bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection and explosive growth may hamper the performance of rare variant association tests
Authors: Uricchio Lawrence H. , Witte John S. , Hernandez Ryan D. 
Published: March 2015

AbstractMuch recent debate has focused on the role of rare variants in complex phenotypes. However, it is well known that rare alleles can only contribute a substantial proportion of the phenotypic variance when they have much larger effect sizes than common variants, which is most easily explained by natural selection constraining trait-altering alleles to low frequency. It is also plausible that demographic events will influence the genetic architecture of complex traits. Unfortunately, most rare variant association tests do not explicitly model natural selection or non-equilibrium demography. Here, we develop a novel evolutionary model of complex traits. We perform numerical calculations and simulate phenotypes under this model using inferred human demographic and selection parameters. We show that rare variants only contribute substantially to complex traits under very strong assumptions about the relationship between effect size and selection strength. We then assess the performance of state-of-the-art rare variant tests using our simulations across a broad range of model parameters. Counterintuitively, we find that statistical power is lowest when rare variants make the greatest contribution to the additive variance, and that power is substantially lower under our model than previously studied models. While many empirical studies have attempted to identify causal loci using rare variant association methods, few have reported novel associations. Some authors have interpreted this to mean that rare variants contribute little to heritability, but our results show that an alternative explanation is that rare variant tests have less power than previously estimated.
Lobbying on the integrated reporting framework
Authors: Reuter Marek , Messner Martin 
Published: March 2015

Purpose
– The purpose of this paper is to examine formal participation in the early phase of the International Integrated Reporting Council’s (IIRC’s) standard-setting. The objective of the paper is to shed light on the characteristics of lobbying parties and the determinants of their lobbying behavior toward the IIRC. Additionally, the most important points of contestation regarding the IIRC’s initial proposal for integrated reporting are identified and discussed.

Design/methodology/approach
– The authors analyze comment letters issued toward the IIRC’s 2011 discussion paper on the basis of a content analysis. The analysis is guided mainly by Sutton’s (1984) rational-choice model of lobbying and by findings from extant financial accounting lobbying research. The analysis of the data is both quantitative and qualitative.

Findings
– The paper improves the understanding of the political nature of standard-setting in the context of integrated reporting. Among other things, the authors find that comment letters toward the IIRC’s discussion paper are mainly written by large multinational firms (as opposed to small- and medium-sized ones) and by preparers (as opposed to users). The authors also observe active lobbying by sustainability service firms and professional bodies which tend to take a critical position vis-à-vis the discussion paper’s emphasis on investor needs and shareholder value creation. Moreover, the qualitative analysis reveals that respondents voice different concerns regarding, for instance, the scope of audience of integrated reporting, issues of materiality and the relationship between integrated reporting and other existing reporting frameworks.

Research limitations/implications
– The analysis is limited to a consideration of the 2011 discussion paper of the IIRC. The IIRC’s more recent and forthcoming proposals will likely provide a basis to extend the paper’s findings and allow investigation of the role of lobbying for the further development of the framework.

Originality/value
– The paper is, to the best of the knowledge, the first one to explore lobbying behavior by means of comment letters in the context of integrated reporting.
A day in the life of a Peer Support Worker: One of those make or break visits
Authors: Watson Emma 
Published: March 2015

Purpose
– The purpose of this paper is to describe the experience of being a peer support worker (PSW).

Design/methodology/approach
– Narrative account of a one to one meeting with a peer written from the perspective of a PSW.

Findings
– Key reflections centre on the importance of establishing and maintaining boundaries, the role of trust, and a different understanding of what constitutes risk.

Originality/value
– While there is a great deal written about the theory of peer support work, little is published about PSWs experience. This paper provides important insights into the nature of peer support work.
Real lives: promoting recovery through personalisation and peer support
Authors: Perkins Rachel , Atkins Julie , Hunter Nicole , Repper Poppy , Robertson Peter David , Thornton Phoebe , Thornton Sue 
Published: March 2015

Purpose
– The purpose of this paper is to describe the development of Real Lives: a community interest company that provides peer support for people who face significant mental health challenges using personal budgets.

