bluuebunny/crossref_metadata_2025 huggingface dataset:
Mice Lacking FXR Are Susceptible to Liver Ischemia-Reperfusion Injury
Authors: Li Yuxin , Xu Rui , Rao Prahlad K. , Gomes Charles K , Moran E. Richard , Puchowicz Michelle , Chang Eugene B. , Yin Deng Ping , Pierre Joseph F.
Published: August 2019

Activation of bile acid (BA) receptor, farnesoid X receptor (FXR) has been shown to inhibit inflammatory responses and improve tissue ischemia-reperfusion injury (IRI). This study investigated the effect of FXR deficiency on liver IRI, using a liver warm IRI mouse model. We demonstrate that liver IRI resulted in decreased FXR expression in the liver of WT mice. FXR-/-mice displayed greater liver damage and inflammatory responses than WT mice, characterized by significant increases in liver weight, serum AST and ALT, hepatocyte apoptosis and liver inflammatory cytokines. Liver IRI increased expression of X box binding protein 1 (XBP1) and FGF21 in WT liver, but not in FXR-/-liver, which conversely increased CHOP expression, suggesting a loss of ER stress protection in the absence of FXR. FXR deficiency increased circulating total BAs and altered BA composition with reduced TUDCA and hepatic BA synthesis markers. FXR deficiency also reshaped gut microbiota composition with increased Bacteroidetes and Proteobacteria and decreased Firmicutes. Curiously, Bacteroidetes were positively and Firmicutes were negatively correlated with serum ALT levels. Administration of FXR agonist CDCA inhibited NF-κB activity and TNFα expressionin vitroand improved liver IRIin vivo. Our findings demonstrate that FXR signaling plays an important role in the modulation of liver IRI.
Effects of breed, management and personality on cortisol reactivity in sport horses
Authors: Sauer Fay J. , Hermann Marco , Ramseyer Alessandra , Burger Dominik , Riemer Stefanie , Gerber Vinzenz
Published: August 2019

Sport horses need to fulfill high physical and psychological requirements during training and competition. These as well as certain conditions of modern husbandry may affect their wellbeing. Here we aimed to (1) evaluate effects of demographic and management factors as well as personality traits on stress reactivity of sport horses, (2) investigate if elite sport horses have elevated stress levels compared to amateur sport horses, and (3) assess whether different equestrian disciplines differentially influence horses’ adrenal cortex responsiveness. For this purpose, we visited 149 healthy elite (n=94) and amateur (n=54) sport horses in Switzerland and performed an adrenocorticotropic hormone (ACTH) stimulation test. Additionally, a person who was familiar with the horse completed a questionnaire about demographic and management factors and horses’ personality traits. Linear models were calculated to assess associations between the questionnaire data and salivary cortisol 60 and 90 minutes after ACTH stimulation. While the model at T90 was not significant, post-stimulatory cortisol after 60 min appears most informative in line with a previous study and was significantly affected by the horses’ breed and by three management factors: “number of riders”, “hours spent outside” and “group housing” (adjusted r2=15%, p<0.001). Thoroughbred and Warmblood horses displayed an increased adrenal response compared to Franches-Montagnes horses. Horses with several riders had a less pronounced reaction than horses with one rider, and horses that spent more time outside had a decreased response compared to horses that were stabled most of the time. Horses living in groups showed higher post-stimulatory cortisol values than horses that were housed singly. However, no significant associations of cortisol responsiveness with personality traits were found, and neither the horses’ use as elite or as amateur sport horses nor the discipline had an effect on the cortisol response. This suggests that optimizing husbandry conditions may be more important for improving horses’ welfare than changing their use.
High circulating elafin levels are associated with Crohn’s disease-associated intestinal strictures
Authors: Wang Jiani , Ortiz Christina , Fontenot Lindsey , Xie Ying , Ho Wendy , Mattai S. Anjani , Shih David Q , Koon Hon Wai
Published: August 2019

Objective

Nearly 33% of Crohn’s disease (CD) patients develop intestinal strictures. Antimicrobial peptide or protein expression is associated with disease activity in inflammatory bowel disease (IBD) patients. Circulating blood cells and intestine of IBD patients have abnormal expression of elafin, a human elastase-specific protease inhibitor and antimicrobial peptide. However, the association between elafin and CD-associated intestinal stricture is unknown. We hypothesize the elafin expression in stricturing CD patients is abnormal. We determined the expression of elafin in blood, intestine, and mesenteric fat in IBD patients.

Methods

Human colonic and mesenteric fat tissues and serum samples were collected from the Cedars-Sinai Medical Center and UCLA, respectively.

Results

High serum elafin levels were associated with a significantly elevated risk of intestinal stricture in CD patients. Machine learning algorithm using serum elafin levels and clinical data identified stricturing CD patients with high accuracy. Serum elafin levels had weak positive correlation with clinical disease activity (Partial Mayo Score and Harvey Bradshaw Index) in IBD patients. Ulcerative colitis (UC) patients had high serum elafin levels, but the increase was not associated with endoscopic Mayo score. Colonic elafin mRNA and protein expression were not associated with clinical disease activity in IBD patients, while stricturing CD patients had low colonic elafin expression. Mesenteric fat in stricturing CD patients had significantly increased elafin mRNA expression, which may contribute to high circulating elafin level.

