bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA-PKcs phosphorylation at the T2609 cluster alters the repair pathway choice during immunoglobulin class switch recombination
Authors: Crowe Jennifer L. , Wang Xiaobin S. , Shao Zhengping , Lee Brian J. , Estes Verna , Zha Shan
Published: April 2020

The DNA-dependent protein kinase (DNA-PK), composed of the KU heterodimer and the large catalytic subunit (DNA-PKcs), is a classical non-homologous end-joining (cNHEJ) factor. Naïve B cells undergo class switch recombination (CSR) to generate antibodies with different isotypes by joining two DNA double-strand breaks at different switching regions via the cNHEJ pathway. DNA-PK and the cNHEJ pathway play important roles in the DNA repair phase of CSR. To initiate cNHEJ, KU binds to DNA ends, and recruits and activates DNA-PK. DNA-PKcs is the best-characterized substrate of DNA-PK, which phosphorylates DNA-PKcs at both the S2056 and T2609 clusters. Loss of T2609 cluster phosphorylation increases radiation sensitivity, suggesting a role of T2609 phosphorylation in DNA repair. Using theDNA-PKcs5Amouse model carrying an alanine substitution at the T2609 cluster, here we show that loss of T2609 phosphorylation of DNA-PKcs does not affect the CSR efficiency. Yet, the CSR junctions recovered fromDNA-PKcs5A/5AB cells reveal increased chromosomal translocation, excess end-resection, and preferential usage of micro-homology – all signs of the alternative end-joining pathway. Thus, these results uncover a role of DNA-PKcs T2609 phosphorylation in promoting cNHEJ repair pathway choice during CSR.

Key points

Loss of T2069 cluster phosphorylation of DNA-PKcs promotes Alt-EJ-mediated CSR.
Sources of Intraspecific Morphological Variation inVipera seoanei: Allometry, Sex, and Colour Phenotype
Authors: Lucchini Nahla , Kaliontzopoulou Antigoni , Val Guillermo Aguado , Martínez-Freiría Fernando
Published: April 2020

Snakes frequently exhibit ontogenetic and sexual variation in head dimensions, as well as the occurrence of distinct colour morphotypes which might be fitness-related. In this study, we used linear biometry and geometric morphometrics to investigate intraspecific morphological variation related to allometry and sexual dimorphism inVipera seoanei, a species that exhibits five colour morphotypes, potentially subjected to distinct ecological pressures. We measured body size (SVL), tail length and head dimensions in 391 specimens, and examined variation in biometric traits with respect to allometry, sex and colour morph. In addition, we analysed head shape variation by recording the position of 29 landmarks in 123 specimens and establishing a low-error protocol for implementing geometric morphometrics to European vipers. All head dimensions exhibited significant allometry, while sexual differences occurred for SVL, relative tail length and snout height. After considering size effects, we found significant differences in body proportions between the sexes and across colour morphs, which suggests an important influence of lowland and montane habitats in shaping morphological variation. By contrast, head shape did not exhibit significant variation across sexes or colour morphs. Instead it was mainly associated to allometric variation, where the supraocular and the rear regions of the head were the areas that varied the most throughout growth and across individuals. Overall, this study provides a thorough description of morphological variability inVipera seoaneiand highlights the relevance of combining different tools (i.e. linear and geometric morphometrics) and analyses to evaluate the relative contribution of different factors in shaping intraspecific variation.
Sphingosine-1-phosphate receptors 1 and 3 regulate the expression of scavenger receptor B1 in human aortic endothelial cells
Authors: Wang Dongdong , Rohrer Lucia , von Eckardstein Arnold
Published: April 2020

Several vasoprotective functions of high-density lipoproteins (HDL) on the endothelium have been shown to depend on the presence of sphingosine-1-phosphate (S1P) receptors (S1PRs) as well as scavenger receptor class B type 1 (SR-B1). Interference with the presence of S1P or the activity of S1PR1 or S1PR3 mimics many effects seen by the interference with SR-B1. This raises the question on interactions between S1P receptors and SR-B1. We investigated the influence of S1PRs on SR-B1 expression in human aortic endothelial cells. Silencing or pharmacological inhibition of S1PR1 or S1PR3 down-regulatedSCARB1mRNA expression as well as SR-B1 protein abundance. RNA interference with S1PR1 or S1PR3 also decreased cellular association of125I-HDL with HAECs. Further mechanistic studies showed that knockdown of S1PR1 or S1PR3 reduced SR-B1 protein by inducing its degradation through deceasing Akt activity. Moreover, silencing of S1PR1 or S1PR3 suppressedSCARB1mRNA expression by decreasing cellular cAMP levels. In conclusion, we provide evidence for an as yet unappreciated interaction, namely the regulation of SR-B1 abundance by S1PRs on both transcriptional and post-translational levels, suggesting that interactions of S1PRs and SR-B1 regulate signaling functions of HDL as well as uptake of lipoproteins in endothelial cells.
Allelic heterogeneity of Proteus syndrome
Authors: Buser Anna , Lindhurst Marjorie J. , Kondolf Hannah C. , Yourick Miranda R. , Keppler-Noreuil Kim M. , Sapp Julie C. , Biesecker Leslie G.
Published: April 2020

