bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a digital library maturity model (DLMM)
Authors: Sheikhshoaei Fatemeh , Naghshineh Nader , Alidousti Sirous , Nakhoda Maryam
Published: September 2018

Purpose

There are many challenges in the development of a digital library (DL) and their complexity can be approached effectively with a maturity model. In a maturity model, the features of a phenomenon are divided into different levels and at each level, they are first improved before going on to the improvement or realization of the next level. The purpose of this study is to design a digital library maturity model (DLMM) in Iran.

Design/methodology/approach

The DLMM was designed using a qualitative approach, meta-synthesis and the Delphi technique. First, the maturity features of a DL were identified by assessing 68 sources of study concerning DLs and maturity models using meta-synthesis. The maturity features were then validated by experts using the three-round Delphi technique. Finally, the experts were asked to categorize these features into the five levels of the capability maturity model (CMM) as the base model.

Findings

By analyzing these sources, three categories, seven concepts and 35 codes for the maturity features of a DL were identified. The majority of previous studies focused on the use of hardware/software systems as the backup and empowerment of DLs and the concept of DL content. The maturity features were then validated by experts using the three-round Delphi technique. Like the base model, DLMM has five levels, and most features were categorized into the third and fourth levels by the experts. Features such as human resources, needs assessment of DL and readiness to create a DL were included in the second level.

Originality/value

This work adds the concept of the maturity model to the literature of DLs.
Do Twitter phenomena check-in popular venues on Foursquare too?
Authors: Bozanta Aysun , Kutlu Birgul
Published: September 2018

Purpose

The purpose of this study is to figure out the visiting behaviors of the users who have different characteristics on Twitter.

Design/methodology/approach

The visit history of users who share their Foursquare check-ins on Twitter and the characteristics of visited venues (category, check-in count, tip count, like count, rating, and price tier) was collected with Foursquare API. In addition, the number of followers, friends, tweets and favorite-count were collected via Twitter API. First, users were clustered according to their Twitter related attributes. After that, profiling was applied on clusters according to the characteristics of the venues that were visited by the users.

Findings

Clustering analysis generated three clusters, namely, ordinary, talkative and popular. For each cluster, the visited venues were investigated according to the price classification, check-in, like, tip counts and the categories. The users in ordinary class prefer cheaper venues rather than talkative and popular users. On the other hand, popular users prefer the venues with the highest average number of check-ins, likes and tip counts. The top two categories for all clusters are cafe and shopping mall.

Originality/value

This study differentiates from the other studies in the literature by examining the data from Twitter with clustering and profiling these clusters with Foursquare data to understand venue preferences of Twitter users having various characteristics. The findings of this study will provide new insights for business owners to understand the customers more comprehensively and design better marketing strategies.
Responsible entrepreneurship: outlining the contingencies
Authors: Vallaster Christine , Kraus Sascha , Kailer Norbert , Baldwin Brooke
Published: September 2018

Purpose

The purpose of this paper is to give an up-to-date assessment of key topics and methods discussed in the current literature on responsible entrepreneurship. In the past years, sustainable development itself has become a more popular and important topic in the academic literature and hence the field of sustainable entrepreneurship has become a greater topic of interest and opportunity for solution. Therefore, a systematic literature review is conducted to assess new contributions to the field and its potential for the future of sustainable development, with a focus on responsible innovation.

Design/methodology/approach

Systematic, evidence-informed literature review following Tranfieldet al.(2003).

Findings

Based on a conceptual literature review, five streams of research that responsible entrepreneurs distinguish from purely for-profit entrepreneurs are identified and discussed: walking the line between profit creation and value creation for society; business models of responsible entrepreneurs; their role in transforming society; getting ready to innovate responsibly; and the role of market incentives to foster sustainable business practices.

Originality/value

The structured literature review allows to identify future research paths. In detail, ideas as regards the management of upcoming tensions when trying to combine profit creation and value creation for society, and finally, the way innovation processes need to be rethought when innovating responsibly are discussed and outlined.
What’s the fuss? Gender and academic leadership
Authors: Wong Anne , McKey Colleen , Baxter Pamela
Published: September 2018

Purpose

Women continue to be disproportionately represented in top leadership positions. Leadership development programs typically focus on skills attainment. The purpose of this paper is to explore the perceptions and experiences of academic leaders in order to inform how leadership development programs may more effectively address the gender gap in leadership.

Design/methodology/approach

A sequential mixed methods study design was used. Participants completed the Leadership Practice Inventory ®(LPI) survey followed by individual interviews of a subset of participants. The survey results were analyzed and compared by gender using the t-test. Thematic analysis was used to compare themes across and between genders. Quantitative and qualitative findings were integrated in the final analysis.

