bluuebunny/crossref_metadata_2025 huggingface dataset:
The highly conserved stem-loop II motif is dispensable for SARS-CoV-2
Authors: Jiang Hongbing , Joshi Astha , Gan Tianyu , Janowski Andrew B , Fujii Chika , Bricker Traci L , Darling Tamarand L , Harastani Houda H. , Seehra Kuljeet , Chen Hongwei , Tahan Stephen , Jung Ana , Febles Binita , Blatter Joshua A , Handley Scott A , Parikh Bijal A , Wang David , Boon Adrianus CM
Published: March 2023

The stem-loop II motif (s2m) is a RNA structural element that is found in the 3’ untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growthin vitro, or growth and viral fitness in Syrian hamstersin vivo. We also compared the secondary structure of the 3’ UTR of wild type and s2m deletion viruses using SHAPE-MaP and DMS-MaPseq. These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3’UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2.

IMPORTANCE

RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contain functional structures to support virus replication, translation and evasion of the host antiviral immune response. The 3’ untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is a RNA structural element that is found in many RNA viruses. This motif was discovered over twenty-five years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growthin vitro, or growth and viral fitness in Syrian hamstersin vivo. We also observed no impact of the deletion on other known RNA structures in the same region of the genome. These experiments demonstrate that the s2m is dispensable for SARS-CoV-2.
Promoting a resilient food supply chain model facing disruptions associated with black sky hazards
Authors: Orengo Serra Karen Lizzette , Sánchez-Jauregui María
Published: March 2023

Purpose

This study explores how small- and medium-sized enterprises (SMEs) in the food industry in Puerto Rico can enhance resilience to cope with critical infrastructure (CI) collapse due to natural disasters. This study aims to validate the food supply chain (FSC) resilience model for SMEs in rural areas.

Design/methodology/approach

This study used qualitative in-depth interviews to gather data and a coding process for the analysis. The participants were members of the FSC located in the municipality of Adjuntas and nearby towns in Puerto Rico. For this study, the sample participants selected to conduct the interviews were the farmers, producers and retailers.

Findings

The results show the importance of local CI backup, networks and flexibility among FSC members in alternating supply chain logistics and distribution. Other transportation modes include drone pilots, aerial and land, facilities to transport and deliver merchandise and positioning farmers and producers as important players in the FSC.

Originality/value

A modified FSC resilience model from previous research is presented to include SMEs located in highly vulnerable remote zones, where access to resources is limited after a disruptive event, and a typology of enterprises with local CI backup according to their level of adoption of resilient practices. This study contributes to enhancing resilience and mitigating the vulnerabilities of SMEs after the CI collapses.
Music sentiment classification based on an optimized CNN-RF-QPSO model
Authors: Tian Rui , Yin Ruheng , Gan Feng
Published: March 2023

Purpose

Music sentiment analysis helps to promote the diversification of music information retrieval methods. Traditional music emotion classification tasks suffer from high manual workload and low classification accuracy caused by difficulty in feature extraction and inaccurate manual determination of hyperparameter. In this paper, the authors propose an optimized convolution neural network-random forest (CNN-RF) model for music sentiment classification which is capable of optimizing the manually selected hyperparameters to improve the accuracy of music sentiment classification and reduce labor costs and human classification errors.

Design/methodology/approach

A CNN-RF music sentiment classification model is designed based on quantum particle swarm optimization (QPSO). First, the audio data are transformed into a Mel spectrogram, and feature extraction is conducted by a CNN. Second, the music features extracted are processed by RF algorithm to complete a preliminary emotion classification. Finally, to select the suitable hyperparameters for a CNN, the QPSO algorithm is adopted to extract the best hyperparameters and obtain the final classification results.

Findings

The model has gone through experimental validations and achieved a classification accuracy of 97 per cent for different sentiment categories with shortened training time. The proposed method with QPSO achieved 1.2 and 1.6 per cent higher accuracy than that with particle swarm optimization and genetic algorithm, respectively. The proposed model had great potential for music sentiment classification.

Originality/value

The dual contribution of this work comprises the proposed model which integrated two deep learning models and the introduction of a QPSO into model optimization. With these two innovations, the efficiency and accuracy of music emotion recognition and classification have been significantly improved.
How high-involvement HRM practices motivate knowledge sharing and innovation: the role of market turbulence
Authors: Le Hung Manh , Le Phong Ba
Published: March 2023

Purpose

The purpose of this paper is to examine the impact of high-involvement human resource management (HRM) practices on innovation capabilities via the mediating role of knowledge sharing (KS) behaviors. This paper also investigates the potential moderating role of market turbulence in fostering the influence of KS behaviors on two forms of innovation capability, namely exploitative and exploratory innovation.

Design/methodology/approach

Analysis of moment structures and structural equation modeling are applied to examine the correlation among the latent constructs based on the survey data collected from 125 manufacturing and service firms.

Findings

The findings of this study support the mediating role of KS behaviors in the relationship between high-involvement HRM practices and aspects of innovation capability. It highlights the important role of market turbulence in strengthening the influence of KS on exploitative and exploratory innovation.

