bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the effectiveness of corrective maintenance of an oil pump using the proportional intensity model (PIM)
Authors: Bacha Sidali , Bellaouar Ahmed , Dron Jean-Paul
Published: November 2021

Purpose

Complex repairable systems (CRSs) are generally modeled by stochastic processes called “point processes.” These are generally summed up in the nonhomogeneous Poisson process (NHPP) and the renewal process (RP), which represent the minimum and maximum repair, respectively. However, the industrial environment affects systems in some way. This is why the main objective of this work is to model the CRS with a concept reflecting the real state of the system by incorporating an indicator in the form of covariate. This type of model, known as the proportional intensity model (PIM), will be analyzed with simulated failure data to understand the behavior of the failure process, and then it will be tested for real data from a petroleum company to evaluate the effectiveness of corrective actions carried out.

Design/methodology/approach

To solve the partial repair modeling problem, the PIM was used by introducing, on the basis of the NHPP model, a multiplicative scaling factor, which reflects the degree of efficiency after each maintenance action. Several values of this multiplicative factor will be considered to generate data. Then, based on the reliability and maintenance history of 12-year pump's operation obtained from the SONATRACH Company (south industrial center (CIS), Hassi Messaoud, Algeria), the performance of the PIM will be judged and compared with the model of NHPP and RP in order to demonstrate its flexibility in modeling CRS. Using the maximum likelihood approach and relying on the Matlab software, the best fitting model should have the largest likelihood value.

Findings

The use of the PIM allows a better understanding of the physical situation of the system by allowing easy modeling to apply in practice. This is expressed by the value which, in this case, represents an improvement in the behavior of the system provided by a good quality of the corrective maintenance performed. This result is based on the hypothesis that modeling with the PIM can provide more clarification on the behavior of the system. It can indicate the effectiveness of the maintenance crew and guide managers to confirm or revise their maintenance policy.

Originality/value

The work intends to reflect the real situation in which the system operates. The originality of the work is to allow the consideration of covariates influencing the behavior of the system during its lifetime. The authors focused on modeling the degree of repair after each corrective maintenance performed on an oil pump. Since PIM does not require a specific reliability distribution to apply it, it allows a wide range of applications in the various industrial environments. Given the importance of this study, the PIM can be generalized for more covariates and working conditions.
Modern mediators: intermediaries’ informational roles in sourcing from China
Authors: Virtanen Yuan , Salmi Asta , Qin Xiao
Published: November 2021

Purpose

Sourcing intermediaries, commonly known as agents or trading companies, represent a useful organisational solution for assisting companies to manage supply risks and to overcome the liability of foreignness. However, the landscape of global business is experiencing rapid and fundamental changes, which leads us to ask whether intermediaries will continue to play a role in global sourcing. This paper aims to understand how sourcing intermediaries ensure a lasting position in the changing setting of global sourcing and information sharing.

Design/methodology/approach

This paper investigates the operations of both Chinese and Nordic (Finnish and Swedish) intermediaries in sourcing from China by analysing qualitative data collected over a period of four years.

Findings

Through the lens of information asymmetry, this paper identifies four distinct informational roles that are used by intermediaries to reduce information asymmetry between suppliers and buyers located in different countries. The paper also examines intermediaries’ signalling activities under these roles in a cross-border triad.

Originality/value

The paper contributes to the scientific debate on the usefulness of intermediaries by underlining intermediaries’ informational advantage, which provides a new explanation for the survival of intermediaries in a rapidly changing business context. Additionally, this study contributes to research on intermediation strategies by empirically examining both Chinese and Western intermediaries, highlighting the importance of institutional contexts in affecting intermediaries’ informational roles.
Rent index forecasting through neural networks
Authors: Xu Xiaojie , Zhang Yun
Published: November 2021

Purpose

Chinese housing market has been growing fast during the past decade, and price-related forecasting has turned to be an important issue to various market participants, including the people, investors and policy makers. Here, the authors approach this issue by researching neural networks for rent index forecasting from 10 major cities for March 2012 to May 2020. The authors aim at building simple and accurate neural networks to contribute to pure technical forecasting of the Chinese rental housing market.

Design/methodology/approach

To facilitate the analysis, the authors examine different model settings over the algorithm, delay, hidden neuron and data spitting ratio.

Findings

The authors reach a rather simple neural network with six delays and two hidden neurons, which leads to stable performance of 1.4% average relative root mean square error across the ten cities for the training, validation and testing phases.

Originality/value

The results might be used on a standalone basis or combined with fundamental forecasting to form perspectives of rent price trends and conduct policy analysis.
Reflections on systemic barriers for ethnic minorities in accessing community-based forensic services for people with intellectual disabilities and autism
Authors: Coleman Mercedez
Published: November 2021

Purpose

Community-based forensic support services (CBFSSs) were commissioned nationally by National Health Service (NHS) England in 2017 in response to “Building the Right Support” (NHS England, 2015). CBFSSs provide multidisciplinary support to adults with intellectual disabilities and/or autism who are in (or at risk of) contact with the criminal justice system and those transitioning from inpatient secure care. This paper aims to highlight potential systemic barriers to accessing community forensic services for people from an ethnic minority background. in one CBFSSs in Northern England.

