bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of COPD by clinical phenotypes: putting old evidence into clinical practice
Authors: Miravitlles Marc , Soler-Cataluña Juan José , Calle Myriam , Soriano Joan B. 
Published: October 2012

The new Global Initiative for Chronic Obstructive Lung Disease update has moved the principles of treatment of stable chronic obstructive pulmonary disease (COPD) forward by including the concepts of symptoms and risks into the decision of therapy. However, no mention of the concept of clinical phenotypes is included. It is recognised that COPD is a very heterogeneous disease and not all patients respond to all drugs available for treatment. The identification of responders to therapies is crucial in chronic diseases to provide the most appropriate treatment and avoid unnecessary medications. The classically defined phenotypes of chronic bronchitis and emphysema, together with the newly described phenotypes of overlap COPD-asthma and frequent exacerbator, allow a simple classification of patients that share clinical characteristics and outcomes and, more importantly, similar responses to existing treatments.These clinical phenotypes can help clinicians identify patients that respond to specific pharmacological interventions. For example, frequent exacerbators are the only subjects with an indication for anti-inflammatory treatment in COPD. Among them, those with chronic bronchitis are the only candidates to receive phosphodiesterase-4 inhibitors. Patients with overlap COPD-asthma phenotype show an enhanced response to inhaled corticosteroids and infrequent exacerbators should only receive bronchodilators. These well-defined clinical phenotypes could potentially be incorporated into treatment guidelines.
Quantitative intact proteomics investigations of alveolar macrophages in sarcoidosis
Authors: Silva Ernesto , Souchelnytskyi Serhiy , Kasuga Kie , Eklund Anders , Grunewald Johan , Wheelock Åsa M. 
Published: October 2012

Alveolar macrophages are important for granuloma formation, which is the histological hallmark in sarcoidosis. Their function as antigen-presenting cells in sarcoidosis is also believed to be relevant to the outcome of disease, resulting either in remission or a prolonged chronic inflammation in the lungs.Our aim was to study alterations in the expression levels of the soluble proteome of alveolar macrophages in pulmonary sarcoidosis as compared with healthy controls, with the goal of identifying specific proteins and pathways important for the mechanisms of disease and/or disease phenotype.Quantitative proteomics approach using two-dimensional difference gel electrophoresis coupled to mass spectrometry was applied. Data was evaluated using multivariate modelling and pathway analyses. 69 protein spots were found to be significantly altered between sarcoidosis and healthy controls. Among these, 25 unique proteins were identified. Several of the identified proteins were related to key alveolar macrophage functionality, including the Fcγ-mediated phagocytosis and clathrin-mediated endocytosis pathways.Global proteomics analysis provided identification of alterations of a subset of proteins not previously reported in sarcoidosis. These alterations primarily affect biological pathways related to phagocytic macrophage functionality. These findings provide important insights into the role of macrophages in sarcoidosis pathogenesis.
Functional and genetic interactions of TOR in the budding yeast Saccharomyces cerevisiae with myosin type II-deficiency (myo1Δ)
Authors: Pagán-Mercado Glorivee , Santiago-Cartagena Ednalise , Akamine Pearl , Rodríguez-Medina José R 
Published: October 2012

Abstract

Background
Yeast has numerous mechanisms to survive stress. Deletion of myosin type II (myo1Δ) in Saccharomyces cerevisiae results in a cell that has defective cytokinesis. To survive this genetically induced stress, this budding yeast up regulates the PKC1 cell wall integrity pathway (CWIP). More recently, our work indicated that TOR, another stress signaling pathway, was down regulated in myo1Δ strains. Since negative signaling by TOR is known to regulate PKC1, our objectives in this study were to understand the cross-talk between the TOR and PKC1 signaling pathways and to determine if they share upstream regulators for mounting the stress response in myo1Δ strains.