Research limitations/implications

Future research should investigate the impact of high-involvement HRM practices on innovation capability under the moderating effects of organizational variables, such as perceived organizational support, to bring better understanding on a new mechanism to pursuit innovation.

Originality/value

The paper significantly contributes to increasing knowledge and insights into the correlation between high-involvement HRM practices and specific forms of innovation. The understanding on the mediating role of KS behaviors and the moderating role of market turbulence contribute to advancing the body of knowledge of HRM and innovation theory.
Learning in the workplace: evidence on the role of behavioural job crafting on fostering self-perceived employability
Authors: Sartori Riccardo , Tommasi Francesco , Ceschi Andrea , Noventa Stefano , Zene Mattia
Published: March 2023

Purpose

Given the instability and volatility of the labour market and the global talent scarcity, placing more attention on job employability is fundamental. In this context, the literature has already extensively examined employability as a crucial individual aspect, identifying some significant antecedents, including the applicability of training on the job. The present study aims to examine the impact that teaching employees to craft their job may have on the levels of applicability of training and if, in turn, this improves self-perceived employability.

Design/methodology/approach

The authors involved three private organizations that followed three workshops on job crafting behaviour. To empirically assess the intervention, the authors asked participants of the workshop to complete four quantitative diaries on a weekly basis, i.e. one per week, one before the intervention and three after the intervention. The diaries comprised measures of job crafting behaviours, applicability of training and self-perceived employability.

Findings

Multi-level analysis of data collected provided support to the positive associations between job crafting behaviour and self-perceived employability with the mediating effect of applicability of training. Notably, the applicability of training improves when individuals search for challenges, which indirectly affects perceived employability in terms of organizational sense.

Research limitations/implications

In the present study, no control group was used with which the results of our intervention could be compared. However, this does not affect the overall results, given the amount of intraindividual variability.

Originality/value

The paper proposes initial avenues for promoting employability at work via the use of behavioural job crafting intervention.
Diffusion of intellectual property knowledge in Zimbabwean universities: tools, programmes and strategies
Authors: Ngwenya Sibongile , Onyancha Omwoyo Bosire
Published: March 2023

Purpose

This paper aims to explore the diffusion of Intellectual Property (IP) knowledge in universities in Zimbabwe. Specifically, the study examines the tools, policies, programmes and unique strategies used by the universities.

Design/methodology/approach

The paper reports the findings of a survey that was conducted on a population of lecturers (1,546), research officers (RO) (11), IP officer (1), faculty librarians (FLs) (27) and final year undergraduate students (9,224) at universities in Zimbabwe. Questionnaires were administered to the lecturers and students while interviews were administered to the IP officer, ROs and FLs. Data analysis comprised the use of Google forms and Microsoft Excel software.

Findings

The findings reveal diffusing IP knowledge in Zimbabwean universities involves mainly the use of policies and regulations, library web pages, workshops, although not specifically on IP, presentations on IP in the university, advice and guidance services and IP lectures/teaching.

Research limitations/implications

This study presents the IP situation in Zimbabwe and its findings may be applied to Africa and other developing countries.

Practical implications

This study endorses IP as a national issue and suggests a benchmark for diffusing knowledge on IP in Zimbabwean universities.

Originality/value

This study acknowledges the multi-disciplinary nature of IP and should lead to all university students graduating with adequate knowledge on IP.
Towards a better measure of productivity in India: a case of chemical and chemical products industry
Authors: Valiyattoor Vipin , Bhandari Anup Kumar
Published: March 2023

Purpose

A brief review of earlier studies on the productivity scenario of Indian industry shows that most of the studies analysed are confined to either parametric approach or growth accounting approach of measuring productivity. At the same time, the few studies based on the non-parametric [namely, Malmquist productivity index (MPI)] overlook the returns to scale conditions as well as the bias involved in the estimation of distance functions. Given this backdrop, this study aims to provide a robust measure of productivity, which considers the returns to scale assumptions and correct for the bias involved in the estimation of productivity.

Design/methodology/approach

This study empirically tests for the returns to scale that exists in the chemical and chemical products industry in India. The test result suggests that Ray and Desli (1997) approach of MPI is the appropriate one for the present context. Initially, the conventional Ray and Desli (1997) estimation and decomposition of MPI for the period 2001 to 2017 is being used. Subsequently, to correct for the bias in the estimation of efficiency scores used for the estimation of MPI, the bootstrapping algorithm of Simar and Wilson (2007) has been extended into the context of MPI estimation.

Findings

The results from the conventional Malmquist productivity estimates testifies to an improvement of total factor productivity (TFP) in seven out of 16 years under consideration. On the contrary, TFP growth is recorded only in the four years throughout the period after the bias correction. A greater discrepancy between the two measures has been found in the case of scale change factor component of MPI.

Practical implications

The technical change (TC) component positively influences TFP, whereas scale change factor (SCF) deteriorates the TFP condition of this industry. It will be appropriate for these firms to identify and operate under an optimal scale of operation, along with reaping the benefits of technological change. From a methodological perspective, researchers should consider the potential bias that arise in estimation of TFP and use a larger sample whenever possible.

