bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma
Authors: Otto Claudia , Giefing Maciej , Massow Anne , Vater Inga , Gesk Stefan , Schlesner Matthias , Richter Julia , Klapper Wolfram , Hansmann Martin‐Leo , Siebert Reiner , Küppers Ralf 
Published: April 2012

SummaryHodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) show constitutive activation of nuclear factor (NF)‐κB. Several genetic lesions contribute to this deregulated NF‐κB activity. Here, we analysed two further NF‐κB regulators for genetic lesions, the inhibitory factor TRAF3 and the key signalling component of the alternative NF‐κB pathway, MAP3K14 (NIK). Single nucleotide polymorphism (SNP) array analysis of cHL cell lines revealed a uniparental disomy of the long arm of chromosome 14 associated with a biallelic deletion of TRAF3 located on this chromosome in cell line U‐HO1. Cloning of the deletion breakpoint showed a 123 371 bp deletion. No inactivating mutations of TRAF3 were found in six other cHL cell lines or in microdissected HRS cells from seven cHL. However, in primary cHL samples interphase cytogenetic analyses revealed signal patterns indicating monoallelic deletion of TRAF3 in 3/20 other cases. SNP array analysis revealed a gain of copy number for MAP3K14 in three cHL cell lines. Gains of MAP3K14 were detected in 5/16 cases of primary cHL. In conclusion, in rare instances, HRS cells harbour inactivating mutations of the TRAF3 gene and recurrently show gains of MAP3K14, indicating that more components of NF‐κB signalling show genetic lesions in HRS cells than previously known.
Sox2 targets cyclinE, p27 and survivin to regulate androgen‐independent human prostate cancer cell proliferation and apoptosis
Authors: Lin F. , Lin P. , Zhao D. , Chen Y. , Xiao L. , Qin W. , Li D. , Chen H. , Zhao B. , Zou H. , Zheng X. , Yu X. 
Published: April 2012

AbstractObjectivesSox2 is a major transcription factor and the transforming growth factor‐α (TGF‐α)/EGFR autocrine loop is a hallmark of prostate cancer progression. In this study, we have evaluated the effects and potential mechanisms of Sox2 on cell proliferation and apoptosis, and investigated effects of TGF‐α on expression of Sox2 on androgen‐independent human prostate cancer cells.Materials and methodsExpression of Sox2 has been determined by RT‐PCR, western blot analysis and immunocytochemistry, using RNAi and over‐expression strategy to study functions of Sox2 in DU145 and PC‐3 cells. Changes in level of proliferation, cell cycle and apoptosis profiles were measured by MTT, colony‐forming, bromodeoxyuridine incorporation assays, cell cycle and annexin V analysis.ResultsSox2 was expressed in six human prostate cancer cell lines, and its inhibition reduced cell proliferation and induced apoptosis in DU145 cells. We have shown that knock‐down of Sox2 inhibited G1 to S phase transition concomitantly with down‐regulation of cyclin E and up‐regulation of p27 proteins. Conversely, over‐expression of Sox2 led to the opposite effect in PC‐3 cells but its inhibition induced apoptosis by down‐regulation of survivin in DU145 cells. We also found that TGF‐α up‐regulated Sox2 and survivin protein expression via the EGFR/PI3K/AKT pathway.ConclusionsSox2 expression is necessary for cell proliferation and evasion of apoptosis in prostate cancer cells and TGF‐α could regulate Sox2 and survivin expression by activating the EGFR/PI3K/AKT pathway.
Inhibition of phosphodiestrase 9 induces cGMP accumulation and apoptosis in human breast cancer cell lines, MCF‐7 and MDA‐MB‐468
Authors: Saravani R. , Karami‐Tehrani F. , Hashemi M. , Aghaei M. , Edalat R. 
Published: April 2012