Conclusion

High serum elafin levels and adipose elafin expression are associated with intestinal strictures, which may help identify intestinal strictures in CD patients.
Transethnic meta-analysis of genome-wide association studies identifies three new loci and characterizes population-specific differences for coronary artery disease
Authors: Matsunaga Hiroshi , Ito Kaoru , Akiyama Masato , Takahashi Atsushi , Koyama Satoshi , Nomura Seitaro , Ieki Hirotaka , Ozaki Kouichi , Onouchi Yoshihiro , Suna Shinichiro , Ogishima Soichi , Yamamoto Masayuki , Hozawa Atsushi , Satoh Mamoru , Sasaki Makoto , Yamaji Taiki , Sawada Norie , Iwasaki Motoki , Tsugane Shoichiro , Tanaka Keitaro , Arisawa Kokichi , Ikezaki Hiroaki , Takashima Naoyuki , Naito Mariko , Wakai Kenji , Tanaka Hideo , Sakata Yasuhiko , Morita Hiroyuki , Sakata Yasushi , Matsuda Koichi , Murakami Yoshinori , Akazawa Hiroshi , Kubo Michiaki , Kamatani Yoichiro , Komuro Issei
Published: August 2019

Background

Genome-wide association studies (GWAS) provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. GWAS in diverse populations have the potential to advance our understanding of CAD.

Methods and Results

We conducted two GWAS for CAD in the Japanese population, which included 12,494 cases and 28,879 controls, and 2,808 cases and 7,261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the CARDIoGRAMplusC4D 1000 Genomes meta-analysis with UK Biobank. We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands and fat tissues in the development of CAD. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies, and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans.

Conclusions

We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.
Freshwater soundscapes: a cacophony of undescribed biological sounds now threatened by anthropogenic noise
Authors: Rountree Rodney A. , Juanes Francis , Bolgan Marta
Published: August 2019

The soundscape composition of freshwater habitats is poorly understood. Our goal was to document the occurrence of biological sounds in a large variety of freshwater habitats over a large geographic area. The underwater soundscape was sampled in freshwater habitat categorized as brook/creek, pond/lake, or river, from five major river systems in North America (Connecticut, Kennebec, Merrimack, Presumpscot, and Saco) over a five-week period in the spring of 2008. Over 7,000 sounds were measured from 2,750 minutes of recording in 173 locations, and classified into major anthropophony (airplane, boat, traffic, train and other noise) and biophony (fish air movement, also known as air passage, other fish, insect-like, bird, and other biological) sound categories. Anthropogenic noise dominated the soundscape of all habitats averaging 15 % of time per recording compared to less than 2 % for biological sounds. Anthropophony occurred in 79 % of recordings and was mainly due to traffic and boat sounds, which exhibited significant differences among habitats and between non-tidal and tidal river regions. Most biophonic sounds were from unidentified insect-like, air movement fish, and other fish sound sources that occurred in 57 % of recordings. Mean frequencies of anthropogenic noises overlapped strongly with the biophony, and comparisons of spectra suggest that insect- like and air movement sounds may be more susceptible to masking than other fish sounds. There was a significant decline in biodiversity and biophony with increasing ambient sound levels. Our poor understanding of the biophony of freshwater ecosystems, together with an apparent high temporal exposure to anthropogenic noise across all habitats, suggest a critical need for studies aimed at identification of biophonic sound sources and assessment of potential threats from anthropogenic noises.
Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44
Authors: Malik Nazma , Nirujogi Raja S , Peltier Julien , Macartney Thomas , Wightman Melanie , Prescott Alan R , Gourlay Robert , Trost Matthias , Alessi Dario R. , Karapetsas Athanasios
Published: August 2019

The serum- and glucocorticoid-regulated kinase (SGK) isoforms contribute resistance to cancer therapies targeting the PI3K pathway. SGKs are homologous to Akt and these kinases display overlapping specificity and phosphorylate several substrates at the same residues, such as TSC2 to promote tumor growth by switching on the mTORC1 pathway. The SGK3 isoform is upregulated in breast cancer cells treated with PI3K or Akt inhibitors and recruited and activated at endosomes, through its phox homology domain binding to PtdIns(3)P. We undertook genetic and pharmacological phosphoproteomic screens to uncover novel SGK3 substrates. We identified 40 potential novel SGK3 substrates, including 4 endosomal proteins STX7 (Ser126) and STX12 (Ser139), RFIP4 (Ser527) and WDR44 (Ser346) that were efficiently phosphorylated in vitro by SGK3 at the sites identified in vivo, but poorly by Akt. We demonstrate that these substrates are poorly phosphorylated by Akt as they possess an n+1 residue from the phosphorylation site that is unfavorable for Akt phosphorylation. Phos-tag analysis revealed that stimulation of HEK293 cells with IGF1 to activate SGK3, promoted phosphorylation of a significant fraction of endogenous STX7 and STX12, in a manner that was blocked by knock-out of SGK3 or treatment with 14H inhibitor. SGK3 phosphorylation of STX12 enhanced interaction with the VAMP4/VTI1A/STX6 containing SNARE complex and promoted plasma membrane localization. Our data reveal novel substrates for SGK3 and suggest a mechanism by which STX7 and STX12 SNARE complexes are regulated by SGK3. They reveal new biomarkers for monitoring SGK3 pathway activity.
Investigations on the void coalescence and corrosion behaviour of titanium grade 4 sheets during single point incremental forming process
Authors: Yoganjaneyulu G. , Phaneendra Y. , Ravikumar V.V. , Sathiya Narayanan C.
Published: August 2019

