bluuebunny/crossref_metadata_2025 huggingface dataset:
Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques
Authors: Snyder-Mackler Noah , Sanz Joaquín , Kohn Jordan N. , Voyles Tawni N. , Pique-Regi Roger , Wilson Mark E. , Barreiro Luis B. , Tung Jenny
Published: July 2018

Low social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used anin vitroglucocorticoid challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression, but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression post-GC exposure. Regions that were more accessible in high status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the glucocorticoid receptor co-factor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation, and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.
Elevated plasma ceramide levels in post-menopausal women
Authors: Vozella Valentina , Basit Abdul , Piras Fabrizio , Realini Natalia , Armirotti Andrea , Bossù Paola , Assogna Francesca , Sensi Stefano L. , Spalletta Gianfranco , Piomelli Daniele
Published: July 2018

Circulating ceramide levels are abnormally elevated in age-dependent pathologies such as cardiovascular diseases, obesity and Alzheimer’s disease. Nevertheless, the potential impact of age on plasma ceramide levels has not yet been systematically examined. In the present study, we quantified a focused panel of plasma ceramides and dihydroceramides in a cohort of 164 subjects (84 women) 19 to 80 years of age. After adjusting for potential confounders, multivariable linear regression analysis revealed a positive association between age and ceramide (d18:1/24:0) (β (SE) = 5.67 (2.38);p= .0198) and ceramide (d18:1/24:1) (β (SE) = 2.88 (.61);p< .001) in women, and between age and ceramide (d18:1/24:1) in men (β (SE) = 1.86 (.77);p= .0179). In women of all ages, but not men, plasma ceramide (d18:1/24:1) was negatively correlated with plasma estradiol (r = −0.294;p= .007). Finally,in vitroexperiments in human cancer cells expressing estrogen receptors showed that incubation with estradiol (10 nM, 24 h) significantly decreased ceramide accumulation. Together, the results suggest that aging is associated with an increase in circulating ceramide levels, which in post-menopausal women may be at least partially dependent on lower estradiol levels.
Familiarity modulates social approach toward stressed conspecifics in female rats
Authors: Rogers-Carter Morgan M. , Djerdjaj Anthony , Culp Amelia R. , Elbaz Joshua A. , Christianson John P.
Published: July 2018

Familiarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naïve and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.
RepB C-terminus mutation of an ori pRi vector affects plasmid copy number inAgrobacteriumand transgene copy number in plants
Authors: Vaghchhipawala Zarir , Radke Sharon , Nagy Ervin , Russell Mary L. , Johnson Susan , Gelvin Stanton B. , Gilbertson Larry , Ye Xudong
Published: July 2018

A nativerepABCreplication origin, ori pRi, was previously reported as a single copy plasmid inAgrobacterium tumefaciensand can improve the production of transgenic plants with a single copy insertion of transgenes when it is used in binary vectors forAgrobacterium-mediatedtransformation. A high copy ori pRi variant plasmid, pTF::Ri, which does not improve the frequency of single copy transgenic plants, has been reported in the literature. Sequencing the high copy pTF::RirepABCoperon revealed the presence of two mutations: one silent mutation and one missense mutation that changes a tyrosine to a histidine (Y299H) in a highly conserved area of the C-terminus of the RepB protein (RepBY299H). Reproducing these mutations in the wild-type oriRi binary vector showed thatAgrobacteriumcells with the RepBY299Hmutation grow faster on both solidified and in liquid medium, and have higher plasmid copy number as determined by ddPCR. In order to investigate the impact of the RepBY299Hmutation on transformation and quality plant production, the RepBY299Hmutated ori pRi binary vector was compared with the original wild-type ori pRi binary vector and a multi-copy oriV binary vector in canola transformation. Molecular analyses of the canola transgenic plants demonstrated that the multi-copy ori pRi with the RepBY299Hmutation inAgrobacteriumcells lost the advantage of generating high frequency single copy, backbone-free transgenic plants compared to using the single copy wild-type ori pRi binary vector.
Functional grading of pericellular matrix surrounding chondrocytes: potential roles in signaling and fluid transport
Authors: Saadat F. , Lagieski M.J. , Birman V. , Thomopoulos S. , Genin G.M.
Published: July 2018

