bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of sorafenib in patients with relapsed or refractory lymphoma
Authors: Guidetti Anna , Carlo‐Stella Carmelo , Locatelli Silvia L. , Malorni Walter , Pierdominici Marina , Barbati Cristiana , Mortarini Roberta , Devizzi Lilli , Matteucci Paola , Marchianò Alfonso , Lanocita Rodolfo , Farina Lucia , Dodero Anna , Tarella Corrado , Di Nicola Massimo , Corradini Paolo , Anichini Andrea , Gianni Alessandro M. 
Published: May 2012

SummaryThe safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18–74) received a median of 4 months of therapy. Grade 3–4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal‐regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.
De novo childhood myelodysplastic/myeloproliferative disease with unique molecular characteristics
Authors: Ismael Olfat , Shimada Akira , Hama Asahito , Elshazley Momen , Muramatsu Hideki , Goto Aya , Sakaguchi Hirotoshi , Tanaka Makito , Takahashi Yoshiyuki , Yinyan Xu , Fukuda Minoru , Miyajima Yuji , Yamashita Yuka , Horibe Keizo , Hanada Ryoji , Ito Masafumi , Kojima Seiji 
Published: May 2012

SummaryMyelodysplastic/myeloproliferative uclassifiable (MDS/MPN‐U) is a rare myeloid neoplasm characterized by myelodysplasia and myeloproliferation at the time of initial presentation, which is usually a diagnosis of exclusion. The molecular pathogenesis of MDS/MPN‐U patients remains to be elucidated. Among five patients diagnosed with MDS/MPN‐U, three patients harboured RUNX1 (AML1) mutations; one carried somatic mosaicism of RUNX1 mutation with JAK2V617F mutation and one had dual RUNX1 and FLT3‐internal tandem duplication mutations with progression to acute myeloid leukaemia (AML). Germline mutation of TP53 was detected as a sole genetic lesion in one patient. JAK2V617F and somatic mosaicism of KRAS and TET2 mutations co‐existed in one patient. Otherwise, no alterations were detected in PTPN11, NRAS, CBL and ASXL1 genes. ETV6‐PDGFRB fusion transcript was not detected in all patients. Four patients recieved haematopoietic stem cell transplantation (HSCT); three patients relapsed and one achieved complete remission after three donor lymphocyte infusions. Our findings suggest that the mutational spectrum observed in childhood MDS/MPN‐U is quite different from that seen in juvenile myelomonocytic leukaemia and, to some extent, resemble chronic myelomonocytic leukaemia. Moreover, two patients had constitutional alterations of genes frequently found in AML. Further investigations are required to define the roles of these genetic alterations in the pathogenesis of childhood MDS/MPN‐U.
Short‐ and long‐term risks of splenectomy for benign haematological disorders: should we revisit the indications?
Authors: Rodeghiero Francesco , Ruggeri Marco 
Published: May 2012

SummarySplenectomy has represented a key treatment option in the treatment of many benign haematological diseases, including immune thrombocytopenia (ITP) and disorders associated with ongoing haemolysis (thalassaemia major and intermedia, sickle cell disease, and hereditary or acquired haemolytic anaemias). Improvements in surgical techniques have reduced perioperative complications and mortality. Preventive measures (new protein conjugate vaccines, antibiotic prophylaxis, and increased vigilance) are thought to greatly reduce the risk of overwhelming post‐splenectomy infection (OPSI), although their implementation is inconsistent. Nevertheless, there is increasing documentation of the short‐ and long‐term risks of splenectomy, which vary according to the underlying indication. Splenectomized patients are at increased risk of venous thromboembolism, particularly within the splenoportal system. The long‐term thromboembolic risk is higher in haematological disorders associated with ongoing haemolysis, particularly in thalassaemia intermedia, which has led to a more conservative approach. In comparison, patients with ITP appear to be at lower risk of adverse effects of splenectomy, which maintains its place as the potentially most curative and safe second‐line treatment. However, a splenectomy‐sparing approach is also emerging for ITP, and recent guidelines recommend that this procedure is deferred until ≥12 months from ITP diagnosis, to allow sufficient time for possible remission.
Bortezomib combined with low‐dose cytarabine in Intermediate‐2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM
Authors: Natarajan‐Amé Shanti , Park Sophie , Ades Lionel , Vey Norbert , Guerci‐Bresler Agnès , Cahn Jean‐Yves , Etienne Gabriel , Bordessoule Dominique , Ravoet Christophe , Legros Laurence , Cheze Stephane , Stamatoullas Aspasia , Berger Elisabeth , Schmidt Aline , Charbonnier Aude , Chaury Marie‐Pierre , Braun Thorsten , Fenaux Pierre , Dreyfus Francois ,   on behalf of the Groupe Francophone des Myélodysplasies (GFM)
Published: May 2012

