bluuebunny/crossref_metadata_2025 huggingface dataset:
The Teenage Brain
Authors: Dosenbach Nico U. F. , Petersen Steven E. , Schlaggar Bradley L.
Published: April 2013

Distant brain regions are organized into large-scale functional networks specialized for specific cognitive processes. The brain’s functional-network architecture and its development can be investigated using functional connectivity MRI (fcMRI), which measures correlations in spontaneous fluctuations of brain activity. fcMRI studies have provided important insights into typical brain organization and development, as well as insights into the atypical organization of the brain in neuropsychiatric disorders. fcMRI data can be easily collected and carry much information. Therefore, they are now being analyzed using powerful multivariate-pattern-analysis (MVPA) methods, with the goal of one day being able to diagnose disease states in individuals. However, great care must be taken during these analyses to eliminate confounds such as head movement.
The Teenage Brain
Authors: Somerville Leah H.
Published: April 2013

Relative to childhood, peer relationships take on a heightened importance during adolescence. Might adolescents be highly attuned to information that concerns when and how they are being evaluated and what their peers think of them? This review evaluates how continuing brain development—which influences brain function—partially explains and reflects adolescents’ attunement to social evaluation. Though preliminary, evidence is mounting to suggest that while processing information relevant to social evaluation and the internal states of other people, adolescents respond with heightened emotional intensity and corresponding nonlinear recruitment of socioaffective brain circuitry. This review highlights research findings that relate trajectories of brain development to social behavior and discusses promising avenues of future research that will inform how brain development might lead adolescents to be sensitized to social evaluation.
The Teenage Brain
Authors: Casey B. J. , Caudle Kristina
Published: April 2013

Adolescence refers to the transition from childhood to adulthood that begins with the onset of puberty and ends with successful independence from the parent. A paradox for human adolescence is why, during a time when the individual is probably faster, stronger, of higher reasoning capacity, and more resistant to disease, there is such an increase in mortality relative to childhood. This is due not to disease but, rather, to preventable forms of death (accidental fatalities, suicide, and homicide) associated with adolescents putting themselves in harm’s way, in part because of diminished self-control—the ability to suppress inappropriate emotions, desires, and actions. This article highlights how self-control varies as a function of age, context, and the individual and delineates its neurobiological basis.
Social Validation of Shared and Nonvalidation of Unshared Information in Group Discussions
Authors: Boos Margarete , Schauenburg Barbara , Strack Micha , Belz Michael
Published: April 2013

Research on information sharing within groups confirms a favoring of shared compared to unshared information. Social validation is considered to be the primary psychological mechanism explaining this group bias (Wittenbaum, Hubbell, & Zuckerman, 1999). Our focus here is on a process-related measurement of the social validation of shared information, as well as the social nonvalidation of unshared information in the discussion protocols of 31 decision-making groups. Results confirmed that mentioning shared information evoked social validations, whereas mentioning unshared information evoked nonvalidations (H1). Contrary to our expectation that social validation would encourage the repetition of shared information and social nonvalidation would discourage the repetition of nonshared information (H2), we found that nonvalidation of information enhanced the probability of repetition. We conclude that the need for social validation found in face-to-face groups can be overcome in a more task-oriented, goal-focused, and depersonalized media-based communication setting such as the one in this study.
A Proposed Multisite Double-Blind Randomized Clinical Trial of Neurofeedback for ADHD
Authors: Kerson Cynthia ,   The Collaborative Neurofeedback Group
Published: April 2013

Objective: Additional treatments with persisting benefit are needed for ADHD. Because ADHD often shows excessive theta electroencephalogram (EEG) power, low beta, and excessive theta-beta ratio (TBR), a promising treatment is neurofeedback (NF) downtraining TBR. Although several nonblind randomized clinical trials (RCTs) show a medium-large benefit for NF, a well-blinded, sham-controlled RCT is needed to differentiate specific from nonspecific effects. Method: Experts in NF, ADHD, clinical trials, and statistics collaborated to design a double-blind multisite RCT. Results/Conclusion: At four sites, 180 children aged 7 to 10 years with rigorously diagnosed ADHD and TBR ≥ 5 will be randomized to active TBR-NF versus sham NF of equal duration, intensity, and appearance. Sham, utilizing prerecorded EEGs with participant artifacts superimposed, will keep participants and staff blind. Treatment fidelity will be trained/monitored by acknowledged NF leaders. Multidomain assessments before, during, and after treatment (follow-up to 2 years) will also include tests of blinding and sham inertness.
Corporate social responsibility á la the liberal communist
Authors: Cederström Carl , Marinetto Michael
Published: April 2013