The extracellular matrix surrounding chondrocytes within cartilage and fibrocartilage has spatial gradients in mechanical properties. Although the function of these gradients is unknown, the potential exists for cells to tailor their mechanical microenvironment through these gradients. We hypothesized that these gradients enhance fluid transport around the cell during the slow loading cycles that occur over the course of a day, and that this enhancement changes the nature of the mechanical signals received at the surface of the cell. To test this hypothesis, we studied the effect of these gradients on the mechanical environment around a chondrocyte using a closed form, linearized model. Results demonstrated that functional grading of the character observed around chondrocytes in articular cartilage enhances fluid transport, and furthermore inverts compressive radial strains to provide tensile signals at the cell surface. The results point to several potentially important roles for functional grading of the pericellular matrix.
Fallen Pillars: The Past, Present, and Future Population Dynamics of a Rare, Specialist Coral-Algal Symbiosis
Authors: Chan Andrea N. , Lewis Cynthia L. , Neely Karen L. , Baums Iliana B.
Published: July 2018

Rare and ecologically specialized species are at greater risk of extinction. Rarity in terms of low genotypic diversity may be obscured in sessile foundation species that can reproduce asexually. Asexual propagules are often only distinguishable from sexual recruits through molecular tools. Thus, molecular markers are necessary to assess genotypic variation and population structure in clonal organisms such as corals. The global decline of corals has necessitated marker development for improved conservation of rare coral species. We infer past demographic changes, describe modern population structure, and quantify asexual reproduction of the uncommon Caribbean pillar coral, Dendrogyra cylindrus and its endosymbiotic dinoflagellate, Symbiodinium dendrogyrum using de novo microsatellite markers. Results show that D. cylindrus comprises three distinct populations in the Caribbean whereas the symbiont was differentiated into four populations. Thus, barriers to gene flow differ between host and symbiont. In Florida, host and symbiont reproduced mainly asexually, yielding lower genotypic diversity than predicted from census size. Models of past demographic events revealed no evidence of historical changes in population size, consistent with the geological record of D. cylindrus indicating it has been rare for hundreds of thousands of years. The most recent global thermal stress event triggered a severe disease outbreak among D. cylindrus in Florida, resulting in a precipitous population decline. Projections indicate a high likelihood that this species may become locally extinct within the coming decades. The ecosystem consequences of losing rare coral species and their symbionts with increasingly frequent extreme warming events are not known but require urgent study.
Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis
Authors: Flores E’Lissa M. , Woeller Collynn F. , Falsetta Megan L. , Susiarjo Martha , Phipps Richard P.
Published: July 2018

The obesity epidemic is developing into the most costly health problem facing the world. Obesity, characterized by excessive adipogenesis and enlarged adipocytes, promotes morbidities such as diabetes, cardiovascular disease and cancer. Regulation of adipogenesis is critical to our understanding of how fat cell formation causes obesity and associated health problems. Thy1 (also called CD90), a widely used stem cell marker, blocks adipogenesis and reduces lipid accumulation. Thy1 knockout-mice are prone to diet-induced obesity. While the importance of Thy1 in adipogenesis and obesity is now evident, how its expression is regulated is not. We hypothesized that DNA methylation plays a role in promoting adipogenesis and affects Thy1 expression. Using the methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-dC), we investigated whether DNA methylation alters Thy1 expression during adipogenesis in both mouse 3T3-L1 pre-adipocytes and mouse mesenchymal stem cells. Thy1 protein and mRNA levels were decreased dramatically during adipogenesis. However, 5-aza-dC treatment prevented this phenomenon. Pyrosequencing analysis shows that the CpG sites at the Thy1 locus are methylated during adipogenesis. These new findings highlight the potential role of Thy1 and DNA methylation in adipogenesis and obesity.
cis-regulatory architecture of a short-range EGFR organizing center in theDrosophila melanogasterleg
Authors: Newcomb Susan , Voutev Roumen , Jory Aurelie , Delker Rebecca K. , Slattery Matthew , Mann Richard S.
Published: July 2018

We characterized the establishment of an Epidermal Growth Factor Receptor (EGFR) organizing center (EOC) during leg development inDrosophila melanogaster. Initial EGFR activation occurs in the center of leg discs by expression of the EGFR ligand Vn and the EGFR ligand-processing protease Rho, each through single enhancers,vnEandrhoE, that integrate inputs from Wg, Dpp, Dll and Sp1. Deletion ofvnEandrhoEeliminatesvnandrhoexpression in the center of the leg imaginal discs, respectively. Animals with deletions of bothvnEandrhoE(but not individually) show distal but not medial leg truncations, suggesting that the distal source of EGFR ligands acts at short-range to only specify distal-most fates, and that multiple additional ‘ring’ enhancers are responsible for medial fates. Further, based on thecis-regulatory logic ofvnEandrhoEwe identified many additional leg enhancers, suggesting that this logic is broadly used by many genes duringDrosophilalimb development.

