bluuebunny/crossref_metadata_2025_split huggingface dataset:
Configuration coverage in the analysis of large-scale system software
Authors: Tartler Reinhard , Lohmann Daniel , Dietrich Christian , Egger Christoph , Sincero Julio 
Published: January 2012

System software, especially operating systems, tends to be highly configurable. Like every complex piece of software, a considerable amount of bugs in the implementation has to be expected. In order to improve the general code quality, tools for static analysis provide means to check for source code defects without having to run actual test cases on real hardware. Still, for proper type checking a specific configuration is required so that all header include paths are available and all types are properly resolved.
In order to find as many bugs as possible, usually a "full configuration" is used for the check. However, mainly because of alternative blocks in form of #else-blocks, a single configuration is insufficient to achieve full coverage. In this paper, we present a metric for configuration coverage (CC) and explain the challenges for (properly) calculating it. Furthermore, we present an efficient approach for determining a sufficiently small set of configurations that achieve (nearly) full coverage and evaluate it on a recent Linux kernel version.
Bringing back monad comprehensions
Authors: Giorgidze George , Grust Torsten , Schweinsberg Nils , Weijers Jeroen 
Published: January 2012

This paper is about a Glasgow Haskell Compiler (GHC) extension that generalises Haskell's list comprehension notation to monads. The monad comprehension notation implemented by the extension supports generator and filter clauses, as was the case in the Haskell 1.4 standard. In addition, the extension generalises the recently proposed parallel and SQL-like list comprehension notations to monads. The aforementioned generalisations are formally defined in this paper. The extension will be available in GHC 7.2.
This paper gives several instructive examples that we hope will facilitate wide adoption of the extension by the Haskell community. We also argue why the do notation is not always a good fit for monadic libraries and embedded domain-specific languages, especially for those that are based on collection monads. Should the question of how to integrate the extension into the Haskell standard arise, the paper proposes a solution to the problem that led to the removal of the monad comprehension notation from the language standard.
Lifetime Cancer Risks in Individuals with Germline PTEN Mutations
Authors: Tan Min-Han , Mester Jessica L. , Ngeow Joanne , Rybicki Lisa A. , Orloff Mohammed S. , Eng Charis 
Published: January 2012

Abstract
Purpose: Age-adjusted cancer incidence and age-related penetrance studies have helped guide cancer risk assessment and management. PTEN hamartoma tumor syndrome (PHTS) is a term encompassing subsets of several clinical syndromes with germline mutations in the PTEN tumor suppressor gene. We conducted the first prospective study to clarify corresponding cancer risks to shed biologic insights on human germline PTEN mutations, and to better inform current surveillance recommendations on the basis of expert opinion.
Experimental Design: A series of 3,399 individuals meeting relaxed International Cowden Consortium PHTS criteria were prospectively recruited; 368 individuals were found to have deleterious germline PTEN mutations. Age-adjusted standardized incidence ratio (SIR) calculations and genotype–phenotype analyses were carried out.
Results: Elevated SIRs were found for carcinomas of the breast [25.4, 95% confidence interval (CI), 19.8–32.0], thyroid (51.1, 38.1–67.1), endometrium (42.9, 28.1–62.8), colorectum (10.3, 5.6–17.4), kidney (30.6, 17.8–49.4), and melanoma (8.5, 4.1–15.6). Estimated lifetime risks were, respectively, 85.2% (95% CI, 71.4%–99.1%), 35.2% (19.7%–50.7%), 28.2% (17.1%–39.3%), 9.0% (3.8%–14.1%), 33.6% (10.4%–56.9%), and 6% (1.6%-9.4%). Promoter mutations were associated with breast cancer, whereas colorectal cancer was associated with nonsense mutations.
Conclusion: Lifetime risks for a variety of cancers, now extending to colorectal cancer, kidney cancer, and melanoma, are increased in patients with PTEN mutations. The genotype–phenotype associations here may provide new insights on PTEN structure and function. We propose a comprehensive approach to surveillance of patients with PTEN mutations. Clin Cancer Res; 18(2); 400–7. ©2012 AACR.
EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib
Authors: Corcoran Ryan B. , Ebi Hiromichi , Turke Alexa B. , Coffee Erin M. , Nishino Michiya , Cogdill Alexandria P. , Brown Ronald D. , Della Pelle Patricia , Dias-Santagata Dora , Hung Kenneth E. , Flaherty Keith T. , Piris Adriano , Wargo Jennifer A. , Settleman Jeffrey , Mino-Kenudson Mari , Engelman Jeffrey A. 
Published: January 2012

