bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of geography on the control of type 2 diabetes mellitus: a review of geocoded clinical data from general practice
Authors: Jiwa Moyez , Gudes Ori , Varhol Richard , Mullan Narelle 
Published: December 2015

ObjectiveTo review the clinical data for people with diabetes mellitus with reference to their location and clinical care in a general practice in Australia.Materials and methodsPatient data were extracted from a general practice in Western Australia. Iterative data-cleansing steps were taken. Data were grouped into Statistical Area level 1 (SA1), designated as the smallest geographical area associated with the Census of Population and Housing. The data were analysed to identify if SA1s with people aged 70 years and older, and with relatively high glycosylated haemoglobin (HbA1c) were significantly clustered, and whether this was associated with their medical consultation rate and treatment. The analysis included Cluster and Outlier Analysis using Moran's I test.ResultsThe overall median age of the population was 70 years with more males than females, 53% and 47%, respectively. Older people (>70 years) with relatively high HbA1c comprised 9.3% of all people with diabetes in the sample, and were clustered around two ‘hotspot’ locations. These 111 patients do not attend the practice more or less often than people with diabetes living elsewhere in the practice (p=0.098). There was some evidence that they were more likely to be recorded as having consulted with regard to other chronic diseases. The average number of prescribed medicines over a 13-month time period, per person in the hotspots, was 4.6 compared with 5.1 in other locations (p=0.26). Their prescribed therapy was deemed to be consistent with the management of people with diabetes in other locations with reference to the relevant diabetes guidelines.ConclusionsOlder patients with relatively high HbA1c are clustered in two locations within the practice area. Their hyperglycaemia and ongoing cardiovascular risk indicates causes other than therapeutic inertia. The causes may be related to the social determinants of health, which are influenced by geography.
Protocol for a mixed-methods longitudinal study to identify factors influencing return to work in the over 50s participating in the UK Work Programme: Supporting Older People into Employment (SOPIE)
Authors: Brown Judith , Neary Joanne , Katikireddi Srinivasa Vittal , Thomson Hilary , McQuaid Ronald W , Leyland Alastair H , Frank John , Jeavons Luke , de Pellette Paul , Kiran Sibel , Macdonald Ewan B 
Published: December 2015

IntroductionIncreasing employment among older workers is a policy priority given the increase in life expectancy and the drop in labour force participation after the age of 50. Reasons for this drop are complex but include poor health, age discrimination, inadequate skills/qualifications and caring roles; however, limited evidence exists on how best to support this group back to work. The Work Programme is the UK Government's flagship policy to facilitate return to work (RTW) among those at risk of long-term unemployment. ‘Supporting Older People Into Employment’ (SOPIE) is a mixed-methods longitudinal study involving a collaboration between academics and a major Work Programme provider (Ingeus). The study will investigate the relationship between health, worklessness and the RTW process for the over 50s.Methods and analysisThere are three main study components. Embedded fieldwork will document the data routinely collected by Ingeus and the key interventions/activities delivered. The quantitative study investigates approximately 14 000 individuals (aged 16–64 years, with 20% aged over 50) who entered the Ingeus Work Programme (referred to as ‘clients’) in a 16-month period in Scotland and were followed up for 2 years. Employment outcomes (including progression towards work) and how they differ by client characteristics (including health), intervention components received and external factors will be investigated. The qualitative component will explore the experiences of clients and Ingeus staff, to better understand the interactions between health and (un)employment, Work Programme delivery, and how employment services can be better tailored to the needs of the over 50s.Ethics and disseminationEthical approval was received from the University of Glasgow College of Social Sciences Research Ethics Committee (application number 400140186).ResultsResults will be disseminated through journal articles, national and international conferences. Findings will inform current and future welfare-to-work and job retention initiatives to extend healthy working lives.
Adenoma detection with Endocuff colonoscopy versus conventional colonoscopy: a multicentre randomised controlled trial
Authors: van Doorn SC , van der Vlugt M , Depla ACTM , Wientjes CA , Mallant-Hent RC , Siersema PD , Tytgat KMAJ , Tuynman H , Kuiken SD , Houben GMP , Stokkers PCF , Moons LMG , Bossuyt PMM , Fockens P , Mundt MW , Dekker E 
Published: December 2015