Design/methodology/approach

This paper provides preliminary reflections on potential systemic barriers within the criminal justice system and health-care services that have implications for service users from ethnic minority backgrounds accessing CBFSSs.

Findings

There is a paucity of data, policy and literature that focuses on people with intellectual disabilities and autism with forensic needs from ethnic minority backgrounds. This lack of data obstructs further reforms to meet the needs of this population.

Originality/value

CBFSSs are commissioned across England. While some regional variation is to be expected, services should be aware of the systemic barriers people from ethnic minority backgrounds within their region face. These barriers should be considered and addressed when evaluating service efficacy and delivery. Recommendations are made to review and address issues of under-representation of ethnic minorities within CBFSSs.
A review of responsible management education: practices, outcomes and challenges
Authors: Abdelgaffar Hala A.
Published: November 2021

Purpose

Research on management education (ME) over the past 2 decades signals a growing level of concern in response to increasing societal demands for ethical, responsible and sustainable considerations in management decisions in light of the current economic situation. The purpose of this paper is to review extant literature on responsible management education (RME) over the past decade.

Design/methodology/approach

The author carried out a systematic literature review of peer-reviewed publications, which were mapped and analysed according to the following six categories: (1) types of papers, (2) geographical context, (3) RME purpose, (4) strategies, (5) intended outcomes and (6) challenges. The analysis resulted in a descriptive overview of article content and synthesis of review data categorised by topical focus.

Findings

Analysis of the review sample reveals how scholarly interest in RME has accelerated over the last decade. This is accompanied by a growing institutionalisation and development of RME. The descriptive analysis indicates that the vast majority of publications focus on RME implementation strategies, mostly focussing on on-campus – curricular, pedagogical and operational – changes and the unique experiences of particular schools. Recent publications reveal interest in how RME can respond to triple bottom line (TBL) concerns that benefit the wider society and to sustainable development (SD) goals that target the local and global community. A budding interest is revealed in examining the perceptions of diverse stakeholder groups of sustainability requirements in RME curricula to create relevant and practical content.

Originality/value

This paper contributes to the adoption and/or development of RME.
Users' needs and expectations on information services provided in libraries: case of four public university libraries from the western region of Kenya
Authors: Nyakweba Irene , Bukirwa Joyce Muwanguzi , Sendikadiwa Eunice , Ratanya Felicitas Ciabere
Published: November 2021

Purpose

The purpose of this study is to assess the users' needs and expectations on information services provided in libraries, in four public universities from the western region of Kenya. The study explores the extent to which the libraries address users' needs and expectations examining the challenges being encountered, remedies and best practices put in place to mitigate the challenges. The level of users satisfaction towards the information services provided is also examined.

Design/methodology/approach

Structured questionnaires were distributed among undergraduates (384) and lecturers (86), where 342 were successfully filled and returned, giving a response rate of 73%. The study interviewed ten library staff revealing their views in addressing users' needs and expectations in respective libraries. Collected data were analysed descriptively using statistical methods and presented in figures and tables. Qualitative data were analysed in narrative form.

Findings

Majority of users had a positive perception towards the library, while others indicated that their needs were yet to be meet. The study noted the poor state of affair with inadequacies in information materials infrastructure, dwindling budget, facilities and unskilled personnel. The study recommended the need for additional library budget to facilitate acquisition of additional and up-to-date information resources and facilities.

Originality/value

The concept of user needs and expectations has been widely discussed in developed countries. Identifying and understanding users’ requirements in the context of public libraries in developing countries would start up constructive trends towards building useable collections.
Paper development in qualitative accounting research: bringing social contexts to life
Authors: Ahrens Thomas
Published: November 2021

Purpose

Expanding on an invited talk at the 1st Paper Development Workshop of the Qualitative Management Accounting Research Group, the purpose of this study is to offer some suggestions for developing qualitative accounting papers. Emphasis is put on the potential of qualitative research to situate evocative accounts of the organisational functionings of accounting in their wider social contexts.

Design/methodology/approach

To think about paper development as an exercise in communicating worthwhile findings to the readership by interweaving the researcher’s impressions of the field, recorded field material and different social theories to create qualitative accounting scholarship.

Findings

Qualitative accounting papers can, through the use of different theories, show the embedding of the organisational in the social. Development of qualitative accounting papers is an achievement that emerges in the process of writing.

Practical implications

Outlines five summary recommendations for paper development.

