bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel orthotopic implantation model of human malignant pleural mesothelioma (EHMES‐10 cells) highly expressing vascular endothelial growth factor and its receptor
Authors: Nakataki Emiko , Yano Seiji , Matsumori Yuka , Goto Hisatsugu , Kakiuchi Soji , Muguruma Hiroaki , Bando Yoshimi , Uehara Hisanori , Hamada Hironobu , Kito Katsumi , Yokoyama Akihito , Sone Saburo 
Published: March 2006

Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients in Japan is estimated in the years 2010–2050. The purpose of the present study was to establish a clinically relevant animal model that shows human patient‐like progression of MPM. Here, we demonstrate that a human MPM cell line (EHMES‐10) inoculated orthotopically (thoracic cavity) into severe combined immunodeficiency (SCID) mice produces highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks, suggesting a patient‐like progression of this cell line after orthotopic inoculation. EHMES‐10 cells overexpressed vascular endothelial growth factor (VEGF), a molecule responsible for malignant effusions, and its receptor. Treatment with cisplatin, but not gemcitabine, significantly inhibited the production of pleural effusions, but it was not effective for thoracic tumors, consistent with chemotherapy refractory characteristics of MPM in patients. Our patient‐like orthotopic model using EHMES‐10 cells overexpressing VEGF and its receptor may be useful for examining the molecular pathogenesis of MPM and may contribute to the development of novel treatment strategies for MPM. (Cancer Sci2006; 97: 183 –191)
Pharmacokinetics and pharmacodynamics of protein‐unbound docetaxel in cancer patients
Authors: Minami Hironobu , Kawada Kenji , Sasaki Yasutsuna , Igarashi Tadahiko , Saeki Toshiaki , Tahara Makoto , Itoh Kuniaki , Fujii Hirofumi 
Published: March 2006

α1‐Acid glycoprotein, a plasma protein that binds docetaxel, is a significant determinant of the clearance and activity of docetaxel, but its serum levels in cancer patients are variable. This emphasizes the importance of investigating the pharmacokinetics of unbound drug rather than total drug in the plasma. In the present study, the pharmacokinetics and pharmacodynamics of unbound docetaxel were investigated in cancer patients. Docetaxel was infused over a 1‐h period in 69 patients. The concentration of unbound docetaxel was measured in the plasma ultrafiltrate at the end of infusion and the unbound fraction (fu) was calculated. The pharmacokinetics of total docetaxel in the plasma was investigated. The area under the concentration–time curve (AUC) of unbound docetaxel was calculated by multiplying fu by the AUC of total docetaxel. The peak concentration at the end of infusion (Cmax) and AUC of total and unbound drug were compared between patients who did or did not experience grade 4 neutropenia. The median of fu was 4.0%, ranging from 1.2 to 22.6% (5–95% percentile; 1.4–10.5%). Grade 4 neutropenia was observed in 24 patients. Although Cmax and AUC of total drug were not different in patients with or without grade 4 neutropenia, patients who experienced grade 4 neutropenia had significantly greater Cmax (92.3 vs 63.3 ng/mL, P = 0.01) and AUC (0.137 vs 0.104 µg × h/mL, P = 0.05) of unbound docetaxel. In a logistic regression analysis, the unbound Cmax and α1‐acid glycoprotein were determinants of grade 4 neutropenia. Pharmacokinetics of unbound drug rather than total drug is a better predictor of neutropenia for docetaxel. (Cancer Sci 2006; 97: 235–241)
Propagation of orographic barriers along an active range front: insights from sandstone petrography and detrital apatite fission‐track thermochronology in the intramontane Angastaco basin, NW Argentina
Authors: Coutand Isabelle , Carrapa Barbara , Deeken Anke , Schmitt Axel K. , Sobel Edward R. , Strecker Manfred R. 
Published: March 2006

