bluuebunny/crossref_metadata_2025_split huggingface dataset:
The feasibility of a home-based moderate-intensity physical activity intervention in obese children and adolescents
Authors: Conwell Louise S , Trost Stewart G , Spence Luke , Brown Wendy J , Batch Jennifer A 
Published: May 2008

ObjectivesTo explore the feasibility of conducting a 10-week home-based physical activity (PA) programme and evaluate the changes in insulin sensitivity (SI) commensurate with the programme in obese young people.DesignOpen-labelled intervention.SettingHome-based intervention with clinical assessments at a tertiary paediatric hospital.Subjects18 obese (body mass index (BMI)>International Obesity Task Force age and sex-specific cut-offs) children and adolescents (8–18 years, 11 girls/7 boys) were recruited. 15 participants (nine girls/six boys, mean±SE age 11.8±0.6 years, BMI-SD scores (BMI-SDS) 3.5±0.1, six prepubertal/nine pubertal) completed the intervention.InterventionThe programme comprised biweekly home visits over 10 weeks with personalised plans implemented aiming to increase moderate-intensity PA. Pedometers and PA diaries were used as self-monitoring tools. The goals were to (1) teach participants behavioural skills related to adopting and maintaining an active lifestyle and (2) increase daily participation in PA.Outcome measuresMean steps/day were assessed. SIassessed by the frequently sampled intravenous glucose tolerance test and other components of the insulin resistance syndrome were measured.ResultsMean steps/day increased significantly from 10 363±927 (baseline) to 13 013±1131 (week 10) (p<0.05). SIwas also significantly increased, despite no change in BMI-SDS, and remained so after an additional 10-week follow-up.ConclusionsThe results suggest that such a home-based PA programme is feasible. SIimproved without changes in BMI-SDS. More rigorous evaluations of such programmes are warranted.
Cardiovascular fitness modifies the associations between physical activity and abdominal adiposity in children and adolescents: the European Youth Heart Study
Authors: Ortega F B , Ruiz J R , Hurtig-Wennlöf A , Vicente-Rodríguez G , Rizzo N S , Castillo M J , Sjöström M 
Published: May 2008

ObjectiveTo examine the associations between physical activity (PA) and abdominal adiposity, as measured by waist circumference, in children and adolescents, and to test whether cardiovascular fitness (CVF) modifies these associations.MethodsPA components were measured by accelerometry in 1075 individuals aged 9 or 15 years old. CVF was measured by a maximal cycling test. Self-reported maternal educational level, body mass index, children's birth weight and television viewing were used as confounders.ResultsLinear regression did not show any association between the PA variables and waist circumference, after controlling for sex, age and height. When stratifying by CVF level (low/high), time spent at vigorous PA was inversely associated with waist circumference (p≤0.05) in the low CVF group. Unexpectedly, in the high CVF group, the PA variables were positively associated with waist circumference (p≤0.05). In both groups, the results were unchanged after controlling for the confounders. CVF was inversely associated with waist circumference, after controlling for all PA variables (p≤0.01) and confounders (p≤0.01).ConclusionCVF is inversely associated with abdominal adiposity and seems to modify the associations between PA and abdominal adiposity. In low-fit children and adolescents, time spent in vigorous PA seems to be the key component linked to abdominal adiposity. This finding should be considered in further development of lifestyle intervention strategies. The results found in the high-fit group need to be confirmed.
RESONANT TERAHERTZ SPECTROSCOPY OF BACTERIAL THIOREDOXIN IN WATER: SIMULATION AND EXPERIMENT
Authors: BYKHOVSKI ALEXEI , GLOBUS TATIANA , KHROMOVA TATYANA , GELMONT BORIS , WOOLARD DWIGHT 
Published: May 2008

The experimental and computational study of bacterial thioredoxin, an E. coli protein, at THz frequencies is presented. The absorption spectrum of the entire protein in water was studied numerically in the terahertz range (0.1 – 2 THz). In our work, the initial X-ray molecular structure of thioredoxin was optimized using the molecular dynamical (MD) simulations at room temperature and atmospheric pressure. The effect of a liquid content of a bacterial cell was taken into account explicitly via the simulation of water molecules using the TIP3P water model. Using atomic trajectories from the room-temperature MD simulations, thioredoxin's THz vibrational spectrum and the absorption coefficient were calculated in a quasi harmonic approximation. For our terahertz transmission measurements, we used solutions of thioredoxin in distilled water obtained from Sigma. The experimental and simulated signatures are correlated and dominant peaks are close in frequencies. The results of this study demonstrate that terahertz spectroscopy is a promising tool in generating spectral data for cellular components of bio agents such as bacterial cells and spores.
A Note on the Scope of Developmental Behaviour Genetics
Authors: Dolan Conor V. , Molenaar Peter C.M. 
Published: May 2008

