bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Functional Analysis of the 18 Vibrio cholerae N16961 Toxin-Antitoxin Systems Substantiates Their Role in Stabilizing the Superintegron
Authors: Iqbal Naeem , Guérout Anne-Marie , Krin Evelyne , Le Roux Frédérique , Mazel Didier 
Published: April 2015

ABSTRACTThe role of chromosomal toxin-antitoxin (TA) systems, which are ubiquitous within the genomes of free-living bacteria, is still debated. We have scanned theVibrio choleraeN16961 genome for class 2 TA genes and identified 18 gene pair candidates. Interestingly, all but one are located in the chromosome 2 superintegron (SI). The single TA found outside the SI is located on chromosome 1 and is related to the well-characterized HipAB family, which is known to play a role in antibiotic persistence. We investigated this clustering within the SI and its possible biological consequences by performing a comprehensive functional analysis on all of the putative TA systems. We demonstrate that the 18 TAs identified encode functional toxins and that their cognate antitoxins are able to neutralize their deleterious effects when expressed inEscherichia coli. In addition, we reveal that the 17 predicted TA systems of the SI are transcribed and expressed in their native context from their own promoters, a situation rarely found in integron cassettes. We tested the possibility of interactions between noncognate pairs of all toxins and antitoxins and found no cross-interaction between any of the different TAs. Although these observations do not exclude other roles, they clearly strengthen the role of TA systems in stabilizing the massive SI cassette array ofV. cholerae.IMPORTANCEThe chromosomal toxin-antitoxin systems have been shown to play various, sometimes contradictory roles, ranging from genomic stabilization to bacterial survival via persistence. Determining the interactions between TA systems hosted within the same bacteria is essential to understand the hierarchy between these different roles. We identify here the full set of class 2 TAs carried in theVibrio choleraeN16961 genome and found they are all, with a single exception, located in the chromosome 2 superintegron. Their characterization, in terms of functionality, expression, and possible cross-interactions, supports their main role as being the stabilization of the 176-cassette-long array of the superintegron but does not exclude dual roles, such as stress response elements, persistence, and bacteriophage defense through abortive infection mechanisms.
The Impact of Tonsillectomy upon the Risk of Oropharyngeal Carcinoma Diagnosis and Prognosis in the Danish Cancer Registry
Authors: Fakhry Carole , Andersen Klaus K. , Christensen Jane , Agrawal Nishant , Eisele David W. 
Published: April 2015

AbstractThe incidence of oropharyngeal carcinoma, involving palatine and lingual tonsils, is increasing globally. This significant rise is driven by human papillomavirus. Whether palatine tonsillectomy affects risk of diagnosis with oropharyngeal carcinoma is unknown. The association between tonsillectomy and incidence of oropharyngeal carcinoma was explored in the Danish Cancer Registry. The association between tonsillectomy and oropharyngeal carcinoma was analyzed by time since first registration of tonsillectomy. Tonsillectomy was a time-dependent variable. Individuals were censored for death, emigration, or tonsillectomy within incident year of diagnosis. Incidence rate ratios (RR) were estimated by Poisson regression models and adjusted for confounders. Kaplan–Meier survival analyses were compared by the log-rank test, and HRs were estimated by Cox proportional hazards models. From 1977 to 2012, the incidence of tonsillectomies significantly decreased, whereas the incidence of oropharyngeal carcinoma significantly increased. Tonsillectomy was not associated with risk of oropharyngeal carcinoma or malignancies of other anatomic sites, including base of tongue. However, tonsillectomy significantly reduced risk of diagnosis with tonsil carcinoma [RR, 0.40; 95% confidence interval (CI), 0.22–0.70]. The risk of diagnosis with tonsil carcinoma at age &lt;60 years was significantly decreased (RRadj, 0.15; 95% CI, 0.06–0.41) after tonsillectomy. Tonsillectomy within 1 year of diagnosis with tonsil carcinoma was associated with significantly improved overall survival (HR, 0.53; 95% CI, 0.38–0.74). In conclusion, remote history of tonsillectomy reduces the risk of diagnosis with tonsil carcinoma. These data inform risk and benefit of tonsillectomy, a common procedure and design of secondary prevention trials. Cancer Prev Res; 8(7); 583–9. ©2015 AACR.See related articles by Chaturvedi, p. 577, and Misiukiewicz and Posner, p. 580
The BCL2 Family: Key Mediators of the Apoptotic Response to Targeted Anticancer Therapeutics
Authors: Hata Aaron N. , Engelman Jeffrey A. , Faber Anthony C. 
Published: April 2015