ABSTRACTThe arid Puna plateau of the southern Central Andes is characterized by Cenozoic distributed shortening forming intramontane basins that are disconnected from the humid foreland because of the defeat of orogen‐traversing channels. Thick Tertiary and Quaternary sedimentary fills in Puna basins have reduced topographic contrasts between the compressional basins and ranges, leading to a typical low‐relief plateau morphology. Structurally identical basins that are still externally drained straddle the eastern border of the Puna and document the eastward propagation of orographic barriers and ensuing aridification. One of them, the Angastaco basin, is transitional between the highly compartmentalized Puna highlands and the undeformed Andean foreland. Sandstone petrography, structural and stratigraphic analysis, combined with detrital apatite fission‐track thermochronology from a ∼6200‐m‐thick Miocene to Pliocene stratigraphic section in the Angastaco basin, document the late Eocene to late Pliocene exhumation history of source regions along the eastern border of the Puna (Eastern Cordillera (EC)) as well as the construction of orographic barriers along the southeastern flank of the Central Andes.Onset of exhumation of a source in the EC in late Eocene time as well as a rapid exhumation of the Sierra de Luracatao (in the EC) at about 20 Ma are recorded in the detrital sediments of the Angastaco basin. Sediment accumulation in the basin began ∼15 Ma, a time at which the EC had already built sufficient topography to prevent Puna sourced detritus from reaching the basin. After ∼13 Ma, shortening shifted eastward, exhuming ranges that preserve an apatite fission‐track partial annealing zone recording cooling during the late Cretaceous rifting event. Facies changes and fossil content suggest that after 9 Ma, the EC constituted an effective orographic barrier that prevented moisture penetration into the plateau. Between 3.4 and 2.4 Ma, another orographic barrier was uplifted to the east, leading to further aridification and pronounced precipitation gradients along the mountain front. This study emphasizes the important role of tectonics in the evolution of climate in this part of the Andes.
Atmospheric nitrogen deposition in world biodiversity hotspots: the need for a greater global perspective in assessing N deposition impacts
Authors: PHOENIX GARETH K. , HICKS W. KEVIN , CINDERBY STEVE , KUYLENSTIERNA JOHAN C. I. , STOCK WILLIAM D. , DENTENER FRANK J. , GILLER KEN E. , AUSTIN AMY T. , LEFROY ROD D. B. , GIMENO BEN S. , ASHMORE MIKE R. , INESON PHILIP 
Published: March 2006

AbstractIncreased atmospheric nitrogen (N) deposition is known to reduce plant diversity in natural and semi‐natural ecosystems, yet our understanding of these impacts comes almost entirely from studies in northern Europe and North America. Currently, we lack an understanding of the threat of N deposition to biodiversity at the global scale. In particular, rates of N deposition within the newly defined 34 world biodiversity hotspots, to which 50% of the world's floristic diversity is restricted, has not been quantified previously. Using output from global chemistry transport models, here we provide the first estimates of recent (mid‐1990s) and future (2050) rates and distributions of N deposition within biodiversity hotspots. Our analysis shows that the average deposition rate across these areas was 50% greater than the global terrestrial average in the mid‐1990s and could more than double by 2050, with 33 of 34 hotspots receiving greater N deposition in 2050 compared with 1990. By this time, 17 hotspots could have between 10% and 100% of their area receiving greater than 15 kg N ha−1 yr−1, a rate exceeding critical loads set for many sensitive European ecosystems. Average deposition in four hotspots is predicted to be greater than 20 kg N ha−1 yr−1. This elevated N deposition within areas of high plant diversity and endemism may exacerbate significantly the global threat of N deposition to world floristic diversity. Overall, we highlight the need for a greater global approach to assessing the impacts of N deposition.
Soil‐atmospheric exchange of CO2, CH4, and N2O in three subtropical forest ecosystems in southern China
Authors: TANG XULI , LIU SHUGUANG , ZHOU GUOYI , ZHANG DEQIANG , ZHOU CUNYU 
Published: March 2006