This article explores the ‘liberal communist’, a conceptual and satirical figure originally elaborated in the work of Slavoj Žižek (2008). The liberal communist claims (1) that there is no opposition between capitalism and the social good; (2) that all problems are of a practical nature, and hence best solved by corporate engagement and (3) that hierarchies, authority and centralized bureaucracies should be replaced by dynamic structures, a nomadic lifestyle and a flexible spirit. This analysis of the liberal communist has at least two implications for research on CSR. First, it examines the ideological role of CSR by moving beyond a propaganda view, instead offering an ideological reading that focuses on the ways in which CSR seeks to obliterate any existing contradictions between ‘philanthropic actions’ on the one hand and ‘profit-seeking business activities’ on the other hand. Second, it demonstrates how critique is not necessarily what corporations seek to avoid, but something that they actively engage in.
Facing contempt: Dealing with exclusion among Berlin Hauptschüler
Authors: Wellgraf Stefan
Published: April 2013

This research deals with exclusionary processes of social ascription in which low socio-economic status is linked with disregard, in turn ‘producing’ a disrespectful or contemptuous treatment of others. On the basis of an ethnographic study of Hauptschüler in Berlin, Germany, the production of and dealing with contempt is looked at from different angles: as processes of refused recognition, as discrimination based on race/ethnicity and class in the school system, and with regard to negative and derogatory media representations. A wide range of social practices of Hauptschüler – friendship, body-practices, emotions, and irony – are considered as mechanisms of coping with contempt and thus take on a political meaning.
A study on the polymorphisms of the renin–angiotensin system pathway genes for their effect on blood pressure levels in males from Algeria
Authors: Meroufel Djabaria Naïma , Médiène-Benchekor Sounnia , Dumont Julie , Benhamamouch Soraya , Amouyel Philippe , Brousseau Thierry
Published: April 2013

Introduction

Several studies have assessed the relationship between blood pressure (BP) and polymorphisms within the genes encoding angiotensinogen ( AGT), angiotensin II type 1 receptor ( AT1R) and angiotensin-converting enzyme ( ACE). However, considering the relatively large discrepancy in frequency and impact of these variants between ethnic groups and populations, still unavailable data from Algerian population are needed.

Objective

Our purpose is to evaluate the association between the AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms and variations in systolic (SBP), diastolic (DBP) and pulse pressure (PP) values.

Methods

The associations with BP were assessed in a representative sample of 115 male subjects free of coronary heart disease (CHD). The AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms were determined by PCR-ASO and PCR-RFLP analysis, respectively.

Results

We showed no associations between the AGT M235T, AT1R +1166A/C nor the ACE I/D polymorphisms with variations in BP values. However, concerning the ACE I/D polymorphism, subjects carrying the ACE I allele tended to have higher SBP (+4.1 mmHg) and PP values (+3.2 mmHg) than DD subjects (adjusted p = 0.087 and p = 0.102, respectively).

Conclusion

The ACE I/D polymorphism needs further investigation in a larger Algerian study, especially concerning its putative impact on SBP and PP.
Understanding the Dissemination of Sacral Neuromodulation
Authors: Suskind Anne M. , Dunn Rodney L. , Kaufman Samuel R. , DeLancey John O.L. , Clemens J. Quentin , Stoffel John T. , Hollenbeck Brent K.
Published: April 2013

Objectives. To assess trends in the use of sacral neuromodulation and to measure the magnitude of variation in its use across geographic regions. Methods. We used the State Ambulatory Surgery Database (SASD) from 2002 to 2009 from Florida to identify patients implanted with a neuromodulator. Age- and gender-adjusted rates of implantation were calculated by year and by geographic region, defined by the Hospital Service Area. The coefficient of variation was estimated to quantify the magnitude of variation for different time periods. Results. Adjusted rates of sacral neuromodulation increased significantly from 1.1 per 100 000 population in 2002 to 10.4 per 100 000 population in 2009. The majority of cases were performed for overactive bladder. There was a very large amount of geographic variation in rates of these procedures as evidenced by the high coefficients of variation: 1.67 (2002 and 2003), 1.70 (2004 and 2005), 1.49 (2006 and 2007), and 1.05 (2008 and 2009). Conclusions. Rates of sacral neuromodulation have increased dramatically over the past decade. However, these rates of utilization are highly variable across regions, with some regions performing large numbers of these procedures and other regions performing few to no procedures. This range in practice patterns may reflect medical uncertainty surrounding the role of this procedure.
Classification of dorsal and ventral dimelia in humans
Authors: Al-Qattan M. M.
Published: April 2013