Purpose

The purpose of this paper is to investigate the void coalescence and corrosion behaviour of titanium Grade 4 sheets during single point incremental forming (SPIF) process with various spindle rotational speeds. The development of corrosion pits in 3.5 (%) NaCl solution has also been studied during SPIF process.

Design/methodology/approach

In this current research work, the void coalescence analysis and corrosion behaviour of titanium Grade 4 specimens were studied. A potentio-dynamic polarization (PDP) study was conducted to investigate the corrosion behaviour of titanium Grade 4 processed samples with various spindle speeds in 3.5 (%) NaCl solution. The scanning electron microscope and transmission electron microscope analysis was carried out to study the fracture behaviour and corrosion morphology of processed samples.

Findings

The titanium Grade 4 sheets obtained better formability and corrosion resistance by increasing the CNC spindle rotational speeds. In fact that, the significant plastic deformation affects the corrosion rate with various spindle speeds were recorded.

Originality/value

The spindle rotational speeds and vertical step depths increases then the titanium Grade 4 sheets showed better formability, void coalescence and corrosion behaviour as the same is evidenced in forming limit diagram and PDP curves.
Job satisfaction of project managers in green construction projects
Authors: Hwang Bon-Gang , Zhao Xiaojing , Lim Jane
Published: August 2019

Purpose

Green building is a promising approach to improve resource efficiency and achieving sustainable development. The success of green construction projects is closely associated with the performance of project managers (PMs), while job satisfaction plays a major role in the performance of PMs. However, the emphasis placed on the job satisfaction of PMs in green construction projects remains minimal. The purpose of this paper is to identify the relationships between the job satisfaction of PMs and its key influencing factors in green construction projects, and to propose feasible strategies to improve the job satisfaction of PMs.

Design/methodology/approach

A questionnaire survey is conducted, data collected from 105 construction PMs are analysed using structural equation modelling. Interviews with five industry experts are further conducted to substantiate the results.

Findings

The results identified four major components of job satisfaction, namely, “job content”, “resource adequacy”, “work context” and “the personality and competence of jobholders”. The analysis also found that “technical requirement” and “split incentive” condition of green construction projects, “the expertise and awareness of PMs” and “demand and support from stakeholders” has significant impacts on PMs’ job satisfaction. Furthermore, this study developed eight strategies to improve PMs’ job satisfaction, including “increase recognition opportunities for PMs”, “government incentives and financial support” and “introductory and training courses on green construction legislation and processes”.

Originality/value

The findings assist construction companies in formulating measures to improve the job satisfaction and performance of PMs in green construction projects.
Establishing a start-up in Saudi Arabia: the Innosoft story
Authors: Mohammed Riaz Ahmed , Horoub Mamon , Walwil Husam
Published: August 2019

Subject Area

Entrepreneurship.

Learning outcomes

The learning outcomes are to explain the importance of passion in entrepreneurship, develop an understanding of the business model canvas and its elements, identify typical challenges faced by a startup (during early days and while growing), explain the role of seed fund and customer feedback for small business success and identify the appropriate hiring strategy for startups.

Case overview/synopsis

The case traces the journey of two Saudi under-graduate software engineering students, namely, Loai Labani and Riyadh Al-Tayib, who had a vision to establish the best information technology (IT) services company in Saudi Arabia. With no previous experience of establishing a company or working for a startup, coupled with the fact that the culture of entrepreneurship in Saudi Arabia is still in its ascendancy, they knew it would be challenging. Nevertheless, at the same time, they were convinced it would be totally up to them to do the hard work needed to propel their vision into reality. The case, after introducing the founders, talks about their respective backgrounds and how it complemented their goal/vision of establishing an IT services company. The case, with references from the literature, also throws light on the entrepreneurship culture in Saudi Arabia but the focus is the various challenges faced by the team in setting up their business and the strategies they used in dealing with the challenges. Some of the challenges discussed are securing early customers, initial financing to support startup, business model development, managing daily operations and hiring and marketing strategy. The case ends with another challenge faced by the founders, for the readers to think about the possible ways of dealing with the challenge at hand.

