bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oralversusi.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis
Authors: Lorgelly P. K. , Atkinson M. , Lakhanpaul M. , Smyth A. R. , Vyas H. , Weston V. , Stephenson T. 
Published: August 2009

Community-acquired pneumonia represents a high financial burden to healthcare providers. This manuscript seeks to estimate and compare the costs of treating children hospitalised with community-acquired pneumonia, with oral and intravenous antibiotics, thus determining which treatment is cost minimising.A cost-minimisation analysis was undertaken alongside a randomised controlled non-blinded equivalence trial. 232 children (from eight paediatric centres in England) diagnosed with pneumonia, who required admission to hospital, were randomised to receive oral amoxicillin ori.v.benzyl penicillin. The analysis considered the cost to the health service, patients and society, from pre-admission until the child was fully recovered.Oral amoxicillin andi.v.benzyl penicillin have equivalent efficacy. Children treated withi.v.antibiotics were found to have significantly longer in-patient stays (3.12versus1.93 days; p<0.001).i.v.treatment was found to be more expensive than oral treatment (£1,256versus£769; difference £488; 95% CI: £233–£750), such that treatment of community-acquired pneumonia with oral amoxicillin would result in savings of between £473 and £518 per child (€545 and €596 per child) admitted.The findings demonstrate that oral amoxicillin is a cost-effective treatment for the majority of children admitted to hospital with pneumonia.
Atrophy and hypertrophy signalling in the diaphragm of patients with COPD
Authors: Testelmans D. , Crul T. , Maes K. , Agten A. , Crombach M. , Decramer M. , Gayan-Ramirez G. 
Published: August 2009

We investigated whether atrophy and hypertrophy signalling were altered in the diaphragm of chronic obstructive pulmonary disease (COPD) patients.We studied diaphragm fibre dimensions and proportion, expression of markers of the ubiquitin-proteasome pathway, nuclear factor (NF)-κB pathways, muscle regulatory factors and myostatin in diaphragm biopsies from 19 patients with severe COPD and 13 patients without COPD.Type I proportion was significantly increased in the diaphragm of COPD patients while type II proportion was decreased. The cross-sectional area of all fibre types was reduced in the COPD patients. In addition, MAFbx mRNA was higher in the diaphragm of COPD patients while Nedd4 mRNA decreased. Cytoplasmatic levels of inhibitor protein IκBα and IκBβ were decreased in the COPD patients as was NF-κB p50 DNA-binding activity. MyoD mRNA and its nuclear protein content were decreased in the diaphragm of COPD patients and myogenin mRNA and protein levels remained unchanged. Myostatin mRNA was decreased but its protein levels in the nuclear and cytoplasmic fraction were significantly increased in the COPD patients.These data show that the ubiquitin-proteasome pathway, the NF-κB pathway and myostatin protein were up-regulated in the diaphragm of COPD patients while MyoD expression was reduced. These alterations may contribute to diaphragm remodeling in COPD.
Newer fluoroquinolones for treating respiratory infection: do they mask tuberculosis?
Authors: Chang K. C. , Leung C. C. , Yew W. W. , Lau T. Y. , Leung W. M. , Tam C. M. , Lam H. C. , Tse P. S. , Wong M. Y. , Lee S. N. , Wat K. I. , Ma Y. H. 
Published: August 2009