Abstract
The ability of cancer cells to suppress apoptosis is critical for carcinogenesis. The BCL2 family proteins comprise the sentinel network that regulates the mitochondrial or intrinsic apoptotic response. Recent advances in our understanding of apoptotic signaling pathways have enabled methods to identify cancers that are “primed” to undergo apoptosis, and have revealed potential biomarkers that may predict which cancers will undergo apoptosis in response to specific therapies. Complementary efforts have focused on developing novel drugs that directly target antiapoptotic BCL2 family proteins. In this review, we summarize the current knowledge of the role of BCL2 family members in cancer development and response to therapy, focusing on targeted therapeutics, recent progress in the development of apoptotic biomarkers, and therapeutic strategies designed to overcome deficiencies in apoptosis.
Significance: Apoptosis, long known to be important for response to conventional cytotoxic chemotherapy, has more recently been shown to be essential for the efficacy of targeted therapies. Approaches that increase the likelihood of a cancer to undergo apoptosis following therapy may help improve targeted treatment strategies. Cancer Discov; 5(5); 475–87. ©2015 AACR.
Social class at birth and risk of psychosis
Authors: O’Donoghue Brian , Fanning Felicity , Lyne John , Renwick Laoise , Madigan Kevin , Kinsella Anthony , Lane Abbie , Turner Niall , O’Callaghan Eadbhard , Clarke Mary 
Published: April 2015

Background: Individuals with psychotic disorders are represented more in the lower social classes, yet there is conflicting evidence to whether these individuals drift into the lower social classes or whether lower social class is a risk factor for developing psychosis. The aim of this study was to examine whether the social class at birth is a risk factor for developing psychosis. Methods: We included individuals with a first episode of psychosis (FEP) whose social class at birth was determined from birth records. We employed a case-control study design and also compared the distribution of the social classes at birth of the cases to that of the general population. Results: A total of 380 individuals with an FEP and 760 controls were included in the case-control study. The odds ratio for developing an FEP associated with social class (low vs high) was .62 (95% confidence interval (CI): .46–.85, p < .001), indicating that individuals from a lower social class at birth have a reduced risk of psychosis. Individuals born between 1961 and 1980 with an FEP were more likely to be from a higher social class at birth compared to the general population (60.8% vs 36.7%, χ2 = 60.85, df = 1, p < .001). However, this association was not observed for those born between 1981 and 1990. Conclusion: A higher social class at birth is associated with a greater risk for developing a psychotic disorder; however, this effect may show temporal variation.
Knowledge sharing motivation in the public sector: the role of public service motivation
Authors: Chen Chung-An , Hsieh Chih-Wei 
Published: April 2015

The literature on knowledge sharing motivation has addressed the importance of both extrinsic and intrinsic motivation to sharing knowledge. However, a theory of knowledge sharing motivation in the public sector requires particular consideration since government’s main concern is in public service, not profits. Therefore, the present study introduces the concept of public service motivation (PSM) to the study of knowledge sharing among civil servants. Based on the PSM theory, this study postulates that civil servants’ interest in policy making, commitment to the public interest, compassion, and willingness for self-sacrifice can drive them to share knowledge for a sacred reason – serving the public interest. By using the data collected from middle-level public managers in Taiwan, the authors empirically tested whether PSM predicts knowledge sharing, and our hypotheses received strong support. Thus, PSM opens a new window for researchers interested in the study of knowledge sharing in the public sector. Points for practitioners With the introduction of PSM, the present study connects knowledge sharing with public administration. Public service as a calling leads civil servants to share knowledge in order to create more advanced organizational knowledge and accordingly improve public service performance. Compared to situational factors (e.g. the use of information technology and rewards), PSM plays an even more pivotal role in promoting knowledge sharing, according to the results of our empirical research. Thus, altruistic motivation should be addressed and emphasized if knowledge sharing in the public sector is to be encouraged.
The transformation process for palliative care professionals: The metamorphosis, a qualitative research study
Authors: Mota Vargas Rafael , Mahtani-Chugani Vinita , Solano Pallero María , Rivero Jiménez Borja , Cabo Domínguez Raquel , Robles Alonso Vicente 
Published: April 2015

