bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival curves to support quality improvement in hospitals with excess 30-day mortality after acute myocardial infarction, cerebral stroke and hip fracture: a before–after study
Authors: Kristoffersen Doris Tove , Helgeland Jon , Waage Halfrid Persdatter , Thalamus Jacob , Clemens Dirk , Lindman Anja Schou , Rygh Liv Helen , Tjomsland Ole 
Published: March 2015

ObjectivesTo evaluate survival curves (Kaplan-Meier) as a means of identifying areas in the clinical pathway amenable to quality improvement.DesignObservational before–after study.SettingIn Norway, annual public reporting of nationwide 30-day in-and-out-of-hospital mortality (30D) for three medical conditions started in 2011: first time acute myocardial infarction (AMI), stroke and hip fracture; reported for 2009. 12 of 61 hospitals had statistically significant lower/higher mortality compared with the hospital mean.ParticipantsThree hospitals with significantly higher mortality requested detailed analyses for quality improvement purposes: Telemark Hospital Trust Skien (AMI and stroke), Østfold Hospital Trust Fredrikstad (stroke), Innlandet Hospital Trust Gjøvik (hip fracture).Outcome measuresSurvival curves, crude and risk-adjusted 30D before (2008–2009) and after (2012–2013).InterventionsUnadjusted survival curves for the outlier hospitals were compared to curves based on pooled data from the other hospitals for the 30-day period 2008–2009. For patients admitted with AMI (Skien), stroke (Fredrikstad) and hip fracture (Gjøvik), the curves suggested increased mortality from the initial part of the clinical pathway. For stroke (Skien), increased mortality appeared after about 8 days. The curve profiles were thought to reflect suboptimal care in various phases in the clinical pathway. This informed improvement efforts.ResultsFor 2008–2009, hospital-specific curves differed from other hospitals: borderline significant for AMI (p=0.064), highly significant (p≤0.005) for the remainder. After intervention, no difference was found (p>0.188). Before–after comparison of the curves within each hospital revealed a significant change for Fredrikstad (p=0.006). For the three hospitals, crude 30D declined and they were non-outliers for risk-adjusted 30D for 2013.ConclusionsSurvival curves as a supplement to 30D may be useful for identifying suboptimal care in the clinical pathway, and thus informing design of quality improvement projects.
Safer fluid prescribing at North Bristol Trust: Bringing practice in line with NICE Guidance with a redesign of the fluid prescription chart
Authors: Andersson Johanna , Bull Thomas , Paul Daniel , Reynolds Emily , Nishimura Aimi , Lloyd Jessica , Jetley Amanda , Davies Mari , Eisenhauer Helen , Maggs Daniel , Clapham Sorcha , Trivedi Kaushali , Hair Robert , Plumb Benjamin , Plumb Benjamin 
Published: March 2015

AbstractThe National Institute of Clinical Excellence (NICE) released new fluid guidelines following data suggesting 20% of patients receiving fluids suffer adversely (2013). This quality improvement group assessed fluid prescribing in a tertiary teaching centre and introduced a new fluid- prescribing chart to align practice with NICE recommendations.Notes and corresponding fluid prescription charts were reviewed for evidence of (1) indication, (2) co-morbidities, and (3) further management as surrogate markers of safe prescribing in accordance with NICE. Overall, the data showed practice fell short and prompted a redesign of the Trust fluid prescription chart. Three different variations of the chart were issued consecutively using a PDSA method (plan, do, study, act) over a 6-month period. They all included indication, co-morbidities and further management plans as constant design features. Suggestions from interested parties were incorporated and an educational programme was implemented to promote awareness.Prior to our intervention, an indication for fluids was documented in 26% of notes, it took an average of 4.6 minutes to find co-morbidities, and further management plans were rarely documented. Following the new prescription chart, an indication was recorded in 72% of cases, co-morbidities noted on 63% of charts with 93.1% accuracy, and further management documented in 100% of cases.The new fluid prescription chart encourages prescribers to incorporate NICE recommendations when prescribing fluids. The new fluid prescription design has since been rolled out Trust wide.
Improving documentation of cardiovascular disease risk in patients with diabetes attending non communicable disease clinics at West Bay Health Center in Qatar
Authors: Salem Mohamed , Al-Ali Amal , Bashwar Zelaikha 
Published: March 2015