Dorsal dimelia (appearance of dorsal structures on the palmar aspect of the hand) and ventral dimelia (appearance of palmar structures on the dorsal aspect of the hand) are rare congenital hand malformations that occur due to errors of the dorso-ventral axis of development of the limb. The current literature includes numerous cases and there is now sufficient basic science/genetics research on the topic so that a classification of dorsal/ventral dimelia could be proposed. Dorsal dimelia is subclassified into two types: distal (dorsalization of the digits ± distal palm) and proximal (dorsalization of the proximal palm only) types. Ventral dimelia is classified into three types (mild, moderate, and severe) according to the degree of ventralization. The classification is supported by the genetic basis of each subtype.
Comparative responsiveness of the Hand 20 and the DASH-JSSH questionnaires to clinical changes after carpal tunnel release
Authors: Iwatsuki K. , Nishikawa K. , Chaki M. , Sato A. , Morita A. , Hirata H.
Published: April 2013

This study compared the responsiveness of the Hand 20 and the Japanese version of the disabilities of the arm, shoulder and hand (DASH-JSSH) questionnaires in carpal tunnel syndrome. The scores before and 3 months after surgery were used to calculate the standardized response mean and effect size. Of 57 patients enrolled in the study, 13 underwent open carpal tunnel release and 44 had endoscopic carpal tunnel release. The standardized response mean and the effect size of the Hand 20 scale were 0.60 and 0.54, respectively, and those of the disabilities of the arm, shoulder and hand scale were 0.39 and 0.36, respectively. Compared with the Disabilities of the Arm, Shoulder and Hand questionnaire, the Hand 20 questionnaire appears to have better responsiveness for assessing the effect of treatment by carpal tunnel release.
A European Seal of Approval for ‘gay’ businesses: findings from an HIV-prevention pilot project
Authors: Sherriff Nigel , Gugglberger Lisa
Published: April 2013

Aims:

‘Gay’ businesses can be important settings through which to deliver health promotion interventions to vulnerable populations, such as men who have sex with men (MSM) regarding HIV prevention. This article draws on data from the European Everywhere project, which represents the first scheme to develop and pre-test a common framework for HIV/STI prevention in ‘gay’ businesses across eight European countries.

Methods:

The scientific basis of the Everywhere framework was developed using a comprehensive consensus-building process over 30 months. This process included: formative scoping research; interviews with 54 ‘gay’ businesses; meetings/workshops with representatives from project partners, ‘gay’ businesses, public health administrations and external experts; 15 interviews and three focus groups with project partners; a five-month pilot action phase in eight countries, together with support from the project’s Advisory Group; and all Everywhere project partners including the Scientific Steering Committee.

Results:

A voluntary European code setting out differentiated HIV/STI-prevention standards for ‘gay’ businesses (including sex venues, ‘gay’ and ‘gay’ friendly social spaces, travel agencies, hotels, dating websites) was developed and piloted in eight European cities. During a five-month pilot action, 83 ‘gay’ businesses were certified with the Everywhere Seal of Approval representing a considerable increase on the expected pilot target of 30.

Conclusions:

Everywhere offers a major contribution to the public health and/or health promotion field in the form of a practical, policy-relevant, settings-based HIV-prevention framework for ‘gay’ businesses that is common across eight European countries. Findings suggest that a European-wide model of prevention is acceptable and feasible to businesses.
The gods of institutional life: Weber’s value spheres and the practice of polytheism
Authors: Friedland Roger
Published: April 2013

Weber's theory of value spheres outlines a project of institutional polytheism, each ordered around a ‘god’. This suggests not only that social theory can build a religious sociology, but that a theory of institutions must be an exercise in comparative religions. Weber's comparative sociology of religions, however, does not align with his theory of value spheres in terms of his distinction between polytheism and monotheism, transcendence and immanence, salvation and mysticism, being possessed and possessing. A theory of institutional logics points beyond Weber's separation of value and instrumental rationality, faith and practice, and hence the ways in which he partitioned the institutions of modernity.
North American sociology of religion: Critique and prospects
Authors: Williams Rhys H. , Josephsohn Thomas J.
Published: April 2013

We assess the current state of sociology of religion, particularly in the United States, for the extent to which a “critical sociology of religion” currently exists and how it might look if it did. We focus particular attention on two areas of inquiry: religion and health; and religion and violence.
Queer studies and religion
Authors: Brintnall Kent L.
Published: April 2013

This article provides an introductory guide to queer scholarship in religious studies and theology. It also outlines approaches to queer studies and how they have been, and might be, appropriated in religious studies and theology. Finally, the article argues that greater clarity is needed when naming projects as “queer,” given that the terms “queer,” “queer theory,” and “queer studies” cover such a wide variety of approaches.
Religion and cultural theory
Authors: Styers Randall
Published: April 2013

This article examines the resources offered by various forms of critical cultural theory for the study of religion. It then briefly explores the turn to religion by a range of recent cultural theorists.
The Effectiveness of a Geriatric Hip Fracture Clinical Pathway in Reducing Hospital and Rehabilitation Length of Stay and Improving Short-Term Mortality Rates
Authors: Lau Tak-Wing , Fang Christian , Leung Frankie
Published: April 2013

Background:

A geriatric hip fracture clinical pathway, led by an orthopedic surgeon, was developed in 2007. This clinical pathway team is multidisciplinary and consists of surgeons, physicians, anesthetists, nurses, physiotherapists, occupational therapists, medical social workers, dieticians as well as voluntary support groups.

