bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLACE OF CARE TOWARDS THE END OF LIFE IN CHILDREN AND YOUNG PEOPLE WITH LIFE-THREATENING AND LIFE-LIMITING CONDITIONS: A LITERATURE REVIEW
Authors: Beecham E , Kelly P , Candy B , Jones L , Bluebond-Langner M 
Published: February 2013

IntroductionThe UK palliative care funding review is examining use and costs of palliative care services (PCS) including provision of end of life (EoL) care for children and young people (CYP) with life-limiting and life-threatening conditions (LL/LTC). Current provision is funded through a range of statutory and voluntary organisations. Place of care (POC) towards EoL may be influenced by several factors including service availability, attitudes of health and social care professionals, and patient and family-centred issues.Aims and MethodsWe sought to review the current evidence on POC in CYP with LL/LTC towards the EoL. An initial search was conducted in January 2011 (currently being updated) of databases MEDLINE, EMBASE and CINAHL. We included empirical peer reviewed papers published between 2004–2011 with data on POC for CYP towards the EoL.ResultsTo date 28 papers meet review inclusion criteria. Study quality is variable. We found evidence that CYP with Leukaemia, Lymphoma, and Cystic Fibrosis, those from ethnic minorities and those aged less than 1 year were more likely to die in hospital. CYP with solid tumours, those aged more than 1 year and those of male gender were more likely to die at home. Explanations for POC were poorly evidenced; most studies cited availability/access of services but few explored issues underlying preferences for POC.ConclusionsKnowledge and understanding of factors affecting POC for CYP towards EoL is limited. Robust data are required to inform PCS provision and ensure that funding is available for care in appropriate locations to meet CYP clinical needs and family preferences.
Targeting uPAR with Antagonistic Recombinant Human Antibodies in Aggressive Breast Cancer
Authors: LeBeau Aaron M. , Duriseti Sai , Murphy Stephanie T. , Pepin Francois , Hann Byron , Gray Joe W. , VanBrocklin Henry F. , Craik Charles S. 
Published: February 2013

Abstract
Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and 111In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard 18F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope 177Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology. Cancer Res; 73(7); 2070–81. ©2013 AACR.
Differential Contributions of STAT5A and STAT5B to Stress Protection and Tyrosine Kinase Inhibitor Resistance of Chronic Myeloid Leukemia Stem/Progenitor Cells
Authors: Casetti Luana , Martin-Lannerée Séverine , Najjar Imen , Plo Isabelle , Augé Sylvie , Roy Lydia , Chomel Jean-Claude , Lauret Evelyne , Turhan Ali G. , Dusanter-Fourt Isabelle 
Published: February 2013

Abstract
STAT5 fulfills essential roles in hematopoietic stem cell (HSC) self-renewal and chronic myeloid leukemia (CML), a prototypical stem cell malignancy. However, the specific contributions of the two related genes STAT5A and STAT5B have not been determined. In this study, we used a RNAi-based strategy to establish participation of these genes to CML disease and persistence following targeted therapy. We showed that STAT5A/STAT5B double-knockdown triggers CML cell apoptosis and suppresses both normal and CML HSC long-term clonogenic potential. STAT5A and STAT5B exhibited similar prosurvival activity, but STAT5A attenuation alone was ineffective at impairing growth of normal and CML CD34+ cells isolated at diagnosis. In contrast, STAT5A attenuation was sufficient to enhance basal oxidative stress and DNA damage of normal CD34+ and CML cells. Furthermore, it weakened the ability to manage exogenous oxidative stress, increased p53 (TRP53)/CHK-2 (CHEK2) stress pathway activation, and enhanced prolyl hydroxylase domain (PHD)-3 (EGLN3) mRNA expression. Only STAT5A and its transactivation domain-deficient mutant STAT5AΔ749 specifically rescued these activities. STAT5A attenuation was also active at inhibiting growth of CML CD34+ cells from patients with acquired resistance to imatinib. Our findings show that STAT5A has a selective role in contributing to stress resistance through unconventional mechanisms, offering new opportunities to eradicate the most primitive and tyrosine kinase inhibitor–resistant CML cells with an additional potential to eradicate persistent stem cell populations. Cancer Res; 73(7); 2052–8. ©2013 AACR.
Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?
Authors: Thompson Andrew , Nelson Barnaby , Bruxner Annie , O’Connor Karen , Mossaheb Nilufar , Simmons Magenta B , Yung Alison 
Published: February 2013