Originality/value

Reflects on paper development designed to create qualitative accounting research.
Developing youth justice policy and programme design in Australia
Authors: Butcher Luke , Day Andrew , Miles Debra , Kidd Garry , Stanton Steven
Published: November 2021

The national Closing the Gap reform provides a mandate for mainstream organisations to undergo structural transformation to better address the needs and concerns of Aboriginal and Torres Strait Islander communities. In the criminal justice sector, the reform resonates strongly with ongoing discussions about how both policy and practice can address the significant over‐representation of Aboriginal people across the criminal justice system. One way that structural transformation can occur is through the genuine involvement of Aboriginal knowledge holders and communities in policy development. This study illustrates how this might happen in relation to youth justice policy and programme design. Eighteen Aboriginal community members from a town in rural New South Wales participated in a series of interviews relevant to the Closing the Gap target. Qualitative content analysis was used to identify four key themes relevant to the development of justice policy: supporting cultural identity in a post‐colonial context; articulating strengths and resources which can be mobilised in the community; the centrality of poverty to offending; and responding to intergenerational trauma. The study illustrates how non‐Indigenous policymakers and practitioners might approach the task of engagement and consultation by identifying Aboriginal knowledge as a legitimate epistemic resource that they can draw upon to guide the ongoing development of evidence‐based policy and programmes.
Imagining genomic medicine futures in primary care: General practitioners’ views on mainstreaming genomics in the National Health Service
Authors: Mwale Shadreck , Farsides Bobbie
Published: November 2021

Genomic medicine has captured the imaginations of policymakers and medical scientists keen to harness its health and economic potentials. In 2012, the UK government launched the 100,000 Genomes Project to sequence the genomes of British National Health Service (NHS) patients, laying the ground for mainstreaming genomic medicine in the NHS and developing the UK’s genomics industry. However, the recent research and reports from national bodies monitoring genomic medicine's roll‐out suggest both ethical and practical challenges for health‐care professionals. Against this backdrop, this paper, drawing on qualitative research interviews with general practitioners (GPs) and documentary analysis of policy, explores GPs’ views on mainstreaming genomic medicine in the NHS and implications for their practice. Analysing the NHS’s genomic medicine agenda as a ‘sociotechnical imaginary’, we demonstrate that whilst sociotechnical imaginaries are construed as collectively shared understandings of the future, official visions of genomic medicine diverge from those at the forefront of health‐care service delivery. Whilst policy discourse evokes hope and transformation of health care, some GPs see technology in formation, an unattainable ‘utopia’, with no relevance to their everyday clinical practice. Finding space for genomics requires bridging the gap between ‘work as imagined’ at the policy level and ‘work as done’ in health‐care delivery.
Guidelines: is it time for a change?
Authors: Wojtaszewska A , Hirsch M
Published: November 2021

Linked article: This is a mini commentary on A Amoah et al., pp. 356–364 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.16928
Maternal and neonatal outcomes following waterbirth: a cohort study of 17 530 waterbirths and 17 530 propensity score‐matched land births
Authors: Bovbjerg ML , Cheyney M , Caughey AB
Published: November 2021

Objective

Investigate maternal and neonatal outcomes following waterbirth.

Design

Retrospective cohort study, with propensity score matching to address confounding.

Setting

Community births, United States.

Sample

Medical records‐based registry data from low‐risk births were used to create waterbirth and land birth groups (n = 17 530 each), propensity score‐matched on >80 demographic and pregnancy risk covariables.

Methods

Logistic regression models compared outcomes between the matched waterbirth and land birth groups.

Main outcome measures

Maternal: immediate postpartum transfer to a hospital, any genital tract trauma, severe (3rd/4th degree) trauma, haemorrhage >1000 mL, diagnosed haemorrhage regardless of estimated blood loss, uterine infection, uterine infection requiring hospitalisation, any hospitalisation in the first 6 weeks. Neonatal: umbilical cord avulsion; immediate neonatal transfer to a hospital; respiratory distress syndrome; any hospitalisation, neonatal intensive care unit (NICU) admission, or neonatal infection in the first 6 weeks; and neonatal death.

Results

Waterbirth was associated with improved or no difference in outcomes for most measures, including neonatal death (adjusted odds ratio [aOR] 0.56, 95% CI 0.31–1.0), and maternal or neonatal hospitalisation in the first 6 weeks (aOR 0.87, 95% CI 0.81–0.92 and aOR 0.95, 95% CI 0.90–0.99, respectively). Increased morbidity in the waterbirth group was observed for two outcomes only: uterine infection (aOR 1.25, 95% CI 1.05–1.48) (but not hospitalisation for infection) and umbilical cord avulsion (aOR 1.57, 95% CI 1.37–1.82). Our results are concordant with other studies: waterbirth is neither as harmful as some current guidelines suggest, nor as benign as some proponents claim.