Methods:

From early 2007 onward, all patients older than 65 years with acute isolated hip fractures were included. During the whole inpatient treatment, all relevant data were captured prospectively. The data in 2006, before the implementation of the clinical pathway, were collected retrospectively through computer record system. A study of the length of stay in acute and rehabilitation hospital and also the short-term mortality rate was carried out to compare the difference before and after the implementation of the pathway.

Results:

From 2007 onward, more than 1300 hip fractures were treated. After the implementation of the pathway, the preoperative length of stay was markedly shortened by 4 days, from an average of 6.1 days in 2006 to 1.5 days in 2011 ( P < .05). The postoperative length of stay and the overall acute hospital length of stay also improved significantly. The length of stay in rehabilitation hospital was also significantly shorter in the 4-year period. Although the number of hip fractures increased annually with increased age and number of comorbidities each year, the inpatient mortality rate showed a gradual decrease from 2.7% in 2006 to 1.25% in 2010. The 30 days mortality rate also showed a decrease from 3.65% in 2006 to 2.75% in 2010.

Conclusion:

Geriatric hip fracture clinical pathway is an excellent approach to the geriatric hip fracture service. The most significant improvement is the dramatic shortening of the length of hospital stay. Our success in the past 5 years has proven its value and sustainability.
Motivations Underlying English Language Learning and Achievement
Authors: Khodadady Ebrahim , Ashrafborji Mozhgan
Published: April 2013

The study explored whether the 25-item Motivations Underlying English Language Learning (MUELL) Scale designed in this study is a reliable and valid psychological measure and relates significantly to achievement. To achieve the objectives, the MUELL was administered to 493 female learners who studied English as a foreign language (EFL) in three branches of a semiprivate language institute in Mashhad, Iran. When the data were subjected to principal axis factoring (PAF) and the extracted latent variables (LVs) were rotated via Varimax with Kaiser Normalization, three factors appeared, that is, Intrinsic, Extrinsic, and Communicative. Reliability and correlational analyses showed that the MUELL and its underlying factors are highly reliable and show significant relationships with each other. Although Intrinsic and Extrinsic LVs correlate highly with the Communicative than with each other, none of them show any significant relationship with the total English achievement for three groups of achievers. However, the written achievement scores of high and low achievers correlate significantly not only with the MUELL but also with Extrinsic and Intrinsic LVs, respectively, in opposite directions. The results are discussed and suggestions are made for future research.
The Frequency and Impact of Exposure to Potentially Traumatic Events Over the Life Course
Authors: Ogle Christin M. , Rubin David C. , Berntsen Dorthe , Siegler Ilene C.
Published: April 2013

We examined the frequency and impact of exposure to potentially traumatic events in a nonclinical sample of older adults ( N = 3,575), a population typically underrepresented in epidemiological research concerning the prevalence of traumatic events. Current posttraumatic stress disorder (PTSD) symptom severity and the centrality of events to identity were assessed for events nominated as currently most distressing. Approximately 90% of participants experienced one or more potentially traumatic events. Events that occurred with greater frequency early in the life course were associated with more severe PTSD symptoms compared to events that occurred with greater frequency during later decades. Early life traumas, however, were not more central to identity. Results underscore the differential impact of traumatic events experienced throughout the life course. We conclude with suggestions for further research concerning mechanisms that promote the persistence of posttraumatic stress related to early life traumas and empirical evaluation of psychotherapeutic treatments for older adults with PTSD.
Antimicrobial biocomposites of melt-compounded polylactide films containing silver-based engineered clays
Authors: Busolo María A , Lagaron José M
Published: April 2013

This article reports on two polylactide composites obtained by melt compounding containing two silver-based biocide montmorillonites. The active clays are differentiated by the biocide agent oxidation state, i.e. in one sample silver is in ionic form and in the other as native nanoparticles. In both cases, composites with enhanced thermal stability and good dispersion and distribution of the antimicrobial compounds were obtained. The active engineered organoclays and the corresponding biocomposites showed strong antimicrobial activity against Staphylococcus aureus. The biocidal effect was larger for the ionic silver sample, as expected. The results support these composite material's potential as antimicrobial additives in polylactide active packaging applications obtained via melt compounding.
Remodeling of calcium signaling in tumor progression
Authors: Chen Yih-Fung , Chen Ying-Ting , Chiu Wen-Tai , Shen Meng-Ru
Published: April 2013

