bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Based Case–Control Studies of Infection and Cancer: Muddling the When and Where of Molecular Epidemiology
Authors: Engels Eric A. , Wacholder Sholom , Katki Hormuzd A. , Chaturvedi Anil K. 
Published: July 2014

Abstract
We describe the “tumor-based case–control” study as a type of epidemiologic study used to evaluate associations between infectious agents and cancer. These studies assess exposure using diseased tissues from affected individuals (i.e., evaluating tumor tissue for cancer cases), but they must utilize nondiseased tissues to assess control subjects, who do not have the disease of interest. This approach can lead to exposure misclassification in two ways. First, concerning the “when” of exposure assessment, retrospective assessment of tissues may not accurately measure exposure at the key earlier time point (i.e., during the etiologic window). Second, concerning the “where” of exposure assessment, use of different tissues in cases and controls can have different accuracy for detecting the exposure (i.e., differential exposure misclassification). We present an example concerning the association of human papillomavirus with various cancers, where tumor-based case–control studies likely overestimate risk associated with infection. In another example, we illustrate how tumor-based case–control studies of Helicobacter pylori and gastric cancer underestimate risk. Tumor-based case–control studies can demonstrate infection within tumor cells, providing qualitative information about disease etiology. However, measures of association calculated in tumor-based case–control studies are prone to over- or underestimating the relationship between infections and subsequent cancer risk. Cancer Epidemiol Biomarkers Prev; 23(10); 1959–64. ©2014 AACR.
Discovery-Based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas
Authors: Kirik Ufuk , Hansson Karin , Krogh Morten , Jönsson Mats , Nilbert Mef , James Peter , Carneiro Ana 
Published: July 2014

Abstract
Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas.
Implications: These results suggest that UPS tumors share a similar lineage as leiomyosarcomas and are likely to originate from different stages of differentiation from mesenchymal stem cells to smooth muscle cells. Mol Cancer Res; 12(12); 1729–39. ©2014 AACR.
Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically Induced Skin Cancer
Authors: Jiao Jing , Ishikawa Tomo-O , Dumlao Darren S. , Norris Paul C. , Magyar Clara E. , Mikulec Carol , Catapang Art , Dennis Edward A. , Fischer Susan M. , Herschman Harvey R. 
Published: July 2014

Abstract
Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA–induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type–specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell–specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell–specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2–expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA–treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2–dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type–specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses.
Implications: Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors. Mol Cancer Res; 12(11); 1677–88. ©2014 AACR.
Urinary PGE-M in Colorectal Cancer: Predicting More than Risk?
Authors: Maresso Karen Colbert , Vilar Eduardo , Hawk Ernest T. 
Published: July 2014

Abstract
Progress in cancer chemoprevention has been hindered by a lack of validated biomarkers of risk and interventive response. The identification of accurate, reliable, and easily measurable risk and response biomarkers within the field of cancer prevention could dramatically alter our approach to the disease. Colorectal cancer is associated with substantial morbidity and a limited 5-year survival rate for late-stage disease. The identification of biomarkers to predict (i) those most at risk of clinically significant colorectal neoplasia in conjunction with or building upon current risk models and/or (ii) those most likely to respond to potential colorectal chemopreventive agents, such as aspirin and NSAIDs, would significantly advance colorectal cancer risk management. Urinary PGE-M is an established indicator of systemic prostaglandin E2 production and has previously been demonstrated to predict risk of advanced colorectal neoplasia in a handful of studies. In the July 2014 issue, Bezawada and colleagues confirmed those earlier risk associations and demonstrated that PGE-M can also predict responsiveness to aspirin/NSAIDs in a small subset of women undergoing lower endoscopy in the Nurse's Health Study. PGE-M has the potential to define subsets of the population that may derive greater chemopreventive benefit from NSAIDs, as well as the potential to optimize the use of expensive and/or invasive screening tests. Additional larger and more diverse prospective studies meeting the criteria for phase IV biomarker studies are needed to advance the development of PGE-M as a noninvasive biomarker of both risk and chemopreventive response in populations at risk for colorectal cancer. Cancer Prev Res; 7(10); 969–72. ©2014 AACR.
ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease
Authors: Lathen Christopher , Zhang Yu , Chow Jennifer , Singh Martanday , Lin Grace , Nigam Vishal , Ashraf Yasser A. , Yuan Jason X. , Robbins Ivan M. , Thistlethwaite Patricia A. 
Published: July 2014

Background—
Pulmonary veno-occlusive disease is caused by excessive cell proliferation and fibrosis, which obliterate the lumen of pulmonary venules, leading to pulmonary hypertension, right ventricular failure, and death. This condition has no effective treatment and a 5-year survival of <5%. Understanding the mechanism of this disease and designing effective therapies are urgently needed.