AbstractThe documentation of cardiovascular disease (CVD) in medical records of patients with type 2 diabetes attending non communicable disease (NCD) clinics at West Bay Health Center in Qatar is less than ideal. Poor documentation of CVD will lead to poor preventive and management plans, with negative consequences for patients. Our aim is to improve this documentation of cardiovascular disease risk from 13% to 70% through the use of the WHO CVD risk prediction charts, which ran from September 2014 to January 2015.An intervention in the form of an education session was run on 13th November 2014 for nurses that run the NCD clinic, covering the new NCD format (including the location of risk documentation, the method used for calculation the CVD, and mandatory documentation of CVD scores). A group discussion was also held with a physician for revising the CVD risk that was documented by nurses. Posters were placed in the NCD nurse station and clinics to remind them about CVD calculation and documentation. The average percentage of complete CVD risk documentation for patients with diabetes was 7%, increasing to 59% after the intervention. Overall, our intervention improved the documentation of CVD by 52%.
The no-touch vein graft for coronary artery bypass surgery preserves the left ventricular ejection fraction at 16 years postoperatively: long-term data from a longitudinal randomised trial
Authors: Johansson Benny , Samano Ninos , Souza Domingos , Bodin Lennart , Filbey Derek , Mannion John D , Bojö Leif 
Published: March 2015

ObjectivesTo assess the left ventricular heart function and the clinical outcome 16 years after coronary artery bypass surgery.DesignIn a randomised trial, the no-touch (NT) vein graft in coronary artery bypass surgery has shown a superior patency rate, a slower progression of atherosclerosis and better clinical outcome compared to the conventional (C) vein graft at 8.5 years. All patients at mean time 16 years were offered an echocardiographic and clinical examination.ResultsIn the NT-group 34 patients and in the C-group 31 patients underwent an echocardiography examination. A significantly better left ventricle ejection fraction was seen in the NT-group compared to the C-group (57.9% vs 49.4%; p=0.011). The size of the left atrium in NT was 21.7 cm2compared to 23.9 cm2in C; p=0.034. No patient in NT had atrial fibrillation compared to five patients in C (p=0.021). Patients with a brain natriuretic peptide value (BNP) ≥150 was 30% in NT compared to 38% in C. Total mortality was 25% in NT vs 27% in C. Cardiac-related deaths were 8% and 12% in NT and C respectively.ConclusionsThe NT vein graft preserves the left ventricular ejection fraction after 16 years. A smaller left atrium, a lower BNP and no atrial fibrillation indicatesan improved diastolic left ventricular function in the NT-group.Trial registrationThe study is registered withclinicaltrials.gov(NCT01686100) andThe Research and Development registryin Sweden (no. 102841).
Relationship between age at gonadectomy and health problems in kittens adopted from shelters
Authors: Porters N. , Polis I. , Moons C. P. H. , Van de Maele I. , Ducatelle R. , Goethals K. , Duchateau L. , de Rooster H. 
Published: March 2015