Intracellular Ca2+ is one of the crucial signalings that modulate various cellular functions. The dysregulation of Ca2+ homeostasis has been suggested as an important event in driving the expression of the malignant phenotypes, such as proliferation, migration, invasion, and metastasis. Cell migration is an early prerequisite for tumor metastasis that has a significant impact on patient prognosis. During cell migration, the exquisite spatial and temporal organization of intracellular Ca2+ provides a rapid and robust way for the selective activation of signaling components that play a central role in cytoskeletal reorganization, traction force generation, and focal adhesion dynamics. A number of known molecular components involved in Ca2+ influx pathways, including stromal interaction molecule (STIM)/Orai-mediated store-operated Ca2+ entry (SOCE) and the Ca2+-permeable transient receptor potential (TRP) channels, have been implicated in cancer cell migration and tumor metastasis. The clinical significance of these molecules, such as STIM proteins and the TRPM7 channel, in tumor progression and their diagnostic and prognostic potentials have also been demonstrated in specific cancer types. In this review, we summarize the recent advances in understanding the important roles and regulatory mechanisms of these Ca2+ influx pathways on malignant behaviors of tumor cells. The clinical implications in facilitating current diagnostic and therapeutic procedures are also discussed.
Critical role of aldehydes in cigarette smoke-induced acute airway inflammation
Authors: van der Toorn Marco , Slebos Dirk-Jan , de Bruin Harold G , Gras Renee , Rezayat Delaram , Jorge Lucie , Sandra Koen , van Oosterhout Antoon JM
Published: April 2013

Background

Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation.

Methods

BALB/c mice were exposed to CS, water filtered CS (WF-CS) or air for 5 days. Levels of total particulate matter (TPM) and aldehydes in CS and WF-CS were measured. Six hours after the last exposure, inflammatory cells and cytokine levels were measured in lung tissue and bronchoalveolar lavage fluid (BALF). Furthermore, Beas-2b bronchial epithelial cells were exposed to CS extract (CSE) or WF-CS extract (WF-CSE) in the absence or presence of the aldehyde acrolein and IL-8 production was measured after 24 hrs.

Results

Compared to CS, in WF-CS strongly decreased (CS; 271.1 ± 41.5 μM, WF-CS; 58.5 ± 8.2 μM) levels of aldehydes were present whereas levels of TPM were only slightly reduced (CS; 20.78 ± 0.59 mg, WF-CS; 16.38 ± 0.36 mg). The numbers of mononuclear cells in BALF (p<0.01) and lung tissue (p<0.01) were significantly increased in the CS- and WF-CS-exposed mice compared to air control mice. Interestingly, the numbers of neutrophils (p<0.001) in BALF and neutrophils and eosinophils (p<0.05) in lung tissue were significantly increased in the CS-exposed but not in WF-CS-exposed mice as compared to air control mice. Levels of the neutrophil and eosinophil chemoattractants KC, MCP-1, MIP-1α and IL-5 were all significantly increased in lung tissue from CS-exposed mice compared to both WF-CS-exposed and air control mice. Interestingly, depletion of aldehydes in WF-CS extract significantly reduced IL-8 production in Beas-2b as compared to CSE, which could be restored by the aldehyde acrolein.

Conclusion

Aldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation.
AllerTOP - a server for in silico prediction of allergens
Authors: Dimitrov Ivan , Flower Darren R , Doytchinova Irini
Published: April 2013

Background

Allergy is a form of hypersensitivity to normally innocuous substances, such as dust, pollen, foods or drugs. Allergens are small antigens that commonly provoke an IgE antibody response. There are two types of bioinformatics-based allergen prediction. The first approach follows FAO/WHO Codex alimentarius guidelines and searches for sequence similarity. The second approach is based on identifying conserved allergenicity-related linear motifs. Both approaches assume that allergenicity is a linearly coded property. In the present study, we applied ACC pre-processing to sets of known allergens, developing alignment-independent models for allergen recognition based on the main chemical properties of amino acid sequences.

Results

A set of 684 food, 1,156 inhalant and 555 toxin allergens was collected from several databases. A set of non-allergens from the same species were selected to mirror the allergen set. The amino acids in the protein sequences were described by three z-descriptors (z

1
, z

2
and z

3
) and by auto- and cross-covariance (ACC) transformation were converted into uniform vectors. Each protein was presented as a vector of 45 variables. Five machine learning methods for classification were applied in the study to derive models for allergen prediction. The methods were: discriminant analysis by partial least squares (DA-PLS), logistic regression (LR), decision tree (DT), naïve Bayes (NB) and k nearest neighbours (k NN). The best performing model was derived by k NN at k = 3. It was optimized, cross-validated and implemented in a server named AllerTOP, freely accessible at http://www.pharmfac.net/allertop. AllerTOP also predicts the most probable route of exposure. In comparison to other servers for allergen prediction, AllerTOP outperforms them with 94% sensitivity.