Background: Palliative care professionals are exposed daily to high levels of suffering. This makes them particularly vulnerable to suffering from stress, which can lead to burnout and/or compassion fatigue. Aims: To analyse the professional trajectory of palliative care workers over time and the factors which influence this trajectory. Design: A qualitative study was designed based on the Grounded Theory approach, using semi-structured individual interviews. Interviews were recorded audio-visually and transcribed verbatim for subsequent analysis using the procedure described by Miles and Huberman. This process was supported using ATLAS.ti 6 software. Setting/participants: A total of 10 palliative care professionals from Extremadura (Spain) took part in the study. Results: The analysis revealed a common trajectory followed by participants in their working lives: pre-palliative care/honeymoon/frustration/maturation. In addition, factors which influence this trajectory were identified. Details of the self-care strategies that these professionals have developed are described. The result of this process, which we have metaphorically termed ‘metamorphosis’, is the formation of a professional who can work satisfactorily within a palliative care context. Conclusion: During their professional activity, palliative care professionals go through a series of phases, depending on the relationship between the cost of caring and the satisfaction of caring, which can influence both the care provided to patients and families and their own personal circumstances. Being aware of this risk, and implementing self-care strategies, can protect professionals and enable them to conduct their work in an optimal manner. Reflecting on the experiences of these professionals could be useful for other health professionals.
Intracranial abnormalities and headache: A population-based imaging study (HUNT MRI)
Authors: Honningsvåg Lasse-Marius , Hagen Knut , Håberg Asta , Stovner Lars Jacob , Linde Mattias 
Published: April 2015

Background Most studies on intracranial abnormalities among headache sufferers were performed in selected clinical populations. The aim of this study was to evaluate the relationship between intracranial abnormalities and headache among middle-aged adults in the general population. Methods Participants in a large epidemiological study (the HUNT 3 study; 2006–2008) who answered a headache questionnaire and participated in a population-based imaging study of the head (HUNT MRI; 2007–2009) were included ( n = 864; age, 50–65 at enrollment). Based on the responses to the HUNT 3 questionnaire, respondents were categorized as having migraine, tension-type headache, or unclassified headache. Logistic regression was used to compare the occurrence of intracranial abnormalities between groups. Results Intracranial abnormalities were more common in headache sufferers than in headache-free individuals (29% vs. 22%, respectively; p = 0.041). Adjusted multivariate analyses revealed that those with tension-type headache had higher odds of having minor abnormalities (odds ratio, 2.13; 95% confidence interval = 1.18–3.85). This association disappeared when those with only white matter hyperintensities were removed from the analysis. Conclusions Headache sufferers had increased odds of minor intracranial abnormalities. The increased odds were primarily related to the presence of white matter hyperintensities.
Minimally Invasive Coracoclavicular Ligament Reconstruction With a Flip-Button Technique (MINAR)
Authors: Rosslenbroich Steffen B. , Schliemann Benedikt , Schneider Kristian N. , Metzlaff Sebastian L. , Koesters Clemens A. , Weimann Andre , Petersen Wolf , Raschke Michael J. 
Published: April 2015

