bluuebunny/crossref_metadata_2025_split huggingface dataset:
Voluntary Informed Consent in Paediatric Oncology Research
Authors: Dekking Sara A. S. , Van Der Graaf Rieke , Van Delden Johannes J. M. 
Published: December 2015

AbstractIn paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research‐care context.
Modeling Overdispersion Heterogeneity in Differential Expression Analysis Using Mixtures
Authors: Bonafede Elisabetta , Picard Franck , Robin Stéphane , Viroli Cinzia 
Published: December 2015

Summary
Next-generation sequencing technologies now constitute a method of choice to measure gene expression. Data to analyze are read counts, commonly modeled using negative binomial distributions. A relevant issue associated with this probabilistic framework is the reliable estimation of the overdispersion parameter, reinforced by the limited number of replicates generally observable for each gene. Many strategies have been proposed to estimate this parameter, but when differential analysis is the purpose, they often result in procedures based on plug-in estimates, and we show here that this discrepancy between the estimation framework and the testing framework can lead to uncontrolled type-I errors. Instead, we propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Three consistent statistical tests are developed for differential expression analysis. We show through a wide simulation study that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it reaches the nominal value for the type-I error, while keeping elevate discriminative power between differentially and not differentially expressed genes. The method is finally illustrated on prostate cancer RNA-Seq data.
The haematological features and transfusion management of women who required massive transfusion for major obstetric haemorrhage in the UK: a population based study
Authors: Green Laura , Knight Marian , Seeney Frances , Hopkinson Cathy , Collins Peter W. , Collis Rachel E. , Simpson Nigel A. B. , Weeks Andrew , Stanworth Simon J. 
Published: December 2015

SummaryUnderstanding the coagulopathy of major‐obstetric‐haemorrhage (MOH) that leads to massive‐transfusion (MT) is fundamental to improving outcomes. This study reports on the haematological features and transfusion management of women experiencing MT [defined as transfusion of ≥8 units of red blood cells (RBC) within 24 h of delivery]. One hundred and eighty‐one cases [median (interquartile range; IQR) age 33 years (29–36)] were identified from all UK hospitals, using the UK Obstetric Surveillance System between July 2012 and June 2013. The median (IQR) estimated blood loss was 6 l (4·5–8). At presentation, the median platelet count was lowest for placenta accreta, compared with other causes, while the median prothrombin time and fibrinogen were <1·5 × mean normal and <3 g/l, respectively for all aetiologies. Median platelet count and fibrinogen fell to <75 × 109/l and <2 g/l, respectively for all causes during bleeding, except for trauma. The median (IQR) units of RBC, fresh‐frozen‐plasma (FFP) and cryoprecipitate transfused were 10 (8–14), 6 (4–8) and 2 (2–4), respectively. The median time from the onset of bleeding to delivery of the first RBC unit was significantly shorter for women who delivered via elective caesarean section, compared with others. The coagulopathy of MT during MOH differs significantly depending on its cause, suggesting that more targeted transfusion strategies are required.
Relative frequency of non‐Hodgkin lymphoma subtypes in selected centres in North Africa, the middle east and India: a review of 971 cases
Authors: Perry Anamarija M. , Diebold Jacques , Nathwani Bharat N. , MacLennan Kenneth A. , Müller‐Hermelink Hans K. , Bast Martin , Boilesen Eugene , Armitage James O. , Weisenburger Dennis D. 
Published: December 2015

SummaryComparative data regarding the distribution of non‐Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly‐diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male‐to‐female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low‐grade (LG) and high‐grade (HG) B‐NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B‐NHL (28·4%) and a higher proportion of HG B‐NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B‐cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.
New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B‐cell precursor acute lymphoblastic leukaemia
Authors: van der Velden Vincent H. J. , de Launaij Daphne , de Vries Jeltje F. , de Haas Valerie , Sonneveld Edwin , Voerman Jane S. A. , de Bie Maaike , Revesz Tamas , Avigad Smadar , Yeoh Allen E. J. , Swagemakers Sigrid M. A. , Eckert Cornelia , Pieters Rob , van Dongen Jacques J. M. 
Published: December 2015

