bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a Battery of Preschool Screening Tests for Predicting Special Education Placement
Authors: Stone Brian J. , Gridley Betty , Treloar James 
Published: February 2009

The accuracy and bias of a kindergarten screening battery for predicting educational placement was examined. The battery contained four well-validated commercial instruments. Subjects were 519 White and 183 American Indian children who had been tested prior to entering kindergarten. The children were monitored and 98 of the original 702 (14%) were eventually placed in special education resource classes. The battery predicted educational placement equally for both groups. However, the hit rate for both groups combined was only slightly over chance. While the battery had good accuracy for identifying normals (97%) it correctly identified only 39% of the special education students. A predictive value statistic was used to determine that the battery would have flagged 59 children as at-risk, 38 of which would have qualified for special education (or 64% of those identified). Inasmuch as the overall hit rate masks the low rate of identification of true positives, sensitivity and predictive value are argued as being more meaningful in evaluating the accuracy of a screening battery.
The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo
Authors: Lucas David M. , Edwards Ryan B. , Lozanski Gerard , West Derek A. , Shin Jungook D. , Vargo Melissa A. , Davis Melanie E. , Rozewski Darlene M. , Johnson Amy J. , Su Bao-Ning , Goettl Virginia M. , Heerema Nyla A. , Lin Thomas S. , Lehman Amy , Zhang Xiaoli , Jarjoura David , Newman David J. , Byrd John C. , Kinghorn A. Douglas , Grever Michael R. 
Published: February 2009

Abstract
Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary human B-leukemia cells, established B-leukemia cell lines, and animal models. In CLL cells, silvestrol LC50 (concentration lethal to 50%) is 6.9 nM at 72 hours. At this concentration, there is no difference in sensitivity of cells from patients with or without the del(17p13.1) abnormality. In isolated cells and whole blood, silvestrol is more cytotoxic toward B cells than T cells. Silvestrol causes early reduction in Mcl-1 expression due to translational inhibition with subsequent mitochondrial damage, as evidenced by reactive oxygen species generation and membrane depolarization. In vivo, silvestrol causes significant B-cell reduction in Eμ-Tcl-1 transgenic mice and significantly extends survival of 697 xenograft severe combined immunodeficient (SCID) mice without discernible toxicity. These data indicate silvestrol has efficacy against B cells in vitro and in vivo and identify translational inhibition as a potential therapeutic target in B-cell leukemias.
Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT
Authors: Kang Qiaozhen , Yu Yu , Pei Xinhong , Hughes Richard , Heck Susanne , Zhang Xihui , Guo Xinhua , Halverson Gregory , Mohandas Narla , An Xiuli 
Published: February 2009

AbstractProtein 4.1R (4.1R) was first identified in red cells where it plays an important role in maintaining mechanical stability of red cell membrane. 4.1R has also been shown to be expressed in T cells, but its function has been unclear. In the present study, we use 4.1R-deficient mice to explore the role of 4.1R in T cells. We show that 4.1R is recruited to the immunologic synapse after T cell–antigen receptor (TCR) stimulation. We show further that CD4+ T cells of 4.1R−/− mice are hyperactivated and that they displayed hyperproliferation and increased production of interleukin-2 (IL-2) and interferon γ (IFNγ). The hyperactivation results from enhanced phosphorylation of LAT and its downstream signaling molecule ERK. The 4.1R exerts its effect by binding directly to LAT, and thereby inhibiting its phosphorylation by ZAP-70. Moreover, mice deficient in 4.1R display an elevated humoral response to immunization with T cell–dependent antigen. Thus, we have defined a hitherto unrecognized role for 4.1R in negatively regulating T-cell activation by modulating intracellular signal transduction.
Nutlin-3 up-regulates the expression of Notch1 in both myeloid and lymphoid leukemic cells, as part of a negative feedback antiapoptotic mechanism
Authors: Secchiero Paola , Melloni Elisabetta , di Iasio Maria Grazia , Tiribelli Mario , Rimondi Erika , Corallini Federica , Gattei Valter , Zauli Giorgio 
Published: February 2009