Originality/value

This paper brings in a new perspective to the existing literature on industrial productivity. As against earlier studies, this study empirically tests the returns to scale of the sector under consideration and uses the most appropriate approach to measure productivity. The effect of sampling bias on TFP and its components is analysed.
Modeling duration of building renovation projects
Authors: Lawal Haruna Sa'idu , Ahmadu Hassan Adaviriku , Abdullahi Muhammad , Yamusa Muhammad Aliyu , Abdulrazaq Mustapha
Published: March 2023

Purpose

This study aims to develop a building renovation duration prediction model incorporating both scope and non-scope factors.

Design/methodology/approach

The study used a questionnaire to obtain basic information relating to identified project scope factors as well as information relating to the impact of the non-scope factors on the duration of building renovation projects. The study retrieved 121 completed questionnaires from construction firms on tertiary education trust fund (TETFund) building renovation projects. Artificial neural network was then used to develop the model using 90% of the data, while mean absolute percentage error was used to validate the model using the remaining 10% of the data.

Findings

Two artificial neural network models were developed – a multilayer perceptron (MLP) and a radial basis function (RBF) model. The accuracy of the models was 86% and 80%, respectively. The developed models’ predictions were not statistically different from those of actual duration estimates with less than 20% error margin. Also, the study found that MLP models are more accurate than RBF models.

Research limitations/implications

The developed models are only applicable to projects that suit the characteristics and nature of the data used to develop the models. Hence, models can only predict the duration of building renovation projects.

Practical implications

The developed models are expected to serve as a tool for realistic estimation of the duration of building renovation projects and thus, help construction project managers to effectively plan and manage it.

Social implications

The developed models are expected to serve as a tool for realistic estimation of the duration of building renovation projects and thus, help construction project managers to effectively plan and manage it; it also helps clients to effectively benchmark projects duration and contractors to accurately estimate duration at tendering stage.

Originality/value

The study presents models that combine both scope and non-scope factors in predicting the duration of building renovation projects so as to ensure more realistic predictions.
Organisational drivers of performance in mental health providers
Authors: Mannion Russell , Konteh Frederick Hassan , Jacobs Rowena
Published: March 2023

Purpose

This study aims to compare and contrast the core organisational processes across high and low performing mental health providers in the English National Health Service (NHS).

Design/methodology/approach

A multiple case study qualitative design incorporating a full sample of low and high performing mental health providers.

Findings

This study suggests that the organisational approaches used to govern and manage mental health providers are associated with their performance, and the study’s findings give clues as to what areas might need attention. They include, but are not limited to: developing appropriate governance frameworks and organisational cultures, ensuring that staff across the organisation feel “psychologically safe” and able to speak up when they see things that are going wrong; a focus on enhancing quality of services rather than prioritising cost-reduction; investing in new technology and digital applications; and nurturing positive inter-organisational relationships across the local health economy.

Originality/value

Highlights considerable divergence in organisation and management practices that are associated with the performance of mental health trusts in the English NHS
Worker exploitation in the gig economy: the case of dark kitchens
Authors: Giousmpasoglou Charalampos , Ladkin Adele , Marinakou Evangelia
Published: March 2023

Purpose

The emergence of dark kitchens in the restaurant industry is a contemporary phenomenon, arising most recently in the context of the so-called gig economy. This new business model flourished during the coronavirus disease 2019 (COVID-19) pandemic on a global scale. Despite dark kitchens' popularity, considerable negative publicity exists in the news related to poor working conditions. To highlight this new phenomenon, this paper explores the existing literature on worker exploitation in dark kitchens in the context of the gig economy.

Design/methodology/approach

A systematic literature review of hospitality and tourism databases generated 1,430 articles, of which 18 met the authors' inclusion criteria for the final analysis, and 1,030 anecdotal sources, of which 47 were included. Thematic analysis was used to identify the key themes and summarise the findings to be used for further studies.

Findings

The popularity of dark kitchens as a business model is premised on the fact that dark kitchens' dramatically reduces the operational cost and increases productivity. On the other hand, the working conditions and contractual agreements of the gig workers in dark kitchens raise several questions from operational, legal and ethical perspective. These poor working conditions create the conditions for worker exploitation and further damage the sector's image.

Practical implications

This study advocates that companies and managers are responsible for implementing and monitoring fair working conditions in dark kitchens. The existence of poor working conditions increases employee turnover and, overall, affects the industry's reputation.

Originality/value

This explorative study provides insights into the working conditions and contractual agreements in dark kitchens. Currently, there is no other study (empirical or conceptual) to shed light on the working practices. The authors hope this study will trigger further discussion and empirical research in this field.
Spanish CEOs' perceptions in complex situations: an analysis from a gender perspective
Authors: Expósito-Langa Manuel , Estelles-Miguel Sofia , Ribes-Giner Gabriela , Rueda-Armengot Carlos
Published: March 2023

Purpose

The aim of this paper is to provide empirical evidence of discrepancies in certain management-related business factors in complex situations from a gender perspective.

Design/methodology/approach

The study examined whether there are any differences in the characteristics of Spanish companies run by men and women and how male and female chief executive officers (CEOs) perceive critical situations such as the COVD-19 pandemic. To answer the research questions, the survey carried out by the Ibero-American Observatory of Small and Medium-Sized Enterprises (FAEDPYME) in 2021 was used. The final sample consisted of a total of 1,532 small and medium-sized enterprises.