Author Summary

The EGFR signaling pathway plays a major role in innumerable developmental processes in all animals and its deregulation leads to different types of cancer, as well as many other developmental diseases in humans. Here we explored the integration of inputs from the Wnt- and TGF-beta signaling pathways and the leg-specifying transcription factors Distal-less and Sp1 at enhancer elements of EGFR ligands. These enhancers trigger a specific EGFR-dependent developmental output in the fly leg that is limited to specifying distal-most fates. Our findings suggest that activation of the EGFR pathway during fly leg development occurs through the activation of multiple EGFR ligand enhancers that are active at different positions along the proximo-distal axis. Similar enhancer elements are likely to control EGFR activation in humans as well. Such DNA elements might be ‘hot spots’ that cause formation of EGFR-dependent tumors if mutations in them occur. Thus, understanding the molecular characteristics of such DNA elements could facilitate the detection and treatment of cancer.
Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow
Authors: Bal A. , Pichon M. , Picard C. , Casalegno JS. , Valette M. , Schuffenecker I. , Billard L. , Vallet S. , Vilchez G. , Cheynet V. , Oriol G. , Assant S. , Gillet Y. , Lina B. , Brengel-Pesce K. , Morfin F. , Josset L.
Published: July 2018

Background

In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking.

Methods

A total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7).

Results

The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses).

Conclusions

Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.
Novel mutations associated with autosomal dominant congenital cataract are identified in Chinese families
Authors: Wang Zhenyu , Huang Chen , Sun Yanxiu , Lv Huibin , Zhang Mingzhou , Li Xuemin
Published: July 2018

Purpose

As the leading cause of the impairment of vision of children, congenital cataract is considered as a hereditary disease, especially autosomal dominant congenital cataract (ADCC). The purpose of this study is to identify the genetic defect of six Chinese families with ADCC.

Subjects and Methods

Six Chinese families with ADCC were recruited in the study. (103 members in total, 96 members alive, 27 patients in total) Genomic DNA samples extracting from probands’ peripheral blood cells were captured the mutations using a specific eye disease enrichment panel with next generation sequencing. After initial pathogenicity prediction, sites with specific pathogenicity were screened for further validation. Sanger sequencing was conducted in the other individuals in the families and other 100 normal controls. Mutations definitely related with ADCC will then be analyzed by bioinformatics analysis. The pathogenic effect of the amino acid changes and structural and functional changes of the proteins were finally analyzed by bioinformatics analysis.

Results

Seven mutations in six candidate genes associated with ADCC of six families were detected (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A, WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). All the seven mutations were only detected on affected individuals in the families. Among them there are three novel mutations (MYH9 c.4150G>C, CRYBA4 c.169T>C, RPGRRIP1 c.2669G>A) and four that have been reported (WFS1 c.1235T>C, CRYBA4 c.26C>T, EPHA2 c.2663+1G>A, and PAX6 c.11–2A>G). RPGRIP1 (c.2669G>A) mutation and CRYBA4 (c.26C>T) mutation are predicted to be benign according to bioinformatics analysis while the other five mutations (EPHA2, PAX6, MYH9, CRYBA4 c.169T>C, WFS1) are thought to be pathogenic.

Conclusion

We report two novel heterozygous mutations (MYH9 c.4150G>C and CRYBA4 c.169T>C) in six Chinese families supporting their vital roles in causing ADCC.
The Basel accords, capital reserves, and agricultural lending
Authors: Brester Gary W. , Watts Myles J.
Published: July 2018

Purpose

The safety and soundness of financial institutions has become a leading worldwide issue because of the recent global financial crisis. Historically, financial crises have occurred approximately every 20 years. The worst financial crisis in the last 75 years occurred in 2008–2009. US regulatory efforts with respect to capital reserve requirements are likely to have several unintended consequences for the agricultural lending sector—especially for smaller, less-diversified (and often, rural agricultural) lenders. The paper discusses these issues.

Design/methodology/approach

Simulation models and value-at-risk (VaR) criteria are used to evaluate the impact of capital reserve requirements on lending return on equity. In addition, simulations are used to calculate the effects of loan numbers and portfolio diversification on capital reserve requirements.