Background and aimsColonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC).MethodsWe performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as well as symptomatic patients (>45 years). Consenting patients were randomised 1:1 to EAC or CC. All colonoscopies were performed by experienced colonoscopists (≥500 colonoscopies) who were trained in EAC. All colonoscopy quality indicators were prospectively recorded.FindingsOf the 1063 included patients (52% male, median age 65 years), 530 were allocated to EAC and 533 to CC. More adenomas were detected with EAC, 722 vs 621, but the gain in MAP was not significant: on average 1.36 per patient in the EAC group versus 1.17 in the CC group (p=0.08). In a per-protocol analysis, the gain was 1.44 vs 1.19 (p=0.02), respectively. In the EAC group, 275 patients (52%) had one or more adenomas detected versus 278 in the CC group (52%; p=0.92). For advanced adenomas these numbers were 109 (21%) vs 117 (22%). The adjusted caecal intubation rate was lower with EAC (94% vs 99%; p<0.001), however when allowing crossover from EAC to CC, they were similar in both groups (98% vs 99%; p value=0.25).InterpretationThough more adenomas are detected with EAC, the routine use of Endocuff does not translate in a higher number of patients with one or more adenomas detected. Whether increased detection ultimately results in a lower rate of interval carcinomas is not yet known.Trial registration numberhttp://www.trialregister.nlDutch Trial Register: NTR3962.
The physical activity profiles of South Asian ethnic groups in England
Authors: Bhatnagar Prachi , Townsend Nick , Shaw Alison , Foster Charlie 
Published: December 2015

BackgroundTo identify what types of activity contribute to overall physical activity in South Asian ethnic groups and how these vary according to sex and age. We used the White British ethnic group as a comparison.MethodsSelf-reported physical activity was measured in the Health Survey for England 1999 and 2004, a nationally representative, cross-sectional survey that boosted ethnic minority samples in these years. We merged the two survey years and analysed data from 19 476 adults. The proportions of total physical activity achieved through walking, housework, sports and DIY activity were calculated. We stratified by sex and age group and used analysis of variances to examine differences between ethnic groups, adjusted for the socioeconomic status.ResultsThere was a significant difference between ethnic groups for the contributions of all physical activity domains for those aged below 55 years, with the exception of walking. In women aged 16–34 years, there was no significant difference in the contribution of walking to total physical activity (p=0.38). In the 35–54 age group, Bangladeshi males have the highest proportion of total activity from walking (30%). In those aged over 55 years, the proportion of activity from sports was the lowest in all South Asian ethnic groups for both sexes.ConclusionsUK South Asians are more active in some ways that differ, by age and sex, from White British, but are similarly active in other ways. These results can be used to develop targeted population level interventions for increasing physical activity levels in adult UK South Asian populations.
Affine connection form of Regge calculus
Authors: Khatsymovsky V. M. 
Published: December 2015

Regge action is represented analogously to how the Palatini action for general relativity (GR) as some functional of the metric and a general connection as independent variables represents the Einstein–Hilbert action. The piecewise flat (or simplicial) spacetime of Regge calculus is equipped with some world coordinates and some piecewise affine metric which is completely defined by the set of edge lengths and the world coordinates of the vertices. The conjugate variables are the general nondegenerate matrices on the three-simplices which play the role of a general discrete connection. Our previous result on some representation of the Regge calculus action in terms of the local Euclidean (Minkowsky) frame vectors and orthogonal connection matrices as independent variables is somewhat modified for the considered case of the general linear group GL(4, R) of the connection matrices. As a result, we have some action invariant w.r.t. arbitrary change of coordinates of the vertices (and related GL(4, R) transformations in the four-simplices). Excluding GL(4, R) connection from this action via the equations of motion we have exactly the Regge action for the considered spacetime.
Developing digital fieldwork technologies at the British Geological Survey
Authors: Jordan Colm J. , Napier Bruce 
Published: December 2015

