bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of DNA Repair Protein Foci for the Detection of Putative BRCA1 Pathway Defects in Breast Cancer Biopsies
Authors: Willers Henning , Taghian Alphonse G. , Luo Chen-Mei , Treszezamsky Alejandro , Sgroi Dennis C. , Powell Simon N. 
Published: August 2009

Abstract
The DNA damage response pathway controlled by the breast cancer and Fanconi anemia (FA) genes can be disrupted by genetic or epigenetic mechanisms in breast cancer. Defects in this pathway may render the affected tumors hypersensitive to DNA-damaging agents. The identification of these defects poses a challenge because of the large number of genes involved in the FA/BRCA pathway. Many pathway components form subnuclear repair protein foci upon exposure to ionizing radiation in vitro, but it was unknown whether foci can be detected in live cancer tissues. Thus, the goal of this pilot study was to identify pathway defects by using a novel ex vivo foci biomarker assay on tumor biopsies. Fresh pretreatment biopsy specimens from patients with locally advanced sporadic breast cancer were irradiated or mock-treated in the laboratory (ex vivo). Foci formation of DNA repair proteins BRCA1, FANCD2, and RAD51 was detected by immunofluorescence microscopy. Three out of seven tumors showed intact radiation-induced foci formation, whereas the other four tumors exhibited a defective foci response. Notably, three of the foci-defective tumors were estrogen receptor/progesterone receptor/HER2–negative (triple-negative), a phenotype that has been associated with BRCA1 deficiency. In conclusion, in this pilot study, we report the successful detection of BRCA1, FANCD2, and RAD51 foci in breast cancer biopsies irradiated ex vivo. Our approach represents a potentially powerful biomarker assay for the detection of pre-existing and functionally important defects within the complex FA/BRCA pathway, which may ultimately allow us to tailor cancer treatment to the DNA repair profile of individual tumors. (Mol Cancer Res 2009;7(8):1304–9)
Mortality after First Myocardial Infarction in Greek Patients: A 4-Year Follow-Up Study
Authors: Kolovou Genovefa D. , Mihas Constantinos , Kotanidou Anastasia , Dimoula Yvoni , Karkouli Georgia , Kadda Olga , Anagnostopoulou Katherine , Mikhailidis Dimitri P. , Marvaki Christina 
Published: August 2009

Background Death associated with coronary heart disease (CHD) depends in part on the time since the myocardial infarction (MI) and modification of risk factors. Methods This observational, retrospective 4-year follow-up study consisted of 804 patients (628 men). The participants completed a questionnaire reporting diet, demographic factors, personal behavior (smoking, physical activity), anthropometry, prior medical conditions (hypertension, diabetes mellitus), and recent medication. Results During 48 months of follow-up, 12% of men and 15% of women died. Older age, longer duration of smoking, and frequency of exercise were significantly different between survivors and the deceased ( P = .014, P = .014, P = .001, respectively). Multivariate analysis revealed associations with years of smoking (odds ratio, OR: 1.10, P = .025), treatment with nitrates (OR: 4.81, P = .024), and increased frequency of exercise (OR: 0.42, P = .013), adjusting for age and gender. Conclusions We should emphasize cessation of smoking and increased physical activity in MI survivors. Antismoking programs should start at an early age.
Development of a DiaBEATes Nurse Champion Program
Authors: Uplinger Nadine , Turkel Marian C. , Adams Patricia C. , Nelson-Slemmer Debra , Pierce Susan 
Published: August 2009

Purpose This article shares an innovative educational practice for increasing the knowledge base of direct-care registered nurses related to diabetes management. Outcome data include quantitative analysis of test scores, qualitative responses of changes in practice, and participation in monthly diabetes resource meetings. Conclusion Diabetes educators will find the DiaBEATes Nurse Champion program useful for structuring educational programs within various practice settings. The case studies are useful tools for evaluating specific application of diabetes knowledge. Background The nearly 24 million people with diabetes strain the health care system in terms of resources and health care dollars. According to the American Diabetes Association (ADA) a hospital stay for a patient with diabetes costs almost 3 times the stay of a patient without diabetes.1 The higher costs associated with caring for a patient with diabetes is partly attributed to inadequate knowledge regarding current diabetes treatment options and the failure of some health care workers to accept professional responsibility for diabetes management. 2,3
The effectiveness of a caring protocol: An evaluation study
Authors: Luk Andrew 
Published: August 2009