Design/methodology/approach
– The paper offers a descriptive summary of the vision behind Real Lives and the successful realisation of this vision in practice based on interviews by the first author with the directors, Operational Manager, Cafe Manager and “Peers and Allies for in Living” who provide support to clients.

Findings
– The successful development of Real Lives shows that it is possible to utilise peer support and personal budgets to a create small, values based, financially viable organisation outside the statutory sector that is part of its community and can provide outside the statutory sector. A service for people facing significant mental health challenges that is personalised, recovery-focused and puts the client in control and is focused on helping them to do the things they want to do and pursue their aspirations.

Originality/value
– Real Lives is an innovative recovery-focused service that is part of its community and offers a model for utilising Self-Directed Support and personal budgets and that might be replicated by others.
Remarkable lives: Spencer Insley in conversation with Jerome Carson
Authors: Insley Spencer , Carson Jerome 
Published: March 2015

Purpose
– The purpose of this paper is to provide a profile of Spencer Insley.

Design/methodology/approach
– Spencer gives a short biographical account and is then interviewed by Jerome. Areas covered in the narrative are the misery of mental illness, the prodromal signs of illness, hospital admission and discharge to supported accommodation.

Findings
– Apart from the losses resulting from a diagnosis of major mental disorder, Spencer also talks about the loss of friendships. His admission to hospital was especially traumatic, leaving him frightened and confused and feeling he was treated like an animal.

Research limitations/implications
– While Spencer's is only one story of many, his experiences have a sorry familiarity to them.

Practical implications
– Too long denied in the history of psychiatry, service user narratives help us understand the nature of mental suffering and the often inadequate nature of service responses to mental distress.

Social implications
– Involuntary admissions to hospital need to be handled in a more therapeutic manner.

Originality/value
– So often it is nurses and occupational therapists who have the most impact on the lives of those with lived experience. Psychiatrists were felt not to be interested in Spencer, whereas his community mental health nurse “Had a genuine interest in what I was doing and how I was getting along”.
How does enforcement of smoke free grounds in acute mental health settings sit with “recovery” focused practice? A personal view
Authors: Hurley Di 
Published: March 2015

Purpose
– The purpose of this paper is to outline, from the perspective of someone involved in smoking cessation, concerns about the intention to make all hospital grounds “smoke free”.

Design/methodology/approach
– This paper takes the form of a narrative account.

Findings
– Reflective account offering a personal point of view – no findings presented.

Originality/value
– An important viewpoint relating to an issue of great concern to many people working in and using mental health services.
Malassezia species and their associated skin diseases
Authors: Harada Kazutoshi , Saito Mami , Sugita Takashi , Tsuboi Ryoji 
Published: March 2015

AbstractMalassezia spp. are lipophilic fungi that occur on all skin surfaces of humans and animals as commensal and pathogenic organisms. In the 2000s, several new species were added to the Malassezia genus by Japanese researchers. The genus Malassezia now includes 14 species of basidiomycetous yeast. Culture‐independent molecular analysis clearly demonstrated that the DNA of Malassezia spp. was predominantly detected in core body and arm sites, suggesting that they are the dominant fungal flora of the human body. Malassezia spp. have been implicated in skin diseases including pityriasis versicolor (PV), Malassezia folliculitis (MF), seborrheic dermatitis (SD) and atopic dermatitis (AD). While Malassezia spp. are directly responsible for the infectious diseases, PV and MF, they act as an exacerbating factor in AD and SD. The fatty acids generated by Malassezia lipase can induce inflammation of the skin, resulting in development of SD. Patch and serum immunoglobulin E tests revealed that AD patients were hypersensitive to Malassezia. However, these findings only partially elucidated the mechanism by which Malassezia spp. induce inflammation in the skin; understanding of the pathogenetic role of Malassezia spp. in SD or AD remains incomplete. In this article, the latest findings of Malassezia research are reviewed with special attention to skin diseases.
Immunoresponses in dermatomycoses
Authors: Hau Carren Sy , Tada Yayoi , Kanda Naoko , Watanabe Shinichi 
Published: March 2015