Results
Here we proved that TORC1 signaling was down regulated in the myo1Δ strain. While a tor1 Δ mutant strain had increased viability relative to myo1Δ, a combined myo1Δtor1 Δ mutant strain showed significantly reduced cell viability. Synthetic rescue of the tor2-21

ts
lethal phenotype was observed in the myo1Δ strain in contrast to the chs2 Δ strain, a chitin synthase II null mutant that also activates the PKC1 CWIP and exhibits cytokinesis defects very similar to myo1Δ, where the rescue effect was not observed. We observed two pools of Slt2p, the final Mitogen Activated Protein Kinase (MAPK) of the PKC1 CWIP; one pool that is up regulated by heat shock and one that is up regulated by the myo1Δ stress. The cell wall stress sensor WSC1 that activates PKC1 CWIP under other stress conditions was shown to act as a negative regulator of TORC1 in the myo1Δ mutant. Finally, the repression of TORC1 was inversely correlated with the activation of PKC1 in the myo1Δ strain.

Conclusions
Regulated expression of TOR1 was important in the activation of the PKC1 CWIP in a myo1Δ strain and hence its survival. We found evidence that the PKC1 and TORC1 pathways share a common upstream regulator associated with the cell wall stress sensor WSC1. Surprisingly, essential TORC2 functions were not required in the myo1Δ strain. By understanding how yeast mounts a concerted stress response, one can further design pharmacological cocktails to undermine their ability to adapt and to survive.
The providing resources to enhance African American patients’ readiness to make decisions about kidney disease (PREPARED) study: protocol of a randomized controlled trial
Authors: Ephraim Patti L , Powe Neil R , Rabb Hamid , Ameling Jessica , Auguste Priscilla , Lewis-Boyer LaPricia , Greer Raquel C , Crews Deidra C , Purnell Tanjala S , Jaar Bernard G , DePasquale Nicole , Boulware L Ebony 
Published: October 2012

Abstract

Background
Living related kidney transplantation (LRT) is underutilized, particularly among African Americans. The effectiveness of informational and financial interventions to enhance informed decision-making among African Americans with end stage renal disease (ESRD) and improve rates of LRT is unknown.

Methods/design
We report the protocol of the Providing Resources to Enhance African American Patients’ Readiness to Make Decisions about Kidney Disease (PREPARED) Study, a two-phase study utilizing qualitative and quantitative research methods to design and test the effectiveness of informational (focused on shared decision-making) and financial interventions to overcome barriers to pursuit of LRT among African American patients and their families. Study Phase I involved the evidence-based development of informational materials as well as a financial intervention to enhance African American patients’ and families’ proficiency in shared decision-making regarding LRT. In Study Phase 2, we are currently conducting a randomized controlled trial in which patients with new-onset ESRD receive 1) usual dialysis care by their nephrologists, 2) the informational intervention (educational video and handbook), or 3) the informational intervention in addition to the option of participating in a live kidney donor financial assistance program. The primary outcome of the randomized controlled trial will include patients’ self-reported rates of consideration of LRT (including family discussions of LRT, patient-physician discussions of LRT, and identification of a LRT donor).

Discussion
Results from the PREPARED study will provide needed evidence on ways to enhance the decision to pursue LRT among African American patients with ESRD.

Trial registration
ClinicalTrials.gov NCT01439516
Prognostic analysis of combined curative resection of the stomach and liver lesions in 30 gastric cancer patients with synchronous liver metastases
Authors: Wang Yan-Na , Shen Kun-Tang , Ling Jia-Qian , Gao Xiao-Dong , Hou Ying-Yong , Wang Xue-Fei , Qin Jing , Sun Yi-Hong , Qin Xin-Yu 
Published: October 2012

Abstract

Background
Gastric cancer with synchronous liver metastasis remains a clinical treatment challenge. There has been a longstanding debate on the question whether surgical resection could be beneficial to long-term survival. This study is to investigate the effectiveness and prognostic factors of combined curative resection of the stomach and liver lesions in gastric cancer patients with synchronous liver metastases.

Methods
A total of 30 patients who underwent simultaneous curative gastric and liver resection from March 2003 to April 2008 were analyzed retrospectively. Univariate and multivariate analyses were performed to select independent factors for survival.