Findings

In total, 65 leaders (38 women; 27 men) (37.7 percent response rate) participated in the survey. There were no significant demographic or statistical differences between women and men on any of the LPI® components. Five women and five men were interviewed. Thematic analysis revealed common leadership aspirations and values. Gender differences were noted in leadership attainment, mentorship and the influence of gender on leadership. While the male narratives reflected cognitive awareness of gender inequities, the female narratives also included lived experiences. Male participants focused on the importance of meritocracy whereas the female participants emphasized the gendered social and structural influences on leadership attainment.

Practical implications

Leadership development programs need go beyond generic “skills-building” in order to conceptualize leadership within a gendered social context. This framework will enable critical awareness and tools for developing both women and men’s fullest leadership potential.

Originality/value

This study was conducted in order to better understand how academic health leaders experience the intersection of gender and leadership. The findings contribute to the current literature by providing insight into perceptual gaps that exist at the level of practice between women and men leaders. In doing so, the authors discuss how leadership development programs may play a more effective role in addressing gender equity in leadership.
Darzi Clinical Leadership Fellows: an activity theory perspective
Authors: Malby Rebecca , Mervyn Kieran , Boyle Terry J.
Published: September 2018

Purpose

The purpose of this paper is to review the impact of the clinical leadership programme, in enabling the Darzi fellows to lead change projects in health and care services, and to secure quality healthcare in the NHS beyond the lifetime of the programme.

Design/methodology/approach

A longitudinal empirical investigation of clinical leaders (n=80) over an eight-year period was framed through an activity theory (AT)-driven research methodology using a mixed-methods approach.

Findings

AT illuminated how change was sustained in the NHS in London through the Darzi Clinical Leadership Fellowship. By any reasonable measurement, this programme excels, with learning and positive behavioural change sustained after the Fellowship across the NHS. Further recognition is needed of the continuing development needs of fellows as they take on more responsible leadership roles in their careers.

Research limitations/implications

Darzi fellows are a hard-to-reach group. The sample represents a response rate of 34 per cent. In total, 77 per cent of respondents emanated from cohorts 5 to 8 programmes.

Practical implications

The investment in a clinical leadership programme focused on systems leadership for quality generates value for the NHS.

Social implications

Countless interventions flowed through London’s healthcare community and beyond as a result of the Fellowship. This research exposed how Darzi fellows continue to lead innovation for alternative healthcare outcomes. Many proactive fellows employ a suite of learned skills and capabilities to lead systemic change.

Originality/value

This research is the first known longitudinal clinical leadership development study undertaken. The Darzi programme has created a unique clinical network of mutually supportive, team-centric systems thinkers and doers, with an evidence-based approach to systems change. Many fellows are catalysing sustainable change in the healthcare environment.
Wellbeing and coping strategies of alcohol and other drug therapeutic community workers: a qualitative study
Authors: Butler Mark , Savic Michael , Best David William , Manning Victoria , Mills Katherine L. , Lubman Dan I.
Published: September 2018

Purpose

The purpose of this paper is to examine the strategies utilised to facilitate the wellbeing of workers of an alcohol and other drug (AOD) therapeutic community (TC)

Design/methodology/approach

This paper reports on the findings of a qualitative study that involved in-depth interviews with 11 workers from an Australian AOD TC organisation that provides both a residential TC program and an outreach program. Interviews were analysed using thematic analysis

Findings

Three main interconnected themes emerged through analysis of the data: the challenges of working in an AOD TC organisation, including vicarious trauma, the isolation and safety of outreach workers and a lack of connection between teams; individual strategies for coping and facilitating wellbeing, such as family, friend and partner support and self-care practices; organisational facilitators of worker wellbeing, including staff supervision, employment conditions and the ability to communicate openly about stress. The analysis also revealed cross-cutting themes including the unique challenges and wellbeing support needs of outreach and lived experience workers.

Research limitations/implications

Rather than just preventing burnout, AOD TC organisations can also play a role in facilitating worker wellbeing.

Practical implications

This paper discusses a number of practical suggestions and indicates that additional strategies targeted at “at risk” teams or groups of workers may be needed alongside organisation-wide strategies.

Originality/value

This paper provides a novel and in-depth analysis of strategies to facilitate TC worker wellbeing and has implications for TC staff, managers and researchers.
Traits associated with treatment retention in a therapeutic community for substance dependence
Authors: Lyvers Michael , Jones Valli , Edwards Mark , Wood Kim , Thorberg Fred Arne
Published: September 2018

Purpose

The treatment of severe and chronic substance dependence is challenged by high rates of treatment attrition, highlighting the need to identify factors that hinder treatment retention. The paper aims to discuss this issue.

Design/methodology/approach

The present study examined certain neurocognitive and personality traits in relation to treatment retention in a sample of 46 residents of an Australian therapeutic community (TC). The traits examined were previously found to be associated with problematic substance use in non-clinical samples and were also previously shown to differentiate TC clients from social drinkers. The hypothesis was thus that traits that appear to be risk factors for addictions are also likely to impact on TC treatment retention.