Proteus syndrome is a mosaic disorder that can cause progressive postnatal overgrowth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively associated with the mosaic c.49G > A p.(Glu17Lys) pathogenic variant in AKT1, a variant that is also present in many cancers. Here we describe an individual with severe Proteus syndrome who died at 7.5 yr of age from combined parenchymal and restrictive pulmonary disease. Remarkably, this individual was found to harbor a mosaic c.49_50delinsAG p.(Glu17Arg) variant in AKT1 at a variant allele fraction that ranged from <0.01 to 0.46 in fibroblasts established from an overgrown digit. This variant was demonstrated to be constitutively activating by phosphorylation of AKT(S473). These data document allelic heterogeneity for Proteus syndrome. We recommend that individuals with a potential clinical diagnosis of Proteus syndrome who are negative for the p.(Glu17Lys) variant be tested for other variants in AKT1.
Synergistic effect of lean practices on lead time reduction: mediating role of manufacturing flexibility
Authors: Nawanir Gusman , Lim Kong Teong , Ramayah T. , Mahmud Fatimah , Lee Khai Loon , Maarof Mohd Ghazali
Published: April 2020

Purpose

This study scrutinized the synergistic effects of lean manufacturing (LM) on lead time reduction (LR) while investigating the mediating role of manufacturing flexibility (MF) in that relationship within the context of batch and mass customization manufacturers.

Design/methodology/approach

This cross-sectional survey involved 160 large batch and mass customization manufacturers in Indonesia. Data were analyzed by using the PLS path modeling approach and multigroup analysis.

Findings

The positive synergistic direct effects of LM on LR and MF were revealed in both process types. In mass customization, MF mediates the effect of LM on LR. However, such a mediating effect was not found in the batch process due to the insignificant effect of MF on LR.

Practical implications

The findings offered theoretical and practical insights supporting the manufacturers to grasp potential benefits through the holistic LM implementation as well as the suitable strategies to improve MF and reduce lead time by considering the types of the production process.

Originality/value

This study bridged the gaps regarding the comparison of LM implementation and its influence on MF and LR in mass customization and batch production.
Cyber physical system for safety management in smart construction site
Authors: Jiang Weiguang , Ding Lieyun , Zhou Cheng
Published: April 2020

Purpose

Construction safety has been a long-term problem in the development of the construction industry. An increasing number of smart construction sites have been designed using different techniques to reduce injuries caused by construction accidents and achieve proactive risk control. However, comprehensive smart construction site safety management solutions and applications have yet to be developed. Thus, this study proposes a smart construction site framework for safety management.

Design/methodology/approach

A safety management system based on a cyber-physical system is proposed. The system establishes risk data synchronization mapping between the virtual construction and physical construction sites through scene reconstruction design, data awareness, data communication and data processing modules. Personnel, mechanical and other risks on site will be warned and controlled.

Findings

The results of the case study have proved the management benefits of the system. On-site workers gradually realized that they should enter the construction site based on the standard process. And the number of people close to the construction hazard areas decreased.

Research limitations/implications

There are some limitations in the technology of smart construction site. The modeling speed can be faster, the data collection can be timelier, and the identification of unsafe behavior can be integrated into the system. Construction quality and efficiency issues in a virtual construction site will also be solved in further research.

Practical implications

In this paper, this system is actually applied in the mega project management process. More practical projects can use the management ideas and method of this paper to ensure on-site safety.

Originality/value

This study is among the first attempts to build a complete smart construction site based on CPS and apply it in practice. Personnel, mechanical, components, environment information will be displayed on the virtual construction site. It will greatly promote the development of the intellectualized construction industry in the future.
Mechanisms for hiring discrimination of immigrant applicants in the United States
Authors: Akinlade Ekundayo Y. , Lambert Jason R. , Zhang Peng
Published: April 2020

Purpose

Few studies examine how hiring discrimination can be an antecedent to the labor exploitation of immigrant workers. The main purpose of this paper is to advance the theoretical understanding of how the intersectionality of race and immigrant status affects differential hiring treatment, and how it affects job offers, job acceptance and hiring decision outcomes for immigrant job seekers.

Design/methodology/approach

The paper draws from theories on status and intersectionality, and literature on immigration labor and racial hierarchy, addressing the unequal power relations that underlie race and immigration status affecting the hiring process, to advance critical understandings of why immigrant job seekers accept positions where they may be exploited.

Findings

This paper provides a conceptual model to critically synthesize the complexity between race and immigrant status, and their effect on the experience of immigrant job seekers differently. Exploitation opportunism is introduced to better understand the mechanisms of hiring discrimination among immigrant job seekers to include the role of race, immigrant status, economic motivations and unequal power relations on the hiring process.