Tweetable abstract

New study demonstrates #waterbirth is neither as harmful as some current guidelines suggest, nor as benign as some proponents claim. @TheUpliftLab @BovbjergMarit @31415926abc @NICHD_NIH.
Applications of bioactive compounds extracted from olive industry wastes: A review
Authors: Madureira Joana , Margaça Fernanda M. A. , Santos‐Buelga Celestino , Ferreira Isabel C. F. R. , Verde Sandra Cabo , Barros Lillian
Published: November 2021

The wastes generated during the olive oil extraction process, even if presenting a negative impact for the environment, contain several bioactive compounds that have considerable health benefits. After suitable extraction and purification, these compounds can be used as food antioxidants or as active ingredients in nutraceutical and cosmetic products due to their interesting technological and pharmaceutical properties. The aim of this review, after presenting general applications of the different types of wastes generated from this industry, is to focus on the olive pomace produced by the two‐phase system and to explore the challenging applications of the main individual compounds present in this waste. Hydroxytyrosol, tyrosol, oleuropein, oleuropein aglycone, and verbascoside are the most abundant bioactive compounds present in olive pomace. Besides their antioxidant activity, these compounds also demonstrated other biological properties such as antimicrobial, anticancer, or anti‐inflammatory, thus being used in formulations to produce pharmaceutical and cosmetic products or in the fortification of food. Nevertheless, it is mandatory to involve both industries and researchers to create strategies to valorize these byproducts while maintaining environmental sustainability.
Tenebrio molitoras a source of interesting natural compounds, their recovery processes, biological effects, and safety aspects
Authors: Errico Simona , Spagnoletta Anna , Verardi Alessandra , Moliterni Stefania , Dimatteo Salvatore , Sangiorgio Paola
Published: November 2021

Nowadays, it is urgent to produce in larger quantities and more sustainably to reduce the gap between food supply and demand. In a circular bioeconomy vision, insects receive great attention as a sustainable alternative to satisfy food and nutritional needs. Among all insects,Tenebrio molitor(TM) is the first insect approved by the European Food Safety Authority as a novel food in specific conditions and uses, testifying its growing relevance and potential. This review holistically presents the possible role of TM in the sustainable and circular solution to the growing needs for food and nutrients. We analyze all high value‐added products obtained from TM (powders and extracts, oils and fatty acids, proteins and peptides, and chitin and chitosan), their recovery processes (evaluating the best ones in technical and environmental terms), their nutritional and economical values, and their biological effects. Safety aspects are also mentioned. TM potential is undoubted, but some aspects still need to be discussed, including the health effects of substances and microorganisms in its body, the optimal production conditions (that affect product quality and safety), and TM capacity to convert by‐products into new products. Environmental, economic, social, and market feasibility studies are also required to analyze the new value chains. Finally, to unlock the enormous potential of edible insects as a source of nutritious and sustainable food, it will be necessary to overcome the cultural, psychological, and regulatory barriers still present in Western countries.
Efficacy of medium cut‐off dialyzers and comparison with high‐flux dialyzers in patients on maintenance hemodialysis: A systematic review and meta‐analysis
Authors: Yang Jia , Ke Guibao , Liao Yuanjiang , Guo Yong , Gao Xiaoling
Published: November 2021

Medium cut‐off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta‐analysis comparing MCO with high‐flux (HF) dialyzers for the effect on uremic toxins in maintenance hemodialysis (HD) patients. Five databases were systematically searched for relevant studies and nine studies were identified finally. Reduction ratio (RR) of urea, urea, creatinine, β2‐macroglobulin (β2‐MG), kappa free light chain (κFLC), and lambda FLC (λFLC) levels were not significantly different between MCO and HF dialyzers. But RR of β2‐MG, κFLC, and λFLC were greater for MCO than HF dialyzers. MCO dialyzers could better reduce tumor necrosis factor‐α (TNF‐α) levels. Subgroup analysis stratified by study design indicated that in randomized controlled trial (RCT) studies, albumin levels was lower in MCO than HF dialyzers group, but the two dialyzers treatments were equivalent in non‐RCT subgroup. Compared with HF dialyzers, MCO dialyzers provided higher middle‐molecules uremic toxins clearance and obviously reduced TNF‐α levels.
Efficiency of calcined Aluminum‐Magnesium layered double hydroxide for adsorption of aflatoxin M1 from solution and matrix of milk
Authors: Jahanmard Elham , Keramat Javad , Nasirpour Ali , Emadi Rahmatollah
Published: November 2021

Detoxification of aflatoxin M1 from solution and milk using layered double hydroxides was investigated. The Aluminum‐Magnesium layered double hydroxide (Al‐Mg LDH) and Iron‐Magnesium layered double hydroxide (Fe‐Mg LDH) were selected in their calcined and non‐calcined forms to evaluate the effect of the calcination on detoxification. These materials were produced using the co‐precipitation method. Preliminary adsorption tests confirmed use of Al‐Mg LDH as the selected adsorbent. Characteristics of the adopted adsorbent were studied and confirmed by XRD, FTIR, SEM, and BET methods. Effects of the initial content of aflatoxin, amount of the adsorbents and detoxification time were investigated. Influence of the adsorbents on the nutritional aspects of milk were also studied. The study showed that while the non‐calcined forms of LDH were not able to adsorb aflatoxin M1 more than 23%, the calcined form of Al‐Mg LDH exhibited 100% adsorption in the solutions and about 70–100% in the contaminated milk samples. The reason is pointed to the fact that calcination of Al‐Mg LDH considerably increased the surface area, the total pore volume, and the pore size of the material. Multivariate regression analysis and calculation of the Pearson correlation factor showed that the remained aflatoxin at each time was more strongly correlated with the initial amount of aflatoxin and the elapsed time and less strongly with the amount of the adsorbent. It was found that the adsorption isotherms fitted to the Freundlich equation with a high adsorption capacity of 555.5 mg g−1.

