bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild increases in serum hepcidin and interleukin‐6 concentrations impair iron incorporation in haemoglobin during an experimental human malaria infection
Authors: De Mast Quirijn , Van Dongen‐Lases Edmee C. , Swinkels Dorine W. , Nieman An‐Emmie , Roestenberg Meta , Druilhe Pierre , Arens Theo A. , Luty Adrian J. , Hermsen Cornelis C. , Sauerwein Robert W. , Van Der Ven Andre J. 
Published: March 2009

SummaryThe correct selection of individuals who will benefit from iron supplements in malaria‐endemic regions requires improved insight in the effects of malaria on host iron homeostasis and innovative biomarkers. We assessed sequential changes in serum hepcidin and in traditional biochemical iron status indicators during an experimental Plasmodium falciparum malaria infection with five adult volunteers. The haemoglobin content of reticulocytes (Ret‐He) and of mature red blood cells (RBC‐He) represented iron incorporation into haemoglobin. Low‐density parasitaemia and its treatment induced a mild increase in interleukin (IL)‐6 and serum hepcidin concentrations. Despite this only mild increase, a marked hypoferraemia with a strong increase in serum ferritin concentrations developed, which was associated with a sharp fall in Ret‐He, while RBC‐He remained unchanged. The ratio of soluble transferrin receptor (sTfR) to log ferritin concentrations decreased to an average nadir of 63% of the baseline value. We concluded that even mild increases in serum hepcidin and IL‐6 concentrations result in a disturbed host iron homeostasis. Serum hepcidin, Ret‐He and Delta‐He (Ret‐He minus RBC‐He) are promising biomarkers to select those individuals who will benefit from iron supplements in malaria endemic regions, while the sTfR/log ferritin ratio should be used with caution to assess iron status during malaria.
Long‐term follow‐up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis
Authors: Else Monica , Dearden Claire E. , Matutes Estella , Garcia‐Talavera Juan , Rohatiner Ama Z. S. , Johnson Steve A. N. , O’Connor Nigel T. J. , Haynes Andy , Osuji Nnenna , Forconi Francesco , Lauria Francesco , Catovsky Daniel 
Published: March 2009

SummaryHairy cell leukaemia (HCL) was first described 50 years ago. Median survival was then 4 years. The purine analogues, introduced in the 1980s, transformed this prognosis. We reviewed data retrospectively from 233 patients, treated with pentostatin (n = 188) or cladribine (n = 45), to investigate the current long‐term outlook. Median follow‐up was 16 years. There were no significant differences in outcome between the two agents. Overall, the complete response (CR) rate was 80% and median relapse‐free survival was 16 years. After relapse (n = 79) or non‐response (n = 5), 26 patients received pentostatin and 58 cladribine; 69% achieved CR and median relapse‐free survival was 11 years. After third‐line therapy (n = 23), 50% achieved CR and median relapse‐free survival was 6·5 years. However, CRs were equally durable, whether after first, second or third‐line therapy. Complete responders and those with both haemoglobin >100 g/l and platelet count >100 × 109/l before treatment had the longest relapse‐free survival (P < 0·0001). Patients still in CR at 5 years had only a 25% risk of relapse by 15 years. Outcomes for patients with recurrent disease improved with the monoclonal antibody rituximab, combined with either purine analogue. Overall only eight patients died of HCL‐related causes. Patients achieving a CR can expect a normal lifespan.
Risk of non‐Hodgkin lymphoma in association with germline variation in complement genes
Authors: Cerhan James R. , Novak Anne J. , Fredericksen Zachary S. , Wang Alice H. , Liebow Mark , Call Timothy G. , Dogan Ahmet , Witzig Thomas E. , Ansell Stephen M. , Habermann Thomas M. , Kay Neil E. , Slager Susan L. 
Published: March 2009

SummaryGermline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non‐Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene‐level tests of NHL risk, while individual SNPs were modelled as having a log‐additive effect. In gene level PC analyses, C2 (P = 0·023), C5 (P = 0·0032) and C9 (P = 0·020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0·046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0·05). In SNP level results from these genes, 10 SNPs had a P < 0·05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0·015; OR = 1·54, 95% CI 1·21–1·95) and rs2416810 (q = 0·015; OR = 1·57; 95% CI 1·22–2·01), and the C9 SNP rs187875 (q = 0·015; OR = 0·68; 95% 0·56–0·84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.
A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas
Authors: Brown Jennifer R. , Friedberg Jonathan W. , Feng Yang , Scofield Sarah , Phillips Kimberly , Dal Cin Paola , Joyce Robin , Takvorian Ronald W. , Fisher David C. , Fisher Richard I. , Liesveld Jane , Marquis Diana , Neuberg Donna , Freedman Arnold S. 
Published: March 2009