Findings

This paper illustrates that increasing capital reserve requirements reduces lending return on equity. Furthermore, increases in the number of loans and portfolio diversification reduce capital reserve requirements.

Research limitations/implications

The simulation methods are a simplification of complex lending practices and VaR calculations. Lenders use these and other procedures for managing capital reserves than those modeled in this paper.

Practical implications

Smaller lending institutions will be pressured to increase loan sector diversification. In addition, traditional agricultural lenders will likely be under increased pressure to diversify portfolios. Because agricultural loan losses have relatively low correlations with other sectors, traditional agricultural lenders can expect increased competition for agricultural loans from non-traditional agricultural lenders.

Originality/value

This paper is novel in that the authors illustrate how lender capital requirements change in response to loan payment correlations both within and across lending sectors.
The impact of trade liberalization on poverty reduction in rural China
Authors: Wang Jun , Hu Yong
Published: July 2018

Purpose

The purpose of this paper is to investigate how trade liberalization influences rural poverty reduction in China.

Design/methodology/approach

The authors make use of China Family Panel Studies survey data, take annual income of farmers of RMB2,300 and RMB3,450 as the poverty lines (poverty line 1 and poverty line 2, respectively). Residents below poverty line 1 and poverty line 2 are 2,580 and 2,661, respectively. Probit model is used to estimate the impact of trade liberalization on the poverty probability. Income-deciding equation is used to estimate the impact of trade liberalization on the income level of poor residents in rural areas. Income-deciding equation is also used to examine the transmission mechanism of trade liberalization affecting rural poverty.

Findings

This study finds that trade liberalization can reduce the poverty probability of rural residents and promote the income growth of poor residents in rural areas. Trade liberalization increases the income of poor residents and reduces poverty through transmission mechanisms such as promoting economic growth and financial expenditure.

Originality/value

To the authors’ knowledge, this is the first empirical study to quantitatively model the impact of trade liberalization on rural poverty reduction in China using residents’ survey data.
Perceived service quality, repeat use of healthcare services and inpatient satisfaction in emerging economy
Authors: Trivedi Rohit , Jagani Khyati
Published: July 2018

Purpose

The purpose of this study is to understand that how different demographic variables and repeated availing of service from the same doctor or same hospital shape the overall perception of health-care service quality and satisfaction among inpatients admitted in private hospitals in an emerging economy.

Design/methodology/approach

A self-administered, cross-sectional survey of inpatients using a questionnaire was translated into Hindi and Gujarati. The data were collected from 702 inpatients from 18 private clinics located in three selected cities from Western India.

Findings

The results indicate that experience with hospital administration, doctors, nursing staff, physical environment, hospital pharmacy and physical environment is significant predictor of inpatient satisfaction. Physical environment was found to be significantly associated with satisfaction only among female inpatient. It was also found that repeat availing of services either from the same hospital or doctor does not increase patient satisfaction. The feasibility, reliability and validity of the instrument that measures major technical and nontechnical dimensions of quality of health-care services were established in the context of a developing country.

Originality/value

The study makes important contribution by empirically investigating the inpatient assessment of health-care service quality based upon their demographic information and repeated availing of services to understand how repeat visit shapes the service quality perception.
Self-organized innovation networks from the perspective of complex systems
Authors: Silva Adauto Lucas , Guerrini Fabio Müller
Published: July 2018

Purpose

In order to deepen the understanding of self-organization, the purpose of the paper is to raise and analyze the state of the art in the area of innovation networks, particularly the characteristics of self-organizing, relying on the theory of complex systems to overcome any shortcomings.

Design/methodology/approach

The databases selected for the search were Web of Science and Scopus; the keywords searched in the titles of articles were innovation networks, complex systems, self-organization and self-organizing; the timeline of the search covers the period between 2000 and 2014 due to the presence of important studies in the field of networks starting in the early 2000s; only studies published in English were used; the articles selected were examined by first reading the titles, then the abstracts, and finally the texts in full.

Findings

The way the main constructs from the analytical perspective of innovation networks intersect with complex systems explains how self-organization is presented and how it can be allowed to occur within a view of expected benefits for the purposes of these networks.