Findings

The main results show that female CEOs are more likely to have a university education than male CEOs, but they run smaller companies in Spain. On the other hand, they are more risk averse and evaluate the impact of complex and risky situations more negatively.

Research limitations/implications

The findings open up new research questions. This is a cross-sector study, but are there differences in behaviour between sectors? The view of the crisis is negative, but which types of companies have been strengthened?, finally, do other countries have similar results?

Originality/value

The originality and value of this document lies in the fact that it makes an interesting contribution to the open debate on the management of complex situations from a gender perspective.
Rating pressure factors affecting logistics systems during the pandemic and the ideal logistic decision selection under the Pythagorean fuzzy environment
Authors: Mishra Arunodaya Raj , Ergün Mustafa , Okoth Basil Oluoch , Korucuk Selçuk , Aytekin Ahmet , Karamaşa Çağlar
Published: March 2023

Purpose

Due to the current pandemic, the importance of logistics functions and decisions is well understood both at the level of companies and users. Logistics systems and related decisions are of vital importance in making supply chains effective, efficient and without disruption. Logistic pressure factors may emerge at different points along the logistics process, and given the role of logistics decisions as one of the important indicators of competitiveness, the determination of the logistics pressures that are likely to increase the costs of business, and their causative factors are a vital aspect of the logistics decision-making process. The study aims to provide assistance in the selection of the most ideal logistics decision by ranking the pressure factors affecting the logistics system, especially during the pandemic period for logistics enterprises operating in Ordu and Giresun provinces and which have a corporate identity.

Design/methodology/approach

In this study, it is aimed to make the most ideal logistics decision selection by ranking the pressure factors affecting the logistics system, especially during the pandemic period for the logistics enterprises operating in Ordu and Giresun provinces and having a corporate identity. For that purpose interval-valued Pythagorean fuzzy (IVPF)–analytic hierarchy process (AHP) based combinative distance-based assessment (CODAS) methodology was used. Additionally sensitivity and comparison analysis were discussed.

Findings

Competitive pressure was found as the most important pressure factor affecting the logistics system during the pandemic period. Change in regulatory rules was the pressure factor found to have the least effect on the logistics system. Using the weights of logistics pressure factors, “Operational Decisions” was found to be the most ideal logistics decision selection.

Research limitations/implications

The findings provide support for the evaluation of logistical pressures and decision options by presenting a decision model capable of processing ambiguous information. During a pandemic or similar period, the study assists decision makers in determining a new route. The findings will also call business managers' attention to logistical pressure factors and lead them toward more realistic and feasible practices in the logistics decision-making process.

Originality/value

This study provided an effective and applicable solution to a decision-making problem in the logistics sector including logistics pressure factors and the selection of logistics decisions. In this context, a methodology was presented that will allow businesses to self-evaluate their own logistics pressure factors and the selection of optimal solutions.
A MAD7‐based genome editing system for Escherichia coli
Authors: Mund Markus , Weber Wadim , Degreif Daniel , Schiklenk Christoph
Published: March 2023

A broad variety of biomolecules is industrially produced in bacteria and yeasts. These microbial expression hosts can be optimized through genetic engineering using CRISPR tools. Here, we designed and characterized such a modular genome editing system based on the Cas12a‐like RNA‐guided nuclease MAD7 in Escherichia coli. This system enables the efficient generation of single nucleotide polymorphisms (SNPs) or gene deletions and can directly be used with donor DNA from benchtop DNA assembly to increase throughput. We combined multiple edits to engineer an E. coli strain with reduced overflow metabolism and increased plasmid yield, highlighting the versatility and industrial applicability of this approach.
Secukinumab‐induced IgA vasculitis in a patient with psoriatic arthritis
Authors: Ozince Rana Berru , Ak Tumay , Erzin Yusuf Ziya , Melikoglu Melike , Seyahi Emire
Published: March 2023

Objectives

Secukinumab (SEC) is an effective and widely used drug in psoriatic disease and axial spondyloarthritis. However, SEC has been found to be associated with inflammatory conditions and vasculitis. These inflammatory adverse effects may complicate the treatment of underlying disease, and clinicians may experience difficulties in recognizing and managing this unusual condition.

Case Report

A man aged 56 years with psoriatic disease refractory to conventional disease‐modifying antirheumatic drugs was given adalimumab for 6 weeks, then switched to SEC when his psoriatic lesions were exacerbated. After 3 weeks of SEC treatment, he developed systemic features of IgA vasculitis while his skin lesions and arthritis persisted.

