, signals of selection are accounted for in conservation management plans.
Long‐term consequences in critically ill COVID‐19 patients: A prospective cohort study
Authors: Schandl Anna , Hedman Anders , Lyngå Patrik , Fathi Tachinabad Sozan , Svefors Jessica , Roël Mari , Geborek Anne , Andersson Franko Mikael , Söderberg Mårten , Joelsson‐Alm Eva , Darlington Pernilla
Published: June 2021

Background

COVID‐19 can cause severe disease with need of treatment in the intensive care unit (ICU) for several weeks. Increased knowledge is needed about the long‐term consequences.

Methods

This is a single‐center prospective follow‐up study of COVID‐19 patients admitted to the ICU for respiratory organ support between March and July 2020. Patients with invasive ventilation were compared with those with high‐flow nasal oxygen (HFNO) or non‐invasive ventilation (NIV) regarding functional outcome and health‐related qualify of life. The mean follow‐up time was 5 months after ICU discharge and included clinical history, three well‐validated questionnaires about health‐related quality of life and psychological health, pulmonary function test, 6‐minute walk test (6MWT) and work ability. Data were analyzed with multivariable general linear and logistic regression models with 95% confidence intervals.

Results

Among 248 ICU patients, 200 patients survived. Of these, 113 patients came for follow‐up. Seventy patients (62%) had received invasive ventilation. Most patients reported impaired health‐related quality of life. Approximately one‐third suffered from post‐traumatic stress, anxiety and depression. Twenty‐six percent had reduced total lung capacity, 34% had reduced 6MWT and 50% worked fulltime. The outcomes were similar regardless of ventilatory support, but invasive ventilation was associated with more bodily pain (MSD −19, 95% CI: −32 to −5) and <80% total lung capacity (OR 4.1, 95% CI: 1.3‐16.5).

Conclusion

Among survivors of COVID‐19 who required respiratory organ support, outcomes 5 months after discharge from ICU were largely similar among those requiring invasive compared to non‐invasive ventilation.
Association between punitive policies and neonatal abstinence syndrome among Medicaid‐insured infants in complex policy environments
Authors: Faherty Laura J. , Heins Sara , Kranz Ashley M. , Patrick Stephen W. , Stein Bradley D.
Published: June 2021

Aims

To estimate the association between punitive policies for women with substance use during pregnancy and odds of neonatal abstinence syndrome (NAS) diagnosis among Medicaid‐insured infants, and to estimate this association controlling for the presence of four other policies related to substance use in pregnancy.

Design, Setting and Participants

Analysis of live births in Medicaid claims data from 39 US states in varying years between 2006 and 2014 using weighted generalized linear models with clustered standard errors and state and year fixed‐effects.

Measurements

NAS rates in states without punitive policies were compared with rates in states with policies before and after policy enactment using logistic regression models adjusted for individual and county‐level factors and including state and year fixed‐effects. We estimated odds of NAS controlling for the presence of a potentially treatment‐deterring policy requiring reporting of suspected prenatal substance use, and three treatment‐supportive policies that create targeted programs for pregnant and postpartum women, prioritize pregnant women's access to substance use disorder treatment programs and prohibit discrimination towards pregnant women in treatment programs.

Findings

Among 9 714 798 weighted live births (1 896 082 unweighted), 49 670 (0.51%) had an NAS diagnosis. The findings were inconclusive as to whether or not punitive policies were associated with odds of NAS either in the short or long term. Odds of NAS among infants born in states with reporting policies were lower than those born in states without such policies [adjusted odds ratio (aOR) = 0.77, 95% confidence interval (CI) = 0.61–0.98].

Conclusions

In the United States, punitive policies for women with substance use during pregnancy do not appear to be associated with lower odds of neonatal abstinence syndrome (NAS). Reporting policies, which are heterogenous in their components and implementation, appear to be associated with lower odds of NAS when controlling for other relevant policies.
Genome‐wide association study and inbreeding depression on body size traits in Qira black sheep (Ovis aries)
Authors: Tao L. , Liu Y. F. , Zhang H. , Li H. Z. , Zhao F. P. , Wang F. Y. , Zhang R. S. , Di R. , Chu M. X.
Published: June 2021