Findings

Group comparisons of those retained for more than the recommended 90 days vs those who left treatment prematurely showed that after controlling for the influence of depression, those who left treatment prematurely reported significantly higher levels of trait impulsivity, punishment sensitivity and executive cognitive dysfunction. There was a very high rate of alexithymia in the sample (52 per cent), but alexithymia was unrelated to retention.

Research limitations/implications

The final sample size was less than planned but reflected the strict participation criteria and temporal limitations of this study. No statistical assumptions were violated and the reliability indices of the scales completed by clients ranged from acceptable to excellent. Another limitation was that dropout cannot be assumed to mean relapse, as the reasons for client dropout were not available.

Originality/value

Findings highlight the important roles of trait factors in TC treatment retention in addition to the motivational and interpersonal factors identified in previous work.
Omega‐3 fatty acids in coronary heart disease: Recent updates and future perspectives
Authors: Ajith Thekkuttuparambil A. , Jayakumar Thankamani G.
Published: September 2018

Incidence of coronary heart disease (CHD) increases worldwide with varying etiological factors. In addition to the control of risk factors, dietary modification has been recommended to reduce the prevalence. Omega‐3 (ω‐3) fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of fish oil are beneficial for the prevention of CHD. The effect can be ascribed to anti‐inflammatory, vasodilating, antiarrhythmic, antihypertensive activities and lowering of triacyl glycerol level. The American Heart Association advises two fish meals per week in subjects without CHD or supplementation of 1 g of EPA plus DHA per day in subjects with CHD. Despite the beneficial effects of EPA/DHA reported in some of the clinical trials, results of many others were inconsistent that can be ascribed to short duration of studies, low doses of ω‐3 FAs, variations in the EPA:DHA ratio, selection of patients with different risk factors or interaction of ω‐3 FAs with drugs used in the therapy. Therefore, well designed clinical trials in various populations are warranted. This article discusses the current situation and future prospective of ω‐3 FAs in CHD.
Transport of ACE Inhibitory Peptides Ile‐Gln‐Pro and Val‐Glu‐Pro Derived from Spirulina platensis Across Caco‐2 Monolayers
Authors: He Yuan‐Yuan , Li Tao‐Tao , Chen Jia‐Xin , She Xing‐Xing , Ren Di‐Feng , Lu Jun
Published: September 2018

This study evaluated transepithelial transport mechanisms of Ile‐Gln‐Pro (IQP) and Val‐Glu‐Pro (VEP), two ACE‐inhibitory peptides derived from Spirulina platensis, using human intestinal Caco‐2 cell monolayers. IQP and VEP were absorbed intact through Caco‐2 cell monolayers with Papp values of 7.48 ± 0.58 × 10−6 and 5.05 ± 0.74 × 10−6 cm/s, respectively. The transport of IQP and VEP were affected neither by Gly‐Pro nor by wortmannin, indicating that they were not PepT1‐mediated and did not involve endocytosis. However, transport of IQP and VEP were increased significantly by sodium deoxycholate, suggesting that the major transport mechanism was paracellular. In addition, the increased transport of VEP and IQP were followed with the addition of sodium azide, suggesting influence of energy to the process. The transport of VEP was also increased by verapamil, indicating an apical‐to‐basolateral flux mediated by P‐gp.

Practical Application

Bioactive peptides derived from food proteins have been considered as potentially ideal products to reduce hypertension because of their safety and positive impacts on health. IQP and VEP are the 2 ACE inhibitory peptides derived from Spirulina platensis, a kind of edible cyanobacteria with rich nutrition and multiple physiological functions, and were demonstrated to inhibit ACE and lower blood pressure in spontaneously hypertensive rats. However, it is prerequisite that such bioactive peptides must be absorbed intact across the intestinal epithelium, so as to exert antihypertensive effects in vivo. This study evaluated transepithelial transport mechanisms of IQP and VEP. It contributes to the study of Spirulina in lowering blood pressure and supports the development of bioactive peptide products.
Mandibular canines with additional roots: An ex vivo study of the external and internal morphology
Authors: Beltes Panagiotis , Kantilieraki Eleni , Kalaitzoglou Maria‐Elpida , Beltes Charalampos , Angelopoulos Christos
Published: September 2018

The aim of this study was to investigate the root and root canal morphologies of mandibular canines with additional roots using cone‐beam computed tomography. Seventy‐seven extracted two‐rooted and one‐three‐rooted permanent human mandibular canines were selected. Aspects of the external morphology evaluated were crown length, root length, total length, root bifurcation distance from the cementoenamel junction, root size, and direction of the root curvature in the apical third. Features of internal morphology assessed were root canal number per root, root canal bifurcation distance from the cementoenamel junction, and the angle between the buccal or lingual canal and the main canal. The root size and length presented considerable diversity. Most of the roots bifurcated at the middle third and exhibited a buccal curvature. The main root canal bifurcated coronally in two root canals, a buccal and a lingual. The majority of the buccal and lingual root canal angles were blunt. The presence of a third root in a specimen was a novel finding of this study.
Population structure, genetic diversity and selection signatures within seven indigenous Pakistani goat populations
Authors: Kumar C. , Song S. , Dewani P. , Kumar M. , Parkash O. , Ma Y. , Malhi K. K. , Yang N. , Mwacharo J. M. , He X. , Jiang L.
Published: September 2018

