bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ion mobility–mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5
Authors: Scott Daniel , Layfield Robert , Oldham Neil J. 
Published: January 2015

Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well‐defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM–MS), offers a rapid and sensitive means of probing ensembles of protein structures through measurement of gas‐phase collisional cross sections. We have applied IM–MS analysis to the multidomain deubiquitinating enzyme ubiquitin specific protease 5 (USP5), which is believed to exhibit significant conformational flexibility. Native ESI–MS measurement of the 94‐kDa USP5 revealed two distinct charge‐state distributions: [M + 17H]+ to [M + 21H]+ and [M + 24H]+ to [M + 29H]+. The collisional cross sections of these ions revealed clear groupings of 52 ± 4 nm2 for the lower charges and 66 ± 6 nm2 for the higher charges. Molecular dynamics simulation of a compact form of USP5, based on a crystal structure, produced structures of 53–54 nm2 following 2 ns in the gas phase, while simulation of an extended form (based on small‐angle X‐ray scattering data) led to structures of 64 nm2. These data demonstrate that IM–MS is a valuable tool in studying proteins with different discrete conformational states.
Oncology staff: burnout, job satisfaction and coping with stress
Authors: Guveli Hulya , Anuk Dilek , Oflaz Serap , Guveli Murat Emin , Yildirim Nazmiye Kocaman , Ozkan Mine , Ozkan Sedat 
Published: January 2015

AbstractObjectiveThe oncology staff is at high risk for developing psychological disorders and burnout. In this study, we aimed to evaluate their burnout levels, job satisfaction, psychological statement and ways of coping with stress and the relationship between these variables and their sociodemographic and occupational characteristics.MethodsAmong all health workers at the Istanbul University Institute, of Oncology, 159 were included in the study. A sociodemographic data form, the Maslach Burnout Inventory, the Minnesota Job Satisfaction Questionnaire, the General Health Questionnaire (GHQ) and the Styles of Coping Inventory‐Short Form were used to evaluate burnout and its contributing factors.ResultsHigh levels of ‘emotional exhaustion’, ‘depersonalization’ and ‘low sense of personal accomplishment’ were determined in 30.2%, 8.2% and 44% of all participants, respectively. The variables that affected emotional exhaustion were assessed by logistic regression analysis. Accordingly, the ratio of emotional exhaustion was approximately 10 times higher in those for whom job stress was the most important stress factor compared with those who indicated nonjob stress for each one point increase on the GHQ and depersonalization scores, which were other predictors, with odds ratio (OR) : 1.23, p = 0.006 and OR : 1.67, p < 0.001, respectively. A negative correlation was detected between adaptive coping styles and ‘burnout,’ and a positive correlation was found between maladaptive coping strategies and exhaustion.ConclusionsIt is necessary to monitor the psychological status of employees in oncology units with scanning tools such as GHQ to understand their job stress perceptions and to help them develop adaptive coping methods. Copyright © 2015 John Wiley & Sons, Ltd.
Loss of MyD88 leads to more aggressive TRAMP prostate cancer and influences tumor infiltrating lymphocytes
Authors: Peek Elizabeth M. , Song Wang , Zhang Hanwei , Huang Jiaoti , Chin Arnold I. 
Published: January 2015