AbstractThe small molecule inhibitor of the MDM2/p53 interaction Nutlin-3 significantly up-regulated the steady-state mRNA and protein levels of Notch1 in TP53wild-type (OCI, SKW6.4) but not in TP53deleted (HL-60) or TP53mutated (BJAB) leukemic cell lines. A direct demonstration that NOTCH1 was a transcriptional target of p53 in leukemic cells was obtained in experiments carried out with siRNA for p53. Moreover, inhibition of Notch1 expression using Notch1-specific siRNA significantly increased cytotoxicity in TP53wild-type leukemic cells. Of note, Nutlin-3 up-regulated Notch1 expression also in primary TP53wild-type B-chronic lymphocytic leukemia (B-CLL) cells and the combined use of Nutlin-3 plus pharmacological γ-secretase inhibitors of the Notch signaling showed a synergistic cytotoxicity in both TP53wild-type leukemic cell lines and primary B-CLL cells. A potential drawback of γ-secretase inhibitors was their ability to enhance osteoclastic maturation of normal circulating preosteoclasts induced by RANKL + M-CSF. Notwithstanding, Nutlin-3 completely suppressed osteoclastogenesis irrespective of the presence of γ-secretase inhibitors. Taken together, these data indicate that the p53-dependent up-regulation of Notch1 in response to Nutlin-3 represents an antiapoptotic feedback mechanism able to restrain the potential therapeutic efficacy of Nutlin-3 in hematologic malignancies. Therefore, therapeutic combinations of Nutlin-3 + γ-secretase inhibitors might potentiate the cytotoxicity of Nutlin-3 in p53wild-type leukemic cells.
Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration
Authors: Lämmermann Tim , Renkawitz Jörg , Wu Xunwei , Hirsch Karin , Brakebusch Cord , Sixt Michael 
Published: February 2009

Abstract
Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated, which leads to impaired leading edge coordination. Although this defect still allows the cells to move on 2-dimensional surfaces, their in vivo motility is completely abrogated. We show that this difference is entirely caused by the geometric complexity of the environment, as multiple competing protrusions lead to instantaneous entanglement within 3-dimensional extracellular matrix scaffolds. This demonstrates that the decisive factor for migrating DCs is not specific interaction with the extracellular environment, but adequate coordination of cytoskeletal flow.
In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent
Authors: Zolfaghari Parjam S , Packer Samantha , Singer Mervyn , Nair Sean P , Bennett Jon , Street Cale , Wilson Michael 
Published: February 2009

Abstract

Background
The widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models.

Results
Following irradiation of wounds with 360 J/cm2 of laser light (670 nm) in the presence of 100 μg/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours.

Conclusion
The results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites.
An extension to a statistical approach for family based association studies provides insights into genetic risk factors for multiple sclerosis in the HLA-DRB1gene
Authors: Ramagopalan Sreeram V , McMahon Roisin , Dyment David A , Sadovnick A Dessa , Ebers George C , Wittkowski Knut M 
Published: February 2009

Abstract

Background
Multiple sclerosis (MS) is a complex trait in which genes in the MHC class II region exert the single strongest effect on genetic susceptibility. The principal MHC class II haplotype that increases MS risk in individuals of Northern European descent are those that bear HLA-DRB1*15. However, several other HLA-DRB1 alleles have been positively and negatively associated with MS and each of the main allelotypes is composed of many sub-allelotypes with slightly different sequence composition. Given the role of this locus in antigen presentation it has been suggested that variations in the peptide binding site of the allele may underlie allelic variation in disease risk.

Methods
In an investigation of 7,333 individuals from 1,352 MS families, we assessed the nucleotide sequence of HLA-DRB1 for any effects on disease susceptibility extending a recently published method of statistical analysis for family-based association studies to the particular challenges of hyper-variable genetic regions.

Results
We found that amino acid 60 of the HLA-DRB1 peptide sequence, which had previously been postulated based on structural features, is unlikely to play a major role. Instead, empirical evidence based on sequence information suggests that MS susceptibility arises primarily from amino acid 13.

Conclusion
Identifying a single amino acid as a major risk factor provides major practical implications for risk and for the exploration of mechanisms, although the mechanism of amino acid 13 in the HLA-DRB1 sequence's involvement in MS as well as the identity of additional variants on MHC haplotypes that influence risk need to be uncovered.
Knowledge of modifiable risk factors of Coronary Atherosclerotic Heart Disease (CASHD) among a sample in India
Authors: Saeed Omar , Gupta Vineet , Dhawan Naveen , Streja Leanne , Shin John S , Ku Melvin , Bhoi Sanjeev , Verma Sanjay 
Published: February 2009

Abstract

Background
The prevalence of Coronary Atherosclerotic Heart Disease (CASHD) is increasing in India. Several modifiable risk factors contribute directly to this disease burden. Public knowledge of such risk factors among the urban Indian population is largely unknown. This investigation attempts to quantify knowledge of modifiable risk factors of CASHD as sampled among an Indian population at a large metropolitan hospital.