Conclusions

Although SEC‐related inflammatory adverse events, including vasculitis, are rarely encountered in clinical practice, it is essential to recognize them because they can be mistaken as a component of the underlying inflammatory disease. In addition, the dramatic improvement in many cases after the cessation of SEC underlines the importance of making an accurate diagnosis. Pathogenetically, these adverse events are likely to be paradoxical reactions, except for SEC‐induced inflammatory bowel diseases. However, in many aspects, their pathogenesis is controversial and needs clarification.
The roles of risk preferences, selection, and uncertain returns on land contracts
Authors: Lee Jun Yeong , Durbahn Grant , Orazem Peter F. , Zhang Wendong
Published: March 2023

Using panel data on a statistically representative sample of Iowa farmland parcels from 1997 to 2017, we analyze the factors determining whether land is farmed by the owner or rented out under a cash rent or crop share contract. The landowner's decision to rent or operate the land depends on the distribution of expected net returns to the land, and so estimates of the factors affecting rental terms will be biased if the sample only includes rental contracts and excludes the owner‐operator. Land with higher mean and/or lower variance of expected net returns is most likely to be rented out. Participants in the rental market will include the most risk‐averse landowners and the least risk‐averse tenants, while the least risk‐averse landowners operate their own land. Our empirical results suggest that the rising use of cash rent contracts and declining incidence of owner‐operation and crop‐share rental contracts is consistent with falling coefficient of variation in expected net returns per acre.
Does variation in plant diversity and abundance influence browsing intensity in black rhinos?
Authors: Sisya Emanuel S. , Moyo Francis , Martin Emanuel H. , Munishi Linus K.
Published: March 2023

Variations in forage availability, selection and preferences can lead to intense foraging competition and depletion of food consequently lowering diet quality and population performance of black rhino species. This study investigated seasonal variations in rhino diet, foraging, preference and browsing intensity and how this is influenced by plant diversity and availability in Mkomazi National Park (MKONAPA). Fifty‐eight square grids were randomly selected in each season, and plots were laid for vegetation assessment during wet and dry seasons in the sanctuary. Browsed species by rhinos were compared with rhino feeding data from fourteen rhino range areas within Africa. More than 85% of species edible in MKONAPA were similar to those in rhino range areas. Acalypha ornata, Grewia similis and Commiphora africana were highly utilised specie in both seasons. Diversity and abundance of consumed browses decreased towards the dry season while browsing intensity increased with forage preference in both seasons and was prominent when browse availability was low in dry seasons. Our study established seasonal variation in dietary composition, browsing intensity and preferences for black rhinos. We suggest establishing nutritional composition of preferred forages, assessing density of competitor browsers, translocating excess rhinos or expanding the sanctuary to meet the recommended ecological carrying capacity.
Tramadol as a patient‐initiated component of multimodal pain management: a pilot study of 364 lower limb arthroplasty cases
Authors: Wu Yu Wen (Kevin) , Mitchell David James
Published: March 2023

Background

Multimodal therapy (MMT) for analgesia following joint arthroplasty continues to reduce cost and the requirement of strong opioids post‐operatively. Tramadol immediate release is an important MMT component providing synergistic pain relief via dual μ‐opioid agonism and serotonin and noradrenaline reuptake inhibition. Case reports have shown tramadol when combined with antidepressants cause serotonin syndrome, but this has yet to be demonstrated in larger studies. We undertook a pilot study assessing the functional outcomes and incidence of side effects associated with tramadol in lower limb arthroplasty patients with a focus on those taking concomitant antidepressants.

Methods

Primary and revision hip and knee arthroplasties performed in 2018–2019 by a senior surgeon were included (n = 364). Patient records were assessed to determine pain scores, length of hospitalization, prescription of tramadol and antidepressants, self‐reported side effects and previous adverse reactions associated with tramadol.

Results

Nine‐five percentage of patients had been prescribed tramadol, and 16% had concurrent prescription of tramadol and one or more antidepressants. The total rate of adverse effects associated with tramadol before and during the study was 7% (n = 25) including two cases of concomitant tramadol and antidepressant use. For patients on tramadol, median 2‐week post‐operative pain score was 1.5 (IQR 1–2.5) out of 10 and hospitalization length was 1 (IQR 1–2) days.

Conclusion

Tramadol immediate release appears to be well tolerated among our patient population with no significantly increased prevalence of side effects when co‐administered with low and moderate dose antidepressants.
A method to reduce the width of confidence intervals by using a normal scores transformation
Authors: O’Gorman T. W.
Published: March 2023

In stating the results of their research, scientists usually want to publish narrow confidence intervals because they give precise estimates of the effects of interest. In many cases, the researcher would want to use the narrowest interval that maintains the desired coverage probability. In this manuscript, we propose a new method of finding confidence intervals that are often narrower than traditional confidence intervals for any individual parameter in a linear model if the errors are from a skewed distribution or from a long‐tailed symmetric distribution. If the errors are normally distributed, we show that the width of the proposed normal scores confidence interval will not be much greater than the width of the traditional interval. If the dataset includes predictor variables that are uncorrelated or moderately correlated then the confidence intervals will maintain their coverage probability. However, if the covariates are highly correlated, then the coverage probability of the proposed confidence interval may be slightly lower than the nominal value. The procedure is not computationally intensive and an R program is available to determine the normal scores 95% confidence interval. Whenever the covariates are not highly correlated, the normal scores confidence interval is recommended for the analysis of datasets having 50 or more observations.
Monitoring paxillin in astrocytes reveals the significance of the adhesion G protein coupled receptor VLGR1/ADGRV1 for focal adhesion assembly
Authors: Güler Baran E. , Linnert Joshua , Wolfrum Uwe
Published: March 2023