Results
The overall 1-, 2-, 3- and 5-year survival rates of 30 patients were 43.3%, 30.0%, 16.7% and 16.7%, respectively, with a median survival of 11.0 months and 5 patients still living by the time of last follow-up. Single liver metastasis (p = 0.028) and an absence of peritoneal dissemination (p = 0.007) were significantly independent prognostic factors for these gastric cancer patients with synchronous liver metastases. Major adverse events were protracted stomach paralysis in 2 patients and pulmonary infection in another 2 patients, all of whom recovered after conservative treatment.

Conclusions
This descriptive study without control group found that patients with solitary liver metastasis and absence of peritoneal dissemination could have better survival benefit from simultaneous curative resection of the gastric cancer and liver metastases.
Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
Authors: Duangmano Suwit , Sae-lim Phorntip , Suksamrarn Apichart , Domann Frederick E , Patmasiriwat Pimpicha 
Published: October 2012

Abstract

Background
Cucurbitacin B, an oxygenated tetracyclic triterpenoid compound extracted from the Thai medicinal plant Trichosanthes cucumerina L., has been reported to have several biological activities including anti-inflammatory, antimicrobial and anticancer. Cucurbitacin B is great of interest because of its biological activity. This agent inhibits growth of various types of human cancer cells lines.

Methods
In this study, we explored the novel molecular response of cucurbitacin B in human breast cancer cells, MCF-7 and MDA-MB-231. The growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT assay. The effects of cucurbitacin B on microtubules morphological structure and tubulin polymerization were analyzed using immunofluorescence technique and tubulin polymerization assay kit, respectively. Proteomic analysis was used to identify the target-specific proteins that involved in cucurbitacin B treatment. Some of the differentially expressed genes and protein products were validated by real-time RT-PCR and western blot analysis. Cell cycle distributions and apoptosis were investigated using flow cytometry.

Results
Cucurbitacin B exhibited strong antiproliferative effects against breast cancer cells in a dose-dependent manner. We show that cucurbitacin B prominently alters the cytoskeletal network of breast cancer cells, inducing rapid morphologic changes and improper polymerization of the microtubule network. Moreover, the results of 2D-PAGE, real-time RT-PCR, and western blot analysis revealed that the expression of nucleophosmin/B23 and c-Myc decreased markedly after cucurbitacin B treatment. Immunofluorescence microscopy showed that cucurbitacin B induced translocation of nucleophosmin/B23 from the nucleolus to nucleoplasm. Treatment with cucurbitacin B resulted in cell cycle arrest at G2/M phase and the enhancement of apoptosis.

Conclusions
Our findings suggest that cucurbitacin B may inhibit the proliferation of human breast cancer cells through disruption of the microtubule network and down-regulation of c-Myc and nucleophosmin/B23 as well as the perturbation in nucleophosmin/B23 trafficking from the nucleolus to nucleoplasm, resulting in G2/M arrest.
Are students kidding with health research ethics? The case of HIV/AIDS research in Cameroon
Authors: Munung Nchangwi Syntia , Tangwa Godfrey B , Che Chi Primus , Vidal Laurent , Ouwe-Missi-Oukem-Boyer Odile 
Published: October 2012

Abstract

Background
Universities in Cameroon are playing an active part in HIV/AIDS research and much of this research is carried out by students, usually for the purpose of a dissertation/thesis. Student theses/dissertations present research findings in a much more comprehensive manner and have been described as the stepping-stone of a budding scientist’s potential in becoming an independent researcher. It is therefore important to verify how students handle issues of research ethics.

Method
Theses/dissertations on HIV/AIDS that described research studies involving the use of human research participants were screened to verify if research ethics approval and informed consent were obtained and documented. The contents of the consent forms were also qualitatively analyzed.

Results
Of 174 theses/dissertations on HIV, ethics approval was documented in 17 (9.77%) and informed consent in 77 (47.83%). Research ethics approval was first mentioned at all in 2002 and highly reported in the year 2007. Evidence of ethics approval was found for the first time in 2005 and informed consent first observed and evidenced in 1997. Ethics approval was mostly reported by students studying for an MD (14.01%) and was not reported in any Bachelors’ degree dissertation. Informed consent was also highly reported in MD theses (64.58%) followed by undergraduate theses (31.58%). Voluntary participation and potential benefits of the study were some of the common aspects dealt with in most of the consent forms. The right to discontinue participation in the study and management of residual samples were scarcely ever mentioned.