Methods
A hospital-based, cross sectional study was conducted at All India Institute of Medical Sciences (AIIMS), a major tertiary care hospital in New Delhi, India. Participants (n = 217) recruited from patient waiting areas in the emergency room were provided with standardized questionnaires to assess their knowledge of modifiable risk factors of CASHD. The risk factors specifically included smoking, hypertension, elevated cholesterol levels, diabetes mellitus and obesity. Identifying 3 or less risk factors was regarded as a poor knowledge level, whereas identifying 4 or more risk factors was regarded as a good knowledge level. A multiple logistic regression model was used to isolate independent demographic markers predictive of a participant's level of knowledge.

Results
41% of the sample surveyed had a good level of knowledge. 68%, 72%, 73% and 57% of the population identified smoking, obesity, hypertension, and high cholesterol correctly, respectively. 30% identified diabetes mellitus as a modifiable risk factor of CASHD. In multiple logistic regression analysis independent demographic predictors of a good knowledge level with a statistically significant (p < 0.05) adjusted odds ratio (aOR) were: routine exercise of moderate intensity, aOR 8.41 (compared to infrequent or no exercise), no history of smoking, aOR 8.25, and former smokers, aOR 48.28 (compared to current smokers). Although statistically insignificant, a trend towards a good knowledge level was associated with higher levels of education.

Conclusion
An Indian population in a hospital setting shows a lack of knowledge pertaining to modifiable risk factors of CASHD. By isolating demographic predictors of poor knowledge, such as current smokers and persons who do not exercise regularly, educational interventions can be effectively targeted and implemented as primary and secondary prevention strategies to reduce the burden of CASHD in India.
The association between foot‐care self efficacy beliefs and actual foot‐care behaviour in people with peripheral neuropathy: a cross‐sectional study
Authors: Perrin Byron M , Swerissen Hal , Payne Craig 
Published: February 2009

AbstractBackgroundPeople with diabetes and peripheral neuropathy often do not implement the foot‐care behavioural strategies that are suggested by many health professionals. The concept of self‐efficacy has been shown to be an effective predictor of behaviour in many areas of health. This study investigated the relationships between foot‐care self‐efficacy beliefs, self‐reported foot‐care behaviour and history of diabetes‐related foot pathology in people with diabetes and loss of protective sensation in their feet.MethodsNinety‐six participants were included in this cross‐sectional study undertaken in a regional city of Australia. All participants had diabetes and clinically diagnosed loss of protective sensation in their feet. The participants completed a self‐report pen‐paper questionnaire regarding foot‐care self efficacy beliefs (the “Foot Care Confidence Scale”) and two aspects of actual foot‐care behaviour‐preventative behaviour and potentially damaging behaviour. Pearson correlation coefficients were then calculated to determine the association between foot‐care self‐efficacy beliefs and actual reported foot‐care behaviour. Multiple analysis of variance was undertaken to compare mean self‐efficacy and behaviour subscale scores for those with a history of foot pathology, and those that did not.ResultsA small positive correlation (r = 0.2, p = 0.05) was found between self‐efficacy beliefs and preventative behaviour. There was no association between self‐efficacy beliefs and potentially damaging behaviour. There was no difference in self‐efficacy beliefs in people that had a history of foot pathology compared to those that did not.ConclusionThere is little association between foot‐care self‐efficacy beliefs and actual foot‐care behaviour. The usefulness of measuring foot‐care self‐efficacy beliefs to assess actual self foot‐care behaviour using currently available instruments is limited in people with diabetes and loss of protective sensation.
Complete remission of primary plasma cell leukemia with bortezomib, doxorubicin, and dexamethasone: a case report
Authors: Chan Steven M , George Tracy , Cherry Athena M , Medeiros Bruno C 
Published: February 2009

Abstract

Background
Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder considered to be a variant of multiple myeloma. It is an aggressive disease with a poor clinical response to standard chemotherapeutic agents.

Case presentation
A novel regimen consisting of bortezomib, doxorubicin, and dexamethasone is currently under active evaluation for the treatment of multiple myeloma. We employed this combination as front-line chemoinduction therapy for a case of primary PCL.