Qira black sheep is a famous indigenous sheep breed in China. The objectives of this study are to identify candidate genes related to body size, and to estimate the level of inbreeding depression on body size based on runs of homozygosity in Qira black sheep. Here, 188 adult Qira black sheep were genotyped with a high density (630 K) SNP chip and genome‐wide association study for body weight and body size traits (including withers height, body slanting length, tail length, chest girth, chest width, and chest depth) were performed using an additive linear model. In consequence, 12 genome‐ and chromosome‐wide significant SNPs and, accordingly, six candidate genes involved in muscle differentiation, metabolism and cell processes were identified. Of them, ZNF704 (zinc finger protein 704) was identified for body weight; AK2 (adenylate kinase 2) and PARK2 (parkin RBR E3 ubiquitin protein ligase) for tail length; MOCOS (molybdenum cofactor sulfurase) and ELP2 (elongator acetyltransferase complex subunit 2) for chest width; and MFAP1 (microfibril associated protein 1) for chest girth. Additionally, inbreeding depressions on body size were observed in the current herd. These results will provide insightful understandings into the genetic mechanisms of adult body size, and into the conservation and utilization of Qira black sheep.
Removing the large uterus without morcellation – The Colpo‐V incision for specimen extraction at hysterectomy
Authors: Rosen David M. B. , Conrad Dean H. , Saar Tal D. , Cario Greg M. , Chou Danny , Bukhari Mujahid
Published: June 2021

Background

Hysterectomy is the most commonly performed benign gynaecological surgery. Recently, the rates of minimally invasive hysterectomy have fallen due to the banning of mechanical morcellation techniques that rendered minimal invasive gynaecology surgeons unable to extract large uteri from the relatively small colpotomy incisions.

Aims

This study aims to share our experience in utilising Colpo‐V incision to remove large uterine specimens transvaginally and report its success and complication rates to promote a minimal invasive approach in patients with large uteri without the need to perform large abdominal incisions or transabdominal morcellation.

Methods

This is a prospective case series study in which women with large uteri and|or narrow vaginal canal underwent total laparoscopic hysterectomy and a subsequent posterior vaginal wall incision (Colpo‐V) to facilitate the intact extraction of the uterus through the vagina. Patients were seen in the clinic six weeks after the surgery for post‐operative assessment and documentation of late complications.

Results

Seventeen women underwent the procedure, and the intact extraction of the specimen was successful in 16 out of the 17 cases (94%). No major complications were encountered during or after the procedure.

Conclusion

Colpo‐V incision is a simple and effective technique for the intact extraction of larger uterine specimens at hysterectomy.
Virus‐triggered secondary hemophagocytic lymphohistiocytosis
Authors: Imashuku Shinsaku , Morimoto Akira , Ishii Eiichi
Published: June 2021

Primary (familial/hereditary) and secondary (non‐familial/hereditary) hemophagocytic lymphohistiocytosis (HLH) are hyperinflammatory and hypercytokinemic syndromes. Secondary HLH includes infection‐ (eg viral/bacterial/fungal/parasitic) and non–infection‐ (eg collagen disease or malignancy) related diseases. Viral HLH is the major type among all age groups. Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection(s), and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation (HSCT). Epstein‐Barr virus (EBV)‐related HLH (EBV‐HLH) is the most common type of viral HLH in childhood. For non–EBV‐HLH, appropriate treatment of viral infection, followed by immunomodulatory agent(s) such as corticosteroids, intravenous immunoglobulin or cyclosporine A, is usually successful; however, recent SARS‐CoV‐2‐related HLH may become life‐threatening. EBV‐HLH may occur heterogeneously associated with the primary infection, with chronic active EBV infection or with underlying primary HLH. Although immunomodulatory agent(s) are effective in the majority of EBV‐HLH cases, management differs from that of non–EBV‐HLH because severe and refractory cases may require etoposide‐containing HLH‐1994/2004 regimens or other experimental agents. The novel agent, emapalumab (an anti–IFN‐γ monoclonal antibody) can be used to treat EBV‐HLH cases to avoid the risk of secondary malignancy due to etoposide. Finally, HSCT is required for refractory EBV‐HLH cases and can also be curative in some other cases.
Editorial: tegoprazan—the newest advance in the management of acid‐related diseases
Authors: Marcus Elizabeth A. , Pisegna Joseph R.
Published: June 2021

LINKED CONTENT

This article is linked to Cho et al paper. To view this article, visit https://doi.org/10.1111/apt.15865
The impact of genetic risk on liver fibrosis in non‐alcoholic fatty liver disease as assessed by magnetic resonance elastography
Authors: Ajmera Veeral , Liu Amy , Bettencourt Ricki , Dhar Debanjan , Richards Lisa , Loomba Rohit
Published: June 2021

Background

Variants in multiple genetic loci modify the risk of non‐alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.