The behaviour genetic decomposition of individual differences has been presented as being irrelevant to the study of human behavioural ontogeny. This introduces two problems. First, the analysis of systematic differences constitutes the basis for most statistical models used in the social sciences. If, generally speaking, this type of analysis is uninformative regarding development, how then can one empirically investigate human development? Second, behaviour genetic analyses are the only way to arrive at meaningful statements regarding the contributions of heredity and environment to human development. If results thus obtained are irrelevant, it is impossible to say anything on the subject of heredity, environment, and human ontogeny that is both meaningful and informative. It is argued that developmental behaviour genetics should not be viewed as a theory of development, but rather as a method of testing certain well-defined hypotheses regarding the contributions of genetic and environmental influences to human development. Individual differences assessed at any point in time reflect developmental processes prior to that time-gene-environment models are in a very basic sense inherently developmental... (Loehlin, 1975, p.41). Obviously the finding of innate differences in behaviour does not illuminate the development of that behaviour in any way (Johnston, 1988, p. 623).
Myelodysplastic syndromes
Authors: Nimer Stephen D. 
Published: May 2008

AbstractThere has been a remarkable explosion of knowledge into the molecular defects that underlie the acute and chronic leukemias, leading to the introduction of targeted therapies that can block key cellular events essential for the viability of the leukemic cell. Our understanding of the pathogenesis of the myelodysplastic syndromes (MDSs) has lagged behind, at least in part, because they represent a more heterogeneous group of disorders. The significant immunologic abnormalities described in this disease, coupled with the admixture of MDS stem or progenitor cells within the myriad types of dysplastic and normal cells in the bone marrow and peripheral blood, have made it difficult to molecularly characterize and model MDS. The recent availability of several, effective (ie, FDA-approved) therapies for MDS and newly described mouse models that mimic aspects of the human disease provide an opportune moment to try to leverage this new knowledge into a better understanding of and better therapies for MDS.
Acquired factor VIII inhibitors
Authors: Franchini Massimo , Lippi Giuseppe 
Published: May 2008

AbstractAcquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with high-titer inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors.
The clathrin-binding motif and the J-domain of Drosophila Auxilin are essential for facilitating Notch ligand endocytosis
Authors: Kandachar Vasundhara , Bai Ting , Chang Henry C 
Published: May 2008

Abstract

Background
Ligand endocytosis plays a critical role in regulating the activity of the Notch pathway. The Drosophila homolog of auxilin (dAux), a J-domain-containing protein best known for its role in the disassembly of clathrin coats from clathrin-coated vesicles, has recently been implicated in Notch signaling, although its exact mechanism remains poorly understood.

Results
To understand the role of auxilin in Notch ligand endocytosis, we have analyzed several point mutations affecting specific domains of dAux. In agreement with previous work, analysis using these stronger dAux alleles shows that dAux is required for several Notch-dependent processes, and its function during Notch signaling is required in the signaling cells. In support of the genetic evidences, the level of Delta appears elevated in dAux deficient cells, suggesting that the endocytosis of Notch ligand is disrupted. Deletion analysis shows that the clathrin-binding motif and the J-domain, when over-expressed, are sufficient for rescuing dAux phenotypes, implying that the recruitment of Hsc70 to clathrin is a critical role for dAux. However, surface labeling experiment shows that, in dAux mutant cells, Delta accumulates at the cell surface. In dAux mutant cells, clathrin appears to form large aggregates, although Delta is not enriched in these aberrant clathrin-positive structures.

Conclusion
Our data suggest that dAux mutations inhibit Notch ligand internalization at an early step during clathrin-mediated endocytosis, before the disassembly of clathrin-coated vesicles. Further, the inhibition of ligand endocytosis in dAux mutant cells possibly occurs due to depletion of cytosolic pools of clathrin via the formation of clathrin aggregates. Together, our observations argue that ligand endocytosis is critical for Notch signaling and auxilin participates in Notch signaling by facilitating ligand internalization.
Performance of a 70-mer oligonucleotide microarray for genotyping of Campylobacter jejuni
Authors: Rodin Sandra , Andersson Anders F , Wirta Valtteri , Eriksson Lena , Ljungström Marianne , Björkholm Britta , Lindmark Hans , Engstrand Lars 
Published: May 2008

Abstract

Background

Campylobacter jejuni is widespread in the environment and is the major cause of bacterial gastroenteritis in humans. In the present study we use microarray-based comparative genomic hybridizations (CGH), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to analyze closely related C. jejuni isolates from chicken and human infection.