Conclusions
Overall, and given the current state of the art of research ethics around the world, student-scientists in Cameroon would seem to be merely kidding with research ethics. It is thus essential that training in health research ethics (HRE) be incorporated in the curriculum of universities in Cameroon in order that the next generation of scientists may be better equipped with thorough knowledge and practice of HRE. This, we believe, would be one way of fighting the occurrence of research scandals, which have not yet abated significantly, especially those arising from negligence or inexcusable ignorance.
Validation of administrative data sources for endoscopy utilization in colorectal cancer diagnosis
Authors: Li Xue , Hilsden Robert , Hossain Shakhawat , Fleming John , Winget Marcy 
Published: October 2012

Abstract

Background
Validation of administrative data is important to assess potential sources of bias in outcome evaluation and to prevent dissemination of misleading or inaccurate information. The purpose of the study was to determine the completeness and accuracy of endoscopy data in several administrative data sources in the year prior to colorectal cancer diagnosis as part of a larger project focused on evaluating the quality of pre-diagnostic care.

Methods
Primary and secondary data sources for endoscopy were collected from the Alberta Cancer Registry, cancer medical charts and three different administrative data sources. 1672 randomly sampled patients diagnosed with invasive colorectal cancer in years 2000–2005 in Alberta, Canada were included. A retrospective validation study of administrative data for endoscopy in the year prior to colorectal cancer diagnosis was conducted. A gold standard dataset was created by combining all the datasets. Number and percent identified, agreement and percent unique to a given data source were calculated and compared across each dataset and to the gold standard with respect to identifying all patients who underwent endoscopy and all endoscopies received by those patients.

Results
The combined administrative data and physician billing data identified as high or higher percentage of patients who had one or more endoscopy (84% and 78%, respectively) and total endoscopy procedures (89% and 81%, respectively) than the chart review (78% for both).

Conclusions
Endoscopy data has a high level of completeness and accuracy in physician billing data alone. Combined with hospital in/outpatient data it is more complete than chart review alone.
Determinants of vascular function in patients with type 2 diabetes
Authors: Naka Katerina K , Papathanassiou Katerina , Bechlioulis Aris , Kazakos Nikolaos , Pappas Konstantinos , Tigas Stelios , Makriyiannis Dimitrios , Tsatsoulis Agathocles , Michalis Lampros K 
Published: October 2012

AbstractBackgroundType 2 diabetes mellitus (T2DM) is independently associated with an increased risk for cardiovascular diseases that is primarily due to the early development of advanced atherosclerotic vascular changes. The aim of our study was to investigate the predictors of vascular dysfunction in T2DM patients.MethodsWe studied 165 T2DM patients without known macrovascular or microvascular disease. Standard demographic (age, gender, cardiovascular risk factors, medications), clinical (body mass index, blood pressure) and laboratory (glucose, glycated hemoglobin, lipids, renal function) parameters were included in analyses. Brachial artery flow-mediated dilation (FMD), nitrate mediated dilation (NMD) and Carotid-Femoral Pulse Wave Velocity (PWV) were measured.ResultsMedian age was 66 years and duration since T2DM diagnosis was 10 years, 70% were females and 79% hypertensives, while only 10% had a glycated hemoglobin <7%. FMD was positively associated with NMD (r 0.391, P < 0.001), while PWV was inversely associated with FMD (r -0.218, P = 0.014) and NMD (r -0.309, P < 0.001). Time since diagnosis of diabetes was the single independent predictor of FMD (β -0.40, P = 0.003). Increased age and fasting glucose and the presence of hypertension were independent predictors of decreased NMD (P < 0.001). Increased age and systolic blood pressure were independently associated with increased PWV (P < 0.001).ConclusionsIn T2DM patients, impairment of endothelium-dependent vasodilation was independently associated only with longer diabetes duration while no association with other established risk factors was found. Vascular smooth muscle dysfunction and increased arterial stiffness were more prominent in older T2DM patients with hypertension. Worse glycemic control was associated with impaired vascular smooth muscle function.
Asymptotic analysis of flooding in CSMA-based large scale ad-hoc wireless networks
Authors: Shah-Mansouri Hamed , Khalaj Babak Hossein , Shariatpanahi Seyed Pooya , Ser Javier Del , Pérez-Sánchez Susana 
Published: October 2012