SummaryThe marginal zone lymphomas (MZLs) are a recently defined group of related diseases that probably arise from a common cell of origin, the marginal zone B cell. Data on therapy for subtypes other than gastric mucosa‐associated lymphoid tissue (MALT) lymphoma has been largely limited to retrospective case series. This prospective phase 2 study of fludarabine and rituximab for the treatment of marginal zone lymphomas enrolled 26 patients, 14 with nodal MZL, eight with MALT lymphomas and four with splenic MZL; 81% were receiving initial systemic therapy. Only 58% [95% confidence interval (CI) 37–77%] of patients completed the planned six cycles, due to significant haematological, infectious and allergic toxicity. Four late toxic deaths occurred due to infections [15% (95% CI 4·3–35%)], two related to delayed bone marrow aplasia and two related to myelodysplastic syndrome. Nonetheless, the overall response rate was 85% (95% CI 65–96%), with 54% complete responses. The progression‐free survival at 3·1 years of follow‐up is 79·5% (95% CI 63–96%). We conclude that, although concurrent fludarabine and rituximab given at this dose and schedule is a highly effective regimen in the treatment of MZLs, the significant haematological and infectious toxicity observed both during and after therapy is prohibitive in this patient population, emphasizing the need to study MZLs as a separate entity.
Simultaneous targeting of MCL1 and ABCB1 as a novel strategy to overcome drug resistance in human leukaemia
Authors: Ji Min , Li Jie , Yu Haiqing , Ma Daoxin , Ye Jingjing , Sun Xiulian , Ji Chunyan 
Published: March 2009

SummaryDrug resistance is a major obstacle to chemotherapy success in leukaemia. Although ABCB1 (MDR1) overexpression represents a critical mechanism of drug resistance, modulation of ABCB1 shows unsatisfactory clinical outcome. Recent studies showed that MCL1 was upregulated in numerous haematological and solid tumour malignancies. The present study found that patients with newly diagnosed or relapsed/refractory leukaemia expressed higher MCL1 levels than patients that were in complete remission. We demonstrated that overexpression of MCL1 decreased sensitivity of human leukaemia cell lines to cytotoxic drugs and inhibited drug‐induced apoptosis. Specific downregulation of MCL1 via RNA interference sensitized multidrug resistant leukaemia cells towards chemotherapy and induced apoptosis. Our study also demonstrated that MCL1 and ABCB1 mediated drug resistance through different mechanisms and the depletion of both MCL1 and ABCB1 showed an additive effect in reversing drug resistance and promoting drug‐induced apoptosis. Thus, this study documented an important role of MCL1 in drug resistance and apoptosis. Simultaneous targeting of MCL1 and ABCB1 could be a novel approach to overcome drug resistance in leukaemia.
Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia
Authors: Williams R. M. , Deeb A. , Ong K. K. , Bich W. , Murgatroyd P. R. , Hughes I. A. , Acerini C. L. 
Published: March 2009

SummaryBackground  Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late‐presenting) CAH compared with normal controls.Subjects and methods  Thirty‐seven children with CAH (26 classical and 11 nonclassical) median (range) age 9·4 year (0·5–15·8) were compared with 41 healthy control children age 11·0 year (3·2–17·1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status.Results  Classical CAH children had more fat mass than controls (P = 0·03), while nonclassical CAH children had more lean mass (P = 0·006) and higher systolic blood pressure (P = 0·003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0–120 min; P = 0·04), stimulated insulin (0–30 min; P = 0·02), 120 min insulin (P = 0·004) and 120 min glucose levels (P = 0·03) than controls, but no difference in disposition index.Discussion  Greater body fat in classical (early‐presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late‐presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess.
Strong pH influence on N2O and CH4 fluxes from forested organic soils
Authors: Weslien P. , Kasimir Klemedtsson Å. , Börjesson G. , Klemedtsson L. 
Published: March 2009

SummaryGreenhouse gas (GHG) emissions from farmed organic soils can have a major impact on national emission budgets. This investigation was conducted to evaluate whether afforestation of such soils could mitigate this problem. Over the period 1994–1997, emissions of methane (CH4) and nitrous oxide (N2O) were recorded from an organic soil site in Sweden, forested with silver birch (Betula pendula Roth), using static field chambers. The site was used for grazing prior to forestation. Soil pH and soil carbon content varied greatly across the site. The soil pH ranged from 3.6 to 5.9 and soil carbon from 34 to 42%.The mean annual N2O emission was 19.4 (± 6.7) kg N2O‐N ha−1 and was strongly correlated with soil pH (r = −0.93, P < 0.01) and soil carbon content (r = 0.97, P < 0.001). The N2O emissions showed large spatial and temporal variability with greatest emissions during the summer periods. The site was a sink for CH4 (i.e. −0.8 (± 0.5) kg CH4 ha−1 year−1) and the flux correlated well with the C/N ratio (r = 0.93, P < 0.01), N2O emission (r = 0.92, P < 0.01), soil pH (r = −0.95, P < 0.01) and soil carbon (r = 0.97, P < 0.001). CH4 flux followed a seasonal pattern, with uptake dominating during the summer, and emission during winter.This study indicates that, because of the large N2O emissions, afforestation may not mitigate the GHG emissions from fertile peat soils with acidic pH, although it can reduce the net GHG because of greater CO2 assimilation by the trees compared with agricultural crops.
Increasing ocean temperatures allow tropical fishes to survive overwinter in temperate waters
Authors: FIGUEIRA WILL F. , BOOTH DAVID J. 
Published: March 2009