Goat farming in Pakistan depends on indigenous breeds that have adapted to specific agro‐ecological conditions. Pakistan has a rich resource of goat breeds, and the genetic diversity of these goat breeds is largely unknown. In this study, genetic diversity and population structure were characterized from seven indigenous goat breeds using the goat 50K SNP chip. The genetic diversity analysis showed that Bugi toori goats have the highest inbreeding level, consistent with the highest linkage disequilibrium, lowest diversity and long run of heterozygosity segments. This indicates that this breed should be prioritized in future conservation activities. The population structure analysis revealed four fairly distinct clusters (including Bugi toori, Bari, Black Tapri and some Kamori) and three other breeds that are seemingly the results of admixture between these or related groups (some Kamori, Pateri, Tapri and White Tapri). The selection signatures were evaluated in each breed. A total of 2508 putative selection signals were reported. The 26 significant windows were identified in more than four breeds, and selection signatures spanned several genes that directly or indirectly influence traits included coat colour variation (KIT), reproduction (BMPR1B, GNRHR, INSL6, JAK2 and EGR4), body size (SOCS2), ear size (MSRB3) and milk composition (ABCG2, SPP1, CSN1S2, CSN2, CSN3 and PROLACTIN).
Somatic innervation contributes to the release of bulbourethral gland secretion in male rats
Authors: Palacios J. L. , Arellano J. , Lucio R. A. , Hernández M. E. , Manzo J. , Tlachi J. L. , Cruz Y.
Published: September 2018

Background

In male rats, the bulbourethral glands (Bu‐Gs) are the unique accessory sexual glands surrounded by striated musculature. However, until now the role of this musculature was unknown.

Objectives

(i) To characterize the Bu‐Gs striated muscular layer in male rats and determine its innervation and response to genital stimulation. (ii) To reveal the role of the Bu‐Gs striated musculature in the release of glandular secretion. (iii) To elucidate the effect of bilateral ablation of the Bu‐Gs on copulatory behavior and seminal fluid characteristics.

Materials and methods

Adult Wistar male rats were allocated in three experiments: in Experiment 1, the Bu‐Gs striated musculature, innervation and reflex activity were determined by gross anatomy and histological and electrophysiological techniques; electromyographic activity of the Bu‐Gs striated musculature was evoked with genital stimulation. In Experiment 2, Bu‐Gs were analyzed after copulatory behavior of intact or animals with unilateral transected motor branch of the sacral plexus (MBSP). In Experiment 3, copulatory behavior and spermatobioscopy of males with bilateral ablation of the Bu‐Gs or sham surgery were analyzed.

Results

The Bu‐Gs striated fibers discharged in response to mechanostimulation of the prepuce, glans, and penile‐urethra. Innervation of the Bu‐Gs striated musculature originated from the MBSP; this nerve also innervates striated penile muscles. Unilateral transection of the MBSP significantly decreased the secretion from the ipsilateral Bu‐G to the nerve transection. Bilateral ablation of Bu‐Gs did not affect seminal plug formation but decreased semen viscosity.

Discussion and conclusion

The Bu‐Gs striated musculature contributes to expel glandular secretion during sexual intercourse. The somatic control of Bu‐Gs secretion is additional to the reported autonomic innervation supplied by the cavernosus nerve, which may underlie the synthesis of secretion as well as contraction of Bu‐Gs smooth muscle.
Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Decreases During the Summer in Dialysis Patients
Authors: Ramsauer Bernd , Graaff Reindert , Sikole Aleksandar , Trajceska Lada , Lundström Sara , Arsov Stefan , Hadimeri Henrik , Stegmayr Bernd
Published: September 2018