BACKGROUNDThe influence of pattern recognition receptor (PRR) signaling in the prostate tumor microenvironment remains unclear. Although there may be a role for PRR agonists as adjuvants to therapy, prior evidence suggests tumor promoting as well as tumor inhibiting mechanisms. The purpose of this study is to examine the role of the key Toll‐like receptor (TLR) signaling adaptor protein myeloid differentiation primary response gene 88 (MyD88) in prostate cancer development.METHODSMyD88‐/‐ mice in a C57Bl6 background were crossed with transgenic adenocarcinomas of the mouse prostate (TRAMP) mice to create MyD88‐/‐ TRAMPTg+/− animals, which were compared to MyD88+/+ TRAMPTg+/− animals and their non‐transgenic counterparts at 30 weeks. Prostates were examined histologically, by immunohistochemistry and immunofluorescence staining, and by qPCR, to characterize tumor‐infiltrating immune populations as well as activation of the downstream NF‐κB pathway and androgen receptor (AR) expression. Splenocytes were examined for development of distinct immune cell populations.RESULTSAbsence of MyD88 led to increased prostatic intraepithelial neoplasm (PIN) and areas of well‐differentiated adenocarcinoma in TRAMP transgenic mice. Analysis of infiltrating immune populations revealed an increase in CD11b+ Gr1+ myeloid‐derived suppressor cells (MDSCs), as evidenced by increased expression of prostatic arginase‐1 and iNOS as well as the cytokine IL‐10, and a deficiency in NK cells in prostates from MyD88‐/‐ TRAMPTg+/− compared to MyD88+/+ TRAMPTg+/− mice, whereas a decrease in splenocytic NK cell differentiation was observed in MyD88‐/‐ mice. Prostate tumors revealed no significant differences in NF‐κB or AR expression in MyD88+/+ TRAMPTg+/− compared to MyD88‐/‐ TRAMPTg+/− mice.CONCLUSIONSDuring prostate cancer development in the TRAMP model, MyD88 may play a role in limiting prostate tumorigenesis by altering tumor‐infiltrating immune populations. This suggests that in the context of specific cancers, distinct PRRs and signaling pathways of innate immune signaling may influence the tumor microenvironment and represent a novel therapeutic strategy. Prostate 75: 463–473, 2015. © 2015 Wiley Periodicals, Inc.
Prostate atypia: Does repeat biopsy detect clinically significant prostate cancer?
Authors: Dorin Ryan P. , Wiener Scott , Harris Cory D. , Wagner Joseph R. 
Published: January 2015

BackgroundWhile the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia.METHODSWe reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service.RESULTSTen thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987‐March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient.CONCLUSIONSASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. Prostate 75:673–678, 2015. © 2015 Wiley Periodicals, Inc.
Role of Muscle Stem Cells During Skeletal Regeneration
Authors: Abou-Khalil Rana , Yang Frank , Lieu Shirley , Julien Anais , Perry Jaselle , Pereira Catia , Relaix Frédéric , Miclau Theodore , Marcucio Ralph , Colnot Céline 
Published: January 2015

Abstract
Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7−/− mice and satellite cell ablation in Pax7CreERT2/+;DTAf/f mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7CreERT2/+;DTAf/f mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7CreERT2/+;DTAf/f mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications. Stem Cells 2015;33:1501–1511
The managing director wants 100% automated testing. A case history
Authors: Fewster Mark 
Published: January 2015

AbstractManual testing was taking 38 man weeks for every release on every platform. With more hardware platforms coming onto the market and increasing commercial pressure to ship more products sooner, the ability to survive by manual testing alone came into question. Effort was expended on automating integration testing as a trial. The results were good but not as spectacular as had been hoped for. Nonetheless, automated system test was investigated whilst retaining the same test coverage achieved by manual testing. Many changes were made, and many problems encountered with the non‐technical problems having an unexpectedly large impact – some of them almost destroyed the attempt at automation. Test automation has been successful, although the benefits are only now becoming apparent. More products are being released in less time than had ever been achieved before.
Software testing tools: A new classification scheme
Authors: Graham Dorothy R. 
Published: January 2015

AbstractSoftware testing tools have proliferated in recent years, and a number of tool classification schemes have been published. In order to provide common reference points for potential purchasers and tool vendors, to ease the comparison of tools with similar functionality, and to assist future research into tool‐supportable software testing, a new classification scheme for testing tools is proposed. The scheme uses six major categories: Test Management, Test Design, Non‐Execution Evaluation, Test Execution. Test Analysis, and Test Quality Evaluation. Other classification schemes are reviewed and compared with the new scheme, and predictions are made concerning future trends in the area of software testing tools. It is hoped that the proposed classification, which is founded on the combination of two current schemes, will provide a basis for discussions that will lead eventually to an international standardisation of tool descriptions.
A participatory systems approach to understanding climate adaptation needs
Authors: Ross Helen , Shaw Sylvie , Rissik David , Cliffe Neil , Chapman Susie , Hounsell Vanessa , Udy James , Trinh Nghia Trong , Schoeman Jess 
Published: January 2015