Conclusions

AllerTOP is the first alignment-free server for in silico prediction of allergens based on the main physicochemical properties of proteins. Significantly, as well allergenicity AllerTOP is able to predict the route of allergen exposure: food, inhalant or toxin.
Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress
Authors: Yang Chaofeng , Lu Weiqin , Lin Tao , You Pan , Ye Min , Huang Yanqing , Jiang Xianhan , Wang Cong , Wang Fen , Lee Mong-Hong , Yeung Sai-Ching J , Johnson Randy L , Wei Chongjuan , Tsai Robert Y , Frazier Marsha L , McKeehan Wallace L , Luo Yongde
Published: April 2013

Background

FGF21 is a promising intervention therapy for metabolic diseases as fatty liver, obesity and diabetes. Recent results suggest that FGF21 is highly expressed in hepatocytes under metabolic stress caused by starvation, hepatosteatosis, obesity and diabetes. Hepatic FGF21 elicits metabolic benefits by targeting adipocytes of the peripheral adipose tissue through the transmembrane FGFR1-KLB complex. Ablation of adipose FGFR1 resulted in increased hepatosteatosis under starvation conditions and abrogation of the anti-obesogenic action of FGF21. These results indicate that FGF21 may be a stress responsive hepatokine that targets adipocytes and adipose tissue for alleviating the damaging effects of stress on the liver. However, it is unclear whether hepatic induction of FGF21 is limited to only metabolic stress, or to a more general hepatic stress resulting from liver pathogenesis and injury.

Methods

In this survey-based study, we examine the nature of hepatic FGF21 activation in liver tissues and tissue sections from several mouse liver disease models and human patients, by quantitative PCR, immunohistochemistry, protein chemistry, and reporter and CHIP assays. The liver diseases include genetic and chemical-induced HCC, liver injury and regeneration, cirrhosis, and other types of liver diseases.

Results

We found that mouse FGF21 is induced in response to chemical (DEN treatment) and genetic-induced hepatocarcinogenesis (disruptions in LKB1, p53, MST1/2, SAV1 and PTEN). It is also induced in response to loss of liver mass due to partial hepatectomy followed by regeneration. The induction of FGF21 expression is potentially under the control of stress responsive transcription factors p53 and STAT3. Serum FGF21 levels correlate with FGF21 expression in hepatocytes. In patients with hepatitis, fatty degeneration, cirrhosis and liver tumors, FGF21 levels in hepatocytes or phenotypically normal hepatocytes are invariably elevated compared to normal health subjects.

Conclusion

FGF21 is an inducible hepatokine and could be a biomarker for normal hepatocyte function. Activation of its expression is a response of functional hepatocytes to a broad spectrum of pathological changes that impose both cellular and metabolic stress on the liver. Taken together with our recent data, we suggest that hepatic FGF21 is a general stress responsive factor that targets adipose tissue for normalizing local and systemic metabolic parameters while alleviating the overload and damaging effects imposed by the pathogenic stress on the liver. This study therefore provides a rationale for clinical biomarker studies in humans.
Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence
Authors: Alaiyan Bilal , Ilyayev Nadia , Stojadinovic Alexander , Izadjoo Mina , Roistacher Marina , Pavlov Vera , Tzivin Victoria , Halle David , Pan Honguang , Trink Barry , Gure Ali O , Nissan Aviram
Published: April 2013

Background

The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis.

Methods

Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH).

Results

Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods.

Conclusion

CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process.
Association between socioeconomic status and obesity in a Chinese adult population
Authors: Xiao Yuanyuan , Zhao Naiqing , Wang Hao , Zhang Jie , He Qingfang , Su Danting , Zhao Ming , Wang Lixin , Zhang Xinwei , Gong Weiwei , Hu Ruying , Yu Min , Ding Gangqiang , Cong Liming , Ye Zhen
Published: April 2013

Background

Existing studies which regarding to the association between individual socioeconomic status (SES) and obesity are still scarce in developing countries. The major aim of this study is to estimate such association in an adult population which was drawn from an economically prosperous province of China.

Methods

Study population was determined by multilevel randomized sampling. Education and income were chosen as indicators of individual SES, general obesity and abdominal obesity were measured by body mass index (BMI) and waist circumference (WC). Descriptive statistical methods were used to depict overall and factor-specific distributions of general and abdominal obesity among 16,013 respondents. Two-step logistic regression models were fitted on gender basis.

Results

The age-and-sex adjusted rates of general overweight, general obesity, abdominal overweight and abdominal obesity in study population were 28.9% (95%CI: 27.9%-29.9%), 7.5% (95%CI: 7.0%-8.1%), 32.2% (95%CI: 31.2%-33.3%) and 12.3% (95%CI: 11.6%-13.1%), respectively. Based on model fitting results, a significant inverse association between education and obesity only existed in women, while in men, income rather than education was positively related to obesity.