Practical implications

The framework for exploitation opportunism will help employers improve the quality and fairness of their hiring methods, and empower immigrant job seekers to not allow themselves to accept subpar job offers which can lead to exploitation.

Originality/value

The paper provides an original analysis of immigrant job seekers' experience of the hiring process that reveals the intragroup differences among immigrants based on race and status, and the decision-making mechanisms that hiring managers and immigrant job seekers use to evaluate job offers and job acceptance.
The role of HRD in CSR and sustainability: a content analysis of corporate responsibility reports
Authors: Jang Soebin , Ardichvili Alexandre
Published: April 2020

Purpose

This study aims to examine the role of human resource development (HRD) in corporate social responsibility (CSR) and sustainability initiatives of multinational companies (MNCs).

Design/methodology/approach

The authors analyze contents of corporate responsibility (CR) reports disclosed by 23 MNCs from Europe, Asia and North America to examine HRD’s contribution to CSR and sustainability, with particular attention to long-term human development and organization development.

Findings

The analysis of CR reports indicates that HRD is perceived as playing a role in the following areas: diversity, equity and inclusion; community engagement; work–life balance; employee long-term growth and development; performance management; business ethics and ethical culture; and raising CSR awareness. In all areas, HRD was identified as playing a significant role in supporting companies’ CSR agendas.

Originality/value

This study extends research on the intersection of HR, CSR and sustainability and provides evidence of HRD’s important contributions to CSR and sustainability.
Family event participation: building flourishing communities
Authors: Booth Alison Stevens , Cameron Fiona Mary
Published: April 2020

Purpose

Family participation in community events and festivals is framed by certain conditions related to their ability to enhance their quality of life (QOL) and family flourishing. For communities to flourish, families must feel safe, secure, accepted and included. The research has the following aims: (1) to consider whether location is a determinant in family QOL and event participation, and (2) to identify how cultural identity and family issues may affect families' QOL and the role events play in their ability to flourish as a family.

Design/methodology/approach

An integrated mixed-methods design was used derived from quantitative and qualitative traditions, including surveys, interviews and secondary data. The survey component combined Jepson and Stadler's St Albans 2015 QOL study survey with research instruments used by the Rotorua Lakes Council (RLC). The Rotorua sample included 521 valid anonymous online surveys and 11 semi-structured interviews. The RLC's Arts and Culture team provided expert advice, strategic plans and reports; secondary data were gathered from media reports.

Findings

When comparing key Rotorua and St Albans data, the participants' responses were very similar. What appear significant are socio-economic and cultural differences and family-flourishing factors specific to Rotorua's location and population. The findings show that the biggest obstacles for families attending events are money, work commitments and family obligations. The events reflect the region's unique cultural profile and provide a distinctive identifier of place and people that create a unique small-city event portfolio.

Research limitations/implications

This study's findings have reinforced that for small-city events to succeed and attract high levels of patronage, council and community must work cooperatively towards common goals. Our findings indicate the importance, to our participants, of emotional attachment to Rotorua's natural landscape, built environment and unique cultural heritage. Additionally, arts and culture research focusing on new-migrant and multi-generational event participation is worth further consideration for preserving Rotorua's cultural history. Perceptions within the Rotorua community of their family experience at local events are central to our ongoing research and the further successful delivery of the RLC's event portfolio.

Originality/value

This research offers a case study that serves to build further areas of inquiry into the role events play in QOL, family flourishing and maintaining indigenous cultures. Study findings have reinforced that organisations, practitioners, festivals and events succeed in attracting high levels of patronage for a small city. This study provides insights for designing culturally inclusive event portfolios that include events and festivals that target family audiences.
Local vs non-local sources of knowledge for the low-tech firms’ product innovation: evidence from the food-processing industry in Thailand
Authors: Tippakoon Phakpoom
Published: April 2020

Purpose

This study aims to examine the effect on firms’ new product development (NPD) and significant product modification of knowledge interaction with local and non-local knowledge actors.

Design/methodology/approach

This study draws insights from the literature on external knowledge sources. The negative binomial regression is used to analyse the data of 245 sample food-processing establishments in Thailand.

Findings

Local knowledge actors play only limited roles in enhancing food-processing establishments’ product innovations. Only knowledge interaction with local universities and public research organisations helps enhance establishments’ ability to modify their products. For the NPD, significant sources of knowledge are non-local industrial actors.

Originality/value

This study adds new empirical evidence on knowledge sources for innovation of low-tech firms in less developed countries. It contributes new findings to an on-going debate on the importance of local vs non-local knowledge sources on firms’ innovativeness. It also contributes some implications for the Thai Government’s cluster-based innovation strategy.
NAFTA and the United States and Mexico maize belts 1994–2017
Authors: Osorio-Antonia José , Bada-Carbajal Lila Margarita , Rivas-Tovar Luis Arturo
Published: April 2020

Purpose

The purpose of this paper is twofold. First, the impact of the North American Free Trade Agreement (NAFTA) on the agribusinesses of corn production in Mexico is analyzed, taking into special consideration the policy of encouragement to small producers, productive restructuring and identification of positive and negative effects. Second, the evolution of the US–Mexican maize belts (1994–2017) is analyzed, establishing the economic and political impacts with respect to NAFTA.