SummaryIn childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1–4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray‐analysis, we discovered multiple differentially expressed genes between B‐cell precursor (BCP) ALL cells in bone marrow (BM) and BCP‐ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real‐time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP‐ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP‐ALL cells (>1%) with a ‘CNS protein profile’ (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP‐ALL cells with a ‘CNS protein profile’ at diagnosis (particularly SCD‐positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.
68Ga‐PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment
Authors: van Leeuwen Pim J. , Stricker Phillip , Hruby George , Kneebone Andrew , Ting Francis , Thompson Ben , Nguyen Quoc , Ho Bao , Emmett Louise 
Published: December 2015

ObjectivesTo examine the detection rates of 68Ga‐PSMA‐positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.Materials and MethodsA total of 300 consecutive patients with prostate cancer (PCa) who underwent 68Ga‐PSMA‐PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan‐I) database. For the present analysis, we included patients with BCR (prostate‐specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito‐Urinary Group (FROGG) guidelines. Two readers assessed each 68Ga‐PSMA‐PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological 68Ga‐PSMA uptake was investigated, and detection rates were determined according to PSA level.ResultsA total of 70 patients were included, and 53 positive 68Ga‐PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05–0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1–0.19 ng/mL, 23%; PSA 0.2–0.29 ng/mL, 58%; PSA 0.3–0.49 ng/mL, 36%; and PSA 0.5–0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological 68Ga‐PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the 68Ga‐PSMA findings there was a major management change in 20 (28.6%) patients.Conclusions68Ga‐PSMA appears to be useful for re‐staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to 68Ga‐PSMA findings.
Involvement of C‐X‐C chemokine receptor type 4 signaling in the efficiency of intercellular transmission of human T‐lymphotropic virus type I
Authors: Nakamura Tatsufumi , Satoh Katsuya , Fukushima Naomi 
Published: December 2015

AbstractObjectiveWe investigated the relationships between the efficiency of intercellular transmission of human T‐lymphotropic virus type I (HTLV‐I) and C‐X‐C chemokine receptor type 4 (CXCR4) signaling in a comparative study of HTLV‐I‐infected T cell lines derived from an HTLV‐I‐associated myelopathy/tropical spastic paraparesis patient (HCT‐5) or an HTLV‐I carrier (TL‐Su).MethodsAfter co‐cultivation of each HTLV‐I‐infected T cell line with H9/K30 luc reporter cells, relative activities of luc were calculated to measure the intercellular transmission of HTLV‐I. The level of stromal cell‐derived factor‐1α was measured using an enzyme‐linked immunoassay. Rap1 activation in HTLV‐I‐infected T cell lines was analyzed by a pull‐down assay.ResultsHCT‐5 had higher intercellular transmission efficiency of HTLV‐I compared with TL‐Su. Intercellular transmission of HTLV‐I in TL‐Su was increased significantly by stromal cell‐derived factor‐1α treatment. Pretreatment with an anti‐CXCR4 blocking antibody for H9/K30 luc reporter cells induced a significant reduction in intercellular transmission of HTLV‐I in HCT‐5, but not in TL‐Su. Stromal cell‐derived factor‐1α was not detected in the culture supernatants of HCT‐5, but existence of a humoral factor that activates CXCR4 signaling in HCT‐5 was suggested from studies with condition media. Bound Rap1‐GTP was detected in HCT‐5, but not in TL‐Su.ConclusionsOur data suggest that CXCR4 signaling is involved in the efficiency of intercellular transmission of HTLV‐I.
Predictors of weight‐loss response with glucagon‐like peptide‐1 receptor agonist treatment among adolescents with severe obesity
Authors: Nathan B. M. , Rudser K. D. , Abuzzahab M. J. , Fox C. K. , Coombes B. J. , Bomberg E. M. , Kelly A. S. 
Published: December 2015