Conclusions

The atypical SES-obesity relationship we found reflected the on-going social economy transformation in affluent regions of China. High-income men and poorly-educated women were at higher risk of obesity in Zhejiang province, thus merit intense focuses.
Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling
Authors: Wachter Franziska , Grunert Michaela , Blaj Cristina , Weinstock David M , Jeremias Irmela , Ehrhardt Harald
Published: April 2013

Background

The p53 protein is the best studied target in human cancer. For decades, p53 has been believed to act mainly as a tumor suppressor and by transcriptional regulation. Only recently, the complex and diverse function of p53 has attracted more attention. Using several molecular approaches, we studied the impact of different p53 variants on extrinsic and intrinsic apoptosis signaling.

Results

We reproduced the previously published results within intrinsic apoptosis induction: while wild-type p53 promoted cell death, different p53 mutations reduced apoptosis sensitivity. The prediction of the impact of the p53 status on the extrinsic cell death induction was much more complex. The presence of p53 in tumor cell lines and primary xenograft tumor cells resulted in either augmented, unchanged or reduced cell death. The substitution of wild-type p53 by mutant p53 did not affect the extrinsic apoptosis inducing capacity.

Conclusions

In summary, we have identified a non-expected impact of p53 on extrinsic cell death induction. We suggest that the impact of the p53 status of tumor cells on extrinsic apoptosis signaling should be studied in detail especially in the context of therapeutic approaches that aim to restore p53 function to facilitate cell death via the extrinsic apoptosis pathway.
Solutions for a class of nonlinear Volterra integral and integro-differential equation using cyclic "Equation missing" -contraction
Authors: Nashine Hemant Kumar , Pathak RP , Somvanshi Piyusha S , Pantelic Slavisa , Kumam Poom
Published: April 2013

We establish the existence and uniqueness of solutions for a class of nonlinear Volterra integral and integro-differential equations using fixed-point theorems for a new variant of cyclic

(
φ
,
ψ
,
θ
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-contractive mappings. Nontrivial examples are given to support the usability of our results.

MSC:47H10, 54H25.
Analyzing the sources and nature of influence: how the Avahan program used evidence to influence HIV/AIDS prevention policy in India
Authors: Tran Nhan T , Bennett Sara C , Bishnu Rituparna , Singh Suneeta
Published: April 2013

Background

Major investments by development partners in low- and middle-income countries (LMICs) often seek to develop a supportive policy environment. There is limited knowledge about the mechanisms that development partners use to influence government policy, or which mechanisms are effective. This study assessed the influence of Avahan, a large HIV/AIDS prevention program in India supported by the Bill and Melinda Gates Foundation, on the development of HIV/AIDS policies in India, particularly the National AIDS Control Program III (NACP III).

Methods

A retrospective assessment of the contributions of Avahan to the development of NACP III was conducted based upon document review and in-depth interviews with key informants, including Avahan staff and staff of implementing partners. This assessment was carried out within a framework centered on three domains: evidence considered by policy and decision-makers; the channel through which influence is exerted; and the target audience for influence.

Results

Respondents identified a number of respects in which Avahan influenced NACP III policy, notably, Avahan influenced perception of the feasibility of scaling up services (through a demonstration effect) and Avahan, along with others, helped ensure a strong focus on targeted interventions. Overall Avahan’s influence was greatest during policy implementation. While the extent to which research evidence generated by Avahan influenced NACP III was limited, best practice evidence generated by Avahan, including the lessons learned from routine implementation and management, contributed significantly to NACP III. This was largely due to the credibility Avahan had established and strategic ‘inside track’ communications.

Conclusion

While studies of knowledge translation typically focus primarily on scientific evidence, this study suggests that other forms of evidence, notably best practice evidence derived from program experience, and disseminated through personal communication, were particularly influential. The framework developed for the paper provides a useful tool to analyze how evidence-based influence is exerted.
The characteristics of short- and long-term surviving Shiba dogs with chronic enteropathies and the risk factors for poor outcome
Authors: Okanishi Hiroki , Sano Tadashi , Yamaya Yoshiki , Kagawa Yumiko , Watari Toshihiro
Published: April 2013

Background

The objectives of this study were to investigate the differences in the characteristics of short- and long-term surviving dogs, and the factors that predict poor outcome in Shiba dogs with chronic enteropathies (CE).

Methods

A total of 25 Shiba dogs were included in this study, and classified as either short-term (≤6 months) survivors (Ss; n=16) or long-term (>6 months) survivors (Ls; n=9). The clinical and clinicopathological variables, histopathology, response to therapy, and outcomes were investigated between groups. Furthermore, these factors were tested for their ability to predict poor outcome.