Practical Application

This study is focused on examining ability of layered double hydroxides (LDH) for adsorbing AFM1. LDHs are promising layered materials due to some of their interesting characteristics, such as ease of synthesis and uniqueness of structure. In practice, results of this study can be used for detoxification of aflatoxin, especially in milk, at high efficiency in shorter time durations.
LncRNA and mRNA expression associated with myasthenia gravis in patients with thymoma
Authors: Ke Ji , Du Xin , Cui Jian , Yu Lei , Li Hui
Published: November 2021

Objective

Pathological alterations of the thymus are observed in the majority of patients with myasthenia gravis (MG). To explore the potential mechanisms of these alterations, we performed a transcriptome analysis and measured co‐expression of aberrant long non‐coding RNAs (lncRNAs) and messenger RNAs (mRNAs).

Methods

RNA was extracted from eight patients with thymoma, five of whom had MG. Transcriptome profiles were acquired through mRNA and lncRNA microarray analysis. Quantitative reverse transcription polymerase chain reaction was used to verify the results of the microarray analysis. LncRNAs co‐expressed with mRNA were analyzed with Pearson's coefficient. Next, cis‐regulated and trans‐regulated target genes were predicted. The functions of aberrant lncRNAs were explored on the basis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of target mRNAs.

Results

The comparative microarray analysis identified 4360 lncRNAs and 2545 mRNAs with significant differential expression. The most significant GO enrichment terms were phosphoric ester hydrolase activity, phosphatase activity, and hydrolase activity, which were assigned as molecular functions. Regulation of endosome size was the most significant GO enrichment term assigned as a biological process, and Golgi apparatus was the most significant GO enrichment term assigned as cellular component. The reliability prediction terms of KEGG included calcium signaling pathway, glycosphingolipid biosynthesis, and caffeine metabolism.

Conclusion

MG‐positive thymoma is associated with overactive biological processes and molecular functions, especially dephosphorylation and hydrolysis, which may affect thymocyte survival during selection in the thymus.
Estimating allometric energy allocation between somatic and gonadic growth
Authors: Shimadzu Hideyasu , Wang Hui‐Yu
Published: November 2021

Quantifying growth patterns and energy allocation strategies is essential to comprehend the biological characteristics of organisms and their interactions with broader biological communities in which they reside. Mathematical models, such as mono‐ and diphasic allometric energy‐based growth models, play a pivotal role in delineating such body growth patterns. However, modelling approaches often face some major challenges that stem from both model nonlinearity and data limitation in practice.

The present study investigates the nature of the challenges and develops a flexible diphasic allometric growth model. The proposed modelling framework offers an effective parameter estimation approach directly built upon statistical smoothing techniques and numerical optimisation methods.

The simulation study undertaken demonstrates that the proposed approach can provide accurate parameter estimates. The illustrative example analyses the individual body and gonadic weight of subtropical cutlassfish Trichiurus japonicus from the cooler northern and warmer southern coasts of Taiwan. The results reveal the linear growth of fish in the south compared with those in the north, which distinctive growth pattern results from the lower dependency to body mass in the somatic and gonadic growth.

The proposed unified modelling framework offers new advances in growth modelling to shed light upon the intraspecific life‐history strategies, quantifying growth patterns and energy allocation strategies.
Ethanol attenuates presentation of cytotoxic T‐lymphocyte epitopes on hepatocytes of HBV‐infected humanized mice
Authors: Ganesan Murali , Wang Weimin , Mathews Saumi , Makarov Edward , New‐Aaron Moses , Dagur Raghubendra Singh , Malo Antje , Protzer Ulrike , Kharbanda Kusum K. , Casey Carol A. , Poluektova Larisa Y. , Osna Natalia A.
Published: November 2021

Background and Aims

Approximately 3.5% of the global population is chronically infected with Hepatitis B Virus (HBV), which puts them at high risk of end‐stage liver disease, with the risk of persistent infection potentiated by alcohol consumption. However, the mechanisms underlying the effects of alcohol on HBV persistence remain unclear. Here, we aimed to establish in vivo/ex vivo evidence that alcohol suppresses HBV peptides‐major histocompatibility complex (MHC) class I antigen display on primary human hepatocytes (PHH), which diminishes the recognition and clearance of HBV‐infected hepatocytes by cytotoxic T‐lymphocytes (CTLs).