Possible masking of tuberculosis (TB) in treatment of community-acquired respiratory infection by newer fluoroquinolones has not been examined in randomised controlled trials.We undertook a randomised, open-label controlled trial involving adults with community-acquired pneumonia or infective exacerbation of bronchiectasis encountered in government chest clinics in Hong Kong. 427 participants were assigned by random permutated blocks of 20 to receive either amoxicillin clavulanate (n = 212) or moxifloxacin (n = 215). Participants were followed for 1 yr for active pulmonary TB.Excluding three participants with positive baseline culture, 13 developed active pulmonary TB: 10 (4.8%) out of 210 were given amoxicillin clavulanate, and three (1.4%) out of 214 were given moxifloxacin. The difference was significant by both proportion and time-to-event analysis.Post hocanalysis showed a significant decrease in the proportion with active pulmonary TB from 4.8% to 2.4% and 0% among participants given amoxicillin clavulanate (n = 210), moxifloxacin for predominantly 5 days (n = 127) and 10 days (n = 87), respectively. The log rank test for trend also showed a significant difference between the three subgroups. Regression models reaffirmed the linear effect; the adjusted odds ratio (95% confidence interval) of active pulmonary TB after moxifloxacin exposure up to predominantly 10 days was 0.3 (0.1–0.9).Newer fluoroquinolones appear to mask active pulmonary TB.
Is treatment with ICS and LABA cost-effective for COPD? Multinational economic analysis of the TORCH study
Authors: Briggs A. H. , Glick H. A. , Lozano-Ortega G. , Spencer M. , Calverley P. M. A. , Jones P. W. , Vestbo J. 
Published: August 2009

The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed.For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region.SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400–123,500 USD). Estimates for SalmversusP (197,000 USD) and FPversusP (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFCversusP, the cost per QALY was 77,100 (46,200–241,700) USD compared to 24,200 (15,200–56,100) USD in Western Europe.Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.
Effect of manufacturer-inserted mask leaks on ventilator performance
Authors: Louis B. , Leroux K. , Isabey D. , Fauroux B. , Lofaso F. 
Published: August 2009

Most pressure-support devices use a single circuit with an exhalation port integrated in the mask. The aim of the current study was to compare the effects of masks having different manufacturer-inserted leaks on ventilator performance.We simulated chronic obstructive pulmonary disease and restrictive disease. Four ventilators (VENTImotion (Weinmann, Hamburg, Germany), VPAP III STA (ResMed, Saint Priest, France), Synchrony 2 (Respironics, Nantes, France) and Vivo 40 (Breas, Saint Priest)) were tested with the recommended masks and with the masks having the largest and smallest leaks. Tests were performed with pressure support levels of 10, 15 and 20 cmH2O. Thein vivoevaluation compared two ventilators using recommended masks opposed in terms of exhaled port resistance. The ventilators were tested with their recommended mask, and after mask exchange.The mask with the largest leak induced auto-triggering and/or increased inspiratory-trigger sensitivity was the VENTImotion under both simulated conditions and VPAP III STA under the simulated obstructive-disease condition. The mask with the smallest leak-increased inspiratory-trigger delay was Synchrony 2 in the simulated obstructive-disease condition and increased rebreathing. Thein vivostudy confirmed the bench results.When switching to a mask that has a different leak, evaluation is needed to adjust trigger sensitivity and pressurisation level and to check the absence of rebreathing.
Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis
Authors: Yogo Yurika , Fujishima Seitaro , Inoue Takashi , Saito Fumitake , Shiomi Takayuki , Yamaguchi Kazuhiro , Ishizaka Akitoshi 
Published: August 2009

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients.MethodsWe examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization.ResultsBAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients.ConclusionWe speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.
A reliable measure of similarity based on dependency for short time series: an application to gene expression networks
Authors: Campiteli Mônica G , Soriani Frederico M , Malavazi Iran , Kinouchi Osame , Pereira Carlos AB , Goldman Gustavo H 
Published: September 2009

Abstract

Background
Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges.

Results
The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions.

Conclusion
Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.
Endogenous Fms-like Tyrosine Kinase-3 Ligand levels are not altered in mice after a severe burn and infection
Authors: Bohannon Julia K , Cui Weihua , Toliver-Kinsky Tracy 
Published: September 2009

