bluuebunny/crossref_metadata_2025_split huggingface dataset:
Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells
Authors: Ogba Ndiya , Manning Nicole G , Bliesner Brian S , Ambler S Kelly , Haughian James M , Pinto Mauricio P , Jedlicka Paul , Joensuu Kristiina , Heikkilä Päivi , Horwitz Kathryn B 
Published: December 2014

Abstract
Introduction
Luminal, estrogen receptor-positive (ER+) breast cancers can metastasize but lie dormant for years before recurrences prove lethal. Understanding the roles of estrogen (E) or progestin (P) in development of luminal metastases or in arousal from dormancy is hindered by few preclinical models. We have developed such models.

Methods
Immunocompromised, ovariectomized (ovx’d) mice were intracardiac-injected with luminal or basal human breast cancer cells. Four lines were tested: luminal ER+PR+ cytokeratin 5-negative (CK5−) E3 and MCF-7 cells, basal ER−PR−CK5+ estrogen withdrawn-line 8 (EWD8) cells, and basal ER−PR−CK5− MDA-MB-231 cells. Development of micrometastases or macrometastases was quantified in ovx’d mice and in mice supplemented with E or P or both. Metastatic deposits were analyzed by immunohistochemistry for luminal, basal, and proliferation markers.

Results
ER−PR− cells generated macrometastases in multiple organs in the absence or presence of hormones. By contrast, ovx’d mice injected with ER+PR+ cells appeared to be metastases-free until they were supplemented with E or E+P. Furthermore, unlike parental ER+PR+CK5− cells, luminal metastases were heterogeneous, containing a significant (6% to 30%) proportion of non-proliferative ER−PR−CK5+ cells that would be chemotherapy-resistant. Additionally, because these cells lack receptors, they would also be endocrine therapy-resistant. With regard to ovx’d control mice injected with ER+PR+ cells that appeared to be metastases-free, systematic pathologic analysis of organs showed that some harbor a reservoir of dormant micrometastases that are ER+ but PR−. Such cells may also be endocrine therapy- and chemotherapy-resistant. Their emergence as macrometastases can be triggered by E or E+P restoration.

Conclusions
We conclude that hormones promote development of multi-organ macrometastases in luminal disease. The metastases display a disturbing heterogeneity, containing newly emergent ER−PR− subpopulations that would be resistant to endocrine therapy and chemotherapy. Similar cells are found in luminal metastases of patients. Furthermore, lack of hormones is not protective. While no overt metastases form in ovx’d mice, luminal tumor cells can seed distant organs, where they remain dormant as micrometastases and sheltered from therapies but arousable by hormone repletion. This has implications for breast cancer survivors or women with occult disease who are prescribed hormones for contraception or replacement purposes.
Deciphering miRNA transcription factor feed-forward loops to identify drug repurposing candidates for cystic fibrosis
Authors: Liu Zhichao , Borlak Jürgen , Tong Weida 
Published: December 2014

Abstract
Background
Cystic fibrosis (CF) is a fatal genetic disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that primarily affects the lungs and the digestive system, and the current drug treatment is mainly able to alleviate symptoms. To improve disease management for CF, we considered the repurposing of approved drugs and hypothesized that specific microRNA (miRNA) transcription factors (TF) gene networks can be used to generate feed-forward loops (FFLs), thus providing treatment opportunities on the basis of disease specific FFLs.

Methods
Comprehensive database searches revealed significantly enriched TFs and miRNAs in CF and CFTR gene networks. The target genes were validated using ChIPBase and by employing a consensus approach of diverse algorithms to predict miRNA gene targets. STRING analysis confirmed protein-protein interactions (PPIs) among network partners and motif searches defined composite FFLs. Using information extracted from SM2miR and Pharmaco-miR, an in silico drug repurposing pipeline was established based on the regulation of miRNA/TFs in CF/CFTR networks.