Results
With the exception of one isolate, the microarray data clusters the isolates according to the five groups determined by PFGE. In contrast, MLST defines only three genotypes among the isolates, indicating a lower resolution. All methods show that there is no inherit difference between isolates infecting humans and chicken, suggesting a common underlying population of C. jejuni. We further identify regions that frequently differ between isolates, including both previously described and novel regions. Finally, we show that genes that belong to certain functional groups differ between isolates more often than expected by chance.

Conclusion
In this study we demonstrated the utility of 70-mer oligonucleotide microarrays for genotyping of Campylobacter jejuni isolates, with resolution outperforming MLST.
Association between amebic liver abscess and Human Immunodeficiency Virus infection in Taiwanese subjects
Authors: Hsu Meng-Shuian , Hsieh Szu-Min , Chen Mao-Yuan , Hung Chien-Ching , Chang Shan-Chwen 
Published: May 2008

Abstract

Purpose
Invasive amebiasis is an emerging parasitic disorder in Taiwan, especially in patients diagnosed with human immunodeficiency virus (HIV) infection. Thirty-three Taiwanese subjects with amebic liver abscess (ALA) were examined and a possible correlation between ALA and HIV infection was investigated.

Results
Among ALA patients, the proportion of HIV-positive individuals increased during the study period. ALA was the first major clinical presentation in 54% of HIV patients with ALA. Overall, 58% (14/24) of HIV-infected patients had a CD4+ count > 200 cells/μL and 82.1% (23/28) had no concurrent opportunistic infection or other evidence of HIV infection. There was no marked difference in clinical characteristics between HIV-positive and HIV-negative ALA patients except the level of leukocytosis.

Conclusion
While the clinical characteristics described herein cannot be used to determine whether ALA patients have HIV infection, routine HIV testing is recommended in patients with ALA, even in the absence of HIV symptoms.
Discontinuation rates in clinical trials in musculoskeletal pain: meta-analysis from etoricoxib clinical trial reports
Authors: Moore R Andrew , Derry Sheena , McQuay Henry J 
Published: May 2008

Abstract
Introduction
Patient adherence to therapy in clinical practice is often low, and the difference between efficacy measured in clinical trials and effectiveness in clinical practice is probably a function of discontinuation of therapy because of lack of efficacy or because of unmanageable or intolerable adverse events. Discontinuation is frequently measured in clinical trials but is not usually described in detail in published reports, often because of limitations in the size of publications. By contrast, company clinical trial reports include much more detail.

Methods
We examined company clinical trial reports of trials involving etoricoxib in four musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, chronic low back pain and ankylosing spondylitis. Information was available from 18 randomized trials (10,143 patients) lasting 4 to 12 weeks (one 4 weeks, three 6 weeks, one 8 weeks and seven 12 weeks) and from three trials with a mean duration of about 80 weeks (34,695 patients). These clinical trial reports contain over 73,000 pages of information.

Results
Over 12 weeks, lack of efficacy and adverse event discontinuations were similar between osteoarthritis, rheumatoid arthritis and back pain, with lack of efficacy discontinuation rates some three times higher than for adverse events. All-cause and lack of efficacy discontinuations were lower with etoricoxib (all doses combined) and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) than with placebo, although NSAIDs produced higher rates of clinical adverse events and gastrointestinal discontinuations than did placebo. Etoricoxib had fewer discontinuations than NSAIDs for lack of efficacy, clinical adverse events, and laboratory and gastrointestinal adverse events, but with more discontinuations because of hypertension and oedema. Comparison with two similar meta-analyses of other cyclo-oxygenase-2 selective inhibitors (more than 80,000 patients in total) revealed consistency between analyses.

Conclusion
Examining discontinuation data from clinical trials, even when the numbers of patients are very large, does not necessarily predict what will happen in the real world, where clinical effectiveness may differ from clinical efficacy assessed in trials. Data from these analyses appears to agree with findings from real world practice.
Severe hyperlactatemia with normal base excess: a quantitative analysis using conventional and Stewart approaches
Authors: Tuhay Graciela , Pein María Carolina , Masevicius Fabio Daniel , Kutscherauer Daniela Olmos , Dubin Arnaldo 
Published: May 2008

Abstract
Introduction
Critically ill patients might present complex acid–base disorders, even when the pH, PCO2, [HCO3-], and base excess ([BE]) levels are normal. Our hypothesis was that the acidifying effect of severe hyperlactatemia is frequently masked by alkalinizing processes that normalize the [BE]. The goal of the present study was therefore to quantify these disorders using both Stewart and conventional approaches.