Methods

We used fumarylacetoacetate hydrolase (Fah)‐/‐, Rag2‐/‐, common cytokine receptor gamma chain knock‐out (FRG‐KO) humanized mice transplanted with human leukocyte antigen‐A2 (HLA‐A2)‐positive hepatocytes. The mice were HBV‐infected and fed control and alcohol diets. Isolated hepatocytes were exposed ex vivo to HBV 18‐27‐HLA‐A2‐restricted CTLs to quantify cytotoxicity. For mechanistic studies, we measured proteasome activities, unfolded protein response (UPR), and endoplasmic reticulum (ER) stress in hepatocytes from HBV‐infected humanized mouse livers.

Results and Conclusions

We found that alcohol feeding attenuated HBV core 18‐27‐HLA‐A2 complex presentation on infected hepatocytes due to the suppression of proteasome function and ER stress induction, which diminished both the processing of HBV peptides and trafficking of HBV‐MHC class I complexes to the hepatocyte surface. This alcohol‐mediated decrease in MHC class I‐restricted antigen presentation of the CTL epitope on target hepatocytes reduced the CTL‐specific elimination of infected cells, potentially leading to HBV‐infection persistence, which promotes end‐stage liver disease outcomes.
Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals
Authors: Kim Rebecca G. , Kramer‐Feldman Jonathan , Bacchetti Peter , Grimes Barbara , Burchard Esteban , Eng Celeste , Hu Donglei , Hellerstein Marc , Khalili Mandana
Published: November 2021

Background

Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV.

Methods

One hundred fifty‐three nondiabetic Latino individuals (60 HCV+, 93 HCV−) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow‐up of 1.5 years. Peripheral IR and hepatic IR were measured via steady‐state plasma glucose (SSPG) and endogenous glucose production during a two‐step, 240‐min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time.

Results

Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 μU‐mg/kg‐min‐ml, p = 0.04) and HCV status (coef 4.4 μU‐mg/kg‐min‐ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow‐up (coef 5.8 μU‐mg/kg‐min‐ml, p = 0.03).

Conclusions

In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti‐HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.
Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one‐year extension study
Authors: Maurer Marcus , Giménez‐Arnau Ana , Bernstein Jonathan A. , Chu Chia‐Yu , Danilycheva Inna , Hide Michihiro , Makris Michael , Metz Martin , Savic Sinisa , Sitz Karl , Soong Weily , Staubach Petra , Sussman Gordon , Barve Avantika , Burciu Alis , Hua Eva , Janocha Reinhold , Severin Thomas
Published: November 2021

Background

Ligelizumab, a next‐generation, humanized anti‐immunoglobulin E (IgE) monoclonal antibody is in development as a treatment for patients with chronic spontaneous urticaria, whose symptoms are inadequately controlled with standard‐of‐care therapy.

Objective

To evaluate the long‐term safety and re‐treatment efficacy of ligelizumab 240 mg in patients who completed the core study and extension study.

Methods

This open‐label, single‐arm, long‐term Phase 2b extension study was designed to assess patients who were previously administered various doses of ligelizumab, omalizumab or placebo in the Phase 2b, dose‐finding core study and who presented with active disease after Week 32. In the extension study, patients received ligelizumab 240 mg subcutaneously every 4 weeks, for 52 weeks and were monitored post‐treatment for 48 weeks.

Results

Overall, ligelizumab was well‐tolerated with no newly identified safety signals. A total of 95.4% (226/237) screened patients received ligelizumab 240 mg in the extension study; 84.1% (190/226) of patients experienced at least one treatment‐emergent adverse event. Most reported events were mild (41.6%) or moderate (35.8%) and mostly unrelated to the study treatment. At Week 12, 46.5% of patients had a complete response increasing to 53.1% after 52 weeks. Following 52 weeks of extension study treatment, 75.8% (95% confidence interval, 69.9, 81.3) of patients had cumulative complete responses. The median time to relapse in complete responders was 38 weeks.

Conclusion

The long‐term safety profile of ligelizumab 240 mg in patients with chronic spontaneous urticaria was consistent with the core study and re‐treatment efficacy was shown.

Trial Registration: ClinicalTrials.gov Identifier: NCT02477332 and NCT02649218.
Has the time come to stop routine N‐acetylcysteine treatment in young children in Denmark? A review of 300 suspected paracetamol overdoses in children aged 0–6 years
Authors: Gade Christina , Bøgevig Søren , Daoud Alaa , Mathiesen Pernille R. , Christensen Mikkel B. , Dalhoff Kim P. , Petersen Tonny S.
Published: November 2021

Aim

To evaluate the prevalence of potentially hepatoxic paracetamol ingestion and associated N‐acetylcysteine treatment in young children suspected of paracetamol poisoning.