Tissue advanced glycation end products (AGEs) are a measure of cumulative metabolic and oxidative stress and cytokine‐driven inflammatory reactions. AGEs are thought to contribute to the cardiovascular complications of hemodialysis (HD) patients. Skin autofluorescence (SAF) is related to the tissue accumulation of AGEs and rises with age. SAF is one of the strongest prognostic markers of mortality in these patients. The content of AGEs is high in barbecue food. Due to the location in northern Sweden, there is a short intense barbecue season between June and August. The aim of this study was to investigate if seasonal variations in SAF exist in HD patients, especially during the barbecue season. SAF was measured noninvasively with an AGE Reader in 34 HD‐patients (15 of those with diabetes mellitus, DM). Each time the median of three measures were used. Skin‐AF was measured before and after each one HD at the end of February and May in 31 patients (22 men/9 women); the end of May and August in 28 (20 m/8 w); the end of August and March in 25 (19 m/6 w). Paired statistical analyses were performed during all four periods (n = 23, 17 m/6 w); as was HbA1c of those with DM. There was at a median 5.6% increase in skin‐AF during the winter period (February–May, P = 0.004) and a 10.6% decrease in the skin‐AF during the summer (May–August, P < 0.001). HbA1c in the DM rose during the summer (P = 0.013). In conclusion, skin‐AF decreased significantly during the summer. Future studies should look for favorable factors that prevent skin‐AF and subsequently cardiovascular diseases.
Reproductive activity in males of Sceloporus variabilis: Little time to rest, long time to breed
Authors: Peña‐Herrera Eric , Villagrán‐SantaCruz Maricela , Hernández‐Gallegos Oswaldo , Rheubert Justin L. , Gribbins Kevin M. , Granados‐González Gisela
Published: September 2018

The reproductive activity of reptiles is typically assessed using monthly sampling. The spermatogenic cycle of Sceloporus variabilis was recently assessed using the aforementioned methodology, and only two spermatogenic phases (recrudescence and maximum activity) were observed. The authors hypothesized that quiescence and regression must occur in a short period (less than a month), which was not visualized by their monthly sampling methods. Thus, the entire spermatogenic cycle displayed by this species may have not been adequately represented. The present study assessed the spermatogenic cycle of S. variabilis in those months where the spermatogenic activity passes from maximum activity (July) to recrudescence (August) using weekly sampling to test the hypothesis that quiescence and regression do indeed occur. The results showed a regression period for 2 weeks, whereas quiescence was not observed. These results lead us to two hypotheses: (a) quiescence occurs in a very short period (days/hours) or (b) does not occur in this species. The data generated in this study suggest that species exhibiting rapid changes in spermatogenic activity need to be assessed at more frequent intervals to accurately depict the spermatogenic stages.
Safety of bivalent human papillomavirus vaccine in the US vaccine adverse event reporting system (VAERS), 2009–2017
Authors: Suragh Tiffany A. , Lewis Paige , Arana Jorge , Mba‐Jonas Adamma , Li Rongxia , Stewart Brock , Shimabukuro Tom T. , Cano Maria
Published: September 2018

Aims

Human papillomavirus (HPV) vaccines prevent infection with oncogenic virus types. We analysed reports to the US Vaccine Adverse Event Reporting System (VAERS) of adverse events (AE) following bivalent HPV vaccine (2vHPV).

Methods

We conducted descriptive analysis of 2vHPV reports, reviewed individual reports, calculated crude AE reporting rates and conducted empirical Bayesian data mining.

Results

Of 241 2vHPV reports, 158 were in females, 64 in males (2vHPV is approved for females only) and 19 with unknown sex; 95.8% were classified as nonserious. Dizziness, headache, nausea and injection site reactions were the most common symptoms. Crude AE reporting rates were 33.3 reports per 100 000 doses distributed overall, and 1.4 per 100 000 for serious reports. Empirical Bayesian data mining identified disproportional reporting for three types of medical errors; assessment indicated findings that were probably driven by inadvertent 2vHPV use in males.

Conclusions

We did not identify any new or unexpected safety concerns in our review of 2vHPV reports to VAERS.
Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence
Authors: Theodoraki M-N , Hoffmann T K , Jackson E K , Whiteside T L
Published: September 2018

Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(−) exosomes by immune capture. CD3(−) exosomes were largely tumour-derived (CD44v3+). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(−) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+CD39+ regulatory T cells (Treg) co-incubated with these exosomes. The highest level of CD39/CD73 ectoenzymes and of adenosine production was found in CD3(−) exosomes in patients with the stages III/IV HNSCCs). Also, the production of 5′-AMP and purines was significantly higher in Treg co-incubated with CD3(−) than CD3(+) exosomes. Consistently, CD26 and adenosine deaminase (ADA) levels were higher in CD3(+) than CD3(−) exosomes. ADA and CD26 levels in CD3(+) exosomes were significantly higher in patients with early (stages I/II) than advanced (stages III/IV) disease. HNSCC patients receiving and responding to photodynamic therapy had increased ADA levels in CD3(+) exosomes with no increase in CD3(−) exosomes. The opposite roles of CD3(+) ADA+CD26+ and CD3(−)CD44v3+ adenosine-producing exosomes in early versus advanced HNSCC suggest that, like their parent cells, these exosomes serve as surrogates of immune suppression in cancer.
Prevalence and degree of insulin resistance in Chinese Han women with PCOS: Results from euglycemic‐hyperinsulinemic clamps
Authors: Li Weiping , Chen Qingfeng , Xie Yikai , Hu Jinbo , Yang Shumin , Lin Miaozhi
Published: September 2018

Objective

The euglycemic‐hyperinsulinemic clamp is the gold standard to evaluate insulin resistance (IR), but there are only a few studies on the prevalence of IR in Chinese Han women with polycystic ovary syndrome (PCOS). This study investigated: (a) the prevalence of IR in Chinese Han women with PCOS by clamp, (b) the degree of reduction in insulin sensitivity (IS) and the contribution of body mass index (BMI).