VLGR1/ADGRV1 (very large G protein‐coupled receptor‐1) is the largest adhesion G protein‐coupled receptor (aGPCR). Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome, the most common form of deaf‐blindness, and also with epilepsy in humans and mice. VLGR1 is expressed almost ubiquitously but is mainly found in the CNS and in the sensory cells of the eye and inner ear. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FAs) serving as a metabotropic mechanoreceptor controls cell spreading and migration. FAs are highly dynamic and turnover in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washouts and live cell imaging of paxillin‐DsRed2 consistently showed that FA disassembly was not altered, but de novo assembly of FA was significantly delayed in Vlgr1‐deficient astrocytes, indicating that VLGR1 is enrolled in FA assembly. In FRAP experiments, recovery rates were significantly reduced in Vlgr1‐deficient FAs, indicating reduced turnover kinetics in VLGR1‐deficient FAs. We showed that VLGR1 regulates cell migration by controlling the FA turnover during their assembly and expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1.
Structure–activity relationship of GPR15L peptide analogues and investigation of their interaction with the GPR15 receptor
Authors: Deng Yufang , Perez Almeria Claudia V. , van Gijzel Lieke , Schaller Kay , Vedel Line , Gloriam David E. , Ulven Trond , Bräuner‐Osborne Hans
Published: March 2023

The 57‐mer full‐length GPR15L(25‐81) peptide has been identified as the principal endogenous agonist of the G protein‐coupled receptor GPR15. Its main activity resides in the C‐terminal 11‐mer GPR15L(71‐81), which has full efficacy but ~40‐fold lower potency than the full‐length peptide. Here, we systematically investigated the structure–activity relationship of GPR15L(71‐81) by truncations/extensions, alanine‐scanning, and N‐ and C‐terminal capping. The synthesized peptide analogues were tested at GPR15 stably expressed in HEK293A cells using a homogenous time‐resolved Förster resonance energy transfer‐based Gi cAMP functional assay. We show that the C‐terminal α carboxyl group and the residues Leu78, Pro75, Val74, and Trp72 are critical for receptor interaction and contribute significantly to the peptide potency. Furthermore, we tested the ability of GPR15L(71‐81), C‐terminally amidated GPR15L(71‐81), and GPR15L(25‐81) to activate the three GPR15 receptor mutants in a bioluminescence resonance energy transfer‐based G protein activation assay. The results demonstrate that the Lys192 and Glu272 residues in GPR15 are important for the potency of the GPR15L peptide. Overall, our study identifies critical residues in the peptide and receptor sequences for future drug design.
The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopenia
Authors: Liu Jing , Zhang Yuelun , Li Zhuo , Li Ji , Zhang Lejia , Song Yuqing , Lyu Zichao , Wang Changyan , Gou Lijuan , Quan Meiying , Xiao Juan , Song Hongmei
Published: March 2023

Antinuclear antibody (ANA) can be positive in children with primary immune thrombocytopenia (ITP), but the effect of ANA titre and its variation on outcomes of children with primary ITP remains unclear. Here, we conducted a single‐centre retrospective cohort study of children with primary ITP at the Peking Union Medical College Hospital in China. A total of 324 children with primary ITP included in this study were followed for a median time of 25 months. In this cohort, 39.2% had an ANA titre of 1:160 or higher. Results from a generalized estimating equation model revealed that patients with higher ANA titres had lower platelet counts at onset but a higher recovery rate of subsequent platelet counts. Results from Cox regression models adjusted for potential confounders revealed that patients with ANA titres of 1:160 or more were more likely to develop to autoimmune disease (AID) than those without, and the risk of AID development increased with the rise of ANA titres (p value for trend less than 0.001). These data highlight the predictive value of ANA titre for platelet counts and the risk of AID development in children with primary ITP.
An illuminating piece in the jigsaw of Hodgkin lymphoma risk stratification
Authors: Shankar Ananth , Bomanji Jamshed
Published: March 2023

The management strategy of classical Hodgkin lymphoma in children is focussed on maximising therapeutic efficacy while minimising treatment‐related toxicity via a risk‐adapted and response‐based approach. By using volumetric PET parameters, the report of Milgrom and her colleagues shows that combining pretreatment volumetric quantitative PET data with the early response assessment PET2 scan improved risk stratification in children with high‐risk classical Hodgkin lymphoma treated on the COG AHOD0831 trial.

Commentary on: Milgrom et al. Baseline metabolic tumor burden improves risk stratification in Hodgkin lymphoma: A Children's Oncology Group Study. Br J Haematol 2023;201:1192–1199.
“I'm a man now”: Using Narrative Therapy to support an adult with Down syndrome transition to a new life
Authors: Lau‐Zhu Alex , Mann Judith
Published: March 2023

Background

Residential transitions have long been recognised as challenging for people with learning disabilities and can be packed with problem stories. Narrative Therapy practices have the potential to centre the voice of people with learning disabilities; to enable alternative stories to be told; and to shine a light on their own and their support system's resources for change.