Abstract
Geological Surveys are faced with budget constraints and calls for efficiency gains; the effective application of digital techniques is often seen as a route to meeting these demands while increasing the value of outcrop studies and reducing the inherent subsurface uncertainty. The British Geological Survey may be the oldest national Survey in the world (established in 1835); however, developing and implementing new, innovative and efficient technologies for fieldwork is a high priority. Efficient tools for capturing, integrating, manipulating and disseminating outcrop data and information are imperative to enable geoscientists to increase their understanding of geological processes and therefore to reduce subsurface uncertainty and risk. Systems for capturing structured digital field data and for visualizing and interacting with large datasets are increasingly being utilized by geoscientists in the UK and internationally. Augmented reality and unmanned aerial vehicles are amongst the developing technologies being explored for future operational implementation. This paper describes the digital field mapping (BGS·SIGMAmobile) and visualization (GeoVisionary) systems and refers to a case study outlining their contribution to reducing uncertainty and risk in hydrocarbon exploration.
Comprehensive Ex Vivo Transposon Mutagenesis Identifies Genes That Promote Growth Factor Independence and Leukemogenesis
Authors: Guo Yabin , Updegraff Barrett L. , Park Sunho , Durakoglugil Deniz , Cruz Victoria H. , Maddux Sarah , Hwang Tae Hyun , O'Donnell Kathryn A. 
Published: December 2015

Abstract
Aberrant signaling through cytokine receptors and their downstream signaling pathways is a major oncogenic mechanism underlying hematopoietic malignancies. To better understand how these pathways become pathologically activated and to potentially identify new drivers of hematopoietic cancers, we developed a high-throughput functional screening approach using ex vivo mutagenesis with the Sleeping Beauty transposon. We analyzed over 1,100 transposon-mutagenized pools of Ba/F3 cells, an IL3-dependent pro-B-cell line, which acquired cytokine independence and tumor-forming ability. Recurrent transposon insertions could be mapped to genes in the JAK/STAT and MAPK pathways, confirming the ability of this strategy to identify known oncogenic components of cytokine signaling pathways. In addition, recurrent insertions were identified in a large set of genes that have been found to be mutated in leukemia or associated with survival, but were not previously linked to the JAK/STAT or MAPK pathways nor shown to functionally contribute to leukemogenesis. Forced expression of these novel genes resulted in IL3-independent growth in vitro and tumorigenesis in vivo, validating this mutagenesis-based approach for identifying new genes that promote cytokine signaling and leukemogenesis. Therefore, our findings provide a broadly applicable approach for classifying functionally relevant genes in diverse malignancies and offer new insights into the impact of cytokine signaling on leukemia development. Cancer Res; 76(4); 773–86. ©2015 AACR.
Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease
Authors: Murphy Stephen J. , Hart Steven N. , Halling Geoffrey C. , Johnson Sarah H. , Smadbeck James B. , Drucker Travis , Lima Joema Felipe , Rohakhtar Fariborz Rakhshan , Harris Faye R. , Kosari Farhad , Subramanian Subbaya , Petersen Gloria M. , Wiltshire Timothy D. , Kipp Benjamin R. , Truty Mark J. , McWilliams Robert R. , Couch Fergus J. , Vasmatzis George 
Published: December 2015

Abstract
Many somatic mutations have been detected in pancreatic ductal adenocarcinoma (PDAC), leading to the identification of some key drivers of disease progression, but the involvement of large genomic rearrangements has often been overlooked. In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Integration of data from MPseq, exome sequencing, and transcriptome analysis of primary PDAC cases identified limited overlap in genes affected by both rearrangements and point mutations. However, significant overlap was observed in major PDAC-associated signaling pathways, with all PDAC exhibiting reduced SMAD4 expression, reduced SMAD-dependent TGFβ signaling, and increased WNT and Hedgehog signaling. The frequent loss of SMAD4 and FHIT due to genomic rearrangements strongly implicates these genes as key drivers of PDAC, thus highlighting the strengths of an integrated genomic and transcriptomic approach for identifying mechanisms underlying disease initiation and progression. Cancer Res; 76(3); 749–61. ©2015 AACR.
GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells
Authors: Li Chong , Du Ying , Yang Zhao , He Luyun , Wang Yanying , Hao Lu , Ding Mingxia , Yan Ruping , Wang Jiansong , Fan Zusen 
Published: December 2015