Design

Retrospective cross‐sectional analysis.

Patients

Chinese Han women with PCOS (n = 448) visiting the Department of Endocrinology or the Department of Obstetrics and Gynaecology of the First Affiliated Hospital of Chongqing Medical University. Chinese Han women without PCOS (controls) from the same area (n = 40).

Measurements

Clamp‐measured IS, age, BMI, and total testosterone.

Results

The prevalence of IR and reduction in IS were 56.3% and 30.3%, respectively, in Chinese Han women with PCOS (both P < 0.001). The inherent reduction in IS was 18.8% in lean women with PCOS and BMI independently reduced IS by 37.9% in obese women with PCOS. The prevalence of IR estimated by homeostatic model assessment (HOMA) was lower than that determined by clamp. The multivariable analysis showed that IR by clamp (R2 = 0.48, P < 0.001) was independently associated with BMI (β = −0.52, P < 0.001), waist‐hip ratio (β = −0.23, P < 0.001), total testosterone (β = −0.07, P = 0.045) and age (β = 0.17, P < 0.001), while IR by HOMA was only associated with BMI (R2 = 0.25, β = 0.50, P < 0.001). There were no differences in BMI groups distribution, HOMA‐IR and M values among the four PCOS subtypes (all P > 0.05).

Conclusions

56.3% of Chinese Han women with PCOS had IR and their reduction in IS was 30.3%. Obesity exacerbated the reduction in IS. When being evaluated by HOMA, the prevalence and the risk factors of IR in Chinese women with PCOS were underestimated.
Association between the “Timed Up and Go Test” at transplant evaluation and outcomes after kidney transplantation
Authors: Michelson Ariane T. , Tsapepas Demetra S. , Husain S. Ali , Brennan Corey , Chiles Mariana C. , Runge Brian , Lione Jennifer , Kil Byum H. , Cohen David J. , Ratner Lloyd E. , Mohan Sumit
Published: September 2018

Background

Studies have demonstrated the Timed Up and Go Test's (TUGT) ability to forecast postoperative outcomes for several surgical specialties. Evaluations of the TUGT for waitlist and posttransplant outcomes have yet to be examined in kidney transplantation.

Objective

To assess the prognostic utility of the TUGT and its associations with waitlist and posttransplant outcomes for kidney transplant candidates.

Design and Methods

Single‐center, prospective study of 518 patients who performed TUGT during their transplant evaluation between 9/1/2013‐11/30/2014. TUGT times were evaluated as a continuous variable or 3‐level discrete categorical variable with TUGT times categorized as long (>9 seconds), average (8‐9 seconds), or short (5‐8 seconds).

Results

Transplanted individuals had shorter TUGT times than those who remained on the waitlist (8.99 vs 9.79 seconds, P < 0.001). Bivariable and multivariable logistic regression showed that after adjusting for age, there was no association between TUGT times and probability of waitlist removal (OR 0.997 [0.814‐1.221]), prolonged length of stay posttransplant (OR 1.113 [0.958‐1.306] for deceased donor, OR 0.983 [0.757‐1.277] for living donor), and 30‐day readmissions (OR 0.984 [0.845‐1.146] for deceased donor, OR 1.254 [0.976‐1.613] for living donor).

Conclusions

The TUGT was not associated with waitlist removal or prolonged hospitalization for kidney transplant candidates. Alternative assessments of global health, such as functional status or frailty, should be considered for evaluation of potential kidney transplant candidates.
Hepatitis E virus genotype 3 is a common finding in liver‐transplanted patients undergoing liver biopsy for elevated liver enzymes with a low De Ritis ratio and suspected acute rejection: A real‐world cohort
Authors: Darstein Felix , Häuser Friederike , Straub Beate K. , Wenzel Jürgen J. , Conradi Roland , Mittler Jens , Lang Hauke , Galle Peter R. , Zimmermann Tim
Published: September 2018

Background

Hepatitis E virus (HEV) infection is a potential reason for elevated liver enzymes after liver transplantation (LT). Our aim was to analyze a real‐world cohort of LT patients, who underwent liver biopsy for elevated transaminases and suspected acute rejection, to evaluate frequency of post‐transplant HEV infection.

Patients

Data from 160 liver biopsies were analyzed. Seventy‐one patients were biopsied on schedule after LT without elevated liver enzymes. A subgroup of 25 patients with elevated liver enzymes and suspected rejection was chosen for further analysis. Patient demographics and data were retrieved from a clinical database, patients’ charts, and reports.