Methods

Colin, a 36‐year‐old man with Down syndrome and a learning disability, met with the first author for nine sessions. Narrative Therapy practices (also drawing on systemic ideas) were used, including the Tree of Life, Outsider Witness Practice, Therapeutic Documentation and Definitional Ceremony. Feedback from Colin and the staff team was gathered through qualitative and quantitative means.

Findings

Colin was keen to share his life stories and explored ideas about his “new life”, wanting to “stay strong” and “stay happy”. Staff noted an improvement in household stress and perceived ability to support Colin. An improvement in quality of life was also demonstrated with a self‐report questionnaire.

Conclusions

By acknowledging the power of language, narrative practices offer tools to help people with learning disabilities and their support system in making sense of and navigating important life transitions.
S2k‐Leitlinie – Merkelzellkarzinom – Update 2022
Authors: Becker Jürgen C. , Beer Ambros J. , DeTemple Viola K. , Eigentler Thomas , Flaig Michael J. , Gambichler Thilo , Grabbe Stephan , Höller Ulrike , Klumpp Bernhard , Lang Stephan , Pföhler Claudia , Posch Christian , Prasad Vikas , Schlattmann Peter , Schneider‐Burrus Sylke , Ter‐Nedden Jan , Terheyden Patrick , Thoms Kai , Vordermark Dirk , Ugurel Selma
Published: March 2023

Das Merkelzellkarzinom (MCC, ICD‐O M8247/3) ist ein seltener, maligner, primärer Hauttumor mit epithelialer und neuroendokriner Differenzierung. Die Tumorzellen teilen viele morphologische, immunhistochemische und ultrastrukturelle Eigenschaften mit den Merkel‐Zellen der Haut. Die Ursprungszelle (cell of origin) des MCC ist dennoch unklar. Das MCC imponiert klinisch als ein rötlich bis violett farbiger kugeliger Tumor mit glatter glänzender Oberfläche und weicher bis prall‐elastischer Konsistenz, der in der Regel ein schnelles Wachstum aufweist. Spontane, häufig auch komplette Regressionen des Tumors werden beobachtet. Diese wahrscheinlich immunologisch‐vermittelten Regressionen erklären die Fälle, bei denen zum Zeitpunkt der Erstdiagnose nur Lymphknoten‐ oder Fernmetastasen gefunden werden und warum der Tumor auch in weit fortgeschrittenen Stadien sehr gut auf immunmodulierende Therapien anspricht. Aufgrund seiner Aggressivität, der in der Regel gegebenen Indikation zur Schildwächterlymphknotenbiopsie, der zu evaluierenden Indikation adjuvanter Therapien, sowie der Komplexität der notwendigen Diagnostik sollte das Vorgehen bereits bei Erstdiagnose durch ein interdisziplinäres Tumorboard festgelegt werden.
Biomechanische Eigenschaften transgener Haut nach lebensrettender Regeneration der Epidermis durch kombinierte Gen‐ und Stammzelltherapie
Authors: Yeni Burcu , Dermietzel Alexander , Varnava Charalampos , Wiebringhaus Philipp , Aitzetmueller Matthias , Klietz Marie‐Luise , Hirsch Tobias , Kueckelhaus Maximilian
Published: March 2023

Hintergrund

Im Jahr 2017 beschrieben wir die erste lebensrettende Regeneration einer nahezu vollständigen Epidermis durch kombinierte Gen‐ und Stammzelltherapie. Kürzlich berichteten wir über eine ausgezeichnete Langzeitstabilität dieser transgenen Epidermis. Zur Charakterisierung der aus diesem experimentellen Ansatz resultierenden Hautqualität und ihrer potenziellen Anwendung bei anderen Erkrankungen berichten wir hier über die Langzeitergebnisse hinsichtlich der biomechanischen Eigenschaften der Haut.

Patienten und Methodik

Eine detaillierte Analyse der biomechanischen Eigenschaften, einschließlich Hautelastizität, Anisotropie und Friktion, wurde an mehreren Körperstellen 24, 36 und 60 Monate nach der ersten Transplantation durchgeführt. Zunächst wurden die Körperstellen mit den stabilen nicht‐transgenen Bereichen verglichen. Im Weiteren erfolgte ein Vergleich mit einer Kontrollgruppe aus 13 hautgesunden Probanden. Die Messung von Hautelastizität, Anisotropie und Friktion erfolgte mit nichtinvasiven Messungen.

Ergebnisse

Die biomechanischen Hauteigenschaften der transgenen Epidermis zeigten ähnliche Ergebnisse im Vergleich zur verbleibenden nicht‐transgenen Haut und zur gesunden Kontrollgruppe. Die Hautelastizität zeigte vergleichbare Ergebnisse wie bei der Kontrollgruppe. Die Friktion der Haut nahm sowohl in den transgenen als auch in den nicht‐transgenen Bereichen im Vergleich zur Kontrollgruppe ab.