Objectives: Studies have attempted to identify additional risk factors within the group identified as ‘ultra high risk’ (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. Method: A retrospective ‘case–control’ methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Results: Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Conclusions: Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.
Integrating community mental health within primary care in southern Malawi: A pilot educational intervention to enhance the role of health surveillance assistants
Authors: Wright Jerome , Common Stephanie , Kauye Felix , Chiwandira Chikayiko 
Published: February 2013

Background: In response to the significant contribution of mental health problems to the global burden of disease, the World Health Organization (WHO, 2008) renewed its call for the integration of mental health services within primary care. The operationalization of this within resource-constrained settings such as rural Malawi, however, presents a challenge, not least the cultural acceptance of approaches to responding to psychological distress. Aim: This study reports on the development, implementation and evaluation of a mental health care training programme for 271 health surveillance assistants (HSAs) designed to overcome such challenges. Method: A structured evaluation of the impact of training on HSAs’ provision of mental health care was undertaken. Results: Results demonstrated a statistically significant positive effect on HSAs’ knowledge and confidence in providing care and analysis of patient records revealed considerable mental health care and health promotion activity wherein HSAs initiated a new dialogue with the community on mental health and human rights concerns. Conclusion: The HSAs’ focus on the psychosocial concerns of individuals’ ‘distress’ and ‘risk’ prepared the way for a practical set of culturally sensitive and therapeutic interventions and offers a potential path towards increasing the capacity of primary care mental health provision that is responsive to local understandings and experiences of distress.
Constituent Moments, Constitutional Processes
Authors: Ciccariello-Maher George 
Published: February 2013

The “good-left-versus-bad-left” framework disseminated by Jorge Castañeda, among others, obscures the underlying similarities that cut across all leftist regimes in Latin America while drastically oversimplifying the relationship between the so-called bad left and its “good” counterpart. A shift of focus from heads of state to social movements reveals both that the question of social movements and the state transcends such binaries and that it is precisely within the “bad left” that we find some important lessons for the future. El marco de “buena izquierda versus mala izquierda” diseminado por Jorge Castañeda, entre otros, opaca las similitudes básicas que cortan a través de todos los regímenes izquierdistas en América Latina, y a la vez simplifica de manera extrema la relación entre la llamada mala izquierda y su contraparte buena. Un cambio de enfoque de los mandatarios a los movimientos sociales revela tanto que la cuestión de movimientos sociales y el Estado trascienden tales binarias, como que es precisamente dentro de la “mala izquierda” que encontramos importantes lecciones para el futuro.
Numeracy and Dietary Intake in Patients With Type 2 Diabetes
Authors: Bowen Michael E. , Cavanaugh Kerri L. , Wolff Kathleen , Davis Dianne , Gregory Becky , Rothman Russell L. 
Published: February 2013

Purpose The purpose of this study is to describe the association between numeracy and self-reported dietary intake in patients with type 2 diabetes. Methods Numeracy and dietary intake were assessed with the validated Diabetes Numeracy Test and a validated food frequency questionnaire in a cross-sectional study of 150 primary care patients enrolled in a randomized clinical trial at an academic medical center between April 2008 and October 2009. Associations between numeracy and caloric and macronutrient intakes were examined with linear regression models. Results Patients with lower numeracy consumed a higher percentage of calories from carbohydrates and lower percentages from protein and fat. However, no differences in energy consumption or the percentage of energy intake owing to carbohydrates, fat, or protein were observed in adjusted analyses. Patients with lower numeracy were significantly more likely to report extremely high or low energy intake inconsistent with standard dietary intake. Conclusions Numeracy was not associated with dietary intake in adjusted analyses. Low numeracy was associated with inaccurate dietary reporting. Providers who take dietary histories in patients with diabetes may need to consider numeracy in their assessment of dietary intake.
Complications After Tendon Transfers in the Foot and Ankle Using Bioabsorbable Screws
Authors: Clanton Thomas O. , Betech Alex A. , Bott Aaron M. , Matheny Lauren M. , Hartline Braden , Hanson Travis W. , McGarvey William C. 
Published: February 2013