AbstractThe magnitude, temporal, and spatial patterns of soil‐atmospheric greenhouse gas (hereafter referred to as GHG) exchanges in forests near the Tropic of Cancer are still highly uncertain. To contribute towards an improvement of actual estimates, soil‐atmospheric CO2, CH4, and N2O fluxes were measured in three successional subtropical forests at the Dinghushan Nature Reserve (hereafter referred to as DNR) in southern China. Soils in DNR forests behaved as N2O sources and CH4 sinks. Annual mean CO2, N2O, and CH4 fluxes (mean±SD) were 7.7±4.6 Mg CO2‐C ha−1 yr−1, 3.2±1.2 kg N2O‐N ha−1 yr−1, and 3.4±0.9 kg CH4‐C ha−1 yr−1, respectively. The climate was warm and wet from April through September 2003 (the hot‐humid season) and became cool and dry from October 2003 through March 2004 (the cool‐dry season). The seasonality of soil CO2 emission coincided with the seasonal climate pattern, with high CO2 emission rates in the hot‐humid season and low rates in the cool‐dry season. In contrast, seasonal patterns of CH4 and N2O fluxes were not clear, although higher CH4 uptake rates were often observed in the cool‐dry season and higher N2O emission rates were often observed in the hot‐humid season. GHG fluxes measured at these three sites showed a clear increasing trend with the progressive succession. If this trend is representative at the regional scale, CO2 and N2O emissions and CH4 uptake in southern China may increase in the future in light of the projected change in forest age structure. Removal of surface litter reduced soil CO2 effluxes by 17–44% in the three forests but had no significant effect on CH4 absorption and N2O emission rates. This suggests that microbial CH4 uptake and N2O production was mainly related to the mineral soil rather than in the surface litter layer.
High thermal acclimation potential of both photosynthesis and respiration in two lowland Plantago species in contrast to an alpine congeneric
Authors: ATKIN O. K. , SCHEURWATER I. , PONS T. L. 
Published: March 2006

AbstractThermal acclimation of photosynthesis and respiration can enable plants to maintain near constant rates of net CO2 exchange, despite experiencing sustained changes in daily average temperature. In this study, we investigated whether the degree of acclimation of photosynthesis and respiration of mature leaves differs among three congeneric Plantago species from contrasting habitats [two fast‐growing lowland species (Plantago major and P. lanceolata), and one slow‐growing alpine species (P. euryphylla)]. In addition to investigating some mechanisms underpinning variability in photosynthetic acclimation, we also determined whether leaf respiration in the light acclimates to the same extent as leaf respiration in darkness, and whether acclimation reestablishes the balance between leaf respiration and photosynthesis. Three growth temperatures were provided: constant 13, 20, or 27°C. Measurements were made at five temperatures (6–34°C). Little acclimation of photosynthesis and leaf respiration to growth temperature was exhibited by P. euryphylla. Moreover, leaf masses per area (LMA) were similar in 13°C‐grown and 20°C‐grown plants of the alpine species. In contrast, growth at 13°C increased LMA in the two lowland species; this was associated with increased photosynthetic capacity and rates of leaf respiration (both in darkness and in the light). Alleviation of triose phosphate limitation and increased capacity of electron transport capacity relative to carboxylation were also observed. Such changes demonstrate that the lowland species cold‐acclimated. Light reduced the short‐term temperature dependence (i.e. Q10) of leaf respiration in all three species, irrespective of growth temperature. Collectively, our results highlight the tight coupling that exists between thermal acclimation of photosynthetic and leaf respiratory metabolism (both in darkness and in the light) in Plantago. If widespread among contrasting species, such coupling may enable modellers to assume levels of acclimation in one parameter (e.g. leaf respiration) where details are only known for the other (e.g. photosynthesis).
The distributions of a wide range of taxonomic groups are expanding polewards
Authors: HICKLING RACHAEL , ROY DAVID B. , HILL JANE K. , FOX RICHARD , THOMAS CHRIS D. 
Published: March 2006

AbstractEvidence is accumulating of shifts in species' distributions during recent climate warming. However, most of this information comes predominantly from studies of a relatively small selection of taxa (i.e., plants, birds and butterflies), which may not be representative of biodiversity as a whole. Using data from less well‐studied groups, we show that a wide variety of vertebrate and invertebrate species have moved northwards and uphill in Britain over approximately 25 years, mirroring, and in some cases exceeding, the responses of better‐known groups.
Evaluating disease management programme effectiveness: an introduction to the regression discontinuity design
Authors: Linden Ariel , Adams John L. , Roberts Nancy 
Published: March 2006