Results

Hepatitis E virus infection was diagnosed in five of 25 patients with suspected acute rejection (20%). HEV genotype 3 was detected in three of the five HEV‐infected patients. Patients with HEV infection showed higher ALT levels (P = 0.014), lower De Ritis ratio (P = 0.021), and more frequent glucocorticoid therapy (P = 0.012) compared to HEV‐negative patients.

Conclusion

We found a rate of 20% HEV infections in LT patients undergoing liver biopsy for elevated liver enzymes and suspected acute rejection. These data indicate the necessity for HEV testing in all LT patients with elevated liver enzymes and suspected acute rejection.
Impact of hepatic encephalopathy on liver transplant waiting list mortality in regions with different transplantation rates
Authors: Kerbert Annarein J. C. , Reverter Enric , Verbruggen Lara , Tieleman Madelon , Navasa Miguel , Mertens Bart J. A. , Rodríguez‐Tajes Sergio , de Vree Marleen , Metselaar Herold J. , Chiang Fang W. T. , Verspaget Hein W. , van Hoek Bart , Bosch Jaime , Coenraad Minneke J.
Published: September 2018

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing‐risk regression analysis was applied to assess the association of OHE with 1‐year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis‐related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9‐9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1‐year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.
Biosynthesis, structure, and folding of the insulin precursor protein
Authors: Liu Ming , Weiss Michael A. , Arunagiri Anoop , Yong Jing , Rege Nischay , Sun Jinhong , Haataja Leena , Kaufman Randal J. , Arvan Peter
Published: September 2018

Insulin synthesis in pancreatic β‐cells is initiated as preproinsulin. Prevailing glucose concentrations, which oscillate pre‐ and postprandially, exert major dynamic variation in preproinsulin biosynthesis. Accompanying upregulated translation of the insulin precursor includes elements of the endoplasmic reticulum (ER) translocation apparatus linked to successful orientation of the signal peptide, translocation and signal peptide cleavage of preproinsulin—all of which are necessary to initiate the pathway of proper proinsulin folding. Evolutionary pressures on the primary structure of proinsulin itself have preserved the efficiency of folding (“foldability”), and remarkably, these evolutionary pressures are distinct from those protecting the ultimate biological activity of insulin. Proinsulin foldability is manifest in the ER, in which the local environment is designed to assist in the overall load of proinsulin folding and to favour its disulphide bond formation (while limiting misfolding), all of which is closely tuned to ER stress response pathways that have complex (beneficial, as well as potentially damaging) effects on pancreatic β‐cells. Proinsulin misfolding may occur as a consequence of exuberant proinsulin biosynthetic load in the ER, proinsulin coding sequence mutations, or genetic predispositions that lead to an altered ER folding environment. Proinsulin misfolding is a phenotype that is very much linked to deficient insulin production and diabetes, as is seen in a variety of contexts: rodent models bearing proinsulin‐misfolding mutants, human patients with Mutant INS‐gene‐induced Diabetes of Youth (MIDY), animal models and human patients bearing mutations in critical ER resident proteins, and, quite possibly, in more common variety type 2 diabetes.
Time zones of pancreatic islet metabolism
Authors: Petrenko Volodymyr , Philippe Jacques , Dibner Charna
Published: September 2018

Most living beings possess an intrinsic system of circadian oscillators, allowing anticipation of the Earth's rotation around its own axis. The mammalian circadian timing system orchestrates nearly all aspects of physiology and behaviour. Together with systemic signals originating from the central clock that resides in the hypothalamic suprachiasmatic nucleus, peripheral oscillators orchestrate tissue‐specific fluctuations in gene transcription and translation, and posttranslational modifications, driving overt rhythms in physiology and behaviour. There is accumulating evidence of a reciprocal connection between the circadian oscillator and most aspects of physiology and metabolism, in particular as the circadian system plays a critical role in orchestrating body glucose homeostasis. Recent reports imply that circadian clocks operative in the endocrine pancreas regulate insulin secretion, and that islet clock perturbation in rodents leads to the development of overt type 2 diabetes. While whole islet clocks have been extensively studied during the last years, the heterogeneity of islet cell oscillators and the interplay between α‐ and β‐cellular clocks for orchestrating glucagon and insulin secretion have only recently gained attention. Here, we review recent findings on the molecular makeup of the circadian clocks operative in pancreatic islet cells in rodents and in humans, and focus on the physiologically relevant synchronizers that are resetting these time‐keepers. Moreover, the implication of islet clock functional outputs in the temporal coordination of metabolism in health and disease will be highlighted.
Islet stress, degradation and autoimmunity
Authors: Thomaidou Sofia , Zaldumbide Arnaud , Roep Bart O.
Published: September 2018