AbstractContact with fungal pathogens initiates a series of host responses beginning with innate immunity, which leads to fungal recognition and microbial killing. The innate immune system also modulates the adaptive immune responses, leading to the establishment of immunological memory and protection against pathogens. In the case of dimorphic fungi such as Candida albicans and Malassezia, the immune system plays an important role in tolerance and resistance when managing the organisms either as commensal microbiota or invading pathogens, and disruption of this balance can result in pathological consequences for the host. In addition, Malassezia and dermatophytes have immunomodulatory capabilities that allow them to adapt to their environments and they may exert different effects in healthy and diseased skin. Here, we discuss the host immune responses to dermatomycoses caused by dimorphic fungi such as C. albicans and Malassezia as well as dermatophytes such as Trichophyton spp. and Arthroderma benhamiae to gain a better understanding of the mechanisms of the host–dermatomycosis interaction.
Simulated microgravity promotes monocyte adhesion to rat aortic endothelium via nuclear factor‐κB activation
Authors: Liu Huan , Wang Zhong‐Chao , Bai Yun‐Gang , Cai Yue , Yu Jin‐Wen , Zhang Hai‐Jun , Bao Jun‐Xiang , Ren Xin‐Ling , Xie Man‐Jiang , Ma Jin 
Published: March 2015

SummaryMicrogravity‐induced vascular remodelling may play an important role in post‐spaceflight orthostatic intolerance. In this study, we aimed to investigate the effects of simulated microgravity on monocyte adhesion to aortic endothelium in hindlimb unweighted rats and to elucidate the underlying mechanisms associated with this event. Sprague–Dawley rats were subjected to 4‐week hindlimb unweighting to simulate microgravity. The recruitment of monocytes to the abdominal aorta was investigated by en face immunofluorescence staining and monocyte binding assays. The expression of the adhesion molecules E‐selectin and vascular cell adhesion molecule‐1 as well as the cytokine monocyte chemoattractant protein (MCP)‐1 was evaluated by immunohistochemical staining, western blot, and quantitative reverse transcription polymerase chain reaction analyses. Additionally, nuclear factor‐κB (NF‐κB) activation and the messenger RNA expression levels of E‐selectin, vascular cell adhesion molecule‐1, and MCP‐1 were assessed with the administration of an NF‐κB inhibitor, pyrrolidine dithiocarbamate. Results showed that simulated microgravity significantly increased monocyte recruitment to the aortic endothelium, protein expression of E‐selectin and MCP‐1, and NF‐κB activation in the abdominal aorta of rats. Pyrrolidine dithiocarbamate treatment not only significantly inhibited NF‐κB activity but also reduced the messenger RNA levels of E‐selectin, vascular cell adhesion molecule‐1, and MCP‐1 as well as monocyte recruitment in the abdominal aorta of hindlimb unweighted rats. These results suggest that simulated microgravity increases monocyte adhesion to rat aortic endothelium via the NF‐κB‐mediated expression of the adhesion molecule E‐selectin and the cytokine MCP‐1. Therefore, an NF‐κB‐mediated inflammatory response may be one of the cellular mechanisms responsible for arterial remodelling during exposure to microgravity.
Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor‐E2‐related factor 2/haem oxygenase (HO)‐1 signalling pathway
Authors: Liu Liyun , Shang Yunxiao , Li Miao , Han Xiaohua , Wang Jia , Wang Juan 
Published: March 2015

SummaryPrevious studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor‐E2‐related factor 2 (Nrf2)/haem oxygenase (HO)‐1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme–linked immunosorbent assay. Histological analyses were evaluated with haematoxylin‐eosin and periodic acid‐Schiff staining. Airway hyperresponsiveness was examined by whole‐body plethysmography. Nuclear factor‐E2‐related factor 2, HO‐1, nuclear factor‐κB and inhibitory κB/p‐inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor‐α, interleukin (IL)‐1β, and IL‐6 levels in the small interfering RNA‐transfected cells were detected by enzyme–linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor‐E2‐related factor 2 and HO‐1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor‐κB and p‐inhibitory κB levels were elevated in the lung tissue of ovalbumin‐challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase‐1 and nuclear Nrf2 levels were enhanced in dose‐ and time‐dependent manners in curcumin‐treated RAW264.7 cells. Curcumin blocked lipopolysaccharide‐upregulated expression of tumour necrosis factor‐α, IL‐1β, and IL‐6. After the cells were transfected with HO‐1 or Nrf2 small interfering RNA, lipopolysaccharide‐induced pro‐inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO‐1 pathway, potentially making it an effective drug in asthma treatment.
Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells
Authors: Ye Dongping , Liang Weiguo , Dai Libing , Zhou Longqiang , Yao Yicun , Zhong Xin , Chen Honghui , Xu Jiake 
Published: March 2015