Design/methodology/approach

The paper opted for a documentary meta-analysis study using data from the United States Department of Agriculture (USDA) and the System of Agricultural and Fishery Information (SIAP) in Mexico. The data were completed with documentary analysis of research on maize productivity.

Findings

Provided is the information about the impacts of maize belts in the United States (US) and Mexico, where it was determined that the leading states maintained productive hegemony to a greater and lesser extent and that Mexico experienced a productive reorientation. The findings show that it is a myth that there are losers in the maize agroindustry of Mexico and the United States as it is suggested that after twenty-four years they have become complementary.

Research limitations/implications

Summarized is the state of knowledge from 1994 to 2017, aligned to the databases of the United States and Mexico.

Originality/value

A need to study the relation between the productive evolution of maize production and NAFTA is identified.
Optimal energy mix for a reverse osmosis desalination unit considering demand response
Authors: Okampo Ewaoche John , Nwulu Nnamdi I.
Published: April 2020

Purpose

Reverse osmosis (RO) has become an important method of desalination to meet the ever-growing water needs around the world. Its integration with renewable energy source (RES) reduces the environmental impact of gas emissions and cost of conventional fossil energy sources. The optimal sizing of energy sources to power RO desalination system is intended mainly to minimize the annualized cost of the system and by extension minimize freshwater cost while maximizing production.

Design/methodology/approach

In this study, a mathematical optimization approach is used to determine the optimal energy mix, which includes grid power, diesel generator and a photovoltaic (PV) module to supply an RO desalination unit. Three cases of optimal sizing approach were compared. Case 1 is a system with only grid power and diesel generator as energy sources; Case 2 has PV incorporated in the energy supply mix while Case 3 has the three energy sources and a Time of Use (TOU) demand response program on the demand side.

Findings

The results of implementing the optimization models show that Case 3 turnout the highest freshwater production (1,521 m3/day) at a unit cost of 1.36$/m3 when compared to Case 1 with daily freshwater production of 1,250 m3/day at a unit cost of 1.68$/m3 and Case 2 having a daily freshwater production of 1,501 m3/day at a unit cost of 1.33$/m3.

Originality/value

The integration of RES to power desalination system with application of TOU demand response is the significance of this study.
Relationship between retailers’ return policies and consumer ratings
Authors: Rokonuzzaman Md , Mukherjee Atmadeep , Iyer Pramod , Mukherjee Amaradri
Published: April 2020

Purpose

Return policies are major risk-allaying cues for customers, yet they are a critical cost/lost-sales for retailers. Despite their importance in the retailing industry, few studies have examined the interplay of return policies with other cues that customers use to make a purchase decision. Toward this end, this study aims to investigate the interaction effects certain salient high-scope and low-scope cues, such as consumer ratings and brand image, and retailers’ return policies have on consumer purchase decisions.

Design/methodology/approach

Building on literature from signaling theory and cue scope literature (high-scope and low-scope cues), the authors develop a research model that hypothesizes the interrelationships between return policies, price discounts, customer product ratings and brand image. Three experimental studies investigate the potential interplay between return policies (lenient vs stringent), price discounts (low vs high), customer product ratings (low vs high) and brand image (high vs low) on quality certainty perceptions and purchase intentions. The mediating effect of quality certainty perceptions on the interplay of various factors (return policy, price promotions, consumer ratings and brand image) and customer purchase intentions is also investigated.

Findings

Results indicate that a lenient return policy will have a positive effect when consumers encounter high scope cues that signal undesirable aspects of the product (i.e. low consumer ratings, low brand image). In contrast, when high scope cues signal desirable aspects of the product (i.e. high consumer ratings, high brand image), it attenuates the effects of return policy. The findings suggest that quality certainty acts as a psychological process.

Research limitations/implications

Service researchers should seek to examine the role of return policies in a more comprehensive manner.

Practical implications

Return policies are important cues for consumers while making purchase decision. Thus, retailers need to realize that these policies may need to be more dynamic or tiered, rather than one-size-fits-all.

Originality/value

This study provides a more comprehensive view of how consumers consider multiple cues simultaneously in decision-making. Literature has mainly examined the interactions between different high-scope and low-scope cues, but there has been limited research directed toward the interplay between multiple high-scope cues.
Measuring the effect of investor sentiment on liquidity
Authors: Dunham Lee M. , Garcia John
Published: April 2020

Purpose

The purpose of this paper is to examine the effect of firm-level investor sentiment on a firm's share liquidity.