Methods

A retrospective cohort study of children aged 0–6 years suspected of paracetamol poisoning with a related plasma‐paracetamol measurement in the Capital Region of Denmark in the period 2010–2017. Data from the clinical laboratory system were linked to data from electronic patient records via the unique identification number given to all Danish residents.

Results

Of 297 children included, suspected single paracetamol overdoses were present in 281 (95%). Sixty‐nine per cent were treated with N‐acetylcysteine, and the mean treatment period was 20.3 h (SD 20.8). A maximum of 6 (2%) of the children suspected of single overdose had plasma‐paracetamol concentrations that exceeded the recommended treatment thresholds. No cases of severe hepatotoxicity were registered. Adverse events to N‐acetylcysteine‐treatment were registered in 3 (2%) children including one anaphylactoid reaction (0.5%).

Conclusion

This study shows that initiating N‐acetylcysteine as a ‘one size fit all’ treatment regimen in all children aged 0–6 years with a suspected single paracetamol overdose leads to substantial overtreatment. The data support that it is feasible to initiate N‐acetylcysteine within 10 h based on an early plasma‐paracetamol test.
Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment
Authors: Liu Chen‐Hua , Peng Cheng‐Yuan , Kao Wei‐Yu , Yang Sheng‐Shun , Shih Yu‐Lueng , Lin Chin‐Lin , Tsai Meng‐Kun , Lee Chih‐Yuan , Chang Chun‐Chao , Wu Jo‐Hsuan , Liu Chun‐Jen , Su Tung‐Hung , Tseng Tai‐Chung , Chen Pei‐Jer , Kao Jia‐Horng
Published: November 2021

Background

Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment‐induced sustained virologic response (SVR) in patients on haemodialysis.

Aims

To assess the risk of HCV reinfection among patients on haemodialysis with treatment‐induced SVR.

Methods

Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct‐acting antiviral (DAA)‐based treatment received follow‐up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12. The low‐risk general population who achieved SVR12 and who underwent the same post‐SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person‐years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups.

Results

We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post‐SVR12 follow‐up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24. The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09‐0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10‐0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44‐4.38, P = 0.57).

Conclusions

The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low‐risk general population. HCV microelimination in this special population is feasible once universal screening and scaled‐up treatment are implemented.
The conception of organizational integrity: A derivation from the individual level using a virtue‐based approach
Authors: Fuerst Madeleine J. , Luetge Christoph
Published: November 2021

This paper extends previous attempts at understanding the nature of organizational integrity and its increasingly important role for companies which, after all, bear a moral and societal responsibility. Interpretations of organizational integrity in business ethics literature incorporate aspects ranging from the behavior of managers and employees to corporate structures and incentive systems. We argue that virtue ethics builds an indispensable framework for understanding the origin of the concept of integrity and transfer these findings to an organizational level. Hence, we first define organizational integrity, and second operationalize it in a closed three‐step process, consisting of morally sound corporate commitments, their transparent institutionalization within the company, and their implementation into actions. We consider the main goal of organizational integrity to be of a preventative investment nature. Organizational integrity is a company investment that translates into avoiding fines for potential violations of the law or ethical missteps, as well as an investment in the company’s reputation. In turn, organizational integrity can protect a company from disruptions that can threaten its existence. Defining and operationalizing the concept of organizational integrity provides the foundation for future scientific research and the basis for developing practical guidance for organizations and managers.
Time‐dependent dual effect of NLRP3 inflammasome in brain ischaemia
Authors: Palomino‐Antolin Alejandra , Narros‐Fernández Paloma , Farré‐Alins Víctor , Sevilla‐Montero Javier , Decouty‐Pérez Celine , Lopez‐Rodriguez Ana Belen , Fernández Nuria , Monge Luis , Casas Ana I. , Calzada María José , Egea Javier
Published: November 2021

Background

Inflammasomes are cytosolic multiprotein complexes which, upon assembly, activate the maturation and secretion of the inflammatory cytokines IL‐1β and IL‐18. However, participation of the NLRP3 inflammasome in ischaemic stroke remains controversial. Our aims were to determine the role of NLRP3 in brain ischaemia, and explore the mechanism involved in the potential protective effect of the neurovascular unit.

Methods

WT and NLRP3 knock‐out mice were subjected to ischaemia by middle cerebral artery occlusion (60 min) with or without treatment with MCC950 at different time points post‐stroke. Brain injury was measured histologically with 2,3,5‐triphenyltetrazolium chloride (TTC) staining.

Results

We identified a time‐dependent dual effect of NLRP3. While neither the pre‐treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post‐reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose‐dependent manner. Importantly, MCC950 improved the neuro‐motor function and reduced the expression of different pro‐inflammatory cytokines (IL‐1β and TNF‐α), NLRP3 inflammasome components (NLRP3 and pro‐caspase‐1), protease expression (MMP9), and endothelial adhesion molecules (ICAM and VCAM). We observed a marked protection of the blood–brain barrier (BBB), which was also reflected in the recovery of the tight junction proteins (ZO‐1 and Claudin‐5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.