SummaryMarrow cells from patients with higher‐risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)‐κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher‐risk MDS patients with bortezomib (1·5 mg/m2, days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m2, then 20 mg/m2 from days 1–14), every 28 d for four cycles. Median follow‐up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow‐CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow‐CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1–2 pre‐treatment haematotoxicity developed Grade 3–4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher‐risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.
Synergies and tensions in child protection and parent support: policy lines and practitioners cultures1
Authors: Fargion Silvia 
Published: May 2012

ABSTRACTSocial workers' interventions in support of children and their families have often proved a minefield of sort, filled up with conflicting demands, expectations and tasks. This paper sets the resulting debate in the context of both social policy orientations and social work cultures. It argues that partnerships between families and practitioners have to be understood as the result of a complex set of factors. Data from a qualitative study of social work professional cultures suggest that among practitioners, policy orientations intertwine with different styles of conceiving social work; accordingly, professional cultures play an important part in connecting, or failing to connect, child protection and family support.
Effects of Leishmania major clones showing different levels of virulence on infectivity, differentiation and maturation of human dendritic cells
Authors: Markikou-Ouni W , Ben Achour-Chenik Y , Meddeb-Garnaoui A 
Published: May 2012

Summary
Leishmania parasites and dendritic cell interactions (DCs) play an essential role in initiating and directing T cell responses and influence disease evolution. These interactions may vary depending on Leishmania species and strains. To evaluate the correlation between Leishmania major (Lm) virulence and in-vitro human DC response, we compared the ability of high (HV) and low virulent (LV) Lm clones to invade, modulate cytokine production and interfere with differentiation of DCs. Clones derived from HV and LV (HVΔlmpdi and LVΔlmpdi), and deleted for the gene coding for a Lm protein disulphide isomerase (LmPDI), probably involved in parasite natural pathogenicity, were also used. Unlike LV, which fails to invade DCs in half the donors, HV promastigotes were associated with a significant increase of the infected cells percentage and parasite burden. A significant decrease of both parameters was observed in HVΔlmpdi-infected DCs, compared to wild-type cells. Whatever Lm virulence, DC differentiation was accompanied by a significant decrease in CD1a expression. Lm clones decreased interleukin (IL)-12p70 production similarly during lipopolysaccharide (LPS)-induced maturation of DCs. LPS stimulation was associated with a weak increase in tumour necrosis factor (TNF)-α and IL-10 productions in HV-, HVΔlmpdi- and LVΔlmpdi-infected DCs. These results indicate that there is a significant variability in the capacity of Lm clones to infect human DCs which depends upon their virulence, probably involving LmPDI protein. However, independently of their virulence, Lm clones were able to down-regulate CD1a expression during DC differentiation and IL-12p70 production during DC maturation, which may favour their survival.
Rapid loss of fat but not lean mass prior to chick provisioning supports the flight efficiency hypothesis in tree swallows
Authors: Boyle W. Alice , Winkler David W. , Guglielmo Christopher G. 
Published: May 2012

Summary1. Birds often lose body mass during nesting. Determining whether this mass loss represents an energetic cost of reproduction (energetic stress hypothesis), serves an adaptive function (flight efficiency hypothesis), or results from physiological processes that are neutral with respect to fitness (e.g. gonadal regression hypothesis) is important to interpreting variation in body mass and energy stores in the context of life‐history theory.2. New quantitative magnetic resonance technology enables precise, repeated measurements of body composition (fat, lean, and water masses) on the same individuals, and we used this method to test a series of predictions to distinguish among competing hypotheses explaining mass loss in female tree swallows (Tachycineta bicolor, Vieillot, 1808).3. Tree swallows lost mass abruptly prior to the peak foraging demands of feeding chicks. Lean mass and fat mass losses varied independently, with small and gradual losses in lean mass during incubation and dramatic losses of fat immediately prior to and following hatching. Females lost some body water early in incubation, but did not lose more water when brood patches would be expected to atrophy. The period of greatest parental foraging costs was not associated with any significant changes in total body mass, lean mass, fat mass or water. Net change in body mass from early incubation until mid‐way through chick rearing was associated strongly with initial body mass and to a lesser degree, brood size.4. These findings are consistent with the flight efficiency hypothesis. Females appear to facultatively modulate their endogenous energy stores to maximize insurance against bad weather and poor foraging opportunities during incubation, but then lower their body mass to maximize efficiency once chicks hatch, thereby reducing the costs of feeding nestlings.5. This study corroborates results of a growing number of studies of small, insectivorous birds (especially cavity‐nesting species), suggesting that increases in mass prior to reproduction (and the subsequent loss of that mass) are likely best viewed as part of an adaptive suite of interrelated reproductive decisions made by females each year.
A tilted transversely isotropic slowness surface approximation
Authors: Stovas A. , Alkhalifah T. 
Published: May 2012