Methods
A total of 1,592 consecutive patients were prospectively evaluated on intensive care unit admission. Patients with severe hyperlactatemia (lactate level ≥ 4.0 mmol/l) were grouped according to low or normal [BE] values (<-3 mmol/l or >-3 mmol/l).

Results
Severe hyperlactatemia was present in 168 of the patients (11%). One hundred and thirty-four (80%) patients had low [BE] levels while 34 (20%) patients did not. Shock was more frequently present in the low [BE] group (46% versus 24%, P = 0.02) and chronic obstructive pulmonary disease in the normal [BE] group (38% versus 4%, P < 0.0001). Levels of lactate were slightly higher in patients with low [BE] (6.4 ± 2.4 mmol/l versus 5.6 ± 2.1 mmol/l, P = 0.08). According to our study design, the pH, [HCO3-], and strong-ion difference values were lower in patients with low [BE]. Patients with normal [BE] had lower plasma [Cl-] (100 ± 6 mmol/l versus 107 ± 5 mmol/l, P < 0.0001) and higher differences between the changes in anion gap and [HCO3-] (5 ± 6 mmol/l versus 1 ± 4 mmol/l, P < 0.0001).

Conclusion
Critically ill patients may present severe hyperlactatemia with normal values of pH, [HCO3-], and [BE] as a result of associated hypochloremic alkalosis.
Redefining the Role of Doxorubicin for the Treatment of Children With Hepatoblastoma
Authors: Malogolowkin Marcio H. , Katzenstein Howard M. , Krailo Mark , Chen Zhengjia , Quinn John J. , Reynolds Marleta , Ortega Jorge A. 
Published: May 2008

Purpose Systemic chemotherapy has improved the survival of patients with hepatoblastoma (HB). INT-0098 Intergroup Liver Tumor Study demonstrated that patients with HB treated with either cisplatin/fluorouracil/vincristine (CFV) or cisplatin/doxorubicin (CD) had a similar survival. The Children's Oncology Group adopted the less toxic CFV as the standard regimen for treating HB. However, international cooperative groups still favor the CD combination. We therefore decided to revisit the role of doxorubicin for the treatment of HB. Methods Outcomes of patients with HB on the INT-0098 study were reviewed with an emphasis on the postevent survival time for both regimens to elucidate the role of doxorubicin in their retrieval. Results Sixty-four of the 173 randomly assigned patients had an event. Of these, 55 experienced progression or recurrence after initial treatment. Eleven (31%) of 36 patients treated with CFV were successfully retrieved with a doxorubicin-containing regimen and surgery and remain alive at last contact, whereas only one (6%) of 18 patients treated with CD was alive after retrieval therapy. Conclusion CFV is effective for stage I or II HB. Doxorubicin can be omitted as part of initial therapy in the majority of these patients, potentially limiting the long-term cardiac toxicities, without compromising outcome. Doxorubicin is effective in rescuing patients with recurrent disease after CFV and should be incorporated as a means of intensifying initial therapy for advanced-stage, nonmetastatic HB. Outcome of patients with metastatic disease at diagnosis is poor, and improving their survival will require new therapeutic approaches.
Bortezomib With or Without Irinotecan in Relapsed or Refractory Colorectal Cancer: Results From a Randomized Phase II Study
Authors: Kozuch Peter S. , Rocha-Lima Caio Max , Dragovich Tomislav , Hochster Howard , O'Neil Bert H. , Atiq Omar T. , Pipas J. Marc , Ryan David P. , Lenz Heinz-Josef 
Published: May 2008

Purpose To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). Patients and Methods Patients were randomly assigned in a 3:4 ratio to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus irinotecan 125 mg/m2 (arm B). A treatment cycle of 21 days consisted of four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, irinotecan on days 1 and 8. The primary objective of this randomized, multicenter, open-label, phase II study was to determine tumor response to treatment. Secondary objectives were safety and tolerability. Results A preplanned interim analysis to assess efficacy revealed inadequate activity, resulting in early termination of this study. A total of 102 patients were treated, 45 in arm A and 57 in arm B. Baseline characteristics were comparable. The investigator-assessed response rate was 0 in arm A and 3.5% in arm B (all partial responses). Adverse events in both treatment arms were as expected, with no significant additive toxicity. The most common grade ≥ 3 adverse events reported, per patient, during the study were fatigue (27%), vomiting (13%), nausea (11%), and peripheral sensory neuropathy (11%) in arm A, and diarrhea (33%), fatigue (25%), neutropenia (23%), thrombocytopenia (18%), dyspnea (12%), abdominal pain (12%), dehydration (12%), and anemia (11%) in arm B. Conclusion Bortezomib alone or in combination with irinotecan was not effective in patients with relapsed or refractory CRC.