Results
In human airway epithelium, a total of 15 composite FFLs were constructed based on CFTR specific miRNA/TF gene networks. Importantly, nine of them were confirmed in patient samples and CF epithelial cells lines, and STRING PPI analysis provided evidence that the targets interacted with each other. Functional analysis revealed that ubiquitin-mediated proteolysis and protein processing in the endoplasmic reticulum dominate the composite FFLs, whose major functions are folding, sorting, and degradation. Given that the mutated CFTR gene disrupts the function of the chloride channel, the constructed FFLs address mechanistic aspects of the disease and, among 48 repurposing drug candidates, 26 were confirmed with literature reports and/or existing clinical trials relevant to the treatment of CF patients.

Conclusion
The construction of FFLs identified promising drug repurposing candidates for CF and the developed strategy may be applied to other diseases as well.
Organ Donation and Transplantation in Canada: Insights from the Canadian Organ Replacement Register
Authors: Kim Sang Joseph , Fenton Stanley SA , Kappel Joanne , Moist Louise M , Klarenbach Scott W , Samuel Susan M , Singer Lianne G , Kim Daniel H , Young Kimberly , Webster Greg , Wu Juliana , Ivis Frank , de Sa Eric , Gill John S 
Published: December 2014

Purpose of review: To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR). Findings: CORR is the national registry of organ failure in Canada. It has existed in some form since 1972 and currently houses data on patients with end-stage renal disease and solid organ transplants (kidney and/or non-kidney). The transplant component of CORR receives data on a voluntary basis from individual transplant centres and organ procurement organizations across the country. Coverage for transplant procedures is comprehensive and complete. Long-term outcomes are tracked based on follow-up reports from participating transplant centres. The longitudinal nature of CORR provides an opportunity to observe the trajectory of a patient's journey with organ failure over their life span. Research studies conducted using CORR data inform both practitioners and health policy makers alike. Implications: The importance of registry data in monitoring and improving care for Canadian transplant candidates/recipients cannot be over-stated. This paper provides an overview of the transplant data in CORR including its history, data considerations, recent findings, new initiatives, and future directions.
MAP kinase p38α regulates type III interferon (IFN-λ1) gene expression in human monocyte-derived dendritic cells in response to RNA stimulation
Authors: Jiang Miao , O¨sterlund Pamela , Fagerlund Riku , Rios Diana N , Hoffmann Alexander , Poranen Minna M , Bamford Dennis H , Julkunen Ilkka 
Published: December 2014

Abstract
Recognition of viral nucleic acids leads to type I and type III IFN gene expression and activation of host antiviral responses. At present, type III IFN genes are the least well-characterized IFN types. Here, we demonstrate that the p38 MAPK signaling pathway is involved in regulating IFN-λ1 gene expression in response to various types of RNA molecules in human moDCs. Inhibition of p38 MAPK strongly reduced IFN gene expression, and overexpression of p38α MAPK enhanced IFN-λ1 gene expression in RNA-stimulated moDCs. The regulation of IFN gene expression by p38 MAPK signaling was independent of protein synthesis and thus, a direct result of RNA stimulation. Moreover, the RIG-I/MDA5-MAVS-IRF3 pathway was required for p38α MAPK to up-regulate IFN-λ1 promoter activation, whereas the MyD88-IRF7 pathway was not needed, and the regulation was not involved directly in IRF7-dependent IFN-α1 gene expression. The stimulatory effect of p38α MAPK on IFN-λ1 mRNA expression in human moDCs did not take place directly via the activating TBK1/IKKɛ complex, but rather, it occurred through some other parallel pathways. Furthermore, mutations in ISRE and NF-κB binding sites in the promoter region of the IFN-λ1 gene led to a significant reduction in p38α MAPK-mediated IFN responses after RNA stimulation. Altogether, our data suggest that the p38α MAPK pathway is linked with RLR signaling pathways and regulates the expression of early IFN genes after RNA stimulation cooperatively with IRF3 and NF-κB to induce antiviral responses further.
Carbohydrate metabolism and quality of life in patients after surgical treatment of insulinoma
Authors: Dedov Ivan Ivanovich , Melnichenko Galina Afanas'evna , Krivko Alena Anatol'yevna , Kuznetsov Nikolay Sergeevich , Troshina Ekaterina Anatol'evna 
Published: December 2014