Abstract

Abstract
In this article, we study the asymptotic behavior of flooding in large scale wireless networks. Specifically, we derive an upper bound on the coverage of flooding when the number of nodes n in the network goes to infinity. We consider two different regimes of transmission radii: first, the case of constant transmission radius r where the percentage of covered nodes scales as

O
(
n

r

2

e

−

K

S

n

r

2

)

for a constant K

S
> 0. In this case, as an important result, we observe that the percentage of covered nodes is upper bounded by a decreasing function, vanishing as the network size grows. Second, the case of vanishing r

n
(i.e., r decreases as n increases) is considered where it is shown in the literature that the minimum value of r

n
which maintains connectivity is

log
n
/
Π
n

. In this case, a coverage percentage of at most

O
(

n

−

K

S

′

log
n
)

is expected for a constant value of

K

S

′

>
0

, leading to an infinite number of covered nodes. In such case, the rate at which the network coverage is decreased can be controlled and be considerably reduced by a proper choice of network parameters (

K

S

′

). Consequently, this result shows that flooding is a suitable strategy even for large networks.
New perspectives on central and peripheral immune responses to acute traumatic brain injury
Authors: Das Mahasweta , Mohapatra Subhra , Mohapatra Shyam S 
Published: October 2012

AbstractTraumatic injury to the brain (TBI) results in a complex set of responses involving various symptoms and long-term consequences. TBI of any form can cause cognitive, behavioral and immunologic changes in later life, which underscores the problem of underdiagnosis of mild TBI that can cause long-term neurological deficits. TBI disrupts the blood–brain barrier (BBB) leading to infiltration of immune cells into the brain and subsequent inflammation and neurodegeneration. TBI-induced peripheral immune responses can also result in multiorgan damage. Despite worldwide research efforts, the methods of diagnosis, monitoring and treatment for TBI are still relatively ineffective. In this review, we delve into the mechanism of how TBI-induced central and peripheral immune responses affect the disease outcome and discuss recent developments in the continuing effort to combat the consequences of TBI and new ways to enhance repair of the damaged brain.
Performance of small cluster surveys and the clustered LQAS design to estimate local-level vaccination coverage in Mali
Authors: Minetti Andrea , Riera-Montes Margarita , Nackers Fabienne , Roederer Thomas , Koudika Marie Hortense , Sekkenes Johanne , Taconet Aurore , Fermon Florence , Touré Albouhary , Grais Rebecca F , Checchi Francesco 
Published: October 2012

Abstract
Background
Estimation of vaccination coverage at the local level is essential to identify communities that may require additional support. Cluster surveys can be used in resource-poor settings, when population figures are inaccurate. To be feasible, cluster samples need to be small, without losing robustness of results. The clustered LQAS (CLQAS) approach has been proposed as an alternative, as smaller sample sizes are required.

Methods
We explored (i) the efficiency of cluster surveys of decreasing sample size through bootstrapping analysis and (ii) the performance of CLQAS under three alternative sampling plans to classify local VC, using data from a survey carried out in Mali after mass vaccination against meningococcal meningitis group A.

Results
VC estimates provided by a 10 × 15 cluster survey design were reasonably robust. We used them to classify health areas in three categories and guide mop-up activities: i) health areas not requiring supplemental activities; ii) health areas requiring additional vaccination; iii) health areas requiring further evaluation. As sample size decreased (from 10 × 15 to 10 × 3), standard error of VC and ICC estimates were increasingly unstable. Results of CLQAS simulations were not accurate for most health areas, with an overall risk of misclassification greater than 0.25 in one health area out of three. It was greater than 0.50 in one health area out of two under two of the three sampling plans.

Conclusions
Small sample cluster surveys (10 × 15) are acceptably robust for classification of VC at local level. We do not recommend the CLQAS method as currently formulated for evaluating vaccination programmes.