Abstract Caring has long been affirmed as the essence in nursing. A caring protocol was developed to enhance professional caring and served as a tool to establish a caring culture within a cluster of hospitals. The protocol encompasses three essential elements of professional caring: image, attitude and behaviour. It aims to assess the effectiveness of the protocol in two convalescent hospitals with the objectives to: (1) gain the responses from patients and relatives and (2) explore the feedback from nursing and supporting staff. A mixed method was adopted: a pre- and post-test design and focus group interviews. Nursing and supporting staff from 18 wards were recruited for the study using the caring protocol in two convalescent hospitals. A positive response was obtained from patients and relatives after the implementation of the protocol. Nursing and supporting staff appreciated the implementation process, which could enhance caring. Valuable suggestions were also gathered to maintain the caring culture in wards. The caring protocol is an effective way in enhancing professional caring in hospitals shown by the positive responses from patients and relatives. The protocol was also well accepted by nursing and supporting staff and had a significant impact demonstrated on supporting staff.
Commitment expressions of nurses aged 45 and over: Organisational, professional and personal factors
Authors: Bennett Janette , Davey Barbara , Harris Ruth 
Published: August 2009

Abstract The aims of the study were to explore personal, professional and organisational factors that would affect future participation in the workforce of nurses aged 45 and over. The research was proposed against a background of concerns about a shortage of a skilled nursing workforce in London and ever increasing numbers of older nurses taking retirement. Data were collected with 37 mainly senior F grade nurses and health care assistants using a semi-structured interview schedule and biographical methods. There can be multiple expressions of commitment, which may differ at different levels of the organisation. Personal commitment (i.e., to family and children) was also very important. Expressions of commitment were not expressed in isolation, this means commitment is negotiated, contested and sustained across and within multiple situations.
Preparing the air for nursing care: A grounded theory study of first line nurse managers
Authors: Bondas Terese 
Published: August 2009

Abstract The first line nurse managers’ opportunities to lead nursing care seem to be diminishing. The aim of this study was, therefore, to gain an understanding of the first line nurse managers in their experiences in the development of nursing care as part of a wider research programme. Finnish nurse managers wrote narratives at the beginning of five different leadership courses in this grounded theory study. ‘Preparing the Air for Nursing Care’ emerged as a core category. It was formed by two major categories. ‘Being Concerned about Nursing Care’ describes the nurse managers’ focus on the development of nursing care, the nursing caregivers’ health and knowledge and a concern for the whole organisation. The second major category ‘Creating the Direction and Content of Nursing Care’ describes the nurse manager working together with the staff to create individual and family-centred best practice, initiating relationships and dialogues for nursing care, and a culture of caring. A typology was created that explained the four main modalities to emerge from the data: ‘the Active Developer’, ‘the Passive Thinker’, ‘the Impulsive Creator’ and ‘the Routine Manager’.
Comparison of two tools developed to assess the needs of older people with complex care needs
Authors: Lambert Susan , Cheung Wai-Yee , Davies Shan , Gardner Lyn , Thomas Valerie 
Published: August 2009

Abstract Greater standardisation of assessments of older people with complex care needs is a requirement of UK policy. This study explores the practicability and validity of two assessment tools, Minimum Data Set Resident Assessment Instrument (MDS-RAI) and EASY-Care. Participants, aged 65 years or over, living in care homes or awaiting hospital discharge, were assessed using randomly allocated paired instruments. Client evaluation questionnaires on the practicability of the tools were completed. Short Form 12 (SF12) questionnaires were administered to assess participants’ health status. Registered nurses undertook data collection and participated in two focus groups designed to explore the practicability of the tools. Statistical tests were applied to quantitative data to assess practicability and validity. Thematic content analysis was used to analyse focus group transcripts. In all, 238 assessments were completed. Older people and assessors generally reported that both tools were practicable, with EASY-Care preferred to MDS-RAI for practicability measures including ease of use, usefulness and acceptability. Focus groups illustrated the significance of professional judgement when using structured tools. Both tools were reasonable indicators of activities of daily living, but there were shortcomings in measurements of cognitive performance and depression. Both instruments require development to fully capture the older person’s perspectives of needs and to test the validity of key measures.
A qualitative study exploring practice nurses’ experience of participating in a primary care–based randomised controlled trial
Authors: Potter Rachel , Dale Jeremy , Caramlau Isabela 
Published: August 2009