Objectives. T study the quality of life and status of carbohydrate metabolism in patients after surgical treatment insulinoma. Methods: The study involved 20 patients divided in two groups: the first group with a catamnesis duration of up to five years; the second group with a catamnesis duration of more than five years. We studied anthropometric parameters and carbohydrate metabolism as well as psychological questioning of patients using SF-36 questionnaire, the data was considered statistically significant at p0.05. Results. severe combined postoperative complications were more frequent in the first group (63.6% vs. 22.2%, p=0.07), due to extend of the performed surgery. Adrenergic symptoms prior to the surgery were detected in 90.9% of cases in the first group and in 77.7% of cases in the second group. After treatment these numbers decreased to 36.4% and 11.1% respectively (p=0.039 and 0.026). Neuroglycopeniс symptoms before treatment were detected in 90.9% of cases in the first group and for all patients in the second, while after treatment persisted only in 45.5% and 33.3% of cases respectively (p=0.045 and 0.036). Carbohydrate metabolism have normalized for the majority of patients. Two patients (18.2%) of the first group showed impaired glucose tolerance. Improved carbohydrate metabolism was associated with a decrease in body weight in both groups. Results of psychological questionnaires were comparable with the survey data obtained in general population in the Russian Federation. Conclusion. Surgical treatment of insulinomas is highly effective. Physical and psychological status of patients in most cases corresponds with those typical for this age-sex group of the population of the Russian Federation. Long-term treatment results do not depend on duration of the catamnesis. Complications that developed from surgical treatment have the main influence on the health of patients.
Efficacy and comparative analysis of consumer qualities of the Desmopressin intranasal drops in patients with central diabetes insipidus
Authors: Pigarova Ekaterina Aleksamdrovna , Dzeranova Larisa Konstantinovna , Rozhinskaya Lyudmila Yakovlevna 
Published: December 2014

Objective: To evaluate the effectiveness and conduct a comparative analysis of consumer qualities of desmopressin intranasal drops 0.01% 5ml ("Biopharm", Georgia) in patients with central diabetes insipidus (CDI). Materials and Methods: The study included 9 patients (3 men and 6 women, mean age 44 ± 12 years) diagnosed with CDI. Patients for 7 days were switched to desmopressin intranasal drops 0.01% (JSC "Biopharm" Georgia) from there basal desmopressin preparations by means of recalculating daily dose by proposed formular: 10 mg (2 drops) of desmopressin intranasal drops = 0.2 mg of desmopressin tableted = 10 micrograms (one dose) of intranasal spray metered desmopressin = 120 mcg sublingual tablets of desmopressin. Safety biochemical parameters, efficiency to control of the main manifestations of CDI, increase in urine specific gravity, quality of life, basic consumer properties of different desmopressin preparation were evaluates at baseline and after treatment period. Results: Desmopressin nasal drops 0.01% showed to be an effective drug for the treatment of patients with CDI. Dose calculation algorithm daily was adequate in most patients. Hyponatremia was detected in 2 out of 9 patients during the study period but has been related to study drug alone in one case. The investigational drug was marked convenient to use by less than 25% of patients which may be associated with the pharmacological form of the drug as intranasal drops with special storage conditions (refrigerator). Conclusions: The drug desmopressin intranasal drops can be recommended as a second line (reserve) therapy in the treatment of patients CDI. Sodium levels should be checked during initiation of therapy.
Quantification of adult T-cell leukemia/lymphoma cells using simple four-color flow cytometry
Authors: Ishigaki Tomohiro , Zaike Yuji , Nojima Masanori , Kobayashi Seiichiro , Ohno Nobuhiro , Uchimaru Kaoru , Tojo Arinobu , Nakauchi Hiromitsu , Watanabe Nobukazu 
Published: December 2014