Prepubertal gonadectomy (PPG) is promoted as a way of managing overpopulation in cats, but concerns about PPG and potential health issues still exist. The objective of the present study was to evaluate short‐term and long‐term health problems in cats subjected to PPG in comparison to gonadectomy at traditional age (TAG). In a prospective clinical trial, 800 shelter kittens aged between approximately 8 weeks and 12 weeks were recruited before adoption and randomly assigned to either the PPG group (gonadectomy performed immediately) or the TAG group (gonadectomy delayed until six months to eight months of age). Short‐term health issues included mortality between when kittens arrived at the clinic and up to seven days after they returned to the shelter, as well as the occurrence of various other health issues arising in the first month following adoption. Kittens were followed‐up until 24 months of age specifically for feline lower urinary tract disease, urethral obstruction (male cats), lameness, fractures and hypersensitivity disorders with dermatological presentation. In the short term, there were no significant differences between health problems in PPG and TAG kittens. Similarly, no significant differences were observed between treatment groups in terms of the type or number of health issues in the long term. In conclusion, there are no health‐related contraindications to advocating PPG strategies in shelter cats. Ideally, PPG should be performed at the shelter facility itself as long as excellent infectious disease control and postoperative clinical observation before adoption are guaranteed.
GIS-based variability of building materials towards the Île-de-France cuesta (Paris Basin, France): inventory, distribution, uses and relationship with the environment
Authors: Turmel A. , Fronteau G. , Chalumeau L. , Deroin J.-P. , Eyssautier-Chuine S. , Thomachot-Schneider C. , De Kock T. , Cnudde V. , Barbin V. 
Published: March 2015

Abstract

The
Pays rémois
in the eastern Paris Basin is an administrative area of 1394 km
2
; in the surroundings of Reims (France). Two main geological substrata are separated by the Île-de-France cuesta: the Tertiary substratum in the western part is composed of various types of geomaterials (clay, sandstone, limestone, burrstone), whereas the substratum in the eastern part is composed only of Cretaceous Chalk. A field survey in each
commune
of the
Pays rémois
identified 26 building materials documented in a Geographic Information System database (GIS-database) that includes information about them (lithology, petrographical and petrophysical data, weathering) and the corresponding buildings (e.g. town, georeferenced data, building type, position on the façade). The spatial analysis of the building materials’ distribution (Standard Deviational Ellipse) with GIS identifies their uses and the criteria established for the selection of the materials: availability, efficiency, workability and durability. Some lithologies were preferred for particular buildings or selected for their efficiency in specific positions. The study also defines the relation between the stones’ origin (local and non-local stones) and their application. This database is useful to establish stone replacement strategies in the
Pays rémois
.
CDK2 Inhibition Causes Anaphase Catastrophe in Lung Cancer through the Centrosomal Protein CP110
Authors: Hu Shanhu , Danilov Alexey V. , Godek Kristina , Orr Bernardo , Tafe Laura J. , Rodriguez-Canales Jaime , Behrens Carmen , Mino Barbara , Moran Cesar A. , Memoli Vincent A. , Mustachio Lisa Maria , Galimberti Fabrizio , Ravi Saranya , DeCastro Andrew , Lu Yun , Sekula David , Andrew Angeline S. , Wistuba Ignacio I. , Freemantle Sarah , Compton Duane A. , Dmitrovsky Ethan 
Published: March 2015

Abstract
Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacologic targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially eliminate malignant over normal cells. We previously discovered that CDK2 inhibition causes lung cancer cells with more than two centrosomes to undergo multipolar cell division leading to apoptosis, defined as anaphase catastrophe. Cells with activating KRAS mutations were especially sensitive to CDK2 inhibition. Mechanisms of CDK2-mediated anaphase catastrophe and how activated KRAS enhances this effect were investigated. Live-cell imaging provided direct evidence that following CDK2 inhibition, lung cancer cells develop multipolar anaphase and undergo multipolar cell division with the resulting progeny apoptotic. The siRNA-mediated repression of the CDK2 target and centrosome protein CP110 induced anaphase catastrophe of lung cancer cells. In contrast, CP110 overexpression antagonized CDK2 inhibitor–mediated anaphase catastrophe. Furthermore, activated KRAS mutations sensitized lung cancer cells to CDK2 inhibition by deregulating CP110 expression. Thus, CP110 is a critical mediator of CDK2 inhibition–driven anaphase catastrophe. Independent examination of murine and human paired normal–malignant lung tissues revealed marked upregulation of CP110 in malignant versus normal lung. Human lung cancers with KRAS mutations had significantly lower CP110 expression as compared with KRAS wild-type cancers. Thus, a direct link was found between CP110 and CDK2 inhibitor antineoplastic response. CP110 plays a mechanistic role in response of lung cancer cells to CDK2 inhibition, especially in the presence of activated KRAS mutations. Cancer Res; 75(10); 2029–38. ©2015 AACR.
MMP16 Mediates a Proteolytic Switch to Promote Cell–Cell Adhesion, Collagen Alignment, and Lymphatic Invasion in Melanoma
Authors: Tatti Olga , Gucciardo Erika , Pekkonen Pirita , Holopainen Tanja , Louhimo Riku , Repo Pauliina , Maliniemi Pilvi , Lohi Jouko , Rantanen Ville , Hautaniemi Sampsa , Alitalo Kari , Ranki Annamari , Ojala Päivi M. , Keski-Oja Jorma , Lehti Kaisa 
Published: March 2015