AbstractBackgroundFms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine and dendritic cell (DC) growth factor that promotes the proliferation and differentiation of progenitor cells into DCs. We have previously found that treatment of severely burned mice with recombinant Flt3L significantly enhances DC production and bacterial clearance from infected burn wounds, and increases global immune cell activation and survival in response to a burn wound infection. These significant benefits of Flt3L treatment after burn injury have prompted the question of whether or not severe burn injury induces deficits in endogenous Flt3L levels that could affect DCs and subsequent responses to infection.ResultsTo address this, male BALB/c mice received a 30% total body surface area scald burn. Blood, spleens, and wound-draining lymph nodes were harvested at various time-points after injury. Some mice received a wound inoculation withP. aeruginosa. Murine Flt3L and G-CSF levels were measured by ELISA. Burn injury had no significant effect on Flt3L levels at any post-burn time-point examined compared to normal Flt3L levels in the sera, spleen, or lymph nodes. Additionally, Flt3L levels in the sera, spleen, and lymph nodes were not significantly altered when wounds were inoculated on the day of burn injury or at post-burn time points examined. Alternatively, levels of G-CSF were increased in response to burn injury and burn wound infection. Additionally, DC numbers and functions were not altered following burn injury alone. There was no significant difference between the number of DCs in the spleens of sham-injured mice and mice at 5 days after burn injury. When naïve T cells from sham-injured mice were co-cultured with DCs from either sham- or burn-injured mice, IFN-γ production was similar, however, IFN-γ levels produced by T cells harvested from burn-injured mice were significantly lower than those produced by T cells from sham mice, regardless of which DC group, sham or burn, was used in the coculture.ConclusionThese data suggest that the beneficial effects of Flt3L treatments after burn injury are not due to correction of a burn-associated Flt3L deficiency but rather, are likely due to supplementary stimulation of DC production and immune responses to infection.
Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells
Authors: Hutzen Brian , Willis William , Jones Sarah , Cen Ling , Deangelis Stephanie , Fuh Beng , Lin Jiayuh 
Published: September 2009

AbstractThe Signal Transducer and Activator of Transcription (STAT) proteins comprise a family of latent transcription factors with diverse functions. STAT3 has well established roles in cell proliferation, growth and survival, and its persistent activation has been detected with high frequency in many human cancers. As constitutive activation of STAT3 appears to be vital for the continued survival of these cancerous cells, it has emerged as an attractive target for chemotherapeutics. We examined whether the inhibitory activities of bioactive compounds from cruciferous vegetables, such as Benzyl isothiocyanate (BITC) and sulforaphane, extended to STAT3 activation in PANC-1 human pancreatic cancer cells. BITC and sulforaphane were both capable of inhibiting cell viability and inducing apoptosis in PANC-1. Sulforaphane had minimal effect on the direct inhibition of STAT3 tyrosine phosphorylation, however, suggesting its inhibitory activities are most likely STAT3-independent. Conversely, BITC was shown to inhibit the tyrosine phosphorylation of STAT3, but not the phosphorylation of ERK1/2, MAPK and p70S6 kinase. These results suggest that STAT3 may be one of the targets of BITC-mediated inhibition of cell viability in PANC-1 cancer cells. In addition, we show that BITC can prevent the induction of STAT3 activation by Interleukin-6 in MDA-MB-453 breast cancer cells. Furthermore, combinations of BITC and sulforaphane inhibited cell viability and STAT3 phosphorylation more dramatically than either agent alone. These findings suggest that the combination of the dietary agents BITC and sulforaphane has potent inhibitory activity in pancreatic cancer cells and that they may have translational potential as chemopreventative or therapeutic agents.
Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75
Authors: Mediavilla-Varela Melanie , Pacheco Fabio J , Almaguel Frankis , Perez Jossymar , Sahakian Eva , Daniels Tracy R , Leoh Lai Sum , Padilla Amelia , Wall Nathan R , Lilly Michael B , De Leon Marino , Casiano Carlos A 
Published: August 2009

Abstract

Background
Hormone-refractory prostate cancer (HRPC) is characterized by poor response to chemotherapy and high mortality, particularly among African American men when compared to other racial/ethnic groups. It is generally accepted that docetaxel, the standard of care for chemotherapy of HRPC, primarily exerts tumor cell death by inducing mitotic catastrophe and caspase-dependent apoptosis following inhibition of microtubule depolymerization. However, there is a gap in our knowledge of mechanistic events underlying docetaxel-induced caspase-independent cell death, and the genes that antagonize this process. This knowledge is important for circumventing HRPC chemoresistance and reducing disparities in prostate cancer mortality.