AbstractObjectivesPhosphodiesterase 9 (PDE9) is a major isoform of phosphodiesterase hydrolysing cGMP and plays a key role in proliferation of cells, their differentiation and apoptosis, via intracellular cGMP signalling. The study described here was designed to investigate expression, activity and apoptotic effect of PDE9 on human breast cancer cell lines, MCF‐7 and MDA‐MB‐468.Materials and methodsActivity and expression of PDE9 were examined using colorimetric cyclic nucleotide phosphodiesterase assay and real‐time RT‐PCR methods respectively; cGMP concentration was also measured. MTT viability test, annexin V‐FITC staining, Hoechst 33258 staining and caspase3 activity assay were used to detect apoptosis.ResultsTreatment of both cell lines with BAY 73‐6691 lead to reduction in PDE9 mRNA expression, PDE9 cGMP‐hydrolytic activity and elevation of the intracellular cGMP response. BAY 73‐6691 significantly reduced cell proliferation in a dose‐ and time‐dependent manner and caused marked increase in apoptosis through caspase3 activation.ConclusionOur results revealed that BAY 73‐6691 induced apoptosis in these breast cancer cell lines through the cGMP pathway. These data suggest that BAY 73‐6691 could be utilized as an agent in treatment of breast cancer.
A relationship‐based approach to engaging involuntary clients: the contribution of recognition theory
Authors: Turney Danielle 
Published: April 2012

ABSTRACTThis paper focuses on the process of engaging with families where a child is at risk of harm, and considers a relationship‐based approach to work with ‘involuntary clients’ of child protection services. Contextualizing the discussion within a broader understanding of the role and importance of relationship‐based practice, a conceptual and ethical framework is outlined that can, it is suggested, support effective relationship‐based work and moral decision‐making with involuntary clients. Making use of psychoanalytic and more broadly psychodynamic insights, along with perspectives drawn from recognition theory, it is argued that relationship‐based practice offers the potential for recognition, respect and reciprocity, and that these three aspects of relationship provide a foundation for ethical engagement with involuntary clients. However, such an approach is not without tensions, so the latter part of the paper considers some of the challenges and dilemmas that accompany the process of trying to engage parents who do not want to be ‘worked with’.
‘I'm just a mother. I'm nothing special, they're all professionals’: parental advocacy as an aid to parental engagement
Authors: Featherstone Brid , Fraser Claire 
Published: April 2012

ABSTRACTThis paper discusses findings from an evaluation of an advocacy scheme for parents whose children were subject to child protection proceedings including a pilot project where co‐operation between parents and professionals was an issue. Encouraging findings of parents' experiences of being heard, being able to listen, and, in some cases, to act on concerns about their children's welfare are outlined. Three case studies offer accounts of practices that are gendered and occur against a backdrop of ethnic disadvantage. The paper suggests that current debates about reform need to recognize the need to support parents to manage intimidating systems.
Evaluation of residential care from the perspective of older adolescents in care. The need for a new construct: optimum professional proximity
Authors: Soldevila Anna , Peregrino Antonio , Oriol Xavier , Filella Gemma 
Published: April 2012

ABSTRACTThis paper analyses the evaluation of residential care from the perspective of the adolescents in care. Twelve discussion groups were carried out in 12 different centres in Catalonia (Spain). A total of 66 adolescents aged between 16 and 18 years of age participated. The data contributed by the discussion groups were analysed and categorized using descriptive analysis matrices. Most notable from the results is that the majority of those interviewed call for increased emotional involvement from the social workers, more contact with their families and re‐educational intervention within their families, which renders the return to these possible within a shorter period of time. Data provided by the adolescents lead us to reconsider the concept of optimum professional distance and to suggest replacing it with optimum professional proximity; this would be based on emotional involvement and not on emotional distance, although not on emotional dependence either.
Bronchial inflammation and hyperresponsiveness in well controlled asthma
Authors: Muñoz X. , Sanchez‐Vidaurre S. , Roca O. , Torres F. , Morell F. , Cruz M. J. 
Published: April 2012