Abstract
BRAF mutations occur in 10% to 15% of colorectal cancers and confer adverse outcome in the metastatic setting. Although RAF inhibitors such as vemurafenib (PLX4032) have proven effective in the treatment of BRAF-mutant melanoma, they are surprisingly ineffective in BRAF-mutant colorectal cancers, and the reason for this disparity remains unclear. Compared with BRAF-mutant melanoma cells, BRAF-mutant colorectal cancer cells were less sensitive to vemurafenib, and phospho-extracellular signal-regulated kinase (P-ERK) suppression was not sustained in response to treatment. Although transient inhibition of P-ERK by vemurafenib was observed in colorectal cancer, rapid ERK reactivation occurred through epidermal growth factor receptor (EGFR)-mediated activation of RAS and CRAF. BRAF-mutant colorectal cancers expressed greater levels of phospho-EGFR than BRAF-mutant melanomas, suggesting that colorectal cancers are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of mitogen-activated protein kinase (MAPK) signaling in BRAF-mutant colorectal cancer cells and markedly improved efficacy in vitro and in vivo. These findings support the evaluation of combined RAF and EGFR inhibition in patients with BRAF-mutant colorectal cancer.
Significance: BRAF valine 600 (V600) mutations occur in 10% to 15% of colorectal cancers, yet these tumors show a surprisingly low clinical response rate (∼5%) to selective RAF inhibitors such as vemurafenib, which have produced dramatic response rates (60%–80%) in melanomas harboring the identical BRAF V600 mutation. We found that EGFR-mediated MAPK pathway reactivation leads to resistance to vemurafenib in BRAF-mutant colorectal cancers and that combined RAF and EGFR inhibition can lead to sustained MAPK pathway suppression and improved efficacy in vitro and in tumor xenografts. Cancer Discovery; 2(3); 227–35. ©2012 AACR.
This article is highlighted in the In This Issue feature, p. 193
Assisted dying in liberalised jurisdictions and the role of psychiatry: A clinician’s view
Authors: Macleod Sandy 
Published: January 2012

Objective: Assisted dying is a contentious and topical issue. Mental disorder is a relevant influence on requests of hastened death. The psychiatry of dying is not a prominent component in the assessment of euthanasia and physician-assisted suicide (PAS) in jurisdictions with liberalised assisted dying laws. The literature on the assessment processes, with particular reference to mental status, involved in euthanasia requests is considered. Methods: An experienced palliative medicine specialist and psychiatrist selectively reviewed the recent literature published about the mental health issues involved in euthanasia and PAS. Results: Assessments of competency, sustained wish to die prematurely, depressive disorder, demoralisation and ‘unbearable suffering’ in the terminally ill are clinically uncertain and difficult tasks. There is a growing psychiatric and psychological literature on the mental status of the terminally ill. As yet psychiatry does not have the expertise to ‘select’ those whose wish for hastened death is rational, humane and ‘healthy’. Rarely in those societies with liberalised assisted dying laws are psychiatrists involved in the decision-making for individuals requesting early death. This role is fulfilled by non-specialists. Conclusions: There remain significant concerns about the accuracy of psychiatric assessment in the terminally ill. Mental processes are more relevant influences on a hastened wish to die than are the physical symptoms of terminal malignant disease. Psychiatric review of persons requesting euthanasia is relevant. It is not obligatory or emphasised in those legislations allowing assisted dying. Psychiatry needs to play a greater role in the assessment processes of euthanasia and PAS.
Immunological method for the identification of animal hair fibres
Authors: Tonetti Cinzia , Vineis Claudia , Aluigi Annalisa , Tonin Claudio 
Published: January 2012

A new approach to the objective identification of the different animal hair fibres based on the application of monoclonal antibodies has been discussed. Three different extraction methods including metabisulphite/urea, dithiothreitol/urea, thiourea/urea/dithiothreitol were compared to evaluate efficiency and repeatability in extracting keratin from wool and cashmere fibres.  ‘Anti-cashmere’ monoclonal antibodies were produced by immunization of mice with Type II intermediate filament proteins extracted from cashmere, purified by 2D preparative electrophoresis. Two monoclonal antibodies (named P21 and I6) were tested with both wool and cashmere blends for both qualitative and quantitative analysis. The interaction of P21 and I6 antibodies was studied by the immunoblot method.  After a calibration carried out on both the antibodies, the method was applied to unknown wool/cashmere blends and compared with the results of the analysis carried out by the SEM (scanning electron microscopy) method IWTO 58-00 in order to preliminarily assess the method.
First experience with the new portable extracorporeal membrane oxygenation system Cardiohelp for severe respiratory failure in adults
Authors: Haneya A , Philipp A , Foltan M , Camboni D , Müeller T , Bein T , Schmid C , Lubnow M 
Published: January 2012