Abstract
The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. In this study, we generated a mAb (BCMab1) against CD44+ human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1+CD44+ cell subpopulation as BCSCs with stem cell–like properties. Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1+CD44+ subpopulation and was required for BCSC self-renewal. Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1+CD44+ cells and correlated with clinicopathologic features of bladder cancers. Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. Cancer Res; 76(5); 1273–83. ©2015 AACR.
miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer
Authors: Adams Brian D. , Wali Vikram B. , Cheng Christopher J. , Inukai Sachi , Booth Carmen J. , Agarwal Seema , Rimm David L. , Győrffy Balázs , Santarpia Libero , Pusztai Lajos , Saltzman W. Mark , Slack Frank J. 
Published: December 2015

Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell–like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. Cancer Res; 76(4); 927–39. ©2015 AACR.
The Influence of Exercise on the Insulin-like Growth Factor Axis in Oncology: Physiological Basis, Current, and Future Perspectives
Authors: Devin James L. , Bolam Kate A. , Jenkins David G. , Skinner Tina L. 
Published: December 2015

Abstract
Exercise and physical activity have been shown to reduce the risk of many common cancers and strongly influence tumor biology. A cause–effect mechanism explaining this relationship is dependent on cellular pathways that can influence tumor growth and are exercise responsive. The insulin-like growth factor (IGF) axis is reported to promote the development and progression of carcinomas through cellular signaling in cancerous tissues. This review summarizes the physiologic basis of the role of the IGF axis in oncology and the influence of exercise on this process. We examined the effects of exercise prescription on the IGF axis in cancer survivors by evaluating the current scope of the literature. The current research demonstrates a remarkable heterogeneity and inconsistency in the responses of the IGF axis to exercise in breast, prostate, and colorectal cancer survivors. Finally, this review presents an in-depth exploration of the physiologic basis and mechanistic underpinnings of the seemingly disparate relationship between exercise and the IGF axis in oncology. Although there is currently insufficient evidence to categorize the effects of exercise prescription on the IGF axis in cancer survivors, the inconsistency of results suggests a multifaceted relationship, the complexities of which are considered in this review. Cancer Epidemiol Biomarkers Prev; 25(2); 239–49. ©2015 AACR.
Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients
Authors: Yang Baiyu , Bostick Roberd M. , Tran Hao Quang , Gewirtz Andrew T. , Campbell Peter T. , Fedirko Veronika 
Published: December 2015

Abstract
Background: Gut barrier dysfunction contributes to several gastrointestinal disorders, including colorectal cancer, but factors associated with intestinal hyperpermeability have been minimally studied in humans.
Methods: We tested the effects of two doses of calcium (1.0 or 2.0 g/d) on circulating biomarkers of gut permeability [anti-flagellin and anti-lipopolysaccharide (LPS) Ig, measured via ELISA] over a 4-month treatment period among colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193), and evaluated the factors associated with baseline levels of these biomarkers.
Results: Baseline concentrations of anti-flagellin IgA and anti-LPS IgA were, respectively, statistically significantly proportionately higher by 11.8% and 14.1% among men, 31.3% and 39.8% among those with a body mass index ≥ 35 kg/m2, and 19.9% and 22.0% among those in the upper relative to the lowest sex-specific tertile of waist circumference. A combined permeability score (the summed optical densities of all four biomarkers) was 24.3% higher among women in the upper tertile of plasma C–reactive protein (Ptrend &lt; 0.01). We found no appreciable effects of supplemental calcium on anti-flagellin or anti-LPS Igs.
Conclusions: Our results suggest that (i) men and those with higher adiposity may have greater gut permeability, (ii) gut permeability and systemic inflammation may be directly associated with one another, and (iii) supplemental calcium may not modify circulating levels of gut permeability biomarkers within 4 months.
Impact: Our findings may improve the understanding of the factors that influence gut permeability to inform development of treatable biomarkers of risk for colorectal cancer and other health outcomes. Cancer Epidemiol Biomarkers Prev; 25(2); 318–26. ©2015 AACR.