Design/methodology/approach

The authors use Bloomberg's firm-level, daily investor sentiment scores derived from firm-level news and Twitter content in a regression model to explain the variability in a firm's share liquidity.

Findings

The results indicate that improvements (deterioration) in investor sentiment derived solely from Twitter content lead to a decrease (increase) in the average firm's share liquidity. Results, although not as strong, are opposite for investor sentiment derived solely from news articles: improvements (deterioration) in news sentiment leads to an increase (decrease) in the average firm's share liquidity.

Research limitations/implications

The proxy for share liquidity is the bid-ask spread, which may be an imperfect measure of liquidity. The Amihud illiquidity measure was used as an alternative proxy and yield similar results. The results have important implications for investors in assessing the determinants of share liquidity.

Practical implications

The sample period covers four years (2015–2018), which is determined by the availability of the Bloomberg sentiment data.

Social implications

Investors increasing use of social media to express views on particular stocks and seek information that might be used in the investment decision-making process. The study links investor sentiment derived from social media (Twitter) to share liquidity.

Originality/value

By examining the relationship between a firm's sentiment and the firm's share liquidity, this paper advances the authors' understanding of the factors that drive a firm's share liquidity. To the authors' knowledge, this is the first study to link investor sentiment derived from firm-level news and Twitter content to a firm's share liquidity.
Interaction of Al2O3-Ag and Al2O3-Cu hybrid nanoparticles with water on convectively heated moving material
Authors: Ramesh G.K. , Roopa G.S. , Shehzad SabirAli , Khan S.U.
Published: April 2020

Purpose

The aim of present work is to study the flow and heat transport structures of hybrid nanoparticles in a moving material. Two types of hybrid nanoparticles have been chosen namely Al2O3-Cu and Al2O3-Ag nanoparticles (90%) within 10% of pure water.

Design/methodology/approach

Leading governing equations are transformed through similarity technique and then computed for numerical illustration by applying RKF method.

Findings

The author observed that the skin friction value of Al2O3-Cu/water case is lesser in comparison to the values of Nusselt number for Al2O3-Ag/water nanoparticles.

Originality/value

There exist no such study which addressed such phenomenon.
Working in contexts for which transparency is important
Authors: Bunn Jenny
Published: April 2020

Purpose

This paper aims to introduce the topic of explainable artificial intelligence (XAI) and reports on the outcomes of an interdisciplinary workshop exploring it. It reflects on XAI through the frame and concerns of the recordkeeping profession.

Design/methodology/approach

This paper takes a reflective approach. The origins of XAI are outlined as a way of exploring how it can be viewed and how it is currently taking shape. The workshop and its outcomes are briefly described and reflections on the process of investigating and taking part in conversations about XAI are offered.

Findings

The article reinforces the value of undertaking interdisciplinary and exploratory conversations with others. It offers new perspectives on XAI and suggests ways in which recordkeeping can productively engage with it, as both a disruptive force on its thinking and a set of newly emerging record forms to be created and managed.

Originality/value

The value of this paper comes from the way in which the introduction it provides will allow recordkeepers to gain a sense of what XAI is and the different ways in which they are both already engaging and can continue to engage with it.
Patient characteristics and 6‐month dose of basal insulin associated with HbA1c achievement <7.0% in Chinese people with type 2 diabetes: results from the Observational Registry of Basal Insulin Treatment (ORBIT)
Authors: Gao Leili , Zhang Puhong , Weng Jianping , Lu Juming , Guo Xiaohui , Jia Weiping , Yang Wenying , Zou Dajin , Zhou Zhiguang , Pan Changyu , Gao Yan , Li Xian , Zhu Dongshan , Wu Yangfeng , Garg Satish K. , Ji Linong
Published: April 2020

Background

The efficacy of basal insulin (BI) for adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) has been well documented by randomized clinical trials. This post hoc analysis of the Observational Registry of Basal Insulin Treatment (ORBIT) study was performed to explore the 6‐month dose of BI used in insulin‐naïve T2DM patients achieving HbA1c target (<7%) and determine the patient characteristics that affect the 6‐month dose of BI in the setting of real‐world clinics in China.

Methods

This multicenter observational registry screened 19 894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) in China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target were analyzed. Patient characteristics including age, body weight, fasting plasma glucose (FPG), use of OADs, insulin (type and dose), and glycemic control were recorded at baseline and 6‐month follow‐ups.

Results

The 6‐month dose of BI needed for effective glycemic control was 0.20 ± 0.08 U/kg/day. High body mass index, high FPG, young age, longer duration of diabetes or OAD treatment, a greater number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI at 6 months.