Abstract The aim of this study is to explore the views of practice nurses’ recruiting into a primary care–based randomised controlled trial, and to investigate factors that influence the success of trial recruitment. It is known that time pressures, forgetfulness and lack of interest in the research topic negatively influence recruitment into research trials by General Practitioners (GPs), but no studies appear to have explored practice nurses’ experience of recruiting into trials. Semi-structured telephone interviews were conducted with a non-random purposive sample of 10 practice nurses who had participated in recruiting patients for the trial, and data were analysed using a thematic framework approach. Nurses who had been asked to take part in the study found it a positive experience, and had decided to take part because the area of research was of interest and could potentially benefit patients. Nurses who had been delegated the role of recruitment by the GP felt put upon and recruited less well. None of the nurses reported difficulties remembering to recruit patients and developed useful strategies to aid memory. Nurses often acted as gatekeepers, selecting which patients they offered the intervention to. Nurses with dedicated time for research recruited more successfully. For nurses who recruited during routine consultation, it was often the patient’s lack of interest in taking part in the trial, rather than time limitations that hindered recruitment. Overall, nurses were positive about recruiting into the trial, particularly if the research area could benefit patients and if directly asked to take part.
Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome
Authors: Parlati Francesco , Lee Susan J. , Aujay Monette , Suzuki Erika , Levitsky Konstantin , Lorens James B. , Micklem David R. , Ruurs Paulina , Sylvain Catherine , Lu Yan , Shenk Kevin D. , Bennett Mark K. 
Published: August 2009

AbstractCarfilzomib is a proteasome inhibitor in clinical development that primarily targets the chymotrypsin-like (CT-L) subunits in both the constitutive proteasome (c20S) and the immunoproteasome (i20S). To investigate the impact of inhibiting the CT-L activity with carfilzomib, we set out to quantitate the levels of CT-L subunits β5 from the c20S and LMP7 from the i20S in normal and malignant hematopoietic cells. We found that the i20S is a major form of the proteasome expressed in cells of hematopoietic origin, including multiple myeloma (MM) CD138+ tumor cells. Although specific inhibition of either LMP7 or β5 alone was insufficient to produce an antitumor response, inhibition of all proteasome subunits was cytotoxic to both hematologic tumor cells and peripheral blood mononuclear cells. However, selective inhibition of both β5 and LMP7 was sufficient to induce an antitumor effect in MM, non-Hodgkin lymphoma, and leukemia cells while minimizing the toxicity toward nontransformed cells. In MM tumor cells, CT-L inhibition alone was sufficient to induce proapoptotic sequelae, including proteasome substrate accumulation, Noxa and caspase 3/7 induction, and phospho-eIF2α suppression. These data support a hypothesis that hematologic tumor cells are uniquely sensitive to CT-L inhibition and provide a mechanistic understanding of the clinical safety profile and antitumor activity of proteasome inhibitors.
Specific iron chelators determine the route of ferritin degradation
Authors: De Domenico Ivana , Ward Diane McVey , Kaplan Jerry 
Published: August 2009

AbstractDeferoxamine (DFO) is a high-affinity Fe (III) chelator produced by Streptomyces pilosus. DFO is used clinically to remove iron from patients with iron overload disorders. Orally administered DFO cannot be absorbed, and therefore it must be injected. Here we show that DFO induces ferritin degradation in lysosomes through induction of autophagy. DFO-treated cells show cytosolic accumulation of LC3B, a critical protein involved in autophagosomal-lysosomal degradation. Treatment of cells with the oral iron chelators deferriprone and desferasirox did not show accumulation of LC3B, and degradation of ferritin occurred through the proteasome. Incubation of DFO-treated cells with 3-methyladenine, an autophagy inhibitor, resulted in degradation of ferritin by the proteasome. These results indicate that ferritin degradation occurs by 2 routes: a DFO-induced entry of ferritin into lysosomes and a cytosolic route in which iron is extracted from ferritin before degradation by the proteasome.
Ligand scaffold hopping combining 3D maximal substructure search and molecular similarity
Authors: Quintus Flavien , Sperandio Olivier , Grynberg Julien , Petitjean Michel , Tuffery Pierre 
Published: August 2009

Abstract

Background
Virtual screening methods are now well established as effective to identify hit and lead candidates and are fully integrated in most drug discovery programs. Ligand-based approaches make use of physico-chemical, structural and energetics properties of known active compounds to search large chemical libraries for related and novel chemotypes. While 2D-similarity search tools are known to be fast and efficient, the use of 3D-similarity search methods can be very valuable to many research projects as integration of "3D knowledge" can facilitate the identification of not only related molecules but also of chemicals possessing distant scaffolds as compared to the query and therefore be more inclined to scaffolds hopping. To date, very few methods performing this task are easily available to the scientific community.