Abstract
Emerging literature on climate adaptation suggests the need for effective ways of engaging or activating communities and supporting community roles, coupled with whole-of-system approaches to understanding climate change and adaptation needs. We have developed and evaluated a participatory approach to elicit community and stakeholder understanding of climate change adaptation needs, and connect diverse community members and local office bearers towards potential action. The approach was trialed in a series of connected social-ecological systems along a transect from a rural area to the coast and islands of ecologically sensitive Moreton Bay in Queensland, Australia. We conducted ‘climate roundtables’ in each of three areas along the transect, then a fourth roundtable reviewed and extended the results to the region as a whole. Influence diagrams produced through the process show how each climate variable forecast to affect this region (heat, storm, flood, sea-level rise, fire, drought) affects the natural environment, infrastructure, economic and social behaviour patterns, and psychosocial responses, and how sets of people, species and ecosystems are affected, and act, differentially. The participatory process proved effective as a way of building local empathy, a local knowledge base and empowering participants to join towards future climate adaptation action. Key principles are highlighted to assist in adapting the process for use elsewhere.
Effects on cognitive and clinical insight with the use of Guided Self-Determination in outpatients with schizophrenia: A randomized open trial
Authors: Jørgensen R. , Licht R.W. , Lysaker P.H. , Munk-Jørgensen P. , Buck K.D. , Jensen S.O.W. , Hansson L. , Zoffmann V. 
Published: January 2015

AbstractPoor insight has a negative impact on the outcome in schizophrenia; consequently, poor insight is a logical target for treatment. However, neither medication nor psychosocial interventions have been demonstrated to improve poor insight. A method originally designed for diabetes patients to improve their illness management, Guided Self-Determination (GSD), has been adapted for use in patients with schizophrenia (GSD-SZ). The purpose of this study was to investigate the effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as compared to TAU alone in outpatients diagnosed with schizophrenia. The design was an open randomized trial. The primary hypothesis was cognitive insight would improve in those patients who received GSD-SZ + TAU as assessed by the BCIS. We additionally explored whether the intervention led to changes in clinical insight, self-perceived recovery, self-esteem, social functioning and symptom severity. Assessments were conducted at baseline, and at 3-, 6- and 12-month follow-up. Analysis was based on the principles of intention to treat and potential confounders were taken into account through applying a multivariate approach. A total of 101 participants were randomized to GSD-SZ + TAU (n = 50) or to TAU alone (n = 51). No statistically significant differences were found on the cognitive insight. However, at 12-month follow-up, clinical insight (measured by G12 from the Positive and Negative Syndrome Scale), symptom severity, and social functioning had statistically significantly improved in the intervention group as compared to the control group. “Improving insight in patients diagnosed with schizophrenia”, NCT01282307, http://clinicaltrials.gov/.
Give me your self: Gifts are liked more when they match the giver's characteristics
Authors: Paolacci Gabriele , Straeter Laura M. , de Hooge Ilona E. 
Published: January 2015

AbstractResearch on gift giving has devoted considerable attention to understanding whether and how givers succeed in choosing gifts that match recipients' tastes. On the contrary, this article focuses on how recipients' appreciation for a gift depends on the match between the gift and the giver. Four studies demonstrate that recipients are particularly appreciative when they receive gifts that figuratively match the giver, i.e., that contain references to the giver's characteristics, because they perceive such gifts as more congruent with the giver's identity. This effect is not conditional on inferences recipients might make about the giver's motivations or on whether recipients have a good relationship with the giver, but relies on the match concerning core rather than peripheral characteristics of the giver. Importantly for our understanding of identity‐based motivation, these findings demonstrate in a gift‐giving context that identity‐congruence not only drives consumer behavior, but is also appreciated in other people.
Usefulness of admission hematologic parameters as diagnostic tools in acute pulmonary embolism
Authors: Celik Ahmet , Ozcan Ismail Türkay , Gündes Ahmet , Topuz Mustafa , Pektas Idris , Yesil Emrah , Ayhan Selcuk , Kose Ataman , Camsari Ahmet , Cin Veli Gokhan 
Published: January 2015