Aim

To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.

Methods

This is a cross‐sectional analysis derived from a well‐characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE.

Results

Two hundred sixty‐four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1‐8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2‐18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19‐0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype‐age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a −0.41 kPa (95% CI: −0.76 to −0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis.

Conclusion

Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non‐invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.
Novel soluble guanylyl cyclase activators increase glomerular cGMP, induce vasodilation and improve blood flow in the murine kidney
Authors: Stehle Daniel , Xu Min Ze , Schomber Tibor , Hahn Michael G. , Schweda Frank , Feil Susanne , Kraehling Jan R. , Eitner Frank , Patzak Andreas , Sandner Peter , Feil Robert , Bénardeau Agnès
Published: June 2021

Background and Purpose

Generation of cGMP via NO‐sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress and oxidation of sGC to its haem‐free form, apo‐sGC. Apo‐sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with chronic kidney disease progression. We hypothesised that sGC activators, which activate apo‐sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function.

Experimental Approach

Two novel sGC activators, runcaciguat and BAY‐543, were tested on murine kidney. We measured cGMP levels in real time in kidney slices of cGMP sensor mice, vasodilation of pre‐constricted glomerular arterioles and RBF in isolated perfused kidneys. Experiments were performed at baseline conditions, under L‐NAME‐induced NO deficiency, and in the presence of oxidative stress induced by ODQ.

Key Results

Mouse glomeruli showed NO‐induced cGMP increases. Under baseline conditions, sGC activator did not alter glomerular cGMP concentration or NO‐induced cGMP generation. In the presence of ODQ, NO‐induced glomerular cGMP signals were markedly reduced, whereas sGC activator induced strong cGMP increases. L‐NAME and ODQ pretreated isolated glomerular arterioles were strongly dilated by sGC activator. sGC activator also increased cGMP and RBF in ODQ‐perfused kidneys.

Conclusion and Implication

sGC activators increase glomerular cGMP, dilate glomerular arterioles and improve RBF under disease‐relevant oxidative stress conditions. Therefore, sGC activators represent a promising class of drugs for chronic kidney disease treatment.

LINKED ARTICLES

This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma
Authors: Kim Hyun‐Yi , Li Shujin , Lee Dong‐Joon , Park Jin Hoo , Muramatsu Takashi , Harada Hidemitsu , Jung Young‐Soo , Jung Han‐Sung
Published: June 2021

Objectives

The treatment of ameloblastoma, an odontogenic epithelial tumour destroying jawbone, mainly depends on radical destructive resections. Other therapeutic options are limited by the characteristics of ameloblastoma, such as high recurrence rates and resistance to radiation and chemotherapy, which implies possible existence of cancer stem cells (CSCs) in ameloblastoma. Here, we identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population.

Methods

We investigated subpopulations of AM‐1 cell line and human ameloblastoma cells using immunocytochemistry and flow cytometry and the effects of Wnt signalling activators on the 2‐ and 3‐dimensional cultured ameloblastoma cells using molecular biological analyses.

Result

Among heterogenous ameloblastoma cells, small‐sized and round‐shaped cells were found to be proliferative and expressed a marker of dental epithelial stem cells, SRY‐box 2 (Sox2). Exogenous activation of Wnt signalling using glycogen synthase kinase 3β inhibitors, lithium chloride (LiCl) and valproic acid (VPA), increased the cell size and decreased proliferation of cells and expression of Sox2 in 2 dimensionally cultured AM‐1 and human primary ameloblastoma cells. Furthermore, the growth of 3 dimensionally cultured AM‐1 cells as suspended or embedded in gel was suppressed by treatment with Wnt signalling activators, VPA and CHIR99021, or antibodies to sclerostin, an antagonist of Wnt signalling.