Background: Tendon transfers are commonly used for correction of pathology or deformity of the foot and ankle. Bioabsorbable implants have been developed as an alternative to metal interference screws. The purpose of this study was to document complications following tendon transfers of the foot and ankle using bioabsorbable poly-L-lactide interference screws. Methods: A retrospective chart review was used to identify patients in whom either of the 2 senior authors had performed a tendon transfer of the foot and ankle using a bioabsorbable interference screw between 1999 and 2005. A minimum of 6 months of follow-up was required for inclusion in the study. In all, 31 patients were identified who met the inclusion criteria with an average follow-up of 75 weeks. All screws were made of poly-L-lactide (PLLA). Results: Complications were identified in 12 (39%) of patients. All of the complications reported were known complications of the tendon transfer procedure itself, and were not directly related to the bioabsorbable screw. Conclusions: Based on these early results, PLLA implants appear safe and effective for tendon transfers of the foot and ankle. However, until long-term outcomes are available, judicious use of these implants is recommended. Level of Evidence: Level IV, retrospective case series.
Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes
Authors: Satoh Jun-ichi , Tabunoki Hiroko 
Published: February 2013

Background: Vitamin D is a liposoluble vitamin essential for calcium metabolism. The ligand-bound vitamin D receptor (VDR), heterodimerized with retinoid X receptor, interacts with vitamin D response elements (VDREs) to regulate gene expression. Vitamin D deficiency due to insufficient sunlight exposure confers an increased risk for multiple sclerosis (MS). Objective: To study a protective role of vitamin D in multiple sclerosis (MS), it is important to characterize the global molecular network of VDR target genes (VDRTGs) in immune cells. Methods: We identified genome-wide VDRTGs collectively from two distinct chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of VDR-binding sites derived from calcitriol-treated human cells of B cell and monocyte origins. We mapped short reads of next generation sequencing (NGS) data on hg19 with Bowtie, detected the peaks with Model-based Analysis of ChIP-Seq (MACS), and identified genomic locations by GenomeJack, a novel genome viewer for NGS platforms. Results: We found 2997 stringent peaks distributed on protein-coding genes, chiefly located in the promoter and the intron on VDRE DR3 sequences. However, the corresponding transcriptome data verified calcitriol-induced upregulation of only a small set of VDRTGs. The molecular network of 1541 calcitriol-responsive VDRTGs showed a significant relationship with leukocyte transendothelial migration, Fcγ receptor-mediated phagocytosis, and transcriptional regulation by VDR, suggesting a pivotal role of genome-wide VDRTGs in immune regulation. Conclusion: These results suggest the working hypothesis that persistent deficiency of vitamin D might perturb the complex network of VDRTGs in immune cells, being responsible for induction of an autoimmune response causative for MS.
Metazoan-like signaling in a unicellular receptor tyrosine kinase
Authors: Schultheiss Kira P , Craddock Barbara P , Tong Michael , Seeliger Markus , Miller W Todd 
Published: February 2013

Abstract

Background
Receptor tyrosine kinases (RTKs) are crucial components of signal transduction systems in multicellular animals. Surprisingly, numerous RTKs have been identified in the genomes of unicellular choanoflagellates and other protists. Here, we report the first biochemical study of a unicellular RTK, namely RTKB2 from Monosiga brevicollis.

Results
We cloned, expressed, and purified the RTKB2 kinase, and showed that it is enzymatically active. The activity of RTKB2 is controlled by autophosphorylation, as in metazoan RTKs. RTKB2 possesses six copies of a unique domain (designated RM2) in its C-terminal tail. An isolated RM2 domain (or a synthetic peptide derived from the RM2 sequence) served as a substrate for RTKB2 kinase. When phosphorylated, the RM2 domain bound to the Src homology 2 domain of MbSrc1 from M. brevicollis. NMR structural studies of the RM2 domain indicated that it is disordered in solution.

Conclusions
Our results are consistent with a model in which RTKB2 activation stimulates receptor autophosphorylation within the RM2 domains. This leads to recruitment of Src-like kinases (and potentially other M. brevicollis proteins) and further phosphorylation, which may serve to increase or dampen downstream signals. Thus, crucial features of signal transduction circuitry were established prior to the evolution of metazoans from their unicellular ancestors.
Semantic representation of monogenean haptoral Bar image annotation
Authors: Abu Arpah , Susan Lim Lee Hong , Sidhu Amandeep Singh , Dhillon Sarinder Kaur 
Published: February 2013

Abstract

Background
Digitised monogenean images are usually stored in file system directories in an unstructured manner. In this paper we propose a semantic representation of these images in the form of a Monogenean Haptoral Bar Image (MHBI) ontology, which are annotated with taxonomic classification, diagnostic hard part and image properties. The data we used are basically of the monogenean species found in fish, thus we built a simple Fish ontology to demonstrate how the host (fish) ontology can be linked to the MHBI ontology. This will enable linking of information from the monogenean ontology to the host species found in the fish ontology without changing the underlying schema for either of the ontologies.