Results

All CE dogs were diagnosed as having inflammatory bowel disease (IBD) with lymphocytic-plasmacytic enteritis (LPE). Age and canine inflammatory bowel disease activity index (CIBDAI) were significantly higher in the Ss group than in the Ls group (age:p= 0.035, CIBDAI:p= 0.018), as determined via univariate logistic regression analysis. According to receiver operator characteristic (ROC) curve analysis, the best predictors of poor outcome were age and CIBDAI, with the cutoffs determined as 7 years and 9 points, respectively. The majority of the cases (84%) responded to initial treatment; in particular, 75% of dogs in Ss group responded to therapy. The time to response (days) to the initial treatment in the Ss group (median 42.5 days, range: 20-91 days) was significantly shorter than that of the Ls group (median 285 days, range: 196-1026 days). Approximately half (55.5%) of the dogs in the Ls group died due to relapse of CE.

Conclusions

This study suggested that there is a high risk of early mortality in Shiba dogs with CE, particularly if the dogs are older (>7 years) and have a high CIBDAI score (>9 points). There appears to be a possibility of early mortality even if the initial treatment was efficacious. Furthermore, Shiba dogs with CE that become less responsive to initial therapy in the short-term (approximately 3 months) are more likely to have an early mortality. Thus, it is necessary to follow-up Shiba dogs with CE in the long-term, as approximately half of the long-term survivors eventually died due to a relapse of the signs.
Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA125 and HE4
Authors: O’Shannessy Daniel J , Somers Elizabeth B , Palmer Leslie M , Thiel Robert P , Oberoi Pankaj , Heath Ryan , Marcucci Lisa
Published: April 2013

Background

Evaluate and compare the utility of serum folate receptor alpha (FRA) and megakaryocyte potentiating factor (MPF) determinations relative to serum CA125, mesothelin (MSLN) and HE4 for the diagnosis of epithelial ovarian cancer (EOC).

Methods

Electrochemiluminescent assays were developed for FRA, MSLN and MPF and used to assess the levels of these biomarkers in 258 serum samples from ovarian cancer patients. Commercial assays for CA125 and HE4 were run on a subset of 176 of these samples representing the serous histology. Data was analyzed by histotype, stage and grade of disease. A comparison of the levels of the FRA, MSLN and MPF biomarkers in serum, plasma and urine was also performed in a subset of 57 patients.

Results

Serum and plasma levels of FRA, MSLN and MPF were shown to be highly correlated between the two matrices. Correlations between all pairs of markers in 318 serum samples were calculated and demonstrated the highest correlation between HE4 and MPF, and the lowest between FRA and MPF. Serum levels of all markers showed a dependence on both stage and grade of disease. A multi-marker logistic regression model was developed resulting in an AUC=0.91 for diagnosis of serous ovarian cancer, a significant improvement over the AUC for any of the individual markers, including CA125 (AUC=0.84).

Conclusions

FRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC. The lack of correlation between the various markers analyzed in the present study suggests that a panel of markers can aid in the detection and/or monitoring of this disease.
Three are better than one: plasminogen receptors as cancer theranostic targets
Authors: Ceruti Patrizia , Principe Moitza , Capello Michela , Cappello Paola , Novelli Francesco
Published: April 2013

Activation of plasminogen on the cell surface initiates a cascade of protease activity with important implications for several physiological and pathological events. In particular, components of the plasminogen system participate in tumor growth, invasion and metastasis. Plasminogen receptors are in fact expressed on the cell surface of most tumors, and their expression frequently correlates with cancer diagnosis, survival and prognosis. Notably, they can trigger multiple specific immune responses in cancer patients, highlighting their role as tumor-associated antigens. In this review, three of the most characterized plasminogen receptors involved in tumorigenesis, namely Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA), are analyzed to ascertain an overall view of their role in the most common cancers. This analysis emphasizes the possibility of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting plasminogen receptors, as well as their potential application as cancer predictors.
Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity
Authors: Sasagawa Yohei , Nikaido Itoshi , Hayashi Tetsutaro , Danno Hiroki , Uno Kenichiro D , Imai Takeshi , Ueda Hiroki R
Published: April 2013

Development of a highly reproducible and sensitive single-cell RNA sequencing (RNA-seq) method would facilitate the understanding of the biological roles and underlying mechanisms of non-genetic cellular heterogeneity. In this study, we report a novel single-cell RNA-seq method called Quartz-Seq that has a simpler protocol and higher reproducibility and sensitivity than existing methods. We show that single-cell Quartz-Seq can quantitatively detect various kinds of non-genetic cellular heterogeneity, and can detect different cell types and different cell-cycle phases of a single cell type. Moreover, this method can comprehensively reveal gene-expression heterogeneity between single cells of the same cell type in the same cell-cycle phase.