Conclusion

We suggest that Wnt signalling activators are potential drug candidates to suppress CSCs in ameloblastoma.
Becoming society again: Reimagining new social contracts through Scandinavian creation theology
Authors: Gerle Elisabeth
Published: June 2021

This article focuses on bodily care as the basis of economy. Drawing on Luther and Scandinavian Creation Theology, with an emphasis on shared situatedness and society, I discuss contemporary threats to welfare states. Conservative arguments in favor of family and small communities, combined with charity, provide a cultural/religious alibi for a global “neoliberalism,” where citizens are replaced by customers, and where power and resources from professions are transferred to controllers, due to the logic of NPM. In a critical discussion with Hannah Arendt, I argue that we need a politics that reinforce and develop new social contracts, national as well as international, based on an inclusive demos. A pre‐political Lutheran ethos can give inspiration to act for the common good, transcending any homogenous ethnos. The local and national are crucial for sustaining body and mind. However, this is increasingly combined with global and planetary entanglements. Interdependency reveals itself as planetary, where disappearing rain forests, melting icebergs, and the ongoing extinction of species are threats to our shared future. Therefore, rather than emphasizing the individual as a consumer on a global market with neutral administrators administering control and obedience, new kinds of contracts are needed. Core values of the pre‐political, such as care for bodily life and minds, may, in collaboration with national and international political assemblies, develop a planetary consciousness able to act for the common good, for a global demos with structures of solidarity.
Quality appraisal of systematic reviews of interventions for children with cerebral palsy reveals critically low confidence
Authors: Kolaski Kat , Romeiser Logan Lynne , Goss Katherine D , Butler Charlene
Published: June 2021

Aim

To evaluate the methodological quality of recent systematic reviews of interventions for children with cerebral palsy in order to determine the level of confidence in the reviews’ conclusions.

Method

A comprehensive search of 22 databases identified eligible systematic reviews with and without meta‐analysis published worldwide from 2015 to 2019. We independently extracted data and used A Measurement Tool to Assess Systematic Reviews‐2 (AMSTAR‐2) to appraise methodological quality.

Results

Eighty‐three systematic reviews met strict eligibility criteria. Most were from Europe and Latin America and reported on rehabilitative interventions. AMSTAR‐2 appraisal found critically low confidence in 88% (n=73) because of multiple and varied deficiencies. Only 7% (n=6) had no AMSTAR‐2 critical domain deficiency. The number of systematic reviews increased fivefold from 2015 to 2019; however, quality did not improve over time.

Interpretation

Most of these systematic reviews are considered unreliable according to AMSTAR‐2. Current recommendations for treating children with CP based on these flawed systematic reviews need re‐evaluation. Findings are comparable to reports from other areas of medicine, despite the general perception that systematic reviews are high‐level evidence. The required use of current widely accepted guidance for conducting and reporting systematic reviews by authors, peer reviewers, and editors is critical to ensure reliable, unbiased, and transparent systematic reviews.

What this paper adds

Confidence was critically low in the conclusions of 88% of systematic reviews about interventions for children with cerebral palsy (CP).

Quality issues in the sample were not limited to systematic reviews of non‐randomized trials, or to those about certain populations of CP or interventions.

The inclusion of meta‐analysis did not improve the level of confidence in these systematic reviews.

Numbers of systematic reviews on this topic increased over the 5 search years but their methodological quality did not improve.
Patient perspectives in pediatric neurology: a critical shift in the paradigm of outcome measurement
Authors: Ronen Gabriel M , Rosenbaum Peter L , Streiner David L
Published: June 2021

This review explores children’s self‐reported outcome measurements in pediatric neurology. We examine the following questions: (1) What is meant by patient‐reported health, functioning, and quality of life outcomes? (2) How can patients express whether the interventions they receive do more good than harm? (3) Why and how should pediatric neurology patients help determine the outcomes of interest? (4) What tools and recommendations are available to evaluate the outcomes of interest? Applying patients’ perspectives across the processes of evaluation of medical interventions has become an important expectation. These developments, consistent with current healthcare goals, coincide with the evolution of pediatric neurology into a sophisticated diagnostic–interventional field that aims to prolong survival, decrease impairments and symptoms, and improve patients’ well‐being – the recognized essential endpoints of interest in all medicine.
Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions
Authors: Filippa Maria G. , Tektonidou Maria G. , Mantzou Aimilia , Kaltsas Gregory A. , Chrousos George P. , Sfikakis Petros P. , Yavropoulou Maria P.
Published: June 2021

Background

Iatrogenic adrenal insufficiency (AI) secondary to long‐term treatment with exogenous glucocorticoids (GC) is common in patients with systematic rheumatic diseases, including rheumatoid arthritis (RA). Moreover, a proportion of these patients is always in need of even small doses of glucocorticoids to maintain clinical remission, despite concomitant treatment with conventional and biologic disease‐modifying drugs.