AbstractAlthough disease management (DM) has been in existence for over a decade, there is still much uncertainty as to its effectiveness in improving health status and reducing medical cost. The main reason is that most programme evaluations typically follow weak observational study designs that are subject to bias, most notably selection bias and regression to the mean. The regression discontinuity (RD) design may be the best alternative to randomized studies for evaluating DM programme effectiveness. The most crucial element of the RD design is its use of a ‘cut‐off’ score on a pre‐test measure to determine assignment to intervention or control. A valuable feature of this technique is that the pre‐test measure does not have to be the same as the outcome measure, thus maximizing the programme's ability to use research‐based practice guidelines, survey instruments and other tools to identify those individuals in greatest need of the programme intervention. Similarly, the cut‐off score can be based on clinical understanding of the disease process, empirically derived, or resource‐based. In the RD design, programme effectiveness is determined by a change in the pre–post relationship at the cut‐off point. While the RD design is uniquely suitable for DM programme evaluation, its success will depend, in large part, on fundamental changes being made in the way DM programmes identify and assign individuals to the programme intervention.
Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis
Authors: Linden Ariel 
Published: March 2006

AbstractDiagnostic or predictive accuracy concerns are common in all phases of a disease management (DM) programme, and ultimately play an influential role in the assessment of programme effectiveness. Areas, such as the identification of diseased patients, predictive modelling of future health status and costs and risk stratification, are just a few of the domains in which assessment of accuracy is beneficial, if not critical. The most commonly used analytical model for this purpose is the standard 2 × 2 table method in which sensitivity and specificity are calculated. However, there are several limitations to this approach, including the reliance on a single defined criterion or cut‐off for determining a true‐positive result, use of non‐standardized measurement instruments and sensitivity to outcome prevalence. This paper introduces the receiver operator characteristic (ROC) analysis as a more appropriate and useful technique for assessing diagnostic and predictive accuracy in DM. Its advantages include; testing accuracy across the entire range of scores and thereby not requiring a predetermined cut‐off point, easily examined visual and statistical comparisons across tests or scores, and independence from outcome prevalence. Therefore the implementation of ROC as an evaluation tool should be strongly considered in the various phases of a DM programme.
Referral to and discharge from cardiac rehabilitation: key informant views on continuity of care
Authors: Grace Sherry L. , Krepostman Suzan , Brooks Dina , Jaglal Susan , Abramson Beth L. , Scholey Pat , Suskin Neville , Arthur Heather , Stewart Donna E. 
Published: March 2006

AbstractObjectives  To assess the system‐level barriers and facilitators of continuity of care from acute care to cardiac rehabilitation (CR), and from CR discharge to follow‐up with primary health care providers.Method  Semi‐structured individual interviews with 24 key informants including CR staff, research scientists, policy makers, cardiologists and other doctors from a regional to international level were conducted regarding the processes of referral to and discharge from cardiac rehabilitation. Key informant interviews were audio taped, transcribed, and imported into QSR N6 software for Grounded analysis.Results  Themes that emerged related to communication, referral and discharge processes, health care provider practices, inter‐ and intra‐institutional relationships, and alternative models of delivery to improve continuity.Conclusions  Ramifications for enhancing referral of patients to beneficial CR services and follow‐up by primary care providers to ensure maintenance of functional and health‐related gains are discussed.
Quality and productive efficiency in simple laceration treatment
Authors: Kuwabara Kazuaki , Imanaka Yuichi , Ishizaki Tatsuro 
Published: March 2006