AbstractThe purpose of this study was to determine the role of red cell distribution width (RDW), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR) in the diagnostic phase of acute pulmonary embolism (PE). We screened 248 consecutive patients who were admitted to the emergency service with PE foremost in the differential diagnosis. Based on spiral computed chest tomography, the patients were divided into two groups. There were 112 confirmed cases of acute PE and 138 patients without PE. Blood samples were obtained within 2 hours of presentation and before starting any medication. There were no significant differences between the PE and the non‐PE groups with respect to sex, age, frequency of disease, serum creatinine, sodium, and potassium (p > 0.05 for all). NLR, RDW, and PLR were higher in patients with PE than those without PE. High‐sensitivity C‐reactive protein, d‐dimer, and troponin levels were also higher in patients with PE. RDW values were positively correlated with troponin levels (r = 0.147, p = 0.021). There were no correlations between RDW and NLR, PLR, or d‐dimer. NLR had a highly positive correlation with PLR (r = 0.488, p < 0.001). In multivariate logistic regression analysis, troponin I, d‐dimer, high‐sensitivity C‐reactive protein, and RDW were found to be independent predictors of PE [odds ratio (95% confidence interval) respectively: 5.208 (2.534–10.704), 1.242 (1.094–1.409), 1.005 (1.000–1.010), 1.175 (1.052–1.312)]. In receiver operating characteristic analysis of the patients in the study, RDW >18.9 predicted acute PE with a sensitivity of 20.7% and a specificity of 93.4%. In conclusion, RDW can be considered useful as a diagnostic measure for patients with suspected acute PE.
Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti‐tumor mechanisms of Cannabidiol in breast cancer
Authors: Elbaz Mohamad , Nasser Mohd W. , Ravi Janani , Wani Nissar A. , Ahirwar Dinesh K. , Zhao Helong , Oghumu Steve , Satoskar Abhay R. , Shilo Konstantin , Carson William E. , Ganju Ramesh K. 
Published: January 2015

The anti‐tumor role and mechanisms of Cannabidiol (CBD), a non‐psychotropic cannabinoid compound, are not well studied especially in triple‐negative breast cancer (TNBC). In the present study, we analyzed CBD's anti‐tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype. We show here ‐for the first time‐that CBD significantly inhibits epidermal growth factor (EGF)‐induced proliferation and chemotaxis of breast cancer cells. Further studies revealed that CBD inhibits EGF‐induced activation of EGFR, ERK, AKT and NF‐kB signaling pathways as well as MMP2 and MMP9 secretion. In addition, we demonstrated that CBD inhibits tumor growth and metastasis in different mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor‐associated macrophages in primary tumor stroma and secondary lung metastases. Similarly, our in vitro studies showed a significant reduction in the number of migrated RAW 264.7 cells towards the conditioned medium of CBD‐treated cancer cells. The conditioned medium of CBD‐treated cancer cells also showed lower levels of GM‐CSF and CCL3 cytokines which are important for macrophage recruitment and activation. In summary, our study shows ‐for the first time‐that CBD inhibits breast cancer growth and metastasis through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment. These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and metastasis of highly aggressive breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.
The Criminal Corpse, Anatomists, and the Criminal Law: Parliamentary Attempts to Extend the Dissection of Offenders in Late Eighteenth-Century England
Authors: Ward Richard 
Published: January 2015

AbstractIn the later eighteenth century, two schemes were introduced in Parliament for extending the practice of handing over the bodies of executed offenders to anatomists for dissection. Both measures were motivated by the needs of the field of anatomy, including the improvement of surgical skill, the development of medical teaching in the provinces, and public anatomical demonstrations. Yet both failed to pass into law due to concerns about the possibly damaging effects in terms of criminal justice. Through a detailed analysis of the origins and progress of these two parliamentary measures—a moment when the competing claims of anatomy and criminal justice vied for supremacy over the criminal corpse—the article sheds light on judicial attitudes to dissection as a method of punishment and adds to our understanding of the reasons why, in the nineteenth century, the dread of dissection would come to fall upon the dead poor rather than executed offenders.
Joseph Chamberlain and the Third Reform Act: A Reassessment of the “Unauthorized Programme” of 1885
Authors: Blaxill Luke 
Published: January 2015

AbstractThis article provides the first major analysis of the impact of Joseph Chamberlain's “Unauthorized Programme” on the General Election of 1885 in sixty-five years. Instead of focusing on high politics, it investigates the constituencies. Using quantitative analysis of linguistic data, it contends that historians have underestimated the program's impact on the speaking campaign, especially in the countryside, where its proposals of land reform, church disestablishment, and free education emerged as the dominant issues. That the “Unauthorized Programme” became so important so quickly in rural regions such as East Anglia, where radicalism had historically been weak, owed much to the underestimated importance of the enfranchisement of the agricultural laborer in 1884. Chamberlain's remarkable success in immediately setting the post-reform political agenda and in being seen as the chief threat by Conservative opponents fearful of the recently expanded democracy, arguably placed him in a significantly stronger position in the immediate aftermath of the 1885 election than historians—and perhaps he himself—imagined.