Results
We introduce a new approach (LigCSRre) to the 3D ligand similarity search of drug candidates. It combines a 3D maximum common substructure search algorithm independent on atom order with a tunable description of atomic compatibilities to prune the search and increase its physico-chemical relevance. We show, on 47 experimentally validated active compounds across five protein targets having different specificities, that for single compound search, the approach is able to recover on average 52% of the co-actives in the top 1% of the ranked list which is better than gold standards of the field. Moreover, the combination of several runs on a single protein target using different query active compounds shows a remarkable improvement in enrichment. Such Results demonstrate LigCSRre as a valuable tool for ligand-based screening.

Conclusion
LigCSRre constitutes a new efficient and generic approach to the 3D similarity screening of small compounds, whose flexible design opens the door to many enhancements. The program is freely available to the academics for non-profit research at: http://bioserv.rpbs.univ-paris-diderot.fr/LigCSRre.html.
Efficient production of human bivalent and trivalent anti-MUC1 Fab-scFv antibodies in Pichia pastoris
Authors: Schoonooghe Steve , Kaigorodov Vladimir , Zawisza Monika , Dumolyn Caroline , Haustraete Jurgen , Grooten Johan , Mertens Nico 
Published: August 2009

AbstractBackgroundTumour associated antigens on the surface of tumour cells, such as MUC1, are being used as specific antibody targets for immunotherapy of human malignancies. In order to address the poor penetration of full sized monoclonal antibodies in tumours, intermediate sized antibodies are being developed. The cost-effective and efficient production of these molecules is however crucial for their further success as anti-cancer therapeutics. The methylotropicP. pastorisyeast grows in cheap mineral media and is known for its short process times and the efficient production of recombinant antibody fragments like scFvs, bivalent scFvs and Fabs.ResultsBased on the anti-MUC1 PH1 Fab, we have developed bivalent PH1 bibodies and trivalent PH1 tribodies of intermediate molecular mass by adding PH1 scFvs to the C-terminus of the Fab chains using flexible peptide linkers. These recombinant antibody derivatives were efficiently expressed in both mammalian andP. pastoriscells. Stable production in NS0 cells produced 130.5 mg pure bibody and 27 mg pure tribody per litre. This high yield is achieved as a result of the high overall purification efficiency of 77%. Expression and purification of PH1 bibodies and tribodies fromPichiasupernatant yielded predominantly correctly heterodimerised products, free of light chain homodimers. The yeast-produced bi- and tribodies retained the same specific activity as their mammalian-produced counterparts. Additionally, the yields of 36.8 mg pure bibody and 12 mg pure tribody per litre supernatant make the production of these molecules inPichiamore efficient than most other previously described trispecific or trivalent molecules produced inE. coli.ConclusionBi- and tribody molecules are efficiently produced inP. pastoris. Furthermore, the yeast produced molecules retain the same specific affinity for their antigen. These results establish the value ofP. pastorisas an efficient alternative expression system for the production of recombinant multivalent Fab-scFv antibody derivatives.
High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis
Authors: Yeom Chang-Hwan , Lee Gunsup , Park Jin-Hee , Yu Jaelim , Park Seyeon , Yi Sang-Yeop , Lee Hye Ree , Hong Young Seon , Yang Joosung , Lee Sukchan 
Published: August 2009

Abstract
To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high dose concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high dose concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high dose concentration ascorbic acid occurred through inhibition of angiogenesis.
Use of information entropy measures of sitting postural sway to quantify developmental delay in infants
Authors: Deffeyes Joan E , Harbourne Regina T , DeJong Stacey L , Kyvelidou Anastasia , Stuberg Wayne A , Stergiou Nicholas 
Published: August 2009

Abstract

Background
By quantifying the information entropy of postural sway data, the complexity of the postural movement of different populations can be assessed, giving insight into pathologic motor control functioning.

Methods
In this study, developmental delay of motor control function in infants was assessed by analysis of sitting postural sway data acquired from force plate center of pressure measurements. Two types of entropy measures were used: symbolic entropy, including a new asymmetric symbolic entropy measure, and approximate entropy, a more widely used entropy measure. For each method of analysis, parameters were adjusted to optimize the separation of the results from the infants with delayed development from infants with typical development.

Results
The method that gave the widest separation between the populations was the asymmetric symbolic entropy method, which we developed by modification of the symbolic entropy algorithm. The approximate entropy algorithm also performed well, using parameters optimized for the infant sitting data. The infants with delayed development were found to have less complex patterns of postural sway in the medial-lateral direction, and were found to have different left-right symmetry in their postural sway, as compared to typically developing infants.

Conclusion
The results of this study indicate that optimization of the entropy algorithm for infant sitting postural sway data can greatly improve the ability to separate the infants with developmental delay from typically developing infants.