Methods and Results—

We show that mice with homozygous deletion of the Ets transcription factor
Erg
die between embryonic day 16.5 and 3 months of age as a result of pulmonary veno-occlusive disease, capillary hemorrhage, and pancytopenia. We demonstrate that Erg binds to and serves as a transcriptional activator of the G-protein–coupled receptor gene
Aplnr
, the expression of which is uniquely specific for venous endothelium and that knockout of either
Erg
or
Aplnr
results in pulmonary venule–specific endothelial proliferation in vitro. We show that mice with either homozygous-global or endothelium-directed deletion of
Aplnr
manifest pulmonary veno-occlusive disease and right heart failure, detectable at 8 months of age. Levels of pulmonary ERG and APLNR in patients with pulmonary veno-occlusive disease undergoing lung transplantation were significantly lower than those of control subjects.

Conclusions—
Our results suggest that ERG and APLNR are essential for endothelial homeostasis in venules in the lung and that perturbation in ERG-APLNR signaling is crucial for the development of pulmonary veno-occlusive disease. We identify this pathway as a potential therapeutic target for the treatment of this incurable disease.
Introduction
Authors: McGregor JoAnn , Pasura Dominic 
Published: July 2014

This article examines debates over conflict diasporas’ relationships to the African crises that initially produced them. It investigates the difference that crisis makes to frameworks for thinking about diasporic entanglements with political, economic and cultural change in sending countries. We argue that the existing literature and dominant approaches are partial, ahistorical, and constrained in other ways. The special issue contributes to new strands of scholarship that aim to rectify these inadequacies, seeking historical depth, spatial complexity and attention to moral- alongside political-economies. To achieve these aims, the special issue focuses on one country – Zimbabwe. This introductory article provides an overview of the themes and arguments of the special issue, revealing the multitude of ways in which diasporic communities are imbricated with political-economic, developmental, familial, and religious change in the homeland.
Water Mass Transformation in Salinity–Temperature Space
Authors: Hieronymus Magnus , Nilsson Johan , Nycander Jonas 
Published: July 2014

AbstractThis article presents a new framework for studying water mass transformations in salinity–temperature space that can, with equal ease, be applied to study water mass transformation in spaces defined by any two conservative tracers. It is shown how the flow across isothermal and isohaline surfaces in the ocean can be quantified from knowledge of the nonadvective fluxes of heat and salt. It is also shown how these cross-isothermal and cross-isohaline flows can be used to form a continuity equation in salinity–temperature space. These flows are then quantified in a state-of-the-art ocean model. Two major transformation cells are found: a tropical cell driven primarily by surface fluxes and dianeutral diffusion and a conveyor belt cell where isoneutral diffusion is also important. Both cells are similar to cells found in earlier work on the thermohaline streamfunction. A key benefit with this framework over a streamfunction approach is that transformation due to different diabatic processes can be studied individually. The distributions of volume and surface area in S–T space are found to be useful for determining how transformations due to these different processes affect the water masses in the model. The surface area distribution shows that the water mass transformations due to surface fluxes tend to be directed away from S–T regions that occupy large areas at the sea surface.
Surgical Management of Posterior Glottic Diastasis in Children
Authors: Sidell Douglas R. , Zacharias Stephanie , Balakrishnan Karthik , Rutter Michael J. , de Alarcón Alessandro 
Published: July 2014

Introduction: The purpose of this study was to report our clinical experience in the surgical management of patients with posterior glottic diastasis (PGD) secondary to prolonged intubation and/or laryngotracheoplasty (LTP) during childhood. Methods: We reviewed the charts of patients with a history of prolonged intubation and/or LTP who had undergone surgical correction for PGD at our institution between 2010 and 2014. We documented demographic data and pertinent information regarding medical and surgical histories. The Pediatric Voice Handicap Index (pVHI) and/or the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) were used to assess patients both before and after undergoing treatment for voice disorders. Results: Six patients met our inclusion criteria. With 1 exception, all patients with complete voice data demonstrated improvements in perceptual, patient-reported, and acoustic voice measures. There were no perioperative complications. Conclusion: Our case series demonstrates that operative intervention can lead to improved voice in carefully selected patients with PGD secondary to prolonged intubation and/or LTP during childhood. Patients exhibited postoperative improvement in loudness and vocal endurance