Abstract
Lymphatic invasion and accumulation of continuous collagen bundles around tumor cells are associated with poor melanoma prognosis, but the underlying mechanisms and molecular determinants have remained unclear. We show here that a copy-number gain or overexpression of the membrane-type matrix metalloproteinase MMP16 (MT3-MMP) is associated with poor clinical outcome, collagen bundle assembly around tumor cell nests, and lymphatic invasion. In cultured WM852 melanoma cells derived from human melanoma metastasis, silencing of MMP16 resulted in cell-surface accumulation of the MMP16 substrate MMP14 (MT1-MMP) as well as L1CAM cell adhesion molecule, identified here as a novel MMP16 substrate. When limiting the activities of these trans-membrane protein substrates toward pericellular collagen degradation, cell junction disassembly, and blood endothelial transmigration, MMP16 supported nodular-type growth of adhesive collagen-surrounded melanoma cell nests, coincidentally steering cell collectives into lymphatic vessels. These results uncover a novel mechanism in melanoma pathogenesis, whereby restricted collagen infiltration and limited mesenchymal invasion are unexpectedly associated with the properties of the most aggressive tumors, revealing MMP16 as a putative indicator of adverse melanoma prognosis. Cancer Res; 75(10); 2083–94. ©2015 AACR.
Decoy Receptor DcR1 Is Induced in a p50/Bcl3–Dependent Manner and Attenuates the Efficacy of Temozolomide
Authors: Mansour Nassir M. , Bernal Giovanna M. , Wu Longtao , Crawley Clayton D. , Cahill Kirk E. , Voce David J. , Balyasnikova Irina V. , Zhang Wei , Spretz Ruben , Nunez Luis , Larsen Gustavo F. , Weichselbaum Ralph R. , Yamini Bakhtiar 
Published: March 2015

Abstract
Temozolomide is used widely to treat malignant glioma, but the overall response to this agent is generally poor. Resistance to DNA-damaging drugs such as temozolomide has been related to the induction of antiapoptotic proteins. Specifically, the transcription factor NF-κB has been suggested to participate in promoting the survival of cells exposed to chemotherapy. To identify factors that modulate cytotoxicity in the setting of DNA damage, we used an unbiased strategy to examine the NF-κB–dependent expression profile induced by temozolomide. By this route, we defined the decoy receptor DcR1 as a temozolomide response gene induced by a mechanism relying upon p50/NF-κB1. A conserved NF-κB–binding sequence (κB-site) was identified in the proximal promoter and was demonstrated to be required for DcR1 induction by temozolomide. Loss-of-function and gain-of-function studies reveal that the atypical IκB protein, Bcl3, is also required for induction of DcR1 by temozolomide. Mechanistically, DcR1 attenuates temozolomide efficacy by blunting activation of the Fas receptor pathway in p53+/+ glioma cells. Intracranial xenograft studies show that DcR1 depletion in glioma cells enhances the efficacy of temozolomide. Taken together, our results show how DcR1 upregulation mediates temozolomide resistance and provide a rationale for DcR1 targeting as a strategy to sensitize gliomas to this widely used chemotherapy. Cancer Res; 75(10); 2039–48. ©2015 AACR.
Tenascin-C Protects Cancer Stem–like Cells from Immune Surveillance by Arresting T-cell Activation
Authors: Jachetti Elena , Caputo Sara , Mazzoleni Stefania , Brambillasca Chiara Svetlana , Parigi Sara Martina , Grioni Matteo , Piras Ignazio Stefano , Restuccia Umberto , Calcinotto Arianna , Freschi Massimo , Bachi Angela , Galli Rossella , Bellone Matteo 
Published: March 2015

AbstractPrecociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here, we present evidence that prostate cancer stem–like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSCs were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T-cell receptor–dependent T-cell activation, proliferation, and cytokine production. Mechanistically, TNC interacted with α5β1 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T-cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system. Cancer Res; 75(10); 2095–108. ©2015 AACR.
Chronic Inflammation Induces a Novel Epigenetic Program That Is Conserved in Intestinal Adenomas and in Colorectal Cancer
Authors: Abu-Remaileh Monther , Bender Sebastian , Raddatz Günter , Ansari Ihab , Cohen Daphne , Gutekunst Julian , Musch Tanja , Linhart Heinz , Breiling Achim , Pikarsky Eli , Bergman Yehudit , Lyko Frank 
Published: March 2015

Abstract
Chronic inflammation represents a major risk factor for tumor formation, but the underlying mechanisms have remained largely unknown. Epigenetic mechanisms can record the effects of environmental challenges on the genome level and could therefore play an important role in the pathogenesis of inflammation-associated tumors. Using single-base methylation maps and transcriptome analyses of a colitis-induced mouse colon cancer model, we identified a novel epigenetic program that is characterized by hypermethylation of DNA methylation valleys that are characterized by low CpG density and active chromatin marks. This program is conserved and functional in mouse intestinal adenomas and results in silencing of active intestinal genes that are involved in gastrointestinal homeostasis and injury response. Further analyses reveal that the program represents a prominent feature of human colorectal cancer and can be used to correctly classify colorectal cancer samples with high accuracy. Together, our results show that inflammatory signals establish a novel epigenetic program that silences a specific set of genes that contribute to inflammation-induced cellular transformation. Cancer Res; 75(10); 2120–30. ©2015 AACR.
Manic Fringe Promotes a Claudin-Low Breast Cancer Phenotype through Notch-Mediated PIK3CG Induction
Authors: Zhang Shubing , Chung Wen-Cheng , Wu Guanming , Egan Sean E. , Miele Lucio , Xu Keli 
Published: March 2015

Abstract
Claudin-low breast cancer (CLBC) is a poor prognosis disease biologically characterized by stemness and mesenchymal features. These tumors disproportionately affect younger patients and women with African ancestry, causing significant morbidity and mortality, and no effective targeted therapy exists at present. CLBC is thought to originate from mammary stem cells, but little is known on how or why these tumors express a stable epithelial-to-mesenchymal transition phenotype, or what are the driving forces of this disease. Here, we report that Manic Fringe (Mfng), which encodes an O-fucosylpeptide 3-β-N-acetylglucosaminyltransferase known to modify EGF repeats in the Notch extracellular domain, is highly expressed in CLBC and functions as an oncogene in this context. We show that Mfng modulates Notch activation in human and mouse CLBC cell lines, as well as in mouse mammary gland. Mfng silencing in CLBC cell lines reduced cell migration, tumorsphere formation, and in vivo tumorigenicity associated with a decrease in the stem-like cell population. Mfng deletion in the Lfngflox/flox;MMTV-Cre mouse model, in which one-third of mammary tumors resemble human CLBC, caused a tumor subtype shift away from CLBC. We identified the phosphoinositide kinase Pik3cg as a direct transcriptional target of Mfng-facilitated RBPJκ-dependent Notch signaling. Indeed, pharmacologic inhibition of PI3Kγ in CLBC cell lines blocked migration and tumorsphere formation. Taken together, our results define Mfng as an oncogene acting through Notch-mediated induction of Pik3cg. Furthermore, they suggest that targeting PI3Kγ may prove beneficial for the treatment of CLBC subtype. Cancer Res; 75(10); 1936–43. ©2015 AACR.