AbstractObjectives  The surgical management and outcome of outpatient care for patients with simple lacerations were compared across three institutions. We examined the variations in wound infection rate, total charge and medical resource use in terms of prophylactic antibiotic prescription, frequency of outpatient visits and required days for stitch removal.Design  Retrospective and consecutive chart review.Study participants Patients receiving treatment for simple lacerations in the outpatient departments of three institutions in Japan between June 2000 and August 2001.Outcome measures and method  The basic patient characteristics, treatment method for the laceration and incidence of wound infection were collected. Variations in the wound infection rate were examined across the institutions. We then examined the variations in the medical resource use and total charge for patients without wound infection among the institutions by multiple linear regression model.Results  A total of 479 patients were reviewed. The proportion of patients with blunt injury, patients with simple lacerations to the head or face, and those with underlying medical disease were significantly different among the three institutions. The wound infection rate did not significantly differ (1.9% in Institution A, 1.3% in B, 3.0% in C, P = 0.555). The medical resource use for patients without wound infection was significantly different and small in Institution A.Conclusion  We identified variations in the resource use for completing wound care among three institutions, whereas the wound infection rate revealed no significant difference among the institutions. There existed some room for improvement in the productive efficiency of simple laceration treatment.
In tobacco leaf epidermal cells, the integrity of protein export from the endoplasmic reticulum and of ER export sites depends on active COPI machinery
Authors: Stefano Giovanni , Renna Luciana , Chatre Laurent , Hanton Sally L. , Moreau Patrick , Hawes Chris , Brandizzi Federica 
Published: March 2006

SummaryTrafficking of secretory proteins between the endoplasmic reticulum (ER) and the Golgi apparatus depends on coat protein complexes I (COPI) and II (COPII) machineries. To date, full characterization of the distribution and dynamics of these machineries in plant cells remains elusive. Furthermore, except for a presumed linkage between COPI and COPII for the maintenance of ER protein export, the mechanisms by which COPI influences COPII‐mediated protein transport from the ER in plant cells are largely uncharacterized. Here we dissect the dynamics of COPI in intact cells using live‐cell imaging and fluorescence recovery after photobleaching analyses to provide insights into the distribution of COPI and COPII machineries and the mechanisms by which COPI influences COPII‐mediated protein export from the ER. We found that Arf1 and coatomer are dynamically associated with the Golgi apparatus and that the COPII coat proteins Sec24 and Sec23 localize at ER export sites that track with the Golgi apparatus in tobacco leaf epidermal cells. Arf1 is also localized at additional structures that originate from the Golgi apparatus but that lack coatomer, supporting the model that Arf1 also has a coatomer‐independent role for post‐Golgi protein transport in plants. When ER to Golgi protein transport is inhibited by mutations that hamper Arf1‐GTPase activity without directly disrupting the COPII machinery for ER protein export, Golgi markers are localized in the ER and the punctate distribution of Sec24 and Sec23 at the ER export sites is lost. These findings suggest that Golgi membrane protein distribution is maintained by the balanced action of COPI and COPII systems, and that Arf1‐coatomer is most likely indirectly required for forward trafficking out of the ER due to its role in recycling components that are essential for differentiation of the ER export domains formed by the Sar1‐COPII system.
Improved knowledge and practices among end‐users of mother‐to‐child transmission of HIV prevention services in rural Zimbabwe
Authors: Orne‐Gliemann J. , Mukotekwa T. , Perez F. , Miller A. , Sakarovitch C. , Glenshaw M. , Engelsmann B. , Dabis F. 
Published: March 2006

SummaryObjective  To evaluate the influence of a prevention of mother‐to‐child transmission of HIV advocacy and mobilization campaign on awareness and knowledge levels within the community.Method  We used a knowledge, attitudes and practices survey to collect baseline data in November 2002 and again in July 2004 for evaluation purposes.Results  A total of 351 women attending healthcare services were interviewed each time. The proportion of women aware of the service increased from 48.0% in 2002 to 82.8% in 2004 (OR = 4.9, 95% CI 3.3–7.3, P = 0.001). Exclusive breastfeeding was identified as a mother‐to‐child transmission risk factor by 27.1% in 2002 and by 55.8% of respondents in 2004 (OR = 2.9, CI 2.1–4.2, P = 0.001). Although most interviewees agreed that the prevention of sexual transmission of HIV was the best strategy for prevention of mother‐to‐child transmission of HIV (88.3% in 2002 and 96.4% in 2004), few reported having ever used a male condom (24.8% in 2002 vs. 29.8% in 2004, P = 0.16).Discussion  Prevention of mother‐to‐child transmission of HIV strategies at both individual and community level were still insufficiently understood and applied. Targeted educational messages and communication for social change need to be combined. Knowledge, attitudes and practices surveys can be used to monitor programme progress.