Methods

We conducted a literature review up to December 2020 on (a) the incidence of AI in both long‐term GC‐treated and GC‐treatment naïve RA patients; (b) the potential effects of increased levels of circulating proinflammatory cytokines, as well as of chronic stress, in adrenocortical function in RA; (c) the circadian cortisol rhythm in RA; and (d) established and evolving methods of assessment of adrenocortical function.

Results

Up to 48% of RA patients develop glucocorticoid‐induced AI; however, predictors are not established, while adrenocortical dysfunction may also occur in GC‐treatment naïve RA patients. Experimental and clinical data have suggested that inadequate production of endogenous cortisol relative to enhanced clinical needs associated with the systemic inflammatory response, coined as the ‘disproportion principle’, may operate in RA. Although the underlying mechanisms are unknown, both proinflammatory cytokines and chronic stress may contribute the most in the adrenals hyporesponsiveness and the target tissue glucocorticoid resistance that have been described, but not systematically studied. A precise longitudinal assessment of endogenous cortisol production may be needed for optimal RA management.

Conclusion

Apart from iatrogenic AI, an intrinsically compromised adrenal reserve in RA may have a pathogenetic role and interfere with effective management, thus deserving further research.
Experience‐related enhancements in striatal temporal encoding
Authors: Bruce Robert A. , Weber Matthew A. , Volkman Rachael A. , Oya Mayu , Emmons Eric B. , Kim Youngcho , Narayanan Nandakumar S.
Published: June 2021

Temporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium spiny neurons (MSNs) via dorsal striatal microelectrode arrays in mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to “switch” response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time‐related ramping activity and response‐related activity increased with task experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time‐related ramping activity. Finally, we found that a subset of MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.
A cross‐sectional, prospective ocular motor study in 72 patients with Niemann‐Pick disease type C
Authors: Bremova‐Ertl Tatiana , Abel Larry , Walterfang Mark , Salsano Ettore , Ardissone Anna , Malinová Věra , Kolníková Miriam , Gascón Bayarri Jordi , Reza Tavasoli Ali , Reza Ashrafi Mahmoud , Amraoui Yasmina , Mengel Eugen , Kolb Stefan A. , Brecht Andreas , Bardins Stanislavs , Strupp Michael
Published: June 2021

Objective

To characterize ocular motor function in patients with Niemann‐Pick disease type C (NPC).

Methods

In a multicontinental, cross‐sectional study we characterized ocular‐motor function in 72 patients from 12 countries by video‐oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self‐paced saccades, smooth pursuit, and gaze‐holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC).

Results

Some 98.2% of patients generated vertical saccades below the 95% CI of the controls’ peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7–69.3]) downward versus 78.8°/s (65.9, [60.8–96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self‐paced ones. Gaze‐holding was normal. Ocular‐motor performance depended on the age of onset and disease duration.

Conclusions

This is the largest cohort of NPC patients investigated for ocular‐motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.
Measuring the intensive care experience: A cross‐sectional survey of patient and family experiences of critical care
Authors: Williams Helen , Gow Jeff , Rana Rezwanul , Rouse Alan , Chinthamuneedi Meher , Beccaria Gavin , Ralph Nicholas
Published: June 2021

Aims and Objectives

To report patient and family intensive care experiences using the Measuring the Intensive Care Experience (MICE) tool across two intensive care units (ICU).

Background

The patient and family experience of care is an important indicator for quality improvement of ICUs, yet few studies evaluate both patient and family experiences in relation to overall care quality as well as specifically measuring quality of medical care, nursing care and organisational care as well as overall experience of the quality of intensive care.

Design

A cross‐sectional survey.

Methods

A 23 item survey was administered to ICU patients and their family members across two ICUs, a regional 189‐bed hospital and a metropolitan 227‐bed hospital in Queensland, Australia. The response rate was 272 of 394 ICU patients (36.4%). STROBE guidelines were used in reporting this study.

Results

Findings indicate a highly positive overall experience of ICU care among patients and families. However, patients reported areas of unmet needs following their stay in ICU broadly related to (1) symptom management, education and information support, and (2) improving the incorporation of patient and family care ICU‐related shared decision‐making.

Conclusions

Supportive interventions are needed that target improve symptom management and inform and education ICU patients.

Relevance to clinical practice

The MICE survey facilitated the identification of a range of areas requiring quality improvement. Improving the integration of patients and families into shared decision‐making and support is a key aspect for quality improvement.