ABSTRACTThe relation between vertical and horizontal slownesses, better known as the dispersion relation, for transversely isotropic media with a tilted symmetry axis (TTI) requires solving a quartic polynomial equation, which does not admit a practical explicit solution to be used, for example, in downward continuation. Using a combination of the perturbation theory with respect to the anelliptic parameter and Shanks transform to improve the accuracy of the expansion, we develop an explicit formula for the vertical slowness that is highly accurate for all practical purposes. It also reveals some insights into the anisotropy parameter dependency of the dispersion relation including the low impact that the anelliptic parameter has on the vertical placement of reflectors for a small tilt in the symmetry angle.
Study on the flavour of soybean cultivars by sensory analysis and electronic tongue
Authors: Da Silva Josemeyre , Prudencio Sandra , Carrão‐Panizzi Mercedes , Gregorut Camila , Fonseca Fernando , Mattoso Luiz 
Published: May 2012

SummaryThe scope of this study was to assess the sensory attributes of five Brazilian soybean cultivars genetically different (BRS), described as special soybean cultivars for human consumption (BRS 216, BRS 213 and BRS 267) and conventional (BRS 258 and BRS 133), by quantitative descriptive analysis (QDA), and verify the ability of the electronic tongue to discriminate the soybean cultivars according to its flavours. According to QDA, BRS 267 was characterised by increased grain size, more intense cream colour, sweet flavour, sweet and umami taste. BRS 133 showed a dark hilum colouring, cooked bean and rancid aroma, cooked bean and rancid, bitter and astringent attributes. BRS 216 presented smaller grain size, less intense cream colouring and a more rounded grain shape, while the BRS 258 showed a hard texture. BRS 213 was characterised by a neutral flavour. The electronic tongue was able to distinguish between the five soybean cultivars according to their different flavour attributes. Correlation analysis was made among chemical constituents of soybean (hexanal, linoleic and linolenic acid, isoflavones, sucrose and fructose, and glutamic acid and alanine), sensory attributes and electronic sensors. Sensory attributes had a significant correlation, in absolute value, P ≤ 0.05, with electronic tongue (r = 0.50–0.80) and chemical constituents of soybean grains (r = 0.51–0.98). Electronic tongue had a significant correlation (r = 0.50–0.94) with the chemical constituents. It can be used effectively to classify soybean cultivars.
Potential of non‐GMO biofortified pearl millet (Pennisetum glaucum) for increasing iron and zinc content and their estimated bioavailability during abrasive decortication
Authors: Hama Fatoumata , Icard‐Vernière Christèle , Guyot Jean‐Pierre , Rochette Isabelle , Diawara Bréhima , Mouquet‐Rivier Claire 
Published: May 2012

SummaryTwo non‐GMO biofortified and one traditional pearl millet varieties were compared in abrasive decortication studies to evaluate their potential for increasing iron and zinc content. The phytate‐to‐mineral ratios were used to estimate mineral bioavailability. Iron and zinc contents in the biofortified varieties Tabi and GB8735 were two to threefold higher than in the traditional variety. Iron content reached 7.2 and 6.7 mg per 100 g DM in the biofortified varieties, which corresponds to the target values of biofortification programs. Zinc content was, respectively, 5.6 and 4.1 mg per 100 g DM in the GB8735 and Tabi varieties. Because of the presence of phytate and other chelating factors that were only partially removed during decortication, there was no improvement in iron bioavailability in the biofortified varieties. But whatever extraction rate, phytate‐to‐zinc ratios ranged between 6 and 18; zinc absorption could be improved by using these biofortified varieties for food processing.
Extraction of saponin from Camellia oleifera cake and evaluation of its antioxidant activity
Authors: Hu Jie‐Lun , Nie Shao‐Ping , Huang Dan‐Fei , Li Chang , Xie Ming‐Yong 
Published: May 2012

SummaryResponse surface methodology was employed to optimise extraction conditions of saponins from Camellia oleifera cake. Optimal conditions were extraction at 82.2 °C for 3.3 h with an 8.6:1 ratio (mL g−1) of solvent to solid. The saponin extract was further extracted with n‐butanol, and nine saponins were found as the main components. The identification of these saponins was carried out by HPLC–ESI–MS, and their possible structures were given. Antioxidant activities of the saponins were evaluated in vitro by 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH), 1, 2, 3‐phentriol self‐oxidation and metal chelating activity assays. IC50 value of each assay was 3866 ± 3, 4744 ± 2 and 2389 ± 2 μg mL−1, respectively. The effects of environmental factors on antioxidant activity of saponins from C. oleifera cake were studied for the first time. The antioxidant activity is pH dependent with 9.0 as the optimal pH and is also temperature independent.
Frog population viability under present and future climate conditions: a Bayesian state‐space approach
Authors: McCaffery R. , Solonen A. , Crone E. 
Published: May 2012