AbstractThe absolute number of adult T-cell leukemia/lymphoma (ATL) cells in peripheral blood is an essential indicator to evaluate disease status. However, microscopically counting ATL cells based on morphology requires experience and tends to be inaccurate due to the rarity of ATL.Based on our research showing that acute-type ATL cells are specifically enriched in the CD4+/CD7- (CD7N) fraction, a new analytical method to accurately quantify ATL cells was established using an internal bead standard and simple four-color flow cytometry. This method was verified by comparison with microscopic examination of 49 peripheral blood samples and used to follow up patients.A strong correlation was observed between the number of CD7N cells measured by flow cytometry and the number of abnormal lymphocytes measured microscopically by experienced technicians [Pearson’s R, 0.963; Spearman’s rho, 0.921; intercorrelation coefficient, 0.962]. The linear regression coefficient was close to 1 (β=1.013). Our method could detect 1 cell/μL, and the limit of quantitation was between 2.9 and 9.8 cells/μL. The frequency of CD7N cells among CD4+ cells changed during chemotherapy, which reflected differences between chemosensitive and chemoresistant cases. Kaplan-Meier analysis with a log-rank test showed that patients with decreased CD7N proportion after chemotherapy had significantly longer disease-specific survival (p=0.003).Our newly established method quantified tumor cells in patients with acute-type ATL. Furthermore, this method was useful for assessing the efficacy of chemotherapy, and the change of the CD7N proportion could be more important to predict prognosis.
Nitrogen Removal to Minimize Energy Consumption of the Two WWTPs Choutrana II and Menzel Bourguiba in Tunisia
Authors: Hajji Slim , Shayeb Hedi , Marouani Mohamed Lotfi 
Published: December 2014

Abstract
The control of the aeration time and the dissolved oxygen in a reactor plays an important role in the management of the plant and the reduction of energy consumption. For this, two full-scale municipal wastewater treatment plants were chosen. The first plant (Choutrana II) designed for 600,000 population-equivalents (p.e), consists of a primary treatment step (screening, grit and grease removal), followed by four parallel oxidation ditches with a total volume of 60,000 m3. Aeration is ensured by air diffuser. The second plant (Menzel Bourguiba) designed for 140,000 p.e consists of a primary treatment stage (screening, grit and grease removal), followed by anoxic tanks and two aerobic reactors with a total volume of 14,000 m3. Aeration is ensured by six surface aerators which are operated episodically to create aerobic and anoxic conditions. Currently, the aeration management is controlled by a timer with a maintained oxygen concentration at a given level in the aerobic reactor. The nitrogen removal is done during air-on and air-off periods. The process can be seen as a succession of aeration periods followed by an anoxic period. This category of plant operation is far from the optimal and raises energy consumption and operative costs. The purpose of this study is to implement a new strategy to control aeration taking into account the variation of the daily organic load received by plants (feedforward control) and to create favorable conditions for nitrification and denitrification steps (feedback control). The Activated Sludge Model 1, which is calibrated and validated by respirometry tests, is used. Simulation results show the potentialities of the chosen strategy, which could save 28% of aeration energy and could adjust the aerobic and anoxic times. As first results, daily aeration time could be considered enough to produce treated water conform to standard terms. For Choutrana II plant, the results obtained have allowed to achieve a nitrogen removal rate of 85% and an output concentration between 6 and 12 mg/L. Rates of nitrification and denitrification were estimated at 4 mg NO3-N/L/h and 6 mg NH4-N/L/h, respectively. At the same time, aeration periods (on/off) are connected with daily organic load received by the plant and created favorable conditions for nitrification–denitrification. A good agreement between input biological loads, aeration profile and nitrogen removal is approved.
Tonal Processes in the Setswana Verb
Authors: Monich Irina 
Published: December 2014

