bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of the psychometric properties of Quality of Life measures for school aged children with cerebral palsy
Authors: Carlon Stacey , Shields Nora , Yong Katherine , Gilmore Rose , Sakzewski Leanne , Boyd Roslyn 
Published: November 2010

Abstract

Background
This systematic review aimed to evaluate the psychometric properties and clinical utility of all condition specific outcome measures used to assess quality of life (QOL) in school aged children with cerebral palsy (CP).

Methods
Relevant outcome measures were identified by searching 8 electronic databases, supplemented by citation tracking. Two independent reviewers completed data extraction and analysis of the measures using a modified version of the CanChild Outcome Measures Rating Form.

Results
From the 776 papers identified 5 outcome measures met the inclusion criteria: the Care and Comfort Hypertonicity Questionnaire (C&CHQ), the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), CP QOL-Child, DISABKIDS and PedsQL 3.0 CP Module. There was evidence of construct validity for all five measures. Content validity was reported for all measures except PedsQL 3.0. The CPCHILD and CP QOL-Child were the only outcome measures to have reported data on concurrent validity. All measures, with the exception of one (C&CHQ) provided evidence of internal reliability. The CPCHILD and the CP-QOL-Child had evidence of test-retest reliability and DISABKIDS had evidence of inter-rater reliability. There were no published data on the responsiveness of these outcome measures.

Conclusions
The CPCHILD and the CP QOL-Child demonstrated the strongest psychometric properties and clinical utility. Further work is needed, for all measures, on data for sensitivity to change.
Acute effects of fine particulate air pollution on ST segment height: A longitudinal study
Authors: He Fan , Shaffer Michele L , Rodriguez-Colon Sol , Bixler Edward O , Vgontzas Alexandros N , Williams Ronald W , Wu Rongling , Cascio Wayne E , Liao Duanping 
Published: November 2010

Abstract

Background
The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms.

Methods
We investigate the acute effects and the time course of fine particulate pollution (PM2.5) on myocardium ischemic injury as assessed by ST-segment height in a community-based sample of 106 healthy non-smokers. Twenty-four hour beat-to-beat electrocardiogram (ECG) data were obtained using a high resolution 12-lead Holter ECG system. After visually identifying and removing all the artifacts and arrhythmic beats, we calculated beat-to-beat ST-height from ten leads (inferior leads II, III, and aVF; anterior leads V3 and V4; septal leads V1 and V2; lateral leads I, V5, and V6,). Individual-level 24-hour real-time PM2.5 concentration was obtained by a continuous personal PM2.5 monitor. We then calculated, on a 30-minute basis, the corresponding time-of-the-day specific average exposure to PM2.5 for each participant. Distributed lag models under a linear mixed-effects models framework were used to assess the regression coefficients between 30-minute PM2.5 and ST-height measures from each lead; i.e., one lag indicates a 30-minute separation between the exposure and outcome.

Results
The mean (SD) age was 56 (7.6) years, with 41% male and 74% white. The mean (SD) PM2.5 exposure was 14 (22) μg/m3. All inferior leads (II, III, and aVF) and two out of three lateral leads (I and V6), showed a significant association between higher PM2.5 levels and higher ST-height. Most of the adverse effects occurred within two hours after PM2.5 exposure. The multivariable adjusted regression coefficients β (95% CI) of the cumulative effect due to a 10 μg/m3 increase in Lag 0-4 PM2.5 on ST-I, II, III, aVF and ST-V6 were 0.29 (0.01-0.56) μV, 0.79 (0.20-1.39) μV, 0.52 (0.01-1.05) μV, 0.65 (0.11-1.19) μV, and 0.58 (0.07-1.09) μV, respectively, with all p < 0.05.

Conclusions
Increased PM2.5 concentration is associated with immediate increase in ST-segment height in inferior and lateral leads, generally within two hours. Such an acute effect of PM2.5 may contribute to increased potential for regional myocardial ischemic injury among healthy individuals.
ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells
Authors: Thollet Aurélie , Vendrell Julie A , Payen Léa , Ghayad Sandra E , Ben Larbi Sabrina , Grisard Evelyne , Collins Colin , Villedieu Marie , Cohen Pascale A 
Published: November 2010