Complexity academic level

The case will be used for under-graduate level students.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 3: Entrepreneurship.
Corporate governance and risk disclosure quality: Tunisian evidence
Authors: Salem Issal Haj , Ayadi Salma Damak , Hussainey Khaled
Published: August 2019

Purpose

The purpose of this paper is to investigate the potential influence of corporate governance mechanisms on risk disclosure quality in Tunisia.

Design/methodology/approach

The authors examine 152 annual reports of Tunisian non-financial-listed firms during 2008–2013, and use the manual content analysis method to measure the risk disclosure quality.

Findings

The authors find that the quality of risk disclosure in Tunisian companies is relatively low, and also find that the quality of risk disclosure is positively associated with institutional ownership, board independence, the presence of women on the board, the presence of family members on the board and the independence of audit committee. Managerial ownership has a negative effect on risk disclosure quality. Finally, the authors find that the revolution decreases the influence of concentration ownership, government ownership, family ownership and audit committee size on risk disclosure quality.

Originality/value

Using a comprehensive set of corporate governance mechanisms and a new measure for risk disclosure quality in Tunisia, the authors provide the first empirical evidence on the impact of corporate governance mechanisms on risk disclosure quality in a developing country. The study has theoretical and practical implications for both developed and developing countries.
Employee communication for engaging workplaces
Authors: Mazzei Alessandra , Butera Alfonsa , Quaratino Luca
Published: August 2019

Purpose

This paper aims to explore the role of employee engagement for competitiveness. In particular, the role of employee communication to create engaging workplaces.

Design/methodology/approach

Two field surveys were conducted to assess, which are the most relevant leverages that contribute to create engaging (or disengaging) workplaces in Italy: the first one on a statistical sample of large companies, the second one on a snowball sample of employees.

Findings

Italian companies often miss the opportunity to create engaging workplaces and to exploit the potential of employee communication to foster employee engagement.

Research limitations/implications

Further research could focus on a survey on a sample of managers and employees belonging to the same company.

Practical implications

Companies should pursue an inclusive relational approach, using employee communication appropriately.

Originality/value

The study develops and tests a model showing the linkages among managerial approaches and engaging workplace contexts and examines the role of employee communication to foster employee engagement.
Socioeconomic inequality and dental caries among Thai working age population
Authors: Amornsuradech Sirinthip , Vejvithee Warangkana
Published: August 2019

Purpose

The purpose of this paper is to determine the relationship between socioeconomic status (SES) and oral health among Thai adults.

Design/methodology/approach

This study is a cross-sectional analytical study using secondary data from the 7th Thailand National Oral Health Survey (2012). Age group 35–44 years old samples were used to represent the working age population. Oral health outcome was determined by untreated dental caries. SES was indicated by income, education and occupational groups. Demographic background, oral health-related behavior and access to dental service were adjusted for analysis. Binary logistic regression analysis was performed to determine the relationship between independent variables and oral health outcome.

Findings

People with lower education showed a higher odds ratio for having untreated dental caries before and after controlling for related variables. Those living in the north and northeast, using additional cleaning tools and going to the public provider for dental service also showed better oral health.

Research limitations/implications

The limitation of this study is that the cross-sectional study cannot indicate casual relationships. The national oral health survey was not designed to find relationships between factors. The access to data and measurement of SES was limited. The policy maker should emphasize on people with lower education which have a higher risk for dental caries to improve oral health in disadvantaged groups. Future research should include all related factors in the study including diet and knowledge about oral health. Moreover, oral health outcome is a long-term effect which accumulated through a lifetime. The social class might change over time and so do behaviors.

Originality/value

There is socioeconomic inequality in dental caries of Thai working age population.
Development and evaluation of human T‐cell leukemia virus‐1 and ‐2 multiplex quantitative PCR
Authors: Kuramitsu Madoka , Okuma Kazu , Tezuka Kenta , Nakamura Hitomi , Sagara Yasuko , Kurane Ichiro , Hamaguchi Isao
Published: August 2019

The diagnosis of human T ‐cell leukemia virus type 1 (HTLV‐1) infection in Japan is usually performed by serological testing, but the high rate of indeterminate results from western blotting makes it difficult to assess the infection accurately. Nucleic acid tests for HTLV‐1 and/or HTLV‐2 are used to confirm infection with HTLV‐1 and/or HTLV‐2 and are also used for the follow‐up of HTLV‐1 related diseases. To prepare a highly sensitive method that can discern infection with HTLV‐1 and HTLV‐2, a multiplex quantitative polymerase chain reaction (qPCR) by large‐scale primer screening was developed. Sensitivity and specificity were evaluated by serial dilution of cell lines and by testing with known clinical samples. The resulting multiplex qPCR can detect about four copies of HTLV‐1 provirus per 105 cells. Moreover, HTLV‐1 provirus could be detected in 97.2% (205 of 211) of HTLV‐1 seropositive clinical samples. These sensitivities were sufficiently high compared with the methods reported previously. Also, all the HTLV‐2 seropositive clinical samples tested were found to be positive by this method (three of three). In conclusion, this method can successfully and simultaneously detect both types of HTLV‐1 and HTLV‐2 provirus with extremely high sensitivity.
On possible fluid detection in equivalent transversely isotropic media
Authors: Adamus Filip P.
Published: August 2019