Summary

Degeneration of the intervertebral disc (IVD) is a major chronic medical condition associated with back pain. To better understand the pathogenesis of IVD degeneration, we performed comparative and quantitative proteomic analyses of normal and degenerated human annulus fibrosus (AF) cells and identified proteins that are differentially expressed between them. Annulus fibrosus cells were isolated and cultured from patients with lumbar disc herniation (the experimental group, degenerated AF cells) and scoliosis patients who underwent orthopaedic surgery (the control group, normal AF cells). Comparative proteomic analyses of normal and degenerated cultured AF cells were carried out using 2‐D electrophoresis, mass spectrometric analyses, and database searching. Quantitative analyses of silver‐stained 2‐D electrophoresis gels of normal and degenerated cultured AF cells identified 10 protein spots that showed the most altered differential expression levels between the two groups. Among these, three proteins were decreased, including heat shock cognate 71‐kDa protein, glucose‐6‐phosphate 1‐dehydrogenase, and protocadherin‐23, whereas seven proteins were increased, including guanine nucleotide‐binding protein G(i) subunit α‐2, superoxide dismutase, transmembrane protein 51, adenosine receptor A3, 26S protease regulatory subunit 8, lipid phosphate phosphatase‐related protein, and fatty acyl‐crotonic acid reductase 1. These differentially expressed proteins might be involved in the pathophysiological process of IVD degeneration and have potential values as biomarkers of the degeneration of IVD.
Growth Arrest‐Specific 6 and Cardiometabolic Risk Factors in Patients with Psoriasis
Authors: Sunbul Murat , Cagman Zeynep , Gerin Fethullah , Ozgen Zuleyha , Durmus Erdal , Seckin Dilek , Ahmad Sarfraz , Uras Fikriye , Agirbasli Mehmet 
Published: March 2015

SummaryObjectivesAn increased risk for cardiovascular disease with psoriasis has been reported. Growth Arrest‐Specific 6 (GAS6) amplifies pro‐inflammatory endothelial cell activation via TAM receptors. However, it also inhibits inflammation by multiple mechanisms including phagocytosis. The objective of this study was to investigate whether plasma GAS6 levels are associated with conventional cardiometabolic (CM) risk factors in patients with psoriasis.MethodsForty patients diagnosed with psoriasis (22 male, mean age: 43.3 ± 13.8 years) and 40 age‐/sex‐matched healthy controls (22 male, mean age: 39.3 ± 8.9 years) were included in the study. CM risk factors (hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking) were identified. GAS6 levels were measured by ELISA.ResultsThere were no significant differences between the plasma GAS6 levels of patients with psoriasis compared to the control group (6.6 ± 2.0 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P > 0.05). However, GAS6 levels of patients with psoriasis having a smoking history (n = 11) were significantly lower than both patients with psoriasis who had no smoking history (n = 29) and controls (5.5 ± 1.7 ng/mL, 6.9 ± 1.9 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P < 0.05). Similarly, psoriasis patients with at least one CM risk factor showed lower GAS6 levels compared to subjects without any CM risk factor (5.7 ± 1.7 ng/mL, 7.3 ± 2.0 ng/mL, P < 0.01). There was no correlation between the GAS6 level, disease duration or PASI score (r = 0.150, −0.150, and P = 0.310, 0.398, respectively).ConclusionsThis pilot study provides the first evidence in humans for an association between low plasma GAS6 levels and conventional risk factors in psoriasis. Further large scale, prospective studies are needed to confirm these results.
Diabetes‐Specific Quality of Life of Korean Children and Adolescents With Type 1 Diabetes
Authors: Boo Sunjoo , Ahn Youngmee , Lee Ji Eun , Kang Narae , Kang Heesook , Sohn Min 
Published: March 2015