SummaryBackgroundLittle research has been devoted to the characteristics of bronchial inflammation in patients with stable, well controlled asthma.ObjectiveThe aim of this study was to assess the degree and type of airway inflammation and to investigate the relationship between inflammation and bronchial hyperresponsiveness in patients with well controlled asthma.MethodsA cross‐sectional study was conducted in 84 adult patients (43 men, mean age 43 years) with documented well controlled asthma. Induced sputum samples were obtained and cell types determined by differential cell count. Spirometry and methacholine challenge testing were performed. Asthma Control Questionnaire (ACQ) was used to assess symptoms. Patients were included if their ACQ score was < 0.75.ResultsA total of 59 patients had persistent bronchial inflammation: 28 cases were considered eosinophilic, 28 neutrophilic, and 3 mixed. Median (range) percentage of eosinophils was 4% (0–64) in patients testing positive to methacholine challenge (n = 66) and 1% (0–3) in those testing negative (n = 18) (P = 0.003). A positive correlation was found between eosinophil percentage and the methacholine dose/response ratio (r = 0.477, P = 0.0001). The geometric mean (95% CI) of the methacholine PC20 was 1.74 mg/mL (1.04–2.93) in patients with eosinophilic inflammation and 4.14 mg/mL (2.5–6.84) in those with neutrophilic inflammation (P = 0.03).ConclusionsInflammation and bronchial hyperresponsiveness persist in most patients with well controlled asthma.Clinical RelevanceThe study demonstrates that eosinophilic or neutrophilic inflammation persisted in most well controlled asthma patients despite the fact that their condition was controlled and therefore, measurement of bronchial inflammation seems essential to achieve proper asthma control.
Childhood wheezing phenotypes and FeNO in atopic children at age 8
Authors: van der Valk R. J. P. , Caudri D. , Savenije O. , Koppelman G. H. , Smit H. A. , Wijga A. H. , Postma D. S. , Kerkhof M. , Brunekreef B. , de Jongste J. C. 
Published: April 2012

SummaryBackgroundFractional exhaled Nitric Oxide (FeNO) is a surrogate biomarker of the degree of eosinophilic airway inflammation. Using longitudinal latent class analysis, five wheezing phenotypes have been identified, characterized by different ages of onset and prognosis.ObjectivesTo assess FeNO measured at 4 and 8 years in children with different phenotypes of wheeze and atopy.MethodsChildren participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study, a prospective birth cohort in the Netherlands. Respiratory health was assessed yearly by questionnaires until the age of 8 years; these data were used to identify five wheezing phenotypes. Associations between FeNO and wheezing phenotypes were investigated using weighted linear regression.ResultsData on wheezing phenotypes and FeNO at 4 and 8 years were available in 588 and 973 children respectively. Compared with the phenotype of never and transient wheeze, FeNO at 4 years was higher in intermediate onset and persistent wheeze. FeNO at 8 years of age differed significantly between all phenotypes, with highest FeNO values for persistent, intermediate onset, and late onset wheeze. Rise in FeNO from 4 to 8 years in intermediate and late onset wheezers was significantly higher compared to FeNO rise in never and transient wheezers. Stratified analyses showed that the increase in FeNO in persistent, intermediate, and late onset wheeze was only present in children with allergic sensitization at 8 years.Conclusions and Clinical RelevanceThe FeNO measured at 8 years was associated with specific wheezing phenotypes, only among atopic children.
Thyrotrophin receptor antibody characteristics in a woman with long‐standing Hashimoto's who developed Graves' disease and pretibial myxoedema
Authors: Kamath C. , Young S. , Kabelis K. , Sanders J. , Adlan M. A. , Furmaniak J. , Rees Smith B. , Premawardhana L. D. 
Published: April 2012

AbstractContextSequential conversion of Hashimoto's thyroiditis (HT) to Graves' disease (GD) is uncommon. Distinct immune paradigms, paucity of functioning tissue in long‐standing HT, and infrequent conversion of blocking (TBAb) to stimulating (TSAb) thyrotrophin receptor antibody (TRAb) may account for this. Molecular and crystal structure analysis helps delineate TSH receptor (TSHR)/TRAb interactions in detail. Such ‘fingerprinting’ helps determine the behaviour and characteristics of TRAb in longitudinal studies.PatientAn 80‐year‐old woman taking thyroxine for long‐standing HT became hyperthyroid. This persisted despite thyroxine withdrawal – free T3 was 7·3 pmol/l (2·6–5·7) and TSH < 0·01 mU/l (0·2–4·5) and TRAb highly positive. She had a goitre (ultrasound – HT), pretibial myxoedema, with mild inactive Graves' orbitopathy. She had RAI treatment and is on thyroxine replacement.Measurements and ResultsBlood samples at presentation (A) and 1 year (B) showed high TSAb and TPOAb activity but no TBAb. Experiments involving TSHR mutations confirmed that (i) TRAb had stable characteristics over 1 year; (ii) TSHR mutation R255D caused complete inhibition and (iii) R109A caused marked reduction of cAMP production by M22 (TSHR‐stimulating human monoclonal antibody) and A and B; (iv) mutations R80A, E107A and K129A while affecting M22 had little effect on A and B.ConclusionsThe reasons for an immunological paradigm shift in this elderly woman remain speculative. We believe that de‐novo TSAb synthesis occurred converting her long‐standing HT to GD although the mechanisms responsible remain unexplained. TRAb analysis confirmed stable autoantibody characteristics over 1 year and variable effects of TSHR mutations on TRAb and M22 function.
Climate change and health with an emphasis on interactions with ultraviolet radiation: a review
Authors: Thomas Peter , Swaminathan Ashwin , Lucas Robyn M. 
Published: April 2012