We consider a transversely isotropic medium that is long‐wave equivalent to a stack of thin, parallel, isotropic layers and is obtained using the Backus average. In such media, we analyse the relations among anisotropy parameters; Thomsen parameters, ε and δ, and a new parameter ϕ. We discuss the last parameter and show its essential properties; it equals 0 in the case of isotropy of equivalent medium and/or constant Lamé coefficient λ in layers. The second property occurs to make ϕ sensitive to variations of λ in thin‐bedded sequences. According to Gassmann, in isotropic media the variation of fluid content affects only the Lamé coefficient λ, not μ; thus, the sensitivity to changes of λ is an essential property in the context of possible detection of fluids. We show algebraically and numerically that ϕ is more sensitive to these variations than ε or δ. Nevertheless, each of these parameters is dependent on the changes of μ; to understand this influence, we exhibit comprehensive tables that illustrate the behaviour of anisotropy parameters with respect to specific variations of λ and μ. The changes of μ in layers can be presented by the Thomsen parameter γ that depends on them solely. Hence, knowing the values of elasticity coefficients of equivalent transversely isotropic medium, we may compute ϕ and γ, and based on the aforementioned tables, we predict the expected variation of λ; in this way, we propose a new method of possible fluid detection. Also, we show that the prior approach of possible detection of fluids, proposed by Berryman et al., may be unreliable in specific cases. To establish our results, we use the Monte Carlo method; for the range and chosen variations of Lamé coefficients λ and μ – relevant to sandstones – we generate these coefficients in thin layers and, after the averaging process, we obtain an equivalent transversely isotropic medium. We repeat that process numerous times to get many equivalent transversely isotropic media, and – for each of them  – we compute their anisotropy parameters. We illustrate ϕ, ε and δ in the form of cross‐plots that are relevant to the chosen variations of λ and μ. Additionally, we present a table with the computed ranges of anisotropy parameters that correspond to different variations of Lamé coefficients.
Managing hydropower dam releases for water users and imperiled fishes with contrasting thermal habitat requirements
Authors: Zarri Liam J. , Danner Eric M. , Daniels Miles E. , Palkovacs Eric P.
Published: August 2019

The construction of dams on large rivers has negative impacts on native species. Environmental flows have been proposed as a tool to mitigate these impacts, but in order for these strategies to be effective they must account for disparate temperature and flow needs of different species.

We applied a multi‐objective approach to identify trade‐offs in dam release discharge and temperature for imperiled fishes with contrasting habitat requirements, while simultaneously meeting the needs of human water users.

Using the Sacramento River (California, USA) as a case study, our model suggests that current management aimed at providing high discharge for downstream water users and cold water for endangered winter‐run Chinook salmon (Oncorhynchus tshawytscha) has detrimental impacts on threatened green sturgeon (Acipenser medirostris), which require warm water for juvenile growth.

We developed an optimal dam release scenario that can be used to meet the needs of salmon, sturgeon and human water users. Our results show that dam releases can be managed to successfully achieve these multiple objectives in all but the most severe drought years.

Synthesis and applications. This study shows that managing dam releases to meet the needs of a single species can have detrimental effects on other native species with different flow and temperature requirements. We applied a multi‐objective approach to balance environmental requirements of multiple species with the needs of human water users. Our findings can be used to guide management of Shasta Dam and our approach can be applied to achieve multi‐object management goals in other impounded rivers.
Propofol inhibits biological functions of leukaemia stem and differentiated cells through suppressing Wnt/β‐catenin and Akt/mTOR
Authors: Chen Liufang , Wan Yingchun , Liu Youtan , Li Tao
Published: August 2019

The biological roles of intravenous anaesthetic propofol in cancer have been shown by various studies using cancer cell lines that represent differentiated cancer cells. However, the activities of propofol in cancer stem cells have not been elucidated. In this work, we examined the effects and mechanisms of propofol on acute myeloid leukaemia (AML) differentiated and CD34+CD38− stem cells. We found that propofol inhibited growth, differentiation and self‐renewal capabilities of AML stem cells regardless of cellular origin and genetic profiling. In addition, propofol inhibited the growth of AML differentiated cells. Propofol significantly induced apoptosis of AML differentiated but not CD34+CD38− stem cells. We further found that propofol significantly augmented the efficacy of AML standard therapeutic drugs. Consistent with the previous findings, we showed that propofol suppressed the Akt/mTOR pathway in AML cells. We also found that propofol inhibited pathways important for stem cell maintenance and self‐renewal, such as Wnt/β‐catenin. Overexpression of constitutively active Akt partially reversed the inhibitory effects of propofol in AML differentiated cells. Stabilization of β‐catenin using genetic and pharmacological approaches also partially rescued the inhibitory effects of propofol in AML differentiated and stem cells. Our work shows that propofol targets leukaemia cells at all stages of development, in a cell type‐specific manner. Inhibition of both Akt/mTOR and Wnt/β‐catenin is required for the action of propofol in AML. Our findings also highlight the activities of propofol on cancer stem cells.
Embryo growth and dormancy in seeds of six Hosta species native to Korea
Authors: Ryu Sun‐Hee , Walck Jeffrey L. , Hidayati Siti N. , Rhie Yong‐Ha , Yang Jong‐Cheol , Lee Seung‐Youn
Published: August 2019