AbstractBackgroundZNF217 is a candidate oncogene located at 20q13, a chromosomal region frequently amplified in breast cancers. The precise mechanisms involved in ZNF217 pro-survival function are currently unknown, and utmost importance is given to deciphering the role of ZNF217 in cancer therapy response.ResultsWe provide evidence that stable overexpression of ZNF217 in MDA-MB-231 breast cancer cells conferred resistance to paclitaxel, stimulated cell proliferationin vitroassociated with aberrant expression of several cyclins, and increased tumor growth in mouse xenograft models. Conversely, siRNA-mediated silencing of ZNF217 expression in MCF7 breast cancer cells, which possess high endogenous levels of ZNF217, led to decreased cell proliferation and increased sensitivity to paclitaxel. The paclitaxel resistance developed by ZNF217-overexpressing MDA-MB-231 cells was not mediated by the ABCB1/PgP transporter. However, ZNF217 was able to counteract the apoptotic signals mediated by paclitaxel as a consequence of alterations in the intrinsic apoptotic pathway through constitutive deregulation of the balance of Bcl-2 family proteins. Interestingly, ZNF217 expression levels were correlated with the oncogenic kinase Aurora-A expression levels, as ZNF217 overexpression led to increased expression of the Aurora-A protein, whereas ZNF217 silencing was associated with low Aurora-A expression levels. We showed that a potent Aurora-A kinase inhibitor was able to reverse paclitaxel resistance in the ZNF217-overexpressing cells.ConclusionAltogether, these data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects.
The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape
Authors: Tollis Sylvain , Dart Anna E , Tzircotis George , Endres Robert G 
Published: November 2010

AbstractBackgroundPhagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood.ResultsHere, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcγRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes.ConclusionsThis suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.
CTCF regulates the local epigenetic state of ribosomal DNA repeats
Authors: van de Nobelen Suzanne , Rosa-Garrido Manuel , Leers Joerg , Heath Helen , Soochit Widia , Joosen Linda , Jonkers Iris , Demmers Jeroen , van der Reijden Michael , Torrano Verónica , Grosveld Frank , Delgado M Dolores , Renkawitz Rainer , Galjart Niels , Sleutels Frank 
Published: November 2010

Abstract

Background
CCCTC binding factor (CTCF) is a highly conserved zinc finger protein, which is involved in chromatin organization, local histone modifications, and RNA polymerase II-mediated gene transcription. CTCF may act by binding tightly to DNA and recruiting other proteins to mediate its various functions in the nucleus. To further explore the role of this essential factor, we used a mass spectrometry-based approach to screen for novel CTCF-interacting partners.

Results
Using biotinylated CTCF as bait, we identified upstream binding factor (UBF) and multiple other components of the RNA polymerase I complex as potential CTCF-interacting partners. Interestingly, CTCFL, the testis-specific paralog of CTCF, also binds UBF. The interaction between CTCF(L) and UBF is direct, and requires the zinc finger domain of CTCF(L) and the high mobility group (HMG)-box 1 and dimerization domain of UBF. Because UBF is involved in RNA polymerase I-mediated ribosomal (r)RNA transcription, we analyzed CTCF binding to the rDNA repeat. We found that CTCF bound to a site upstream of the rDNA spacer promoter and preferred non-methylated over methylated rDNA. DNA binding by CTCF in turn stimulated binding of UBF. Absence of CTCF in cultured cells resulted in decreased association of UBF with rDNA and in nucleolar fusion. Furthermore, lack of CTCF led to reduced binding of RNA polymerase I and variant histone H2A.Z near the rDNA spacer promoter, a loss of specific histone modifications, and diminished transcription of non-coding RNA from the spacer promoter.

Conclusions
UBF is the first common interaction partner of CTCF and CTCFL, suggesting a role for these proteins in chromatin organization of the rDNA repeats. We propose that CTCF affects RNA polymerase I-mediated events globally by controlling nucleolar number, and locally by regulating chromatin at the rDNA spacer promoter, similar to RNA polymerase II promoters. CTCF may load UBF onto rDNA, thereby forming part of a network that maintains rDNA genes poised for transcription.
CXC chemokine receptor 4 expressed in T cells plays an important role in the development of collagen-induced arthritis
Authors: Chung Soo-Hyun , Seki Keisuke , Choi Byung-Il , Kimura Keiko B , Ito Akihiko , Fujikado Noriyuki , Saijo Shinobu , Iwakura Yoichiro 
Published: November 2010

Abstract
Introduction
Chemokines and their receptors are potential therapeutic targets in rheumatoid arthritis (RA). Among these, several studies suggested the involvement of CXC chemokine 4 (CXCR4) and its ligand CXC ligand 12 (SDF-1) in RA pathogenesis. However, the role of these molecules in T-cell function is not known completely because of embryonic lethality of Cxcr4- and Cxcl12-deficient mice. In this report, we generated T cell-specific Cxcr4-deficient mice and showed that the CXCR4 in T cells is important for the development of collagen-induced arthritis (CIA).

Methods
T cell-specific Cxcr4-deficient mice were generated by using the Cre-loxP system. Mice harboring loxP sites flanking exon 2 of the Cxcr4gene (Cxcr4
flox/flox
) were generated by homologous recombination and crossed with Cre transgenic mice expressing Cre recombinase under the control of Lck promoter (Cxcr4
+/+
/Lck-Cremice) to generate T cell-specific Cxcr4-deficient mice (Cxcr4
flox/flox
/Lck-Cre mice). CIA was induced by immunization with chicken type II collagen and Complete Freund's Adjuvant (CFA).