AbstractThe southeast coast of Australia is a global hotspot for increasing ocean temperatures due to climate change. The temperate incursion of the East Australian Current (EAC) is increasing, affording increased connectivity with the Great Barrier Reef. The survival of tropically sourced juveniles over the winter is a significant stumbling block to poleward range shifts of marine organisms in this region. Here we examine the dependence of overwintering on winter severity and prewinter recruitment for eight species of juvenile coral reef fishes which are carried into temperate SE Australia (30–37 °S) by the EAC during the austral summer. The probability of persistence was most strongly influenced by average winter temperature and there was no effect of recruitment strength. Long‐term (138 years) data indicate that winter water temperatures throughout this region are increasing at a rate above the global average and predictions indicate a further warming of >2 °C by the end of the century. Rising ocean temperatures are resulting in a higher frequency of winter temperatures above survival thresholds. Current warming trajectories predict 100% of winters will be survivable by at least five of the study species as far south as Sydney (34 °S) by 2080. The implications for range expansions of these and other species of coral reef fish are discussed.
An evaluation of the PALS after treatment modelling intervention to reduce dental anxiety in child dental patients
Authors: HOWARD KAREN E. , FREEMAN RUTH 
Published: March 2009

Aim.  The aim of this study was to assess the effectiveness of the passivity to activity through live symbolic (PALS) after treatment modelling intervention to reduce child dental anxiety.Methods.  A convenience sample of consecutive 5‐ to 10‐year‐old dental patients were randomly assigned to intervention or control groups. Self‐reported child dental anxiety was assessed at the start of each visit. At the end of each visit, children in the intervention group were introduced to a glove puppet, which acted as the PALS model. The intervention group children re‐enacted the treatment they had just received on the puppet's teeth. At the end of each visit, the control children received motivational rewards only. The change in dental anxiety scores was examined by t‐tests and analysis of covariance.Results.  The final analysis included 27 intervention children and 26 control children. For the intervention group, there were no statistically significant changes in dental anxiety over a course of treatment, between first and second preventive visits, between first and second invasive treatment visits, or between first attendance and subsequent recall attendance. For the control group, a statistically significant decrease in dental anxiety was observed between the first and second invasive dental treatment visits.Conclusion.  The PALS after treatment modelling intervention was ineffective in reducing child dental anxiety.
Density‐dependence at multiple scales in experimental and natural plant populations
Authors: Gunton Richard M. , Kunin William E. 
Published: March 2009

Summary

The survival and reproduction of individual plants may be related to the distribution of conspecific neighbours with which they interact.
We used 2 years’ data from a field experiment to relate the reproduction and survival of focal Silene latifolia plants to the numbers of conspecific plants and flowers within a range of distances (0.16–150 m) from the focal plants. Thus we consider spatial scale as a continuously‐varying component of population density.
Because the data come from a single continuous population, we fitted regression models in two stages in order to remove spatial autocorrelation induced by environmental factors before modelling density effects. As well as single‐scale models, we fitted multiple‐scale models to explore interaction kernels. We statistically standardized plant size in some analyses to isolate pollination effects.
Reproductive output per plant generally decreased with greater densities of plants and flowers; for example there was a negative effect of female flowers within a 70‐m radius in the second year. However, at low female densities there was a positive effect of male flowers at a scale of 13 m in the first year. Seed‐set per flower decreased with greater densities of flowers in the second year (at radii < 10 m). Seed predation was greater when more female flowers were present within 5–7 m. Plants’ survival probability increased with density within 0.28 m for all but the smallest plants.
We also collected data on the pattern and reproductive success of S. latifolia plants in a natural population nearby and applied similar methodology. Here the negative effects of female flower densities occurred at finer scales and gave way to positive effects above 2 m, contrasting with some patterns from the experiment.
Synthesis. In a sessile population interacting with mobile biota, the effects of density on individual fitness may vary with the way in which density is measured. This, together with the methodological challenges for analysing spatial data from continuous populations, should be considered when designing and interpreting studies of spatial density‐dependence. Taking these issues into account, we may begin to explain the spatial patterns of natural populations.
A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader–Willi syndrome via cognitive, environmental and physiological mechanisms
Authors: Woodcock K. A. , Oliver C. , Humphreys G. W. 
Published: March 2009