Although it has been speculated that Hosta seeds have an underdeveloped embryo and morphological (MD) or morphophysiological dormancy (MPD), no detailed studies have been carried out to definitively confirm this suggestion. Our first purpose was to determine if embryos of six Korean species of Hosta (H. capitata, H. clausa, H. jonesii, H. minor, H. venusta and H. yingeri) grew inside the seeds prior to germination (i.e., were underdeveloped) or did not do so (i.e., were fully developed). Our second purpose was to identify the class of dormancy found in these seeds by examining germination during incubation at 15 and/or 25°C. The initial embryo : seed ratio in seeds of the six Hosta species was between 0.78 and 0.85, and embryos elongated by 9.6 to 17.5% prior to germination. Seeds of H. capitata, H. clausa, H. venusta and H. yingeri germinated to ≥65% in light and darkness at 15 and 25°C within 30 days, those of H. minor germinated to ≥80% in light and darkness at 25°C and to 24% in light and 50% in darkness at 15°C, and those of H. jonesii germinated to 100% in light at 25°C. We conclude that embryos in seeds of these six Hosta species are underdeveloped at maturity. Because high percentages of H. capitata, H. clausa, H. venusta and H. yingeri seeds germinated at cold and warm temperatures within 30 days, they have MD. On the other hand, seeds of H. minor germinated to high and low percentages at warm and cold temperatures, respectively. Thus, some seeds have MD and others may have MPD.
Digital Privacy and Article 12 of the Universal Declaration of Human Rights
Authors: Woods Lorna
Published: August 2019

This article considers the impact of digital technologies on privacy and, specifically, the issues arising from metadata. It takes the 2016 Investigatory Powers Act as an exemplar and argues, by reference to European case law, that while data arising from new technologies undoubtedly fall within the scope of privacy protections, there are questions as to the level of protection awarded. Questions arise from how the nature and intensity of intrusion is understood against a backdrop of ‘dataveillance’, as well as the underlying issue of whether ex post controls—through oversight mechanisms—are sufficient to safeguard privacy.
A research note exploring firm action announcements and consumer attributions of blame: The moderating role of base‐rate information
Authors: Yuan Zhimei , Guo Yi , Wang Xingdong
Published: August 2019

Consumer attributions of negative events have significant implications for crisis communication. This paper employs a scenario‐based between‐subjects design experiment to examine the effects of two types of action announcement, technical and ceremonial, on consumer attributions under different base‐rate conditions (crisis frequency in category). The findings suggest that, under high base‐rate condition, technical action announcements lead to more controllability and stability attributions than ceremonial action announcements for uninvolved firms. Under low base‐rate condition, technical action announcements lead to more stability attributions than ceremonial action announcements for involved firms.
Investigation on the Interaction Behavior Between Oenothein B and Pepsin by Isothermal Titration Calorimetry and Spectral Studies
Authors: Liu Zitao , Wang Li , Shi Lei , Chen Xun , Chang Yanlei , Cao Yong , Zhao Lichao
Published: August 2019

Oenothein B (OeB) is a dimeric macrocyclic ellagitannin isolated from Herbs and fruits that have a variety of biological activities. In order to better understand the effect of OeB on the activity of the digestive enzyme pepsin, interactions between OeB and pepsin were investigated in vitro under simulated physiological conditions based on enzyme inhibition studies, fluorescence, isothermal titration calorimetry, CD, and molecular docking. It was found OeB is an effective inhibitor of pepsin, likely acting in a reversible manner through both competitive and noncompetitive inhibition. Fluorescence quenching of pepsin by OeB was a static quenching. CD spectra showed the addition of OeB causes the main chain of pepsin to loosen and expand and the partial β‐sheet structure to be converted to a disordered structure. Isothermal titration calorimetry and docking studies revealed the main binding mechanism of OeB and pepsin was through noncovalent interactions, hydrophobic interactions with OeB and the internal hydrophobic group of pepsin, and then hydrogen bonding between OeB and the Val243 and Asp77 residues of pepsin. Noncovalent bonds between OeB and pepsin change the polarity and structure of enzymes, decreasing enzymatic activity. Compared with small molecular polyphenols, OeB has a weaker hydrophobic interaction with pepsin and less effect on the secondary structure of pepsin. These findings are the first direct elucidation of the interactions between the oligomer ellagitannin OeB and pepsin, further contributing to understanding binding between oligomer ellagitannins and digestive enzymes.