AbstractThe present article offers an account of how tonal contours of individual verbal forms are generated in Setswana. Its main proposal is that verbal forms have complex structure with internal boundaries that are relevant to tonal processes. The framework of the account, Distributed Morphology (DM), distinguishes between word-building operations that take place in Syntax, in Morphology, and in Phonology, and it is argued that constituency created in the course of these operations is reflected in the tonal melody of individual forms. The present analysis accounts for tonal contours of all forms that posed difficulty under previous treatments while presenting a number of significant theoretical advantages. Most importantly, it offers an insight into Setswana clause structure and defines in precise terms the role that tone plays in making morphosyntactic and prosodic structures phonologically explicit.
Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats
Authors: Oluwole Oluwafemi Gabriel , Esume Celestine 
Published: December 2014

Abstract

Background: Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound.

Objectives: This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation.

Methods: Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours.

Results: The aqueous extract of MI (50–200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.).

Conclusions: The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.
Financial Engineering and the Arms Race Between Accounting Standard Setters and Preparers
Authors: Dye Ronald A. , Glover Jonathan C. , Sunder Shyam 
Published: December 2014

SYNOPSIS
This essay analyzes some problems that accounting standard setters confront in erecting barriers to managers bent on boosting their firms' financial reports through financial engineering (FE) activities. It also poses some unsolved research questions regarding interactions between preparers and standard setters. It starts by discussing the history of lease accounting to illustrate the institutional disadvantage of standard setters relative to preparers in their speeds of response. Then, the essay presents a general theorem that shows that, independent of how accounting standards are written, it is impossible to eliminate all FE efforts of preparers. It also discusses the desirability of choosing accounting standards on the basis of the FE efforts the standards induce preparers to engage in. Then, the essay turns to accounting boards' concepts statements; it points out that no concept statement recognizes the general lack of goal congruence between preparers and standard setters in their desires to produce informative financial statements. We also point out the relative lack of concern in recent concept statements for the representational faithfulness of the financial reporting of transactions. The essay asserts that these oversights may be responsible, in part, for standard setters promulgating recent standards that result in difficult-to-audit financial reports. The essay also discusses factors other than accounting standards that contribute to FE, including the high-powered incentives of managers, the limited disclosures and/or information sources outside the face of firms' financial statements about a firm's FE efforts, firms' principal sources of financing, the increasing complexity of transactions, the difficulties in auditing certain transactions, and the roles of the courts and culture. The essay ends by proposing some other recommendations on how standards can be written to reduce FE.
JEL Classifications: M31.
Design universel et milieu naturel: quelles contraintes et quelles solutions?
Authors: Borioli Jason , Margot-Cattin Pierre , Kessler Sébastien 
Published: December 2014

Universal design and the natural environment: what constraints and what solutions?
In recent years disability studies have seen the emergence of a new paradigm, which considers disability not as an impairment belonging to the person concerned, but as a situation which arises from the interaction between this person and an environment which is not adapted to that person's characteristics and needs. From this point of view, it is important to act on the environment in order to eliminate or limit the mismatch between the environment and the person and thus to allow the person to benefit from a greater social participation as an autonomous and responsible citizen. The universal design – the design of products and environments to be usable by all without the need for adaptation or special design – provides tools for implementing this idea. While there are constraints to implementation in an urban environment, the natural environment seems, at first sight, even more difficult to make universally accessible. After briefly putting these issues in context, the article presents the principles of universal design and tries to show that, on the contrary, it is very relevant also in a natural environment. The article explores solutions that make it possible to respond to three challenges which the authors consider particularly important: reconciliation of different needs, access to places where, at first sight, access seems more difficult than in an urban environment, and the participation of the people concerned as actors, not only visitors.