Background: Acromioclavicular (AC) joint dislocation is a frequent injury in sports. Hypothesis: A minimally invasive flip-button technique, MINAR (minimally invasive acromioclavicular joint reconstruction), will achieve good clinical and radiographic results in the surgical treatment of high-grade AC joint dislocations. Study Design: Case series; Level of evidence, 4. Methods: In this study, 96 patients with AC joint dislocation grades III through V and minimally invasive flip-button repair were identified. Radiographic assessment was performed by use of the Alexander view and by anteroposterior stress radiograph. Clinical outcomes were assessed with the Constant and Taft scores. Factors that influenced outcomes, such as age, time from trauma to surgery, and degree of dislocation, were evaluated. Results: Of the 96 patients, 83 (86.4%; 3 women and 80 men) were able to participate in clinical and radiographic follow-up. The average age of the participants was 39 years (range, 17-80 years). At a mean follow-up of 39 months (range, 12-78 months), clinical assessment revealed excellent results with a mean Constant score of 94.7 (range, 61-100). Clinical and radiological assessment using the Taft score also showed excellent results, with a mean score of 10.8 (range, 3-12). The mean time period from trauma to surgery was 6 days (range, 0-22 days), and mean duration of surgery was 48 minutes (range, 24-98 minutes). Nine patients (10.8%) underwent revision surgery due to recurrent dislocation (n = 8) or wound infection (n = 1). Radiological assessment showed that 18 patients had sustained a loss of reduction defined as subluxation of 50% of the clavicle shaft width in the vertical plane. However, there was no significant correlation ( P = .254) with clinical outcome. Patient age was a relevant factor influencing outcome, as significantly higher outcome values were detected for younger patients ( P = .024). No significant influence was shown for the time period from trauma to surgery ( P = .336) or degree of dislocation after trauma ( P = .987). Conclusion: The MINAR technique is a safe procedure and achieves good to excellent clinical and radiographic results in the surgical treatment of high-grade AC joint dislocations. Despite the simplicity of this technique, the surgeon has to overcome the learning curve to minimize the risk of recurrent dislocation.
Modeling vegetable fractals by means of fractional-order equations
Authors: Lopes António M , Machado JA Tenreiro 
Published: April 2015

Abstract: This paper characterizes four ‘fractal vegetables’: (i) cauliflower ( brassica oleracea var. Botrytis); (ii) broccoli ( brassica oleracea var. italica); (iii) round cabbage ( brassica oleracea var. capitata) and (iv) Brussels sprout ( brassica oleracea var. gemmifera), by means of electrical impedance spectroscopy and fractional calculus tools. Experimental data is approximated using fractional-order models and the corresponding parameters are determined with a genetic algorithm. The Havriliak-Negami five-parameter model fits well into the data, demonstrating that classical formulae can constitute simple and reliable models to characterize biological structures.
Limited specificity of IRF3 and ISGF3 in the transcriptional innate-immune response to double-stranded RNA
Authors: Ourthiague Diana R , Birnbaum Harry , Ortenlöf Niklas , Vargas Jesse D , Wollman Roy , Hoffmann Alexander 
Published: April 2015

Abstract
The innate immune response is largely initiated by pathogen-responsive activation of the transcription factor IRF3. Among other target genes, IRF3 controls the expression of IFN-β, which triggers the activation of the transcription factor ISGF3 via the IFNAR. IRF3 and ISGF3 have been reported to control many of the same target genes and together, control the antimicrobial innate-immune program; however, their respective contributions and specificities remain unclear. Here, we used genomic technologies to characterize their specificity in terms of their physical DNA-binding and genetic function. With the use of ChiP-seq and transcriptomic measurements in WT versus ifnar−/− versus ifnar−/−irf3−/− macrophages responding to intracellular dsRNA, we confirmed the known ISGF3 DNA-binding motif and further specified a distinct IRF3 consensus sequence. The functional specificity of IRF3 is particularly pronounced in cytokine/chemokine regulation; yet, even in the control of IFN-β, that specificity is not absolute. By mathematically modeling IFN-β production within an abstracted tissue layer, we find that IRF3 versus ISGF3 specificity may be critical to limiting IFN-β production and ISGF3 activation, temporally and spatially, but that partial overlap in their specificity is tolerable and may enhance the effectiveness of the innate-immune response.
Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Gettinger Scott N. , Horn Leora , Gandhi Leena , Spigel David R. , Antonia Scott J. , Rizvi Naiyer A. , Powderly John D. , Heist Rebecca S. , Carvajal Richard D. , Jackman David M. , Sequist Lecia V. , Smith David C. , Leming Philip , Carbone David P. , Pinder-Schenck Mary C. , Topalian Suzanne L. , Hodi F. Stephen , Sosman Jeffrey A. , Sznol Mario , McDermott David F. , Pardoll Drew M. , Sankar Vindira , Ahlers Christoph M. , Salvati Mark , Wigginton Jon M. , Hellmann Matthew D. , Kollia Georgia D. , Gupta Ashok K. , Brahmer Julie R. 
Published: April 2015

Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non–small-cell lung cancer (NSCLC) receiving nivolumab in this trial. Patients and Methods Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. Tumor burden was assessed by RECIST (version 1.0) after each cycle. Results Median OS across doses was 9.9 months; 1-, 2-, and 3-year OS rates were 42%, 24%, and 18%, respectively, across doses and 56%, 42%, and 27%, respectively, at the 3-mg/kg dose (n = 37) chosen for further clinical development. Among 22 patients (17%) with objective responses, estimated median response duration was 17.0 months. An additional six patients (5%) had unconventional immune-pattern responses. Response rates were similar in squamous and nonsquamous NSCLC. Eighteen responding patients discontinued nivolumab for reasons other than progressive disease; nine (50%) of those had responses lasting > 9 months after their last dose. Grade 3 to 4 treatment-related adverse events occurred in 14% of patients. Three treatment-related deaths (2% of patients) occurred, each associated with pneumonitis. Conclusion Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.
The civic classroom in higher education: Contested terrain
Authors: Cole Rose M. , Heinecke Walter F. 
Published: April 2015

Abstract
In order to better understand the college classroom as a site of potential citizenship education, this article connects the delimited literature of the contested purposes of citizenship in higher education with scholarship on education for citizenship and provides empirical evidence from an analysis of how macro contextual influences are worked out in the micro practices of pedagogy and curricular design. By analysing two interdisciplinary college classrooms both with civic aims, this research offers a potential typology for understanding citizenship education at institutions of higher education.
Explaining the naming of heavy metal from rock’s ‘Back Pages’: A dialogue with Deena Weinstein
Authors: Brown Andy R. 
Published: April 2015

Abstract
This article debates (with Deena Weinstein’s work, in particular) the origins of the adjectival phrase heavy metal, as it is seen to emerge from rock criticism in the early 1970s. Drawing on an extensive database of rock writing, sourced from the archives of Rock’s Backpages and Rolling Stone magazine, 1967–2007, I offer i) a quantitative analysis of the patterning of the deployment of the phrase over time, noting in particular negative, positive and comparative uses, and ii) a qualitative analysis of how such patterns indicate the process of discursive construction of the genre name, as it emerges from the reviews and think-pieces of key rock writers. On the basis of this evidence I suggest that the emergence of the genre name, superseding that of white blues and hard rock, reflects a profound lack of critical consensus (a dissensus) in North American rock criticism, to the extent that the popularity of ‘third-generation’ heavy metal bands negatively reflects upon the mature development of the counter-cultural youth movement and progressive or authentic rock styles.
Reviews
Authors: Coggins Owen , Riches Gabby , Savigny Heather , Penke Niels , Spracklen Karl 
Published: April 2015

Abstract
Hardcore Punk and Other Junk: Aggressive Sounds in Contemporary Music, Eric James Abbey and Colin Helb (eds) (2014) New York: Lexington Books, 228 pp., ISBN: 0739176054, h/bk, £49.95
The Metal Dictionary: A Compiled Lexicon of Exclusive and Musically-Related Terminology Unique to the Genre of Heavy Metal (Edition 1), Kinzic (2012) Philadelphia: Independent Publication,153 pp., p/bk, £7
Sounds and the City. Popular Music, Place and Globalization, Brett Lashua, Karl Spracklen and Stephen Wagg (eds) (2014) Basingstoke: Palgrave, ISBN: 9781137283108, h/bk, £65.00
Methoden der Heavy Metal-Forschung: Interdisziplinäre Zugänge/Methods of Heavy Metal Studies: Interdisciplinary Approaches, Florian Heesch, Anna-Katharina Höpflinger (Eds) (2014) Münster/New York: Waxmann, 200 pp., ISBN: 9783830930648, p/bk, 34.90 €
Le Guide Rock: Londra, Le Guide Rock: New York, Le Guide Rock: Berlino, Francesca Fabi (2012) Rome: Arcana, 160 pp., ISBN: 9788862311960 (London), ISBN: 9788862312684 (New York), ISBN: 9788862311977 (Berlin), p/bk, €12.00