AbstractBackground  Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences. However, relationships between different aspects of behavioural phenotypes have been less frequently researched and although recent interest in potential cognitive phenotypes or endophenotypes has increased, these are frequently studied independently of the behavioural phenotypes.Method  Taking Prader–Willi syndrome (PWS) as an example, we discuss evidence suggesting specific relationships between apparently distinct aspects of the PWS behavioural phenotype and relate these to specific endophenotypic characteristics.Results  The framework we describe progresses through biological, cognitive, physiological and behavioural levels to develop a pathway from genetic characteristics to behaviour with scope for interaction with the environment at any stage.Conclusions  We propose this multilevel approach as useful in setting out hypotheses in order to structure research that can more rapidly advance theory.
Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods
Authors: Jentzsch N. S. , Camargos P. A. M. , Colosimo E. A. , Bousquet J. 
Published: March 2009

Background:  Suboptimal adherence to inhaled steroids is a known problem in children and adolescents, even when medications are administered under parental supervision. This study aimed to verify the adherence rate to beclomethasone dipropionate (BDP) by four currently available methods.Methods:  In this concurrent cohort study, 102 randomly selected asthmatic children and adolescents aged 3–14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser®; Meditrack Products, Hudson, MA, USA) monitor, and canister weight.Results:  Mean adherence rates to BDP by self and/or parent report, pharmacy records, Doser, and canister weight were 97.9% (95% CI 88.0–98.6), 70.0% (95% CI 67.6–72.4), 51.5% (95% CI 48.3–54.6), and 46.3% (95% CI 44.1–48.4), respectively. Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76 (95% CI 0.65–0.87).Conclusions:  Adherence was a dynamic event and rates decreased progressively for all methods over the 12‐month follow‐up. Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records. Rates obtained by these two methods were very close and statistical analysis also showed a substantial agreement between them. As measurements by canister weight are less costly compared with currently available electronic devices, it should be considered as an alternative method to assess adherence in both clinical research and practice.
Thyroid hormones affect recovery from depression during antidepressant treatment
Authors: Pae Chi‐Un , Mandelli Laura , Han Changsu , Ham Byung‐Joo , Masand Prakash S. , Patkar Ashwin A. , Steffens David C. , De Ronchi Diana , Serretti Alessandro 
Published: March 2009

Aims:  The aim of the present study was to evaluate whether thyroid hormonal changes during menopause may affect the development and the course of major depressive disorder.Methods:  Thirty‐nine female patients (n = 17 in pre‐menopause; n = 22 in post‐menopause) with major depressive disorder based on Diagnostic Statistical Manual of Mental Disorders (4th edition) criteria and who were euthyroid and not on hormonal replacement therapy, participated in a prospective, 6‐week, open‐label naturalistic study. The Hamilton Depression Rating Scale‐17 item, the Montgomery‐Åsberg Depression Rating Scale, the Clinical Global Impression scale and the Cognitive Failure Questionnaire were administered at baseline, week 1, week 3, and week 6. Levels of thyroid stimulating hormone, total thyroxine and total triiodothyronine were collected at baseline visit.Results:  In the whole sample, particularly in pre‐menopausal women, levels of thyroid stimulating hormone‐potential markers of subclinical hypothyroidism were correlated with those of less severe but more resistant depressive form. Conversely, total thyroxine levels were correlated with a more severe depression, but high levels of this hormone favored the response to antidepressants. Overall, a diagnosis of subclinical hypothyroidism was associated with a poor response to antidepressant treatment. Finally, total triiodothyronine levels were associated with better cognitive functioning, though they did not influence improvement occurring with recovery.Conclusions:  Our study suggests that thyroid hormones may have an impact on severity and efficacy of antidepressant treatment. However, our result should be considered with caution and merely as a suggestion due to some methodological limitations. Hence further studies are required to better ascertain the role of thyroid hormones in depression after menopause.
Pulmonary epithelioid haemangioendothelioma mimicking central lung cancer
Authors: SHANG AnDong , WANG XueFen 
Published: March 2009

ABSTRACTA 40‐year‐old woman was hospitalized for investigation of dry cough, dyspnoea, and pain and swelling in the large joints of the arms and legs. Chest CT revealed a left hilar mass with partial atelectasis in the apical segment of the left lower lobe. X‐ray of the wrists, elbows, ankles and knee joints showed a periosteal reaction, associated with hypertrophic pulmonary osteoarthropathy. Endobronchial biopsy suggested a pulmonary epithelioid haemangioendothelioma. Whole left lung resection was performed and the patient died of respiratory failure 1 month postoperatively.