Conclusions

These findings suggest that post‐reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood–brain barrier in cerebral ischaemia with potential clinical translation.
PD‐L1 and PD‐L2 expression status in relation to chemotherapy in primary and metastatic esophageal squamous cell carcinoma
Authors: Okadome Kazuo , Baba Yoshifumi , Yasuda‐Yoshihara Noriko , Nomoto Daichi , Yagi Taisuke , Toihata Tasuku , Ogawa Katsuhiro , Sawayama Hiroshi , Ishimoto Takatsugu , Iwatsuki Masaaki , Iwagami Shiro , Miyamoto Yuji , Yoshida Naoya , Watanabe Masayuki , Komohara Yoshihiro , Baba Hideo
Published: November 2021

Immune checkpoint inhibitors have shown efficacy in various cancers. Although programmed death ligand 1/2 (PD‐L1/L2) expressions have been demonstrated as predictive biomarkers of response to immune checkpoint inhibitors and prognostic markers, whether PD‐L1/L2 expression is altered in esophageal squamous cell carcinoma during the therapeutic course is unclear. Whether PD‐L1/L2 expression in metastatic or recurrent lesions is consistent with that in primary tumors is also unknown. This study included 561 surgically resected esophageal squamous cell carcinomas and PD‐L1/L2 expression was evaluated by immunohistochemistry. We investigated the influence of chemotherapeutic drugs (cisplatin and fluorouracil) on PD‐L1/L2 expression and PD‐L1/L2‐related pathways in vitro. We also examined PD‐L1/L2 expression in 18 surgically resected lymph node metastases and 10 recurrent lesions compared with primary lesions. The positive rate of PD‐L1 was significantly higher in patients with preoperative chemotherapy than in those without preoperative therapy. The positive rate of PD‐L2 expression showed no significant difference between patient groups. Cisplatin increased PD‐L1 expression in cancer cell lines in vitro, but decreased PD‐L2 in some cell lines. The effects of cisplatin on phosphorylated signal transducer and activator of transcription 1/3 (pSTAT1/3) also differed depending on cell lines. Fluorouracil increased PD‐L1 and PD‐L2 expression. PD‐L1/L2 expression in lymph node metastases and recurrent lesions did not always match expression in primary lesions. PD‐L1/L2 expression may be altered by preoperative chemotherapy, and PD‐L1 /L2 expression in primary lesions does not always match that of metastatic/recurrent lesions. Thus, one‐time evaluation is not sufficient to evaluate PD‐L1/L2 expression as a biomarker in esophageal cancer.
Micronutritional supplementation with a holoBLG‐based FSMP (food for special medical purposes)‐lozenge alleviates allergic symptoms in BALB/c mice: Imitating the protective farm effect
Authors: Afify Sheriene Moussa , Regner Andreas , Pacios Luis F. , Blokhuis Bart R. , Jensen Sebastian A. , Redegeld Frank A. , Pali‐Schöll Isabella , Hufnagl Karin , Bianchini Rodolfo , Guethoff Sonja , Kramer Matthias F. , Fiocchi Alessandro , Dvorak Zdenek , Jensen‐Jarolim Erika , Roth‐Walter Franziska
Published: November 2021

Background

Previously, the protective farm effect was imitated using the whey protein beta‐lactoglobulin (BLG) that is spiked with iron‐flavonoid complexes. Here, we formulated for clinical translation a lozenge as food for special medical purposes (FSMP) using catechin‐iron complexes as ligands for BLG. The lozenge was tested in vitro and in a therapeutical BALB/c mice model.

Methods

Binding of iron‐catechin into BLG was confirmed by spectroscopy and docking calculations. Serum IgE binding of children allergic or tolerating milk was assessed to loaded (holo‐) versus empty (apo‐) BLG and for human mast cell degranulation. BLG and Bet v 1 double‐sensitized mice were orally treated with the holoBLG or placebo lozenge, and immunologically analysed after systemic allergen challenge. Human PBMCs of pollen allergic subjects were flow cytometrically assessed after stimulation with apoBLG or holoBLG using catechin‐iron complexes as ligands.

Results

One major IgE and T cell epitope were masked by catechin‐iron complexes, which impaired IgE binding of milk‐allergic children and degranulation of mast cells. In mice, only supplementation with the holoBLG lozenge reduced clinical reactivity to BLG and Bet v 1, promoted Tregs, and suppressed antigen presentation. In allergic subjects, stimulation of PBMCs with holoBLG led to a significant increase of intracellular iron in circulating CD14+ cells with significantly lower expression of HLADR and CD86 compared to their stimulation with apoBLG.

Conclusion

The FSMP lozenge targeted antigen presenting cells and dampened immune activation in human immune cells and allergic mice in an antigen‐non‐specific manner, thereby conferring immune resilience against allergic symptoms.