Conclusions

This post hoc analysis of the ORBIT registry provides key information on the 6‐month dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, it identified crucial patient characteristics that are significant determinants of the dose of BI in a real‐world setting.
Intensive care patient survival after limiting life‐sustaining treatment—The FINNEOL* national cohort study
Authors: Adamski Jan , Weigl Wojciech , Lahtinen Pasi , Reinikainen Matti , Kaminski Tadeusz , Pietiläinen Laura , Musialowicz Tadeusz
Published: April 2020

Background

Few studies have examined survival in intensive care unit (ICU) patients after the restriction of life‐sustaining treatment (LST). We aimed to analyse independent factors associated with hospital and 12‐month survival rates in ICU patients after treatment restrictions.

Methods

This retrospective observational study examined all patients treated in adult ICUs from 1 January 2016 until 31 December 2016 included in the Finnish ICU Registry. Multivariable logistic regression analysis was performed to explain the effect on survival.

Results

Decisions to limit LST were made for 2444 patients (13.7%; 95% CI 13.2‐14.2). ICU, hospital, and 12‐month survival rates were 71% (95% CI 69‐73), 49% (95% CI 47‐51), and 24% (95% CI 22‐26), respectively. In patients for whom life support was withheld, increased 12‐month survival rates were associated with admission from the operating theatre (OR 1.9, 95% CI 1.1‐3.4), good pre‐hospital physical fitness (OR 4.7, 95% Cl 1.2‐16.8) and being housed at home (OR 2.0, 95% Cl 1.4‐2.8). Decreased survival rates were associated with admission from a hospital ward (OR 0.67, 95% Cl 0.5‐0.9), higher comorbidity (OR 0.6, 95% Cl 0.4‐0.9), cancer (OR 0.4, 95%CI 0.2‐0.9), greater illness severity (SAPS II; OR 0.98, 95% Cl 0.98‐0.99), and higher care intensity (TISS‐76; OR 0.93, 95% Cl 0.92‐0.95).

Conclusion

Survival among ICU patients with limited treatment was higher than expected. Advanced age was not associated with higher mortality, potentially because treatment restrictions may be set more easily for older patients.
Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine‐A
Authors: Touchette Jillienne C. , Moen Janna K. , Robinson Jenna M. , Lee Anna M.
Published: April 2020

The prevalence of alcohol use disorders (AUDs) has steadily increased in the United States over the last 30 years. Alcohol acts on multiple receptor systems including the nicotinic acetylcholine receptors (nAChRs), which are known to mediate alcohol consumption and reward. We previously reported that the preclinical drug sazetidine‐A, a nAChR agonist and desensitizer, reduces alcohol consumption without affecting nicotine consumption in C57BL/6J mice. Here, we found that sazetidine‐A enhances the expression of alcohol aversion without affecting the expression or acquisition of conditioned alcohol reward in C57BL/6J mice. Microinjection of sazetidine‐A into the ventral midbrain targeting the ventral tegmental area (VTA) reduced binge alcohol consumption, implicating this region in mediating the effects of sazetidine‐A. Furthermore, the sazetidine‐A‐induced reduction in alcohol consumption was mediated by non‐α4 containing nAChRs, as sazetidine‐A reduced binge alcohol consumption in both α4 knock‐out and wild‐type mice. Finally, we found that in mice pretreated with sazetidine‐A, alcohol induced Fos transcript in Th‐, but not Gad2‐expressing neurons in the VTA as measured by increased Fos transcript expression. In summary, we find that sazetidine‐A enhances the expression of alcohol aversion, which may underlie the reduction in alcohol consumption induced by sazetidine‐A. Elucidating the identity of non‐α4 nAChRs in alcohol aversion mechanisms will provide a better understanding the complex role of nAChRs in alcohol addiction and potentially reveal novel drug targets to treat AUDs.
Chronic endometritis and reproductive failure: Role of syndecan‐1
Authors: Xu Yanhong , Mei Jie , Diao Lianghui , Li Yuye , Ding Lijun
Published: April 2020

Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan‐1 has been identified as a biomarker of plasmacyte, and syndecan‐1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan‐1, the progress of syndecan‐1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.
miR‐322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4
Authors: Liu Yu‐si , Gu Hui , Huang Tian‐chu , Wei Xiao‐wei , Ma Wei , Liu Dan , He Yi‐wen , Luo Wen‐ting , Huang Jie‐ting , Zhao Duan , Jia Shan‐shan , Wang Fang , Zhang Ting , Bai Yu‐zuo , Wang Wei‐lin , Yuan Zheng‐wei
Published: April 2020

Aims

Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR‐322, and we have previously demonstrated that miR‐322 was involved in high glucose‐induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR‐322 that disrupts neurulation by ameliorating cell apoptosis.

Methods

All‐trans‐retinoic acid (ATRA)‐induced mouse model was utilized to study NTDs. RNA pull‐down and dual‐luciferase reporter assays were used to confirm the interaction between NOX4 and miR‐322. In mouse neural stem cells and whole‐embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR‐322 and NOX4 on neuroepithelium apoptosis in NTD formation.

Results

NOX4, as a novel target of miR‐322, was upregulated in ATRA‐induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR‐322; still further, NOX4‐triggered apoptosis was also suppressed by miR‐322. Moreover, in whole‐embryo culture, injection of the miR‐322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4.