SummaryIn two previous, separate clinical trials, we demonstrated significant reductions in body mass index (BMI) with exenatide in adolescents with severe obesity. In the present study, we pooled data from these near identical trials to evaluate factors that may predict BMI reduction at 3 months. Data from 32 patients (mean age 14.3 ± 2.2 years; 69% female; mean BMI 39.8 ± 5.8 kg m−2) were included. Exenatide treatment consisted of 5 mcg twice daily for 1 month, followed by an increase to 10 mcg twice daily for 2 additional months. Predictor variables included baseline BMI, BMI percent change at 1 month, incidence of nausea or vomiting and baseline appetite and satiety measures. Treatment effects of percent change in BMI from baseline were estimated within predictor subgroups using generalized estimating equations with exchangeable working correlation and robust variance estimation for confidence intervals and P‐values to account for paired observations. The pooled data treatment effect on absolute BMI at 3 months was −3.42% (95% confidence interval: −5.41%, −1.42%) compared to placebo. Within treated participants, appetite at baseline (treatment effect in high [−4.28%] vs. low [1.02%], P = 0.028) and sex (treatment effect in female [−4.78%] vs. male [0.76%], P = 0.007) were significant predictors of change in BMI at 3 months. Baseline BMI, BMI percent change at 1 month, age, incidence of nausea, vomiting, or other gastrointestinal symptoms and satiety scores did not predict 3‐month responses. Sex and measures of appetite may serve as useful predictors of glucagon‐like peptide‐1 receptor agonist treatment response among adolescents with severe obesity.
Interaction of Phenol Red with cetyltrimethylammonium bromide in aqueous solution
Authors: Wang Nong , Su Chengwu , Xiao Shijun 
Published: December 2015

This paper studies the interaction of anionic dye Phenol Red with cationic surfactant cetyltrimethylammonium bromide in aqueous solution and its influence on the formation of cetyltrimethylammonium bromide micelles for the first time. We obtain a series of thermodynamic parameters of the interaction by establishing a reasonable physical model of the association. Moreover, an in‐depth study on the variation in the absorption spectrum finds that the value of absorbance at the maximum absorption peak changes regularly with increase in the cetyltrimethylammonium bromide concentration. By establishing the micellisation models and measuring the changes in electrical conductivity with different cetyltrimethylammonium bromide concentrations, the critical micelle concentration values are obtained, which are essentially the same as the range of concentrations of regular change in absorbance, which shows that the formation of the cetyltrimethylammonium bromide micelles have an impact on the association interaction between Phenol Red and cetyltrimethylammonium bromide. All these data and phenomena illustrate a strong interaction between Phenol Red and cetyltrimethylammonium bromide.
Tumour cell population growth inhibition and cell death induction of functionalized 6‐aminoquinolone derivatives
Authors: Franci G. , Manfroni G. , Cannalire R. , Felicetti T. , Tabarrini O. , Salvato A. , Barreca M. L. , Altucci L. , Cecchetti V. 
Published: December 2015

AbstractObjectivesA number of previous studies has provided evidence that the well‐known anti‐bacterial quinolones may have potential as anti‐cancer drugs. The aim of this study was to evaluate potential anti‐tumour activity and selectivity of a set of 6‐aminoquinolones showing some chemical similarity to naphthyridone derivative CX‐5461, recently described as innovative anti‐cancer agent.Materials and methodsIn‐house quinolones 1‐8 and ad hoc synthesized derivatives 9‐13 were tested on Michigan Cancer Foundation‐7 (MCF‐7) breast cancer cells and mesenchymal progenitor (MePR2B) cell lines, analysing their effects on the cell cycle and cell death using FACS methodology. Activation of p53 was evaluated by western blotting.ResultsBenzyl esters 4, 5 and their amide counterparts 12, 13 drastically modulated MCF‐7 cell cycles inducing DNA fragmentation and cell death, thus proving to be potential anti‐tumour compounds. When assayed in non‐tumour MePR2B cells, compounds 4 and 5 were cytotoxic while 12 and 13 had a certain degree of selectivity, with compound 12 emerging as the most promising. Western blot analysis revealed that severe p53‐K382ac activation was promoted by benzylester 5. In contrast, amide 12 exerted only a moderate effect which was, however, comparable to that of suberoylanilide hydoxamic acid (SAHA).ConclusionsTaken together, these results further reinforce evidence that quinolones have potential as anti‐cancer agents. Future work will be focused on understanding compound 12 mechanisms of action, and to obtain more potent and selective compounds.
Atopy: a risk factor of refractory mycoplasma pneumoniae pneumonia?
Authors: Bao Yi‐Xiao , Li Jing , Tian Ye , Liu Quang‐Hua , Bao Jun 
Published: December 2015