Originality/value

The originality of the research lies in the questioning of the classical form of organizational management in innovation networks, essentially based on the concentration of hierarchical power.
Vulvar lichen sclerosus: A single‐center retrospective study in China
Authors: Yang Min , Wen Wei , Chang Jianmin
Published: July 2018

Vulvar lichen sclerosus (VLS) is an uncommon, chronic inflammatory skin disease lacking clinical data of large sample size in China. This study was intended to provide missing data on this condition through investigating the clinical characteristics of Chinese VLS patients. The medical records of 129 VLS patients from our vulvar outpatient clinic were analyzed with SPSS version 18.0 software. The age of onset followed a normal distribution, with the peak at 25–30 years. Of all cases, the incidence rate during the postmenopausal period was 14.0% with an average duration of 9.22 years. The most frequently involved site was the bilateral labia minora (71.3%). Itching was the principal symptom (94.6%); meanwhile, patients with severe itching more commonly experienced longer duration, flaring at night, hyperkeratotic lesions or rashes on the posterior commissure than those with mild to moderate itching (P < 0.05). Furthermore, 60% of the enrolled patients suffered from sexual dysfunction. The major sign was pallor (92.2%), followed by hyperkeratosis (55.0%) and atrophy (40.3%). The patients with atrophy had a significantly longer duration of the disease, and the older patients presented more frequently with edema in the area of lesions (both P < 0.05). Of our patients, 9.3% suffered concomitantly from autoimmune diseases, mostly thyroid with one case being complicated by vulvar squamous cell carcinoma (SCC). In our study, the severity of pruritus was partly related to clinical manifestations. Moreover, Chinese patients could have developed VLS mostly in the reproductive period, with less complications of autoimmune diseases or SCC.
Race Equality after Enoch Powell
Authors: Meer Nasar
Published: July 2018

Enoch Powell's infamous speech casts a long shadow over race equality in the UK. Looking back to the 1968 Race Relations Bill and then forwards to the present social and political landscape this article explores how an uneven race equality story has been characteristic of the UK approach since Powell's intervention. If the intended objective of the initial and later race equality bills was to reduce ethnic and racial disparities to a marginal or ‘negligible’ level, then we are a great distance from success. If the objective was slightly different, but not unrelated, and sought to reshape public conventions on racism (and ethnic and racial diversity more broadly), then the answer is more complicated but also unfinished.
Measuring metagenome diversity and similarity with Hill numbers
Authors: Ma Zhanshan (Sam) , Li Lianwei
Published: July 2018

The first step of any metagenome sequencing project is to get the inventory of OTU abundances (operational taxonomic units) and/or metagenomic gene abundances. The former is generated with 16S‐rRNA‐tagged amplicon sequencing technology, and the latter can be generated from either gene‐targeted or whole‐sample shotgun metagenomics technologies. With 16S‐rRNA data sets, measuring community diversity with diversity indexes such as species richness and Shannon's index has been a de facto standard analysis; nevertheless, similarly comprehensive approaches to metagenomic gene abundances are still largely missing, despite that both OTU and gene abundances are DNA reads. Here, we adapt the Hill numbers, which were reintroduced to macrocommunity ecology recently and are now widely regarded as a most appropriate measure system for ecological diversity, for measuring metagenome alpha‐, beta‐ and gamma‐diversities, and similarity. Our proposal includes the following: (a) Metagenomic gene (MG) diversity measures the single‐gene‐level metagenome diversity; (b) Type‐I metagenome functional gene cluster (MFGC) diversity measures the diversity of functional gene clusters but ignoring within‐cluster gene abundance information; (c) Type‐II MFGC diversity considers within‐cluster gene abundances information and integrates gene‐cluster‐level metagenome diversity and functional gene redundancy information; and (d) Four classes of Hill‐numbers‐based similarity metrics, including local gene overlap, regional gene overlap, gene homogeneity measure and gene turnover complement, were introduced in terms of MG and MFGC, respectively. We demonstrate the proposal with the gut metagenomes from healthy and IBD (inflammatory bowel disease) cohorts. The Hill numbers offer a unified approach to cohesively and comprehensively measuring the ecological and metagenome diversities of microbiomes.
Nutrient deficiencies do not contribute to yield loss after waterlogging events in winter wheat (Triticum aestivum)
Authors: Wollmer A.‐C. , Pitann B. , Mühling K.‐H.
Published: July 2018