Practical Application

The results of this study indicate that the interaction between OeB and pepsin has a certain inhibitory effect on pepsin. In order to reduce the impact of OeB on human digestion and its own activities, nano‐encapsulation technology can be used in the future to protect oligomeric ellagitannin such as OeB.
Drivers of Liking in a Model Retorted Creamy Tomato Soup System with Varying Levels of Sodium, Fat, and Herbs
Authors: Cox Ginnefer O. , Lee Youngsoo , Lee Soo‐Yeun
Published: August 2019

Targeting both sodium and fat reduction in processed foods while maintaining consumer acceptance is a challenge in the food industry due to the innate liking by humans toward both ingredients. Canned soup is one of the leading processed food categories containing high quantities of sodium. Efforts to reduce both sodium and fat content in canned soup products have been problematic due to resulting decreased consumer acceptance. The objective of this study was to characterize the changes in the drivers of liking when sodium, fat, and herb levels are varied in a model retorted soup system. A creamy tomato soup system was developed containing four fat levels (free, low, reduced, regular), three sodium levels (low, reduced, regular), and two herb levels (with, without). Ninety‐six consumers rated the soups for overall liking on a 9‐point hedonic scale. A descriptive analysis panel composed of 10 trained panelists profiled the sensory attributes among the soups. Higher sodium level was found to be a driver of liking when fat content was reduced. Soups were significantly different in saltiness (taste) and tomato (aroma‐by‐mouth), based on varying fat and sodium levels. Herb content increased overall liking of lower sodium and fat soups and impacted attribute characterization of soups. Future steps would include approaches to increase overall liking of lower fat and sodium soups. Formulation modifications that would decrease intensities of attributes that characterize lower fat and sodium soups, such as sour (taste and aftertaste), grainy (texture), and darkness (appearance), will aid in higher consumer acceptance of these soups.

Practical Application

With hypertensive individuals requiring reductions of both dietary sodium and fat, food products lower in fat and sodium while maintaining sensory acceptability are needed. Identifying drivers of liking when sodium and fat levels are reduced in processed food systems can assist in product reformulation to increase overall liking. Additionally, understanding the impact of herbs in consumer acceptance of lower sodium and fat food products will also contribute to further advances in product development.
Compartmentalized effects of aging on group 2 innate lymphoid cell development and function
Authors: D'Souza Shanti S. , Shen Xiaofei , Fung Ivan T. H. , Ye Longyun , Kuentzel Marcy , Chittur Sridar V. , Furuya Yoichi , Siebel Christian W. , Maillard Ivan P. , Metzger Dennis W. , Yang Qi
Published: August 2019

The effects of aging on innate immunity and the resulting impacts on immunosenescence remain poorly understood. Here, we report that aging induces compartmentalized changes to the development and function of group 2 innate lymphoid cells (ILC2), an ILC subset implicated in pulmonary homeostasis and tissue repair. Aging enhances bone marrow early ILC2 development through Notch signaling, but the newly generated circulating ILC2 are unable to settle in the lungs to replenish the concomitantly declining mature lung ILC2 pool in aged mice. Aged lung ILC2 are transcriptomically heterogeneous and functionally compromised, failing to produce cytokines at homeostasis and during influenza infection. They have reduced expression of Cyp2e1, a cytochrome P450 oxidase required for optimal ILC2 function. Transfer of lung ILC2 from young mice enhances resistance to influenza infection in old mice. These data highlight compartmentalized effects of aging on ILC and indicate that targeting tissue‐resident ILCs might unlock therapies to enhance resistance to infections and diseases in the elderly.
Evaluation of patient‐reported outcome measures of functional recovery following caesarean section: a systematic review using the consensus‐based standards for the selection of health measurement instruments (COSMIN) checklist
Authors: Sharawi N. , Klima L. , Shah R. , Blake L. , Carvalho B. , Sultan P.
Published: August 2019

We performed a systematic review using ‘consensus‐based standards for the selection of health measurement instruments’ (COSMIN) criteria to identify and evaluate the quality of patient‐reported outcome measures (PROM) instruments that have been utilised to assess functional recovery following caesarean section, and determine the optimal instrument for use in this setting. A literature search was performed using five databases. Studies were included if a psychometrically validated instrument was used to assess functional recovery following caesarean section. The COSMIN appraisal checklist was utilised to: assess the quality of included studies reporting PROMs; determine psychometric quality of instruments; and identify the most promising instruments for use after caesarean section. We identified 13 PROMs used to assess the quality of recovery after caesarean section in 20 studies that included 9214 patients. All PROMs contained between two and seven domains. Five out of the 13 PROMs were specific to postpartum recovery. Only two of these PROM instruments were specifically designed for use after caesarean section (Obstetric Quality of Recovery‐11 and Recovery from Caesarean Section Scale). We found very few adequate measures of functional recovery following caesarean section. Overall, the Obstetric Quality of Recovery‐11 achieved the highest COSMIN standards for any PROM. Future development of PROMs for use after caesarean section should include multiple domains, and undergo validation as outlined by the COSMIN criteria.
Biventricular Impella use in pediatric patients with severe graft dysfunction from acute rejection after heart transplantation
Authors: Ankola Ashish A. , McAllister Jennie , Turner Mariel E. , Zuckerman Warren A. , Richmond Marc E. , Addonizio Linda J. , Lee Teresa M. , Law Sabrina P.
Published: August 2019