Summary1. World‐wide extinctions of amphibians are at the forefront of the biodiversity crisis, with climate change figuring prominently as a potential driver of continued amphibian decline. As in other taxa, changes in both the mean and variability of climate conditions may affect amphibian populations in complex, unpredictable ways. In western North America, climate models predict a reduced duration and extent of mountain snowpack and increased variability in precipitation, which may have consequences for amphibians inhabiting montane ecosystems.2. We used Bayesian capture–recapture methods to estimate survival and transition probabilities in a high‐elevation population of the Columbia spotted frog (Rana luteiventris) over 10 years and related these rates to interannual variation in peak snowpack. Then, we forecasted frog population growth and viability under a range of scenarios with varying levels of change in mean and variance in snowpack.3. Over a range of future scenarios, changes in mean snowpack had a greater effect on viability than changes in the variance of snowpack, with forecasts largely predicting an increase in population viability. Population models based on snowpack during our study period predicted a declining population.4. Although mean conditions were more important for viability than variance, for a given mean snowpack depth, increases in variability could change a population from increasing to decreasing. Therefore, the influence of changing climate variability on populations should be accounted for in predictive models. The Bayesian modelling framework allows for the explicit characterization of uncertainty in parameter estimates and ecological forecasts, and thus provides a natural approach for examining relative contributions of mean and variability in climatic variables to population dynamics.5. Longevity and heterogeneous habitat may contribute to the potential for this amphibian species to be resilient to increased climatic variation, and shorter‐lived species inhabiting homogeneous ecosystems may be more susceptible to increased variability in climate conditions.
Sapwood area drives growth in mountain conifer forests
Authors: Galván J. Diego , Camarero J. Julio , Sangüesa‐Barreda Gabriel , Alla Arben Q. , Gutiérrez Emilia 
Published: May 2012

Summary1. It is expected that climate warming will enhance tree growth of mountain conifer forests in cold regions. However, trees have shown unstable, age‐related and site‐dependent growth responses to climate throughout the past century, but information on the drivers controlling such responsiveness at the site and tree scales is lacking. We evaluated whether such changing growth responses are more influenced by site features, such as altitude, or by tree features, such as size and sapwood area.2. We quantified the growth trends at the site and tree levels in IberianPinus uncinataforests using dendrochronology. Tree‐ring width was converted to basal area increment (BAI) to assess the relationships between growth and site and tree variables over three time periods (1901–1994, 1901–1947, 1948–1994) using structural equation models.3. Trees were older at higher altitudes, and the amount of sapwood decreased as trees aged. BAI trends were lower in the period 1948–1994 than in the period 1901–1947, that is, tree growth is decelerating, despite BAI values of both periods showing the reverse pattern. Sapwood area and, to a minor extent, tree age were the main positive and negative drivers, respectively, controlling BAI during the 20th century, whereas altitude played a minor role.4. Synthesis. Our results highlight the relevance of tree individual characteristics as the main drivers modulating growth responses to climate warming. We conclude that climate warming will have a lower effect on radial growth in slow‐growing high‐elevation trees than in fast‐growing low‐elevation trees, which produce a greater sapwood area. Trees may become relatively insensitive to climate as they age and reach a size‐related functional threshold linked to reduced sapwood production.
Recent population decline and selection shape diversity of taxol‐related genes
Authors: BURGARELLA C. , NAVASCUÉS M. , ZABAL‐AGUIRRE M. , BERGANZO E. , RIBA M. , MAYOL M. , VENDRAMIN G. G. , GONZÁLEZ‐MARTÍNEZ S. C. 
Published: May 2012

AbstractTaxanes are defensive metabolites produced by Taxus species (yews) and used in anticancer therapies. Despite their medical interest, patterns of natural diversity in taxane‐related genes are unknown. We examined variation at five main genes of Taxus baccata in the Iberian Peninsula, a region where unique yew genetic resources are endangered. We looked at several gene features and applied complementary neutrality tests, including diversity/divergence tests, tests solely based on site frequency spectrum (SFS) and Zeng’s compound tests. To account for specific demography, microsatellite data were used to infer historical changes in population size based on an Approximate Bayesian Computation (ABC) approach. Polymorphism‐divergence tests pointed to positive selection for genes TBT and TAT and balancing selection for DBAT. In addition, neutrality tests based on SFS found that while a recent reduction in population size may explain most statistics’ values, selection may still be in action in genes TBT and DBAT, at least in some populations. Molecular signatures on taxol genes suggest the action of frequent selective waves with different direction or intensity, possibly related to varying adaptive pressures produced by the host–enemy co‐evolution on defence‐related genes. Such natural selection processes may have produced taxane variants still undiscovered.