Background: Over the last decade, technical improvements in extracorporeal membrane oxygenation (ECMO) equipment have reduced procedure-related complications and have made ECMO an effective option for patients with acute respiratory distress syndrome (ARDS) if conventional therapy fails. Methods: In this report, we present our early experience with the Cardiohelp, a new portable miniaturized ECMO system, in 22 consecutive patients with ARDS. All patients were placed on venovenous ECMO. Cannulas were inserted percutaneously, employing the Seldinger technique. Data were collected prospectively. Results: The median patient age was 47 years (36 to 61). Fifteen patients from regional hospitals were too unstable for conventional transport and were placed on Cardiohelp at the referring hospital and then transported to our institution. The patients were transported by ambulance (n=2) or helicopter (n=13) over a distance of 50-250 km. Cardiohelp support resulted in immediate improvement of gas exchange and highly protective ventilation. The median duration of support was 13 days (8 to 19). An exchange of the device was necessary in 9 patients. Sixteen patients (72.7%) were successfully weaned from ECMO and fifteen patients (68.2%) survived. Device-related complications were not observed. Conclusions: The compact portable ECMO device Cardiohelp is a highly effective method to secure vital gas exchange and to reduce further ventilator-induced lung injury in patients with acute respiratory failure. Crucial technical innovations and ease of device transport and implantation allow location-independent stabilization with consecutive inter-hospital transfer.
Anxiety, Stress and Satisfaction among Professionals in Manufacturing and Service Organizations
Authors: Srivastava Manjari 
Published: January 2012

In today’s era of globalization and increased competition, executives working in an organization cannot remain unaffected from changing values and demanding working conditions. Increased anxiety, stress and job dissatisfaction/satisfaction are some of the psychological outcomes of a person’s belief and value system as well as job conditions. Value system, which promotes high achievement orientation and competition both at the individual and organizational levels, is one of the critical issues that need to be addressed. The present article is an exploratory study on the above mentioned issues, wherein the relationship between certain independent variables identified as ‘personal values of executives, work values promoted by organizations’ and dependent variables construed as positive job outcome (satisfaction) and negative job outcome (stress and anxiety) was studied. The study also looked into the influence of ‘demanding job conditions’ on dependent variables. Data was collected using structured interview schedule as well as mailing questionnaire online from 150 junior-, middle- and senior-level managers working in service and manufacturing organizations in Mumbai. Stepwise multiple regression analysis was performed to find out strength of association among variables. Results reflect both positive and negative relationship between independent and outcome variables, suggesting that individuals’ values and work values in the organizations are related to perceived stress and anxiety as well as satisfaction among working professionals. Personal values predicting stress and anxiety are different from those predicting satisfaction. Demanding job conditions have negative impact on professionals as it leads to perception of stress, anxiety and dissatisfaction among professionals.
Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8+T cells in chronic obstructive pulmonary disease
Authors: Nadigel Jessica , Préfontaine David , Baglole Carolyn J , Maltais François , Bourbeau Jean , Eidelman David H , Hamid Qutayba 
Published: January 2012

AbstractBackgroundCigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8+T cells within the central and peripheral airways. We hypothesized that the CD8+T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.MethodsEndobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8+T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.ResultsNo difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+T cells. Exposure of CD8+T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8+T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.ConclusionsOur results demonstrate increased expression of TLR4 and TLR9 on lung CD8+T cells in COPD. CD8+T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8+T cells in COPD.
Convergent evolution in structural elements of proteins investigated using cross profile analysis
Authors: Tomii Kentaro , Sawada Yoshito , Honda Shinya 
Published: January 2012

Abstract

Background
Evolutionary relations of similar segments shared by different protein folds remain controversial, even though many examples of such segments have been found. To date, several methods such as those based on the results of structure comparisons, sequence-based classifications, and sequence-based profile-profile comparisons have been applied to identify such protein segments that possess local similarities in both sequence and structure across protein folds. However, to capture more precise sequence-structure relations, no method reported to date combines structure-based profiles, and sequence-based profiles based on evolutionary information. The former are generally regarded as representing the amino acid preferences at each position of a specific conformation of protein segment. They might reflect the nature of ancient short peptide ancestors, using the results of structural classifications of protein segments.

Results
This report describes the development and use of "Cross Profile Analysis" to compare sequence-based profiles and structure-based profiles based on amino acid occurrences at each position within a protein segment cluster. Using systematic cross profile analysis, we found structural clusters of 9-residue and 15-residue segments showing remarkably strong correlation with particular sequence profiles. These correlations reflect structural similarities among constituent segments of both sequence-based and structure-based profiles. We also report previously undetectable sequence-structure patterns that transcend protein family and fold boundaries, and present results of the conformational analysis of the deduced peptide of a segment cluster. These results suggest the existence of ancient short-peptide ancestors.