Frequent waterlogging increases the risk of possible harvest losses in winter wheat. The aim of this study was to analyse which developmental stage of wheat was impaired by waterlogging and whether yield losses can be explained by nutrient deficiences. A large‐scale container experiment was designed to evaluate growth, yield and nutrient status of two wheat cultivars after 14 days of waterlogging at two different developmental stages: DC 31 (first node visible) and DC 51 (beginning of ear emergence). Early waterlogging treatment impaired vegetative growth stages of winter wheat and nutrient uptake, leading to transient nutrient deficiencies, but yield was not significantly reduced. Late waterlogging at the beginning of ear emergence mainly affected generative growth stages and caused yield reductions ranging up to 61%. The main reason for yield loss was the significantly decreased thousand kernel weight in combination with a decreased number of grains per spike. Yield depressions in winter wheat depend on the timing of waterlogging. Early waterlogging transiently reduces vegetative growth through nutrient deficiencies, whereas late waterlogging results in an impaired grain development and associated therewith, yield losses.
Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection
Authors: Kotake Takeshi , Satake Hironaga , Okita Yoshihiro , Hatachi Yukimasa , Hamada Mamiko , Omiya Masatomo , Yasui Hisateru , Hashida Toru , Kaihara Satoshi , Inokuma Tetsuro , Tsuji Akihito
Published: July 2018

Background

Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown.

Aim

To evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection.

Methods

All 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti‐HBc antibody and/or positive for anti‐HBs antibody), and HBV‐DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case–control study.

Results

The prevalence of HBV‐DNA reactivation was 2.1% (95% confidence interval [CI], 0.3–3.9%). We did not observe any exacerbation of HBV‐DNA by early intervention. A low anti‐HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15–30.6, P = 0.03) and 8.69 (95% CI, 1.27–58.8, P = 0.02), respectively.

Conclusion

HBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.
A clinical audit of combined first trimester screening and non‐invasive prenatal testing offered to pregnant women in a regional Australian hospital
Authors: Abdalla Orit , Woods Cindy , de Costa Caroline
Published: July 2018

The records of women attending a large Australian regional hospital for antenatal care were retrospectively analysed to determine what proportion had undergone or been offered first trimester screening for fetal abnormalities; only 609 (54%) of 1114 women had undergone or been offered screening. Younger women, multiparous women and women living in rural Australia were less likely to be offered screening. Barriers to screening and solutions for overcoming these need to be identified to improve access and equality in antenatal screening for all women.
Association between peri‐operative angiotensin‐converting enzyme inhibitors and angiotensin‐2 receptor blockers and acute kidney injury in major elective non‐cardiac surgery: a multicentre, prospective cohort study
Authors:   STARSurg Collaborative
Published: July 2018

The peri‐operative use of angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri‐operative period. This study aimed to investigate if withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers peri‐operatively reduces the risk of acute kidney injury following major non‐cardiac surgery. Patients undergoing elective major surgery on the gastrointestinal tract and/or the liver were eligible for inclusion in this prospective study. The primary outcome was the development of acute kidney injury within seven days of operation. Adjusted multi‐level models were used to account for centre‐level effects and propensity score matching was used to reduce the effects of selection bias between treatment groups. A total of 949 patients were included from 160 centres across the UK and Republic of Ireland. From this population, 573 (60.4%) patients had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers withheld during the peri‐operative period. One hundred and seventy‐five (18.4%) patients developed acute kidney injury; there was no difference in the incidence of acute kidney injury between patients who had their angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers continued or withheld (107 (18.7%) vs. 68 (18.1%), respectively; p = 0.914). Following propensity matching, withholding angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers did not demonstrate a protective effect against the development of postoperative acute kidney injury (OR (95%CI) 0.89 (0.58–1.34); p = 0.567).
Increased risk of nonalcoholic fatty liver disease in patients with coeliac disease on a gluten‐free diet: beyond traditional metabolic factors
Authors: Tovoli F. , Negrini G. , Farì R. , Guidetti E. , Faggiano C. , Napoli L. , Bolondi L. , Granito A.
Published: July 2018

Background

A gluten‐free diet (GFD) is known to be associated with altered macronutrient intake and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the hepatic hallmark of metabolic syndrome. The risk of NAFLD in patients with coeliac disease (CD) adhering to a GFD remains to be fully investigated; in particular, data from real‐life clinical settings are lacking.

Aim

To assess the prevalence and relative risk of NAFLD in CD patients treated with a GFD.

Methods

Case–control study, with prospective enrolment of CD outpatients following a GFD and controls. Patients were matched for demographic characteristics (age and gender) and metabolic risk factors (overweight, diabetes mellitus, total cholesterol, and triglycerides) using a 1:1 ratio. NAFLD was diagnosed according to the European Association for the Study of the Liver criteria.