Results
In this paper, we utilized the Taxonomic Data Working Group Life Sciences Identifier (TDWG LSID) vocabulary to represent our data and defined a new vocabulary which is specific for annotating monogenean haptoral bar images to develop the MHBI ontology and a merged MHBI-Fish ontologies. These ontologies are successfully evaluated using five criteria which are clarity, coherence, extendibility, ontology commitment and encoding bias.

Conclusions
In this paper, we show that unstructured data can be represented in a structured form using semantics. In the process, we have come up with a new vocabulary for annotating the monogenean images with textual information. The proposed monogenean image ontology will form the basis of a monogenean knowledge base to assist researchers in retrieving information for their analysis.
Insights into the evolution of Darwin’s finches from comparative analysis of the Geospiza magnirostris genome sequence
Authors: Rands Chris M , Darling Aaron , Fujita Matthew , Kong Lesheng , Webster Matthew T , Clabaut Céline , Emes Richard D , Heger Andreas , Meader Stephen , Hawkins Michael Brent , Eisen Michael B , Teiling Clotilde , Affourtit Jason , Boese Benjamin , Grant Peter R , Grant Barbara Rosemary , Eisen Jonathan A , Abzhanov Arhat , Ponting Chris P 
Published: February 2013

AbstractBackgroundA classical example of repeated speciation coupled with ecological diversification is the evolution of 14 closely related species of Darwin’s (Galápagos) finches (Thraupidae, Passeriformes). Their adaptive radiation in the Galápagos archipelago took place in the last 2–3 million years and some of the molecular mechanisms that led to their diversification are now being elucidated. Here we report evolutionary analyses of genome of the large ground finch,Geospiza magnirostris.Results13,291 protein-coding genes were predicted from a 991.0 Mb G. magnirostrisgenome assembly. We then defined gene orthology relationships and constructed whole genome alignments between theG. magnirostrisand other vertebrate genomes. We estimate that 15% of genomic sequence is functionally constrained betweenG. magnirostrisand zebra finch. Genic evolutionary rate comparisons indicate that similar selective pressures acted along theG. magnirostrisand zebra finch lineages suggesting that historical effective population size values have been similar in both lineages. 21 otherwise highly conserved genes were identified that each show evidence for positive selection on amino acid changes in the Darwin's finch lineage. Two of these genes (Igf2randPou1f1) have been implicated in beak morphology changes in Darwin’s finches. Five of 47 genes showing evidence of positive selection in early passerine evolution have cilia related functions, and may be examples of adaptively evolving reproductive proteins.ConclusionsThese results provide insights into past evolutionary processes that have shapedG. magnirostrisgenes and its genome, and provide the necessary foundation upon which to build population genomics resources that will shed light on more contemporaneous adaptive and non-adaptive processes that have contributed to the evolution of the Darwin’s finches.
A synergistic interaction between transcription factors nuclear factor-κB and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion
Authors: Yoon Jiyeon , Cho Sung Jin , Ko Young San , Park Jinju , Shin Dong Hoon , Hwang In Chan , Han Sang Yeun , Nam Seon Young , Kim Min A , Chang Mee Soo , Lee Hye Seung , Kim Woo Ho , Lee Byung Lan 
Published: February 2013

AbstractBackgroundThe transcription factor nuclear factor-κB (NF-κB) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-κB and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells.MethodsImmunohistochemistry for NF-κB p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-κB inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-κB repressor mutant of IκBα, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively.ResultsNF-κB and STAT3 were constitutively activated and were positively correlated (P = 0.038) in gastric cancer tissue specimens. In cell culture experiments, NF-κB inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-κB activation. Moreover, both NF-κB inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-κB activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P = 0.001 andP = 0.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells.ConclusionNF-κB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-κB and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.