Conclusion
Complete remission was achieved with rapid normalization of hematologic parameters. The combination of bortezomib, doxorubicin and dexamethasone demonstrates promise in the treatment of PCL.
The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover
Authors: Bay-Jensen Anne-Christine , Tabassi Nadine CB , Sondergaard Lene V , Andersen Thomas L , Dagnaes-Hansen Frederik , Garnero Patrick , Kassem Moustapha , Delaissé Jean-Marie 
Published: February 2009

Abstract
Introduction
The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen turnover markers known to be affected in osteoarthritis, and whether it relates to its presence in specific areas of cartilage tissue.

Methods
The type II collagen degradation markers CTX-II and Helix-II were measured in the body fluids of premenopausal and postmenopausal women and in those of ovariectomised rats receiving oestrogen or not. Levels of PIIANP, a marker of type II collagen synthesis, were also measured in rats. Rat knee cartilage was analysed for immunoreactivity of CTX-II and PIIANP and for type II collagen expression.

Results
As expected, urinary levels of CTX-II are significantly increased in postmenopausal women and also in oestrogen-deprived rats, although only transiently. However, in neither case were these elevations paralleled by a significant increase of Helix-II levels and PIIANP levels did not change at any time. CTX-II immunoreactivity and collagen expression were detected in different cartilage areas. The upper zone is the area where CTX-II immunoreactivity and collagen expression best reflected the differences in urinary levels of CTX-II measured in response to oestrogen. However, correlations between urinary levels of CTX-II and tissue immunostainings in individual rats were not statistically significant.

Conclusions
We found only a small effect of oestrogen deprivation on cartilage. It was detected by CTX-II, but not by other type II collagen turnover markers typically affected in osteoarthritis.
The Cadenza as Parenthesis
Authors: Bribitzer-Stull Matthew 
Published: February 2009

Conventional wisdom holds that the cadenza is a musical parenthesis. Like linguistic parenthetical remarks, cadenzas may be engaging, illuminating, and insightful, but they are not regarded as intrinsic to structural coherence. Perhaps for this reason, the topic has remained parenthetical in modern music theory discourse. Despite the connotations this neglect implies, the cadenza tradition stands as one endowed with great musical richness, worthy of further analytic investigation.This article seeks to define the dual function of the cadenza. Specifically, the cadenza is heard simultaneously as a local, harmonic event and as a global, formal event. On the local level, it may either prolong one harmony or progress from one to another. On the global level, it can serve a variety of formal functions: highlighting salient cadences; opening a space for virtuosic display; and developing, relating, and rehearing elements of the concerto movement proper.The cadenza's dual function grants it a potential far exceeding the simple characterization as parenthesis. Skillfully composed cadenzas exploit the tension between local and global functions and can initiate subtle yet profound rehearings of music outside cadenza space—rehearings that give us pause to reconsider both the cadenza-as-parenthesis metaphor and the artificial boundaries we construct among composer, performer, and analyst.
Synthesis and control of generalized dynamically substructured systems
Authors: Stoten D P , Tu J Y , Li G 
Published: February 2009

The experimental technique for testing engineering systems via the method of dynamic substructuring is receiving significant global interest, for example in the fields of large-scale structural, aerospace, and automotive system testing. Dynamically substructured systems (DSSs) enable full-size, critical components of a complete system to be physically tested in real-time, within a laboratory environment, while the remainder of the system is modelled numerically. The intention is that the combined physical-numerical DSS behaves as if it were the complete (or emulated) system. In an ideal mechanical DSS, for example, perfect synchronization of displacements and forces at the interfaces between the numerical and physical components (or substructures) is required. Hence, a key design feature of successful DSS systems is the high fidelity of the control action. Equally, a DSS controller must be able to cope with non-linear, time-varying, and uncertain parameters within the physical substructure dynamics. The main purpose of this paper is to present a generalized DSS framework, together with associated linear and adaptive control strategies, that are specifically tailored to achieve high synchronization performance. The initial studies of this problem, as described in an earlier paper by Stoten and Hyde, are therefore continued by generalizing both the DSS dynamics and the control strategies to include (a) a number of newly defined modes of operation and (b) multivariable dynamics. In addition, comparative implementation and simulation studies are included, based upon the DSS testing of a mechanical system (a planar quasi-motorcycle rig), which was specifically designed to highlight the main features of this research. The comparative studies show that excellent DSS control can be achieved, especially with the addition of an adaptive component to the controller, despite significant changes to the physical substructure dynamics.