Results

202 CD patients and 202 controls were compared. The raw prevalence of NAFLD was 34.7% and 21.8% in the CD and control group, respectively (P = 0.006). Binary logistic regression confirmed an increased risk of NAFLD in the CD group (adjusted odds ratio = 2.90, 95% confidence interval: 1.64‐5.15, P < 0.001). Additionally, the relative risk for NAFLD was notably higher in non‐overweight CD patients (adjusted odds ratio = 5.71, 95% confidence interval: 2.30‐14.19, P < 0.001).

Conclusions

More than one‐third of CD patients adhering to a GFD had concurrent NAFLD, accounting for a three‐fold increased risk compared to the general population. Dietary advice provided using a patient‐tailored approach should assist CD patients with NAFLD in achieving an appropriate nutritional intake whilst reducing the risk of long‐term liver‐related events.
Does the addition of cognitive therapy to exposure and response prevention for obsessive compulsive disorder enhance clinical efficacy? A randomized controlled trial in a community setting
Authors: Rector Neil A. , Richter Margaret A. , Katz Danielle , Leybman Michelle
Published: July 2018

Objectives

Exposure and response prevention (ERP) remains the most empirically supported psychological treatment for obsessive compulsive disorder (OCD). Clinical guidelines recommend the addition of cognitive approaches to ERP although the presumed additive benefits have not been directly tested. The aim of this was to compare a treatment that integrated cognitive therapy with ERP (ERP + CT) to traditional, manualized ERP to test the additive benefits.

Design

A longitudinal, randomized control trial design was used.

Methods

Participants (N = 127) with OCD were randomly assigned to receive individual outpatient ERP or ERP + CT. Obsessive‐compulsive symptom severity measures were completed pre‐ and post‐treatment and at 6‐month follow‐up.

Results

While both conditions led to significant symptom and obsessive belief reduction, ERP + CT led to significantly greater symptom and belief reduction as compared to ERP across all main symptom presentations of OCD. Based on a priori definitions of effectiveness, more patients in ERP + CT compared to the ERP group were also deemed treatment responders.

Conclusions

The results of this study suggest that cognitive therapy can be readily integrated with ERP to improve clinical outcomes beyond ERP alone.

Practitioner points

Both ERP and ERP + CT were effective, however a course of ERP + CT was significantly more effective at reducing symptoms of OCD than the ERP treatment condition.

Significantly more participants who received ERP + CT experienced clinically significant change in OCD symptoms compared to those who received ERP.

OCD symptom dimension did not significantly impact response to either ERP or ERP + CT treatments.
The use of erythropoiesis‐stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib
Authors: Crisà Elena , Cilloni Daniela , Elli Elena M. , Martinelli Vincenzo , Palumbo Giuseppe A. , Pugliese Novella , Beggiato Eloise , Frairia Chiara , Cerrano Marco , Lanzarone Giuseppe , Marchetti Monia , Mezzabotta Mauro , Boccadoro Mario , Ferrero Dario
Published: July 2018

Erythropoiesis‐stimulating agents (ESAs) were combined with ruxolitinib in 59 anaemic myelofibrosis patients (93% with Dynamic International Prognostic Scoring System [DIPSS] intermediate‐2/high risk; 52·5% transfusion‐dependent). Anaemia response (AR) rate was 54% and 76% of patients responded at 5 years. A further 15% displayed minor improvement in anaemia and 78% of patients reduced spleen size. Endogenous erythropoietin levels <125 u/l correlated with a higher AR rate (63% vs. 20%, P = 0·008). No thrombotic events or other toxicities occurred. Overall survival was 62% at 4 years, influenced by DIPSS and transfusion dependency. ESAs seem effective in improving anaemia in ruxruxolitinib‐treated myelofibrosis patients.
High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by theEBMTLymphoma Working Party andFIL‐GITMO
Authors: Avivi Irit , Arcaini Luca , Ferretti Virginia V. , Boumendil Ariane , Finel Hervé , Milone Giuseppe , Zaja Francesco , Liliana Devizzi , Musso Maurizio , Didier Blaise , Bachy Emmanuel , Wattad Mohammed , Nicolas‐Virelizier Emmanuelle , Gramatzki Martin , Bourhis Jean‐Henri , Caillot Denis , Haenel Anette , Held Gerhard , Thieblemont Catherine , Jindra Pavel , Pohlreich David , Guilhot François , Kroschinsky Frank , Wahlin Björn , Scheid Christof , Ifrah Norbert , Berthou Christian , Dreger Peter , Montoto Silvia , Conconi Annarita
Published: July 2018