Rejection with severe hemodynamic compromise is a significant source of morbidity and mortality for pediatric heart transplant patients. Traditionally, treatment for these patients includes inotropes and escalation to extracorporeal membrane oxygenation (ECMO) when necessary. There is increasing interest in using percutaneous ventricular assistive devices in the pediatric population as a less invasive alternative to ECMO. We report the largest case series to date of biventricular support using percutaneous Impella devices. Retrospective case series was performed by chart review. Hemodynamics, left ventricular ejection fraction (LVEF), and indices of end organ function were collected before and after Impella placement. A 14‐year‐old male, 18‐year‐old male, and 19‐year‐old female, all status post heart transplant, presented with severely decreased biventricular function due to presumed clinical rejection, requiring maximal inotropic support without improvement. In all the three cases, simultaneous Impella CP and RP devices were placed percutaneously. Prior to implantation, LVEFs were 40%, 23%, and 25%, respectively. Hemodynamics measured invasively prior to device placement showed elevated filling pressures. Adverse events while on support included bleeding, hemolysis, and right femoral arterial dissection during implantation. All patients were successfully weaned from the devices and survived to discharge. The average time of right‐sided support and total support was 11 days and 13 days, respectively. After device removal, right‐sided pressures and echocardiographic measurements showed improvement in all patients. Bilateral Impella configuration (BiPella) is a viable option for temporary mechanical circulatory support in pediatric patients with significant graft dysfunction.
The impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis ‐ A single center experience
Authors: Imamura Hajime , Minami Shigeki , Isagawa Yuriko , Morita Michi , Hirabaru Masataka , Kawahara Daisuke , Tokai Hirotaka , Noda Kazumasa , Inoue Keiji , Haraguchi Masashi , Eguchi Susumu
Published: August 2019

Aim

The risk of developing hemorrhagic complications during or after surgery in patients receiving antithrombotic therapy remains uncertain. Moreover, the impact of antithrombotic therapy under an acute inflammatory status is unclear. We investigated the impact of antithrombotic therapy in patients undergoing emergency laparoscopic cholecystectomy for acute cholecystitis.

Methods

This record‐based retrospective study included patients who underwent emergency laparoscopic cholecystectomy for acute cholecystitis between September 2015 and January 2019. Patients who received elective laparoscopic cholecystectomy, open cholecystectomy, or gallbladder drainage before surgery were excluded. We evaluated the diseases for which antithrombotic therapy was administered, background characteristics, laboratory parameters and perioperative outcomes of patients with acute cholecystitis. The primary outcomes were intraoperative bleeding, blood transfusion requirement, conversion to an open procedure, and postoperative complications, including bleeding.

Results

One hundred and twenty‐one patients (non‐antithrombotic therapy, n = 92; antithrombotic therapy, n = 29) were analyzed. There were differences in age and American Association of Anesthesiologists class (P < .05), but not in the grade of acute cholecystitis (P = .19). There were no differences in the operation time (non‐antithrombotic vs antithrombotic therapy: 142 [58‐313] vs 146 minutes [65‐373], P = .85), bleeding (17.5 mL [1‐1400] vs 25 mL [1‐1337], P = .58), blood transfusion requirement (n = 3 [3.2%] vs n = 2 [6.9%], P = .59) and the number of cases converted to open surgery (n = 8 [9%] vs n = 2 [7%], P = 1). The rates of postoperative complications, including bleeding, did not differ between the two groups and there was no mortality in either group.

Conclusion

Emergency laparoscopic cholecystectomy could be planned for patients receiving single antithrombotic therapy, similar to patients who were not receiving antithrombotic therapy.
How we manage Bing–Neel syndrome
Authors: Castillo Jorge J. , Treon Steven P.
Published: August 2019

Bing–Neel syndrome (BNS) is an uncommon presentation of Waldenström macroglobulinaemia (WM), seen during the course of the disease in about 1% of patients. BNS occurs when WM cells gain access to the central nervous system (CNS) causing neurological deficits. The diagnosis of BNS is suggested by the presence of radiological abnormalities, such as leptomeningeal enhancement on magnetic resonance imaging and confirmed by the presence of clonal lymphoplasmacytic cells and MYD88 L265P in the cerebrospinal fluid. The treatment of BNS requires agents with good penetration into the CNS, such as fludarabine, methotrexate and cytarabine. The novel Bruton Tyrosine Kinase inhibitor ibrutinib has shown CNS‐penetrating properties, and recent data suggest a therapeutic role in BNS. In this review, we will discuss the clinical and pathological features, diagnostic criteria, treatment options and outcomes of patients with BNS.