AbstractClimate change is increasingly recognized as a major risk to human health, and health concerns are assuming more importance in international debates on mitigation and adaptation strategies. Health consequences of climate change will occur through direct and indirect routes, and as a result of interactions with other environmental exposures. Heatwaves will become more common and are associated with higher mortality particularly in the elderly and those with pre‐existing cardiovascular and respiratory illnesses. Warmer ambient temperatures will result in more dehydration episodes and increased risks of renal disease and, through effects on pollen seasons, there may be an increase in allergic disease such as asthma and hayfever. Other adverse effects including on air quality, food safety and security and an expanding distribution of some infectious diseases, including vector‐borne diseases, are postulated. A related but separate environmental exposure is that of ultraviolet radiation (UVR). Interactions between climate change and stratospheric ozone (and the causes of ozone depletion) will cause changes to levels of ambient UVR in the future and warmer temperatures are likely to change sun exposure behaviour. Co‐occurring effects on aquatic and terrestrial ecosystems have potential consequences for food safety, quality and supply. Climate change‐related exposures are likely to affect the incidence and distribution of diseases usually considered as caused by UVR exposure; and changes in UVR exposure will modulate the climate change effects on human health. For example, in some regions warmer temperatures due to climate change will encourage more outdoor behaviour, with likely consequences for increasing skin cancer incidence. Although many of the health outcomes of both climate change and the interaction of climate change and UVR exposure are somewhat speculative, there are risks to over‐ or under‐estimations of health risks if synergistic and antagonistic effects of co‐occurring environmental changes are not considered.
Satellite‐based evidence for shrub and graminoid tundra expansion in northern Quebec from 1986 to 2010
Authors: McManus kelly M. , Morton Douglas C. , Masek Jeffrey G. , Wang Dongdong , Sexton Joseph O. , Nagol Jyoteshwar R. , Ropars Pascale , Boudreau Stéphane 
Published: April 2012

AbstractGlobal vegetation models predict rapid poleward migration of tundra and boreal forest vegetation in response to climate warming. Local plot and air‐photo studies have documented recent changes in high‐latitude vegetation composition and structure, consistent with warming trends. To bridge these two scales of inference, we analyzed a 24‐year (1986–2010) Landsat time series in a latitudinal transect across the boreal forest‐tundra biome boundary in northern Quebec province, Canada. This region has experienced rapid warming during both winter and summer months during the last 40 years. Using a per‐pixel (30 m) trend analysis, 30% of the observable (cloud‐free) land area experienced a significant (P < 0.05) positive trend in the Normalized Difference Vegetation Index (NDVI). However, greening trends were not evenly split among cover types. Low shrub and graminoid tundra contributed preferentially to the greening trend, while forested areas were less likely to show significant trends in NDVI. These trends reflect increasing leaf area, rather than an increase in growing season length, because Landsat data were restricted to peak‐summer conditions. The average NDVI trend (0.007 yr−1) corresponds to a leaf‐area index (LAI) increase of ~0.6 based on the regional relationship between LAI and NDVI from the Moderate Resolution Spectroradiometer. Across the entire transect, the area‐averaged LAI increase was ~0.2 during 1986–2010. A higher area‐averaged LAI change (~0.3) within the shrub‐tundra portion of the transect represents a 20–60% relative increase in LAI during the last two decades. Our Landsat‐based analysis subdivides the overall high‐latitude greening trend into changes in peak‐summer greenness by cover type. Different responses within and among shrub, graminoid, and tree‐dominated cover types in this study indicate important fine‐scale heterogeneity in vegetation growth. Although our findings are consistent with community shifts in low‐biomass vegetation types over multi‐decadal time scales, the response in tundra and forest ecosystems to recent warming was not uniform.
The senses in practice: enhancing the quality of care for residents with dementia in care homes
Authors: Brown Wilson Christine , Swarbrick Caroline , Pilling Mark , Keady John 
Published: April 2012