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoingASCTforMZL. Eligible patients had non‐transformed nodal, extra‐nodal (MALT) or splenicMZL(SMZL), aged ≥18 years, who underwent a firstASCTbetween1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111MALTlymphoma, 55 nodalMZL(NMZL) and 33SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1–8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy‐based high‐dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in theMALTsub‐group and more transplants performed in recent years in the other sub‐groups. After a median follow‐up of 5 years, 5‐year cumulative incidence of relapse/progression and non‐relapse mortality were 38% and 9%, respectively. Five‐year event‐free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five‐year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorterEFSandOS. In addition, patients withSMZLhad a shorterOSthan those withMALT.ASCTmay provide clinical benefit inMZLpatients who have failed multiple lines of chemoimmunotherapy.
Quality of life during and following sequential treatment of previously untreated patients with multiple myeloma: findings of the Medical Research Council Myeloma IX randomised study
Authors: Royle Kara‐Louise , Gregory Walter M. , Cairns David A. , Bell Sue E. , Cook Gordon , Owen Roger G. , Drayson Mark T. , Davies Faith E. , Jackson Graham H. , Morgan Gareth J. , Child J. Anthony
Published: July 2018

In the Medical Research Council (MRC) Myeloma IX trial (ISRCTN684564111) patients were randomised to sodium clodronate or zoledronic acid and induction treatment: cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) or cyclophosphamide, thalidomide and dexamethasone (CTD) followed by autologous stem cell transplant (ASCT) in the intensive pathway; attenuated CTD or melphalan and prednisolone (MP) in the non‐intensive pathway. Subsequent randomisation allocated patients to either thalidomide or observation. The European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaires, QLQ‐C30 and QLQ‐MY24, were administered at baseline, 3, 6 and 12 months and annually thereafter, enabling the effect of sequential treatment on patient‐reported health‐related QoL (HR‐QoL) to be investigated. The protocol specified four subscales of interest: Pain, Fatigue, Global Health Status/Quality of Life and Physical Functioning at 3, 6 and 12 months that were compared using linear models. The intensive pathway showed significant differences in favour of CTD for Fatigue at 3 months and Physical Functioning at 12 months. The non‐intensive pathway and maintenance phase reported significant differences at 3 months; Pain (improved with attenuated CTD) and Global Health status/Quality of Life (improved with observation). The improved outcomes in MRC Myeloma IX were accompanied by some beneficial and few detrimental effects on HR‐QoL.
Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita
Authors: Fioredda Francesca , Iacobelli Simona , Korthof Elisabeth T. , Knol Cora , van Biezen Anja , Bresters Dorine , Veys Paul , Yoshimi Ayami , Fagioli Franca , Mats Brune , Zecca Marco , Faraci Maura , Miano Maurizio , Arcuri Luca , Maschan Michael , O'Brien Tracey , Diaz Miguel A. , Sevilla Julian , Smith Owen , Peffault de Latour Regis , de la Fuente Josue , Or Reuven , Van Lint Maria T. , Tolar Jakub , Aljurf Mahmoud , Fisher Alain , Skorobogatova Elena V. , Diaz de Heredia Cristina , Risitano Antonio , Dalle Jean‐Hugues , Sedláček Petr , Ghavamzadeh Ardeshir , Dufour Carlo
Published: July 2018

Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event‐free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non‐myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft‐versus‐host disease and T‐B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre‐existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.
Priming attachment security improves attitudes towards a range of therapies
Authors: Millings Abigail , Carnelley Katherine B. , Cavanagh Kate , Wilderspin Anna , Wiseman Hannah , Rowe Angela C.
Published: July 2018

We sought to understand how attachment orientation influenced attitudes towards different types of psychological therapies. In two studies, we (1) examined attachment orientation as a predictor of attitudes towards different therapies and (2) tested whether attachment security priming could improve attitudes. Study 1 (n = 339) found associations between attachment orientation and attitudes towards, and likelihood of using different therapies. Positive and negative attitudes about different therapies mediated the relationship between attachment avoidance and likelihood of use. Study 2 (n = 412) showed that primed security (vs. neutral prime) improved attitudes towards relational, non‐relational and distanced‐relational therapies for those with a fearful‐avoidant attachment orientation. For relational and distanced‐relational therapies, the mechanism of this effect was increased cognitive openness. Attachment orientation is a determinant of therapy attitudes and anticipated help‐seeking behaviour. Priming security may promote open‐minded decision‐making about some therapies. Findings are discussed with relevance to attachment theory, research and clinical practice.