Conclusion

miR‐322/NOX4 plays a crucial role in apoptosis‐induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.
Sleep apnoea is associated with hearing impairment: The Paris prospective study 3
Authors: Lisan Quentin , van Sloten Thomas , Climie Rachel E. , Boutouyrie Pierre , Guibout Catherine , Thomas Frederique , Danchin Nicolas , Jouven Xavier , Empana Jean‐Philippe
Published: April 2020

Objectives

Hearing impairment (HI) is a leading impairment worldwide, and identifying modifiable risk factors of HI may have major public health implications. The aim of this study was to investigate the association between obstructive sleep apnoea (OSA) and HI.

Design

Observational longitudinal study (the Paris Prospective Study 3).

Setting

Population‐based.

Participants

Volunteers aged 50‐75 years and consulting at a preventive medical centre were included between 2008 and 2012. 6797 participants were included in the present analysis.

Main outcome measures

Audiometry testing was performed in both ears in all participants, and HI was defined by a pure‐tone average (PTA) >25 decibels (dB) hearing level in the better ear.

Results

Obstructive sleep apnoea (estimated by the Berlin questionnaire) was present in 18.6% (n = 1267) and HI in 13.9% (n = 947) of the participants. Mean age was 59.5 years (SD 6.2) and 63.5% were male (n = 4317). In multiple logistic regression modelling, OSA was significantly associated with a 1.21‐increased odds of HI (95% confidence interval 1.01‐1.44). Several sensitivity analyses supported this finding.

Conclusion

Obstructive sleep apnoea is associated with a 21% increased odds of HI. These results support active screening of HI in subjects with OSA, and future studies should evaluate whether the treatment of OSA can delay the onset of HI.
An infant with an abdominal mass
Authors: Gupta Parikshaa , Rajwanshi Arvind
Published: April 2020

Mesoblastic nephroma, also known as congenital mesoblastic nephroma or fetal renal hamartoma, is a rare renal mesenchymal tumor with low malignant potential, occurring most commonly in infants. A case is presented which could be diagnosed on fine needle aspiration cytology complemented with cell‐block immunocytochemistry. The cytopathologists need to be aware of the cytologic and immunocytochemical features of this entity, to accurately diagnose these cases pre‐operatively, so as to avoid unnecessary administration of chemotherapy to these infants.
Infants of mothers with higher physiological stress show alterations in brain function
Authors: Troller‐Renfree Sonya V. , Brito Natalie H. , Desai Pooja M. , Leon‐Santos Ana G. , Wiltshire Cynthia A. , Motton Summer N. , Meyer Jerrold S. , Isler Joseph , Fifer William P. , Noble Kimberly G.
Published: April 2020

Chronic stress has been increasingly linked with aberrations in children's behavioral, cognitive, and social development, yet the effect of chronic physiological stress on neural development during the first year of life is largely unknown. The present study aims to link a physiological index of chronic stress (maternal hair cortisol concentration) to maturational differences in infant functional brain development during the first year of life. Participants were 94 mother‐infant dyads. To index chronic physiological stress, maternal hair samples were assayed for the previous three months’ cortisol output. To examine the development of brain function during the first year of life, six‐to‐twelve‐month‐old infants (N = 94) completed a resting electroencephalography (EEG) recording. Infants of mothers with evidence of higher physiological stress showed increased relative low‐frequency (theta) power and reduced relative high‐frequency (alpha, high‐gamma) power, compared to infants of mothers with evidence of low physiological stress. This pattern of findings is consistent with other studies suggesting that early life stress may lead to alterations in patterns of infant brain development. These findings are important given that maturational lags in brain development can be long‐lasting and are associated with deficits in cognitive and emotional development. The present research also suggests that reducing maternal physiological stress may be a useful target for future interventions aiming to foster neurodevelopment during the first year of life.
Inhibitory synaptic transmission tuned by Ca2+ and glutamate through the control of GABAAR lateral diffusion dynamics
Authors: Bannai Hiroko , Niwa Fumihiro , Sakuragi Shigeo , Mikoshiba Katsuhiko
Published: April 2020

The GABAergic synapses, a primary inhibitory synapse in the mammalian brain, is important for the normal development of brain circuits, and for the regulation of the excitation‐inhibition balance critical for brain function from the developmental stage throughout life. However, the molecular mechanism underlying the formation, maintenance, and modulation of GABAergic synapses is less understood compared to that of excitatory synapses. Quantum dot‐single particle tracking (QD‐SPT), a super‐resolution imaging technique that enables the analysis of membrane molecule dynamics at single‐molecule resolution, is a powerful tool to analyze the behavior of proteins and lipids on the plasma membrane. In this review, we summarize the recent application of QD‐SPT in understanding of GABAergic synaptic transmission. Here we introduce QD‐SPT experiments that provide further insights into the molecular mechanism supporting GABAergic synapses. QD‐SPT studies revealed that glutamate and Ca2+ signaling is involved in (a) the maintenance of GABAergic synapses, (b) GABAergic long‐term depression, and GABAergic long‐term potentiation, by specifically activating signaling pathways unique to each phenomenon. We also introduce a novel Ca2+ imaging technique to describe the diversity of Ca2+ signals that may activate the downstream signaling pathways that induce specific biological output.
The gender puzzles
Authors: Fileva Iskra
Published: April 2020