AbstractObjectiveTo investigate the relationship of pathogen DNA copies with clinic and laboratory features among children with Mycoplasma pneumoniae (MP) pneumonia.MethodsA total of 95 enrolled children with MP pneumonia were assigned into the high‐MP‐load group (>106/mL) and the low‐MP‐load group (≤106/mL) according to MP‐DNA copies in bronchoalveolar lavage fluid (BALF). Clinical characteristics and any allergy history were collected. Aeroallergens and food allergens were detected with a skin test. Serum IgE and eosinophil cationic protein (ECP) were assessed using enzyme immunoassay. BALF levels of IL‐4, IFN‐γ, IL‐8 and TNF‐α were assessed by ELISA.ResultsCompared with the low‐MP‐load group, 72.7% in the high‐MP‐load group developed refractory MP pneumonia who failed to respond to at least 1‐week treatment with macrolides (72.7% vs 41.9%, P = 0.005). More children in the high‐load group than those in the low‐load group presented with extrapulmonary manifestations, lung consolidation, pleural effusion and atopic conditions including any allergy history, positive findings of aeroallergen test and increased serum IgE and ECP (P < 0.05). A significant higher BALF IL‐4 level was seen in the high‐load group versus the low‐load group (23.00 ± 11.24 vs 14.68 ± 7.12; pg/mL; P < 0.01). There were no significant differences in BALF levels of IFN‐γ, IL‐8 and TNF‐α between the two groups (P > 0.05).ConclusionAtopy may be a risk factor for the presence and severity of refractory MP pneumonia due to the high pathogen load in airway.
Invasion debt – quantifying future biological invasions
Authors: Rouget Mathieu , Robertson Mark P. , Wilson John R. U. , Hui Cang , Essl Franz , Renteria Jorge L. , Richardson David M. 
Published: December 2015

AbstractAimWe develop a framework for quantifying invasions based on lagged trends in invasions (‘invasion debt’) with the aim of identifying appropriate metrics to quantify delayed responses at different invasion stages – from introduction to when environmental impacts occur.LocationWorld‐wide; detailed case study in South Africa.MethodsWe define four components of invasion debt: the number of species not yet introduced but likely to be introduced in the future given current levels of introduction/propagule pressure; the establishment of introduced species; the potential increase in area invaded by established species (including invasive species); and the potential increase in impacts. We demonstrate the approach in terms of number of species for 21 known invasive Australian Acacia species globally and estimate three components of invasion debt for 58 Acacia species already introduced to South Africa by quantifying key invasion factors (environmental suitability, species invasion status, residence time, propagule pressure, spread rate and impacts).ResultsCurrent global patterns of invasive species richness reflect historical trends of introduction – most acacia species that will become invasive in southern Africa have already invaded, but there is a substantial establishment debt in South and North America. In South Africa, the likely consequence of invasion debt over the next 20 years was estimated at: four additional species becoming invasive with an average increase of 1075 km2 invaded area per invasive species. We estimate that this would require over US$ 500 million to clear.Main conclusionsOur results indicate that invasion debt is a valuable metric for reporting on the threats attributable to biological invasions, that invasion debt must be factored into strategic plans for managing global change, and, as with other studies, they highlight the value of proactive management. Given the uncertainty associated with biological invasions, further work is required to quantify the different components of invasion debt.
Legal Pluralism and Hybrid Governance: Bridging Two Research Lines
Authors: Reyntjens Filip 
Published: December 2015

ABSTRACTLegal pluralism and hybrid governance are two lines of research that address the interactions between state (official) and non‐state (unofficial) norms. Both come to similar observations, yet they seem hardly aware of each other's existence. With very few exceptions, the one does not refer to the other. This article seeks to explore whether links can be established. It presents both lines of research, identifies common ground, explores what they can learn from each other, and seeks to find whether the distance can be bridged. It concludes that legal pluralism and hybrid governance could be mutually reinforcing if scholars in the two lines were aware of and used each other's findings and methods, and saw each other as complementary.