Results
The incidence, but not the severity, of CIA was significantly reduced in Cxcr4
flox/flox
/Lck-Cre mice compared with Cxcr4
+/+
/Lck-Cre mice. We found that the expression of CXCR4 was enhanced in activated T cells, and the migration of Cxcr4-deficient T cells toward SDF-1 was severely impaired. However, antibody production, cellular proliferative response, and cytokine production on treatment with type II collagen (IIC) were normal in these knockout mice, suggesting that CXCR4 is not involved in T-helper functions. Interestingly, the proportion of CXCR4-expressing T cells was much increased in affected joints compared with that in draining lymph nodes in CIA-induced mice, and distribution of Cxcr4
flox/flox
/Lck-Cre mouse-derived T cells into affected joints was suppressed compared with that in Cxcr4
+/+
/Lck-Cre T cells.

Conclusions
These results indicate that CXCR4 expression in T cells is important for the development of CIA, by recruiting activated T cells toward inflammatory sites, and suggest that CXCR4 is a good target for the treatment of RA in humans.
A genome-wide association scan on estrogen receptor-negative breast cancer
Authors: Li Jingmei , Humphreys Keith , Darabi Hatef , Rosin Gustaf , Hannelius Ulf , Heikkinen Tuomas , Aittomäki Kristiina , Blomqvist Carl , Pharoah Paul DP , Dunning Alison M , Ahmed Shahana , Hooning Maartje J , Hollestelle Antoinette , Oldenburg Rogier A , Alfredsson Lars , Palotie Aarno , Peltonen-Palotie Leena , Irwanto Astrid , Low Hui Qi , Teoh Garrett HK , Thalamuthu Anbupalam , Kere Juha , D'Amato Mauro , Easton Douglas F , Nevanlinna Heli , Liu Jianjun , Czene Kamila , Hall Per 
Published: November 2010

AbstractIntroductionBreast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.MethodsWe conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.ResultsAssociation with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of smallP-values for SNPs with known regulatory functions in cancer-related pathways was found (globalP= 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.ConclusionsER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.
Clinical aspects and cytokine response in severe H1N1 influenza A virus infection
Authors: Hagau Natalia , Slavcovici Adriana , Gonganau Daniel N , Oltean Simona , Dirzu Dan S , Brezoszki Erika S , Maxim Mihaela , Ciuce Constantin , Mlesnite Monica , Gavrus Rodica L , Laslo Carmen , Hagau Radu , Petrescu Magda , Studnicska Daniela M 
Published: November 2010

Abstract
Introduction
The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.

Methods
Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively.

Results
In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.

Conclusions
In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO2:FiO2 ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.
Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study
Authors: Stopeck Alison T. , Lipton Allan , Body Jean-Jacques , Steger Guenther G. , Tonkin Katia , de Boer Richard H. , Lichinitser Mikhail , Fujiwara Yasuhiro , Yardley Denise A. , Viniegra María , Fan Michelle , Jiang Qi , Dansey Roger , Jun Susie , Braun Ada 
Published: November 2010

Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
Multicenter, Randomized, Cross-Over Clinical Trial of Venlafaxine Versus Gabapentin for the Management of Hot Flashes in Breast Cancer Survivors
Authors: Bordeleau Louise , Pritchard Kathleen I. , Loprinzi Charles L. , Ennis Marguerite , Jugovic Olivera , Warr David , Haq Rashida , Goodwin Pamela J. 
Published: November 2010

Purpose Nonhormonal pharmacologic interventions are recommended for the treatment of hot flashes in breast cancer survivors. Antidepressants and gabapentin have been shown to be both effective and well tolerated; however, it is not clear which is preferred. Patients and Methods This was a group-sequential, open-label, randomized, cross-over trial of 4 weeks of venlafaxine (37.5 mg daily for 7 days followed by 75 mg daily for 21 days) versus gabapentin (300 mg once per day for 3 days, then 300 mg twice per day for 3 days, then 300 mg three times per day for 22 days), with patient preference as the primary outcome. Postmenopausal women with at least 14 bothersome hot flashes per week for the prior month were eligible. A 2-week baseline period and a 2-week tapering/washout time was used before the first and second treatment periods, respectively. Diaries were used to measure hot flashes and potential toxicities throughout the study. Participants completed a preference questionnaire at the end of the study. A predefined Pocock stopping rule was applied. Patient preference and hot flash and toxicity outcomes were compared between treatments. Results Sixty-six patients were randomly assigned, 56 of whom provided a preference (eight dropped out and two had no preference); 18 (32%) preferred gabapentin and 38 (68%) preferred venlafaxine (P = .01). Both agents reduced hot flash scores to a similar extent (66% reduction). Venlafaxine was associated with increased nausea, appetite loss, constipation, and reduced negative mood changes compared with gabapentin, whereas gabapentin was associated with increased dizziness and appetite compared with venlafaxine (all P < .05). Conclusion Breast cancer survivors prefer venlafaxine over gabapentin for treating hot flashes.