PurposeThe purpose of this study was to explore the quality of life of children in Korea with type 1 diabetes and related factors.MethodsChildren were recruited from a diabetes camp. Data were collected using four instruments: the PedsQL™ 3.2 Diabetes Module, Self‐Efficacy for Diabetes Self‐Management, the Center for Epidemiological Studies Depression Scale for Children, and the Diabetes Management Behavior Scale.ResultsChildren who were older (t = 2.197, p = .041), male (t = −3.579, p = .002), and less depressed (t = −2.859, p = .010) were more likely to have better quality of life.ConclusionFurther research is needed in children with type 1 diabetes in countries where this disease is rare, and governmental support and public awareness are limited.
Heat‐Shock Proteins 70 Induce Pro‐Inflammatory Maturation Program in Decidual CD1a+ Dendritic Cells
Authors: Redzovic Arnela , Gulic Tamara , Laskarin Gordana , Eminovic Senija , Haller Herman , Rukavina Daniel 
Published: March 2015

ProblemThe aim of the study was to assess possible binding of a mixture of constitutive Hsc70 and inducible Hsp70 forms (HSP70) to Toll‐like receptor (TLR) 4 and CD91 receptors on decidual CD1a+ dendritic cells (DCs) and their influence on DCs maturation status.Method of studyImmunohistology and immunofluorescence of paraffin‐embedded first trimetester and term pregnancy decidua were performed together with flow cytometry detection of antigens in DCs after stimulation of decidual mononuclear cells with HSP70.ResultsHsc70 and Hsp70 labeling revealed intracellular and nuclear staining in trophoblast cells. The numbers of Hsc70+ and Hsp70+ cells of decidual tissue were higher in early pregnancy decidua than in decidua at term. HSP70 binds CD91 and TLR4 receptors on CD1a+ DCs and increased the expression of CD83, HLA‐DR, CD80, and CD86, but decreased CC receptor (CCR) 5. HSP70 increased CC ligand (CCL) 3 and CCL22. HSP70 in the concentration of 1 μg/mL increased the percentage of interferon‐γ and interleukin (IL)‐15‐expressing cells over the cells expressing IL‐4.ConclusionHSP70 binds CD91 and TLR4 on decidual CD1a+ DCs, causes their maturation, and increases IL‐15 in the context of Th1 cytokine/chemokine domination, which could support immune response harmful for ongoing pregnancy.
Hypnotherapy for irritable bowel syndrome: an audit of one thousand adult patients
Authors: Miller V. , Carruthers H. R. , Morris J. , Hasan S. S. , Archbold S. , Whorwell P. J. 
Published: March 2015

SummaryBackgroundGut‐focused hypnotherapy improves the symptoms of irritable bowel syndrome (IBS) with benefits being sustained for many years. Despite this, the technique has not been widely adopted by healthcare systems, possibly due to relatively small numbers in published studies and uncertainty about how it should be provided.AimTo review the effect of hypnotherapy in a large cohort of refractory IBS patients.MethodsOne thousand IBS patients fulfilling Rome II criteria, mean age 51.6 years (range 17–91 years), 80% female, receiving 12 sessions of hypnotherapy over 3 months, were studied. The primary outcome was a 50 point reduction in the IBS Symptom Severity Score. The fall in scores for Noncolonic Symptoms, Quality of Life and Anxiety or Depression, were secondary outcomes. The Federal Drug Administration's recommended outcome of a 30% or more reduction in abdominal pain was also recorded.ResultsOverall, 76% met the primary outcome which was higher in females (females: 80%, males: 62%, P < 0.001) and those with anxiety (anxious: 79%, non‐anxious: 71%, P = 0.010). The mean reduction in other scores was: IBS Symptom Severity Score, 129 points (P < 0.001), Noncolonic Symptom Score, 65 (P < 0.001) and Quality of Life Score, 66 (P < 0.001). Sixty‐seven per cent reported a 30% or more reduction in abdominal pain scores. Pain days fell from 18 to 9 per month. Patients with anxiety and depression fell from 63% to 34% and 25% to 12% respectively (P < 0.001). Outcome was unaffected by bowel habit subtype.ConclusionThese results provide further evidence that gut‐focused hypnotherapy is an effective intervention for refractory IBS.