Results
We investigated mechanistic events associated with docetaxel-induced death in HRPC cell lines using various approaches that distinguish caspase-dependent from caspase-independent cell death. Docetaxel induced both mitotic catastrophe and caspase-dependent apoptosis at various concentrations. However, caspase activity was not essential for docetaxel-induced cytotoxicity since cell death associated with lysosomal membrane permeabilization still occurred in the presence of caspase inhibitors. Partial inhibition of docetaxel-induced cytotoxicity was observed after inhibition of cathepsin B, but not inhibition of cathepsins D and L, suggesting that docetaxel induces caspase-independent, lysosomal cell death. Simultaneous inhibition of caspases and cathepsin B dramatically reduced docetaxel-induced cell death. Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75), a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal destabilization and cell death. Interestingly, LEDGF/p75 overexpression did not protect cells against DTX-induced mitotic catastrophe, and against apoptosis induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL), suggesting selectivity in its pro-survival activity.

Conclusion
These results underscore the ability of docetaxel to induce concomitantly caspase-dependent and independent death pathways in prostate cancer cells. The results also point to LEDGF/p75 as a potential contributor to cellular resistance to docetaxel-induced lysosomal destabilization and cell death, and an attractive candidate for molecular targeting in HRPC.
Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues
Authors: Li Ning , Long Yunzhu , Fan Xuegong , Liu Hongbo , Li Cui , Chen Lizhang , Wang Zhiming 
Published: August 2009

Abstract

Background
Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues.

Methods
Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB)-developed HCC were analyzed by two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and the results were compared to those of paired adjacent non-tumorous liver tissues.

Results
A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC.

Conclusion
These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.
Cretaceous paleogeography, paleoclimatology, and amniote biogeography of the low and mid-latitude South Atlantic Ocean
Authors: Jacobs Louis L. , Mateus Octávio , Polcyn Michael J. , Schulp Anne S. , Scotese Christopher R. , Goswami Argyha , Ferguson Kurt M. , Robbins John A. , Vineyard Diana P. , Buto Neto André 
Published: September 2009

AbstractThe Cretaceous tropical Atlantic Ocean was the setting for an initial tectonically controlled late Aptian shallow water (≤ 300 m) connection between the northern and southern portions of the Atlantic, followed by a deep-water connection by the Turonian. Ocean currents changed with deepening of the South Atlantic and progressive widening of the Equatorial Atlantic Gateway. Aptian evaporite deposition came to a halt. The Albian-Turonian interval includes a trend toward increasing sea level and was characterized by globally warm sea surface temperatures. Productive areas of coastal upwelling led to the deposition of organic-rich sediments varying in position along the African coast with time, culminating in the Benguela Upwelling that commenced in the Miocene. The drift of Africa in the Late Cretaceous indicates that throughout most of this period, the coastal area around the fossil locality of Iembe, north of Luanda, Angola, lay in arid latitudes (15o S to 30o S), which are generally characterized by sparse vegetation. This presumption is consistent with the utter lack of macroscopic terrestrial plant debris washed into near shore sedimentary environments and indicates that organic rich marine shales have a minimal terrestrial carbon component. The connection of the North and South Atlantic oceans severed a direct terrestrial dispersal route between South America and Africa, but opened a north-south dispersal route for marine amniotes. This seaway was used by late Turonian mosasaurs and sea turtles as evidenced by Angolasaurus and a new turtle taxon close to Sandownia, both found at Iembe and derived from northern clades. The presence of a sauropod in late Turonian sediments, also from Iembe, suggests that this animal was tolerant of warm, arid conditions as the desert elephants of Namibia are today. Further, it suggests that the waning terrestrial dispersal route between South America and Africa was situated in a region where high temperature, low rainfall, and sparse vegetation would be expected to restrict the movement of more mesic and ecologically sensitive species.