What is gender and how do we know what our gender is? These are the questions I propose to answer here. I review and reject several hypotheses: gender as sex or—a more careful version of the view—as subjective experiences that arise from sexual characteristics; gender as brain configuration; and gender as a historical kind. I express sympathy with an existentialist conception of gender but argue that such a conception, even according to its proponents, cannot help solve the problems of what gender is and how we know what our gender is. I then advance a new view.
Effectiveness and tolerability of lacosamide as add‐on therapy in patients with brain tumor–related epilepsy: Results from a prospective, noninterventional study in European clinical practice (VIBES)
Authors: Rudà Roberta , Houillier Caroline , Maschio Marta , Reijneveld Jaap C. , Hellot Scarlett , De Backer Marc , Chan Jane , Joeres Lars , Leunikava Iryna , Glas Martin , Grant Robin
Published: April 2020

Objective

To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor–related epilepsy (BTRE), and to evaluate patients’ global impression of change and quality of life (QoL).

Methods

This was a prospective, multicenter, single‐arm, noninterventional study with a 6‐month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low‐grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure‐free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5‐Level EuroQol‐5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory–Brain Tumor) from baseline to month 6, and Kaplan‐Meier estimated 6‐month retention on lacosamide. Safety variables included adverse drug reactions (ADRs).

Results

Patients were recruited from 24 sites in Europe. Ninety‐three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1‐280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure‐free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. Kaplan‐Meier estimated 6‐month retention rate was 86.0% (N = 93). Fifteen (16.1%) patients reported ADRs; four (4.3%) had ADRs leading to discontinuation (N = 93).

Significance

Results of this prospective, noninterventional study suggest that add‐on lacosamide is effective and generally well tolerated in patients with BTRE.
The Spirit of Truth
Authors: Moltmann Jürgen
Published: April 2020

This article reflects on the theme of the “spirit of truth” in a post‐truth era – a time in which objective truth seems to no longer exist, any given claim can be substantiated, and it is no longer possible to tell falsehood and truth apart. Focusing on the objectivity of science, the humanity of truth, and the spirit of truth revealed by divinity, the article argues for the adoption of a humane and ecological wisdom, seeing it as a way to deal with humanity’s immense knowledge in a way that is conducive to life, to avoid optimizing humans in a “trans‐human” way and making the earth uninhabitable.
Communication for Life in Cyberspace
Authors: Cheon Young‐cheol
Published: April 2020

Cyberspace communication is a key driving force of the neoliberal globalization that has led to worldwide crisis. Despite some positive perspectives, cyberspace communication has played a crucial role in the dominance of global markets by transnational corporations. The ethical foundations of the problematics of cyberspace communication lie in a social Darwinism that leads to ruthless competition based on egoistic morality. This article posits the notion of love as an alternative ethics, drawing on perspectives of Christian love (especially those of US ethicist Paul Ramsey) as unselfish love for others, as well as on East Asian traditions of love (such as Buddhist compassion, Confucian jen, and Korean jung). The article argues that unselfish love offers a perspective to overcome an anthropocentric perspective of communication. In this way, human beings can build a community with all living beings and develop harmonious relationships with them to live together on the earth.
Sallie McFague and an Ecotheological Response to Artificial Intelligence
Authors: Green Erin
Published: April 2020

Military, commercial, and industrial application of artificial intelligence (AI) presents distinct historical challenges for theological reasoning. To date, interdisciplinary theological responses have been limited. Contextual and ecological theologies provide an understanding of the human that is helpful in theological responses to AI. These theologies emphasize a relational, embodied view of the human that responds to and resolves many of the shortcomings found in AI research and related theological responses. Sallie McFague's emphasis on embodiment and the world as God's body is an especially useful contribution to these efforts.
Living in a Digital Culture
Authors: Cloete Anita L.
Published: April 2020

Today our lives are filled with technology through which we communicate, work, play, and even engage with for making meaning. This implies the pervasive presence of digital media as an integral part of our everyday life. Although studies on media are mostly done by sociology and communication students, living in a digital age has significant implications for theological reflections. Despite this being the case, there is a gap in terms of a religious response to technology. In response to this, the aim of this article is to stimulate theological reflections with regard to living in a digital culture. This is achieved by raising theological questions in the hope that theology could take a proactive role in these discussions. The implications of living in a digital culture are quite vast; therefore, the focus will be limited to how a community is formed and sustained, and the possible implications for the church as community.