Conclusions
Cross profile analysis reveals the polyphyletic and convergent evolution of β-hairpin-like structures, which were verified both experimentally and computationally. The results presented here give us new insights into the evolution of short protein segments.
Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta- analysis
Authors: Zhou Ying , Yin Xin , Ying Jun , Zhang BoHeng 
Published: January 2012

Abstract

Backgrounds
There have been conflicting reports about serum golgi protein 73 (GP73) as one of the most promising serum markers for the diagnosis of hepatocellular carcinoma (HCC). This study was to make a systematic review about the diagnostic accuracy of serum GP73 versus alpha-fetoprotein (AFP) for HCC.

Methods
After a systematic review of related studies, sensitivity, specificity and other measures about the accuracy of serum GP73 and AFP in the diagnosis of HCC were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance.

Results
Eight studies were included in our meta-analysis. The summary estimates for serum GP73 and AFP in diagnosing HCC in the studies included were as follows: sensitivity, 76% (95% confidence interval (CI) 51-91%) vs. 70% (47-86%); specificity, 86% (95%CI 65-95%) vs. 89% (69-96%); diagnostic odds ratio (DOR), 18.59 (95%CI 5.33-64.91) vs. 18.00(9.41-34.46); and area under sROC, 0.88 (95%CI 0.77-0.99) vs. 0.86 (95%CI 0.84-0.87).

Conclusions
The current evidence indicates that serum GP73 has a comparable accuracy to AFP for the diagnosis of HCC, while the value of serum GP73 in combination with AFP for HCC detection deserves further investigation.
Changing insurance company claims handling processes improves some outcomes for people injured in road traffic crashes
Authors: Schaafsma Frederieke , De Wolf Annelies , Kayaian Areen , Cameron Ian D 
Published: January 2012

Abstract

Background
Regaining good health and returning to work are important for people injured in road traffic crashes and for society. The handling of claims by insurance companies may play an important role in the rate at which health recovers and return to work is actually attained.

Methods
A novel approach towards claims handling for people injured in road traffic accidents was compared to the standard approach. The setting was a large insurance company (NRMA Insurance) in the state of New South Wales, Australia. The new approach involved communicating effectively with injured people, early intervention, screening for adverse prognostic factors and focusing on early return to work and usual activities. Demographic and injury data, health outcomes, return to work and usual activities were collected at baseline and 7 months post-injury.

Results
Significant differences were found 7 months post-injury on 'caseness' of depression (p = 0.04), perceived health limitation on activities (p = 0.03), and self-reported return to usual activities (p = 0.01) with the intervention group scoring better. Baseline general health was a significant predictor for general health at 7 months (OR 11.6, 95% CI 2.7-49.4) and for return to usual activities (OR 4.6, 95% CI 2.3-9.3).

Conclusion
We found a few positive effects on health from a new claims handling method by a large insurance company. It may be most effective to target people who report low general health and low expectations for their health recovery when they file their claim.
Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans and cytokine secretion by oral epithelial cells
Authors: Feldman Mark , Tanabe Shinichi , Howell Amy , Grenier Daniel 
Published: January 2012

Abstract

Background
Oral candidiasis is a common fungal disease mainly caused by Candida albicans. The aim of this study was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on pathogenic properties of C. albicans as well as on the inflammatory response of oral epithelial cells induced by this oral pathogen.

Methods
Microplate dilution assays were performed to determine the effect of AC-PACs on C. albicans growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled C. albicans to oral epithelial cells and to acrylic resin disks was monitored by fluorometry. The effects of AC-PACs on C. albicans-induced cytokine secretion, nuclear factor-kappa B (NF-κB) p65 activation and kinase phosphorylation in oral epithelial cells were determined by immunological assays.

Results
Although AC-PACs did not affect growth of C. albicans, it prevented biofilm formation and reduced adherence of C. albicans to oral epithelial cells and saliva-coated acrylic resin discs. In addition, AC-PACs significantly decreased the secretion of IL-8 and IL-6 by oral epithelial cells stimulated with C. albicans. This anti-inflammatory effect was associated with reduced activation of NF-κB p65 and phosphorylation of specific signal intracellular kinases.

Conclusion
AC-PACs by affecting the adherence properties of C. albicans and attenuating the inflammatory response induced by this pathogen represent potential novel therapeutic agents for the prevention/treatment of oral candidiasis.