AbstractAim.  The study aimed to develop, deliver, and evaluate a training programme in care homes to enhance the quality of care for people living with dementia based on the principles of relationship‐centred care expressed through the Senses Framework.Background.  There are increasing numbers of people living with dementia worldwide with a growing proportion requiring residential long‐term care. This makes the quest for enhancing the quality of care and quality of life for people with dementia ever more pressing.Design.  A mixed‐methods design was used adopting a Practice Development approach. The findings from one care home in the North West of England are reported.Methods.  Eight facilitated workshops based on the principles of relationship‐centred care were completed and evaluated in 2010, using pre‐ and postintervention design. A focus group was undertaken with staff on completion of the study to gain a more comprehensive understanding of the practice/training context, augmented by case examples of changes in practice identified from the study workshops.Results.  Structured questionnaires were used to profile the care home before and after the training. Following the workshops, staff felt more able to collect and use biographical information. In particular, staff reported how this information supported them to initiate meaningful conversations with the person with dementia as part of everyday care routines, thus improving overall feelings of well‐being.Conclusion.  Using a biographical approach to care planning structured through the Senses Framework helped staff to develop a greater understanding of the person with dementia.
Enhancing team learning in nursing teams through beliefs about interpersonal context
Authors: Ortega Aída , Sánchez‐Manzanares Miriam , Gil Francisco , Rico Ramón 
Published: April 2012

AbstractAim.  This article is a report of a study that examines the relationship between team‐level learning and performance in nursing teams, and the role of beliefs about the interpersonal context in this relationship.Background.  Over recent years, there has been an increasing interest in the learning processes of work teams. Researchers have investigated the impact of team learning on team performance, and the enabling conditions for this learning. However, team learning in nursing teams has been largely ignored.Design.  A cross‐sectional field survey design was used.Methods.  The sample comprises a total of 468 healthcare professionals working in 89 nursing teams at different public hospitals throughout Spain. Members of nursing teams participated voluntarily by completing a confidential individual questionnaire. Team supervisors evaluated nursing teams’ performance. Data were collected over 2007–2008.Results.  The results show a mediating effect of team learning on the relationship between beliefs about interpersonal context (psychological safety, perceived task interdependence, and group potency) and team performance.Conclusion.  Our findings suggest that beliefs about interpersonal context and team learning are important to effective nursing team performance.
Internight sleep variability: its clinical significance and responsiveness to treatment in primary and comorbid insomnia
Authors: SÁNCHEZ‐ORTUÑO MARÍA M. , EDINGER JACK D. 
Published: April 2012

SummaryAlthough sleep diary and actigraphy data are usually collected daily for 1 or 2 weeks, traditional analytical approaches aggregate these data into mean values. Internight variability of sleep often accompanies insomnia. However, few studies have explored the relevance of this ‘construct’ in the context of diagnosis, clinical impact, treatment effects and/or whether having ‘variable sleep’ carries any prognostic significance. We explored these questions by conducting secondary analyses of data from a randomized clinical trial. The sample included primary (PI: n = 40) and comorbid insomnia (CMI: n = 41) sufferers receiving four biweekly sessions of cognitive–behavioural therapy (CBT) or sleep hygiene education. Using the within‐subject standard deviations of diary‐ and actigraphy‐derived measures collected for 2‐week periods [sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE)], we found that CMI sufferers displayed more variable self‐reported SOLs and SEs than PI sufferers. However, higher variability in diary and actigraphy‐derived measures was related to poorer sleep quality only within the PI group, as measured by the Pittsburgh Sleep Quality Index (PSQI). Within both groups, the variability of diary‐derived measures was reduced after CBT, but the variability of actigraphy‐derived measures remained unchanged. Interestingly, the variability of actigraphy measures at baseline was correlated with PSQI scores at 6‐month follow‐up. Higher SOL variability was associated with worse treatment outcomes within the PI group, whereas higher WASO variability was correlated with better treatment outcomes within the CMI group. Sleep variability differences across insomnia diagnoses, along with their distinctive correlates, suggest that mechanisms underlying the sleep disruption/complaint and treatment response in both patient groups are distinct. Further studies are warranted to support variability as a useful metric in insomnia studies.