β‐cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduction of the general protein translation rate, increased production of endoplasmic reticulum chaperones and the initiation of degradation by activation of the ER associated degradation pathway (ERAD) in which newly synthetized proteins are ubiquitinylated and processed through the proteasome. This adaptive phase is also believed to play a critical role in the development of autoimmunity by the generation of neoantigens. While we have previously investigated the effect of stress on transcription, translation and post‐translational events as possible source for neoantigens, the participation of the degradation machinery, yet crucial in the generation of antigenic peptides, remains to be investigated in the context of T1D pathology. In this review, we will describe the relation between the unfolded protein response and the Ubiquitin Proteasome System (UPS) and address the role of the cellular degradation machinery in the generation of antigens. Learning from tumour immunology, we propose how these processes may unmask β‐cells by triggering the generation of aberrant peptides recognized by the immune cells.
Lysosomes in nutrient signalling: A focus on pancreatic β‐cells
Authors: Mészáros Gergő , Pasquier Adrien , Vivot Kevin , Goginashvili Alexander , Ricci Romeo
Published: September 2018

Regulated insulin secretion from pancreatic β‐cells is a major process maintaining glucose homeostasis in mammals. Enhancing insulin release in response to chronic nutrient overload and obesity‐related insulin resistance (pre‐diabetes) requires several adaptive cellular mechanisms maintaining β‐cell health under such stresses. Once these mechanisms are overwhelmed, β‐cell failure occurs leading to full‐blown Type 2 Diabetes (T2D). Nutrient‐dependent macroautophagy represents one such adaptive mechanism in β‐cells. While macroautophagy levels are high and protective in β‐cells in pre‐diabetes, they decrease at later stages contributing to β‐cell failure. However, mechanisms compromising macroautophagy in β‐cells remain poorly understood. In this review, we discuss how recently discovered signalling cascades that emanate from the limiting membrane of lysosomes contribute to changes in macroautophagy flux in physiology and disease. In particular, these mechanisms are put into context with β‐cell function highlighting most recently described links between nutrient‐dependent lysosomal signalling pathways and insulin secretion. Understanding these mechanisms in response to metabolic stress might pave the way for development of more tailored treatment strategies aimed at preserving β‐cell health.
Single molecule approaches for studying gene regulation in metabolic tissues
Authors: Farack Lydia , Egozi Adi , Itzkovitz Shalev
Published: September 2018

Gene expression in metabolic tissues can be regulated at multiple levels, ranging from the control of promoter accessibilities, transcription rates, mRNA degradation rates and mRNA localization. Modulating these processes can differentially affect important performance criteria of cells. These include precision, cellular economy, rapid response and maintenance of DNA integrity. In this review we will describe how distinct strategies of gene regulation impact the trade‐offs between the cells' performance criteria. We will highlight tools based on single molecule visualization of transcripts that can be used to measure promoter states, transcription rates and mRNA degradation rates in intact tissues. These approaches revealed surprising recurrent patterns in mammalian tissues, that include transcriptional bursting, nuclear retention of mRNA, and coordination of mRNA lifetimes to facilitate rapid adaptation to changing metabolic inputs. The ability to characterize gene expression at the single molecule level can uncover the design principles of gene regulation in metabolic tissues such as the liver and the pancreas.
Variants in cardiac GATA genes associated with bicuspid aortic valve
Authors: Alonso‐Montes Cristina , Martín María , Martínez‐Arias Laura , Coto Eliecer , Naves‐Díaz Manuel , Morís César , Cannata‐Andía Jorge B. , Rodríguez Isabel
Published: September 2018

Background

Bicuspid aortic valve (BAV) is a heterogeneous and still not fully understood condition, with diverse genetic aetiology and associated phenotypes ranging from aortic stenosis or regurgitation to aneurysm and dissection. Several genes have been associated with the presence of BAV, notably some members of the GATA family of transcription factors that play important roles in cardiac embryogenesis.

Methods

A case‐control study with 122 unrelated and ethnically matched patients with bicuspid and 154 with tricuspid aortic valve was performed. All exons of GATA4, GATA5, and GATA6 genes were sequenced searching for variants. Frequencies were compared and functional effects of rare variants were analysed by informatic prediction tools.

Results

Four rare and potentially pathogenic variants were identified in only five sporadic cases: a missense p.Arg202Gln (rs782614097) in GATA5 and three synonymous variants, p.Cys274= (rs55980825) and p.His302= (rs201516339) in GATA4, and p.Asn458= (rs143026087) in GATA6. Minor alleles of p.His302=, p.Arg202Gln and rs3764962 are enriched in BAV patients compared to ExAC database (P = 0.01, 0.03, and 0.01 respectively). In addition, a common polymorphism in GATA5 (p.Asp203=, rs41305803) is associated with BAV showing a protective effect in carriers of the minor allele (OR [95%CI] = 0.45[0.25‐0.81]; P = 0.004).

Conclusion

This study associates additional genetic variants in GATA4 and GATA5 with BAV, supporting the implication of these genes in the development of this valvulopathy. The discovery of all the genetic factors involved will contribute to a better understanding of the process and, therefore, to detect a genetic predisposition and even to the identification of therapeutic targets.