Schlussfolgerungen

Die neuartige kombinierte Gen‐ und Stammzelltherapie zeigt hervorragende funktionelle Langzeitergebnisse der vollständig regenerierten transgenen Epidermis. Wegen dieser Ergebnisse sollten weitere Anwendungen dieser Technologie, wie die Behandlung von Verbrennungen, Gegenstand zukünftiger Forschung sein.
Seborrhoische Keratosen
Authors: Barthelmann Sara , Butsch Florian , Lang Berenice M. , Stege Henner , Großmann Bernd , Schepler Hadrian , Grabbe Stephan
Published: March 2023

Die seborrhoische Keratose (SK) ist der häufigste gutartige epidermale Tumor in der klinisch‐dermatologischen Praxis. Diese Übersicht fasst den Kenntnisstand zu Klinik, Histologie, Epidemiologie, Pathogenese und Therapie von SK zusammen. Anhand des klinischen und histologischen Bildes unterscheidet man verschiedene Typen der SK. Es wird vermutet, dass mehrere Faktoren, darunter das Alter, eine genetische Prädisposition und möglicherweise auch die Exposition gegenüber ultravioletter Strahlung mit der Entstehung der Tumoren in Verbindung stehen. Die Läsionen können an allen Körperregionen auftreten, mit Ausnahme der Handflächen und Fußsohlen, die häufigsten Stellen sind jedoch das Gesicht und der obere Rumpf. Die Diagnose erfolgt meistens klinisch, in manchen Fällen unter Zuhilfenahme eines Dermatoskops oder durch Biopsie. Viele Patienten bevorzugen es, SK aus kosmetischen Gründen zu entfernen, obwohl keine medizinische Indikation hierzu vorliegt. Bei den Behandlungsmöglichkeiten wird zwischen chirurgischen, chirurgisch‐destruierenden (Laser, Elektrodesikkation/‐kaustik, Kryotherapie) und topisch‐medikamentösen Verfahren unterschieden. Letztere sind aktuell in klinischer Entwicklung. Die Behandlung wird abhängig vom klinischen Bild und der Präferenz des Patienten individuell angepasst.
Dermatologische Bewertung von Hautveränderungen nach COVID‐19‐Impfung – eine monozentrische Studie in Deutschland
Authors: Wang Rosi , Mathes Sonja , Claussen Carla , Biedermann Tilo , Brockow Knut
Published: March 2023

Hintergrund und Ziele

Hautreaktionen nach COVID‐19‐Impfung werden in dieser Studie präzise mitsamt Schweregrad, Verlauf, Therapie, auslösender Impfstoffe, allergologischer Abklärung und der Verträglichkeit der Folgeimpfung untersucht.

Patienten und Methodik

83 Patienten wurden in dieser monozentrischen Studie an einer dermatologischen Universitätsklinik untersucht.

Ergebnisse

Die Manifestationen (n = 93) gliederten sich in Sofort‐Überempfindlichkeitsreaktionen angelehnt an Soforttypallergien (n = 51; 54,8%), verzögerte Überempfindlichkeitsreaktionen angelehnt an Spättypallergien (n = 10; 10,8%), chronisch‐entzündliche Hauterkrankungen (n = 13; 14,0%), Reaktivierung einer latenten Herpesvirusinfektion (Pityriasis rosea und Herpes zoster; n = 9; 9,7%) und „Sonstige“ (n = 10; 10,8%). Sowohl nicht vorbekannte Hautreaktionen (76,3%) – vorrangig Sofort‐Überempfindlichkeitsreaktionen oder verzögerte Überempfindlichkeitsreaktionen – als auch eine Verschlechterung einer vorbekannten Hauterkrankung (23,7%) – meist chronisch‐entzündliche Hauterkrankungen – traten auf. Meist entwickelten sie sich innerhalb der ersten Woche (72,8%) und initial nach der ersten Impfung (62,0%). In 83,9% der Fälle erfolgte eine Therapie; in 19,4% sogar eine stationäre Behandlung. Eine Folgeimpfung führte bei 48,8% zum Wiederauftreten der gleichen Reaktion. Persistierende Reaktionen bis zum Zeitpunkt der letzten Vorstellung fanden sich in 22,6%, primär bei chronisch‐entzündlichen Hauterkrankungen. Eine allergologische Diagnostik wurde bei 15 Patienten (18,1%) durchgeführt; und zeigte negative Resultate.

Schlussfolgerungen

Eine durch COVID‐19‐Impfungen ausgelöste Aktivierung des Immunsystems kann insbesondere bei prädisponierten Patienten zu kutanen Reaktionen führen.
In Search of an Adequate Response to Pluralism: A Critical Analysis of Liberalism in Philosophy of Education
Authors: Wenneborg Emily G.
Published: March 2023

Nearly everyone recognizes the fact of deep pluralism: it is hard to deny that contemporary America is characterized by widespread diversity of beliefs, practices, and values. We disagree, not on this reality, but on the way we should respond to the pluralism around us. In this paper, Emily G. Wenneborg discusses one of the most common responses to pluralism in contemporary philosophy of education: autonomy‐based liberalism. She praises liberalism for its attempt to navigate certain tensions that accompany its approach to pluralism. At the same time, she raises several critiques of liberalism as a response to pluralism, particularly with regard to religious communities and belief systems. She suggests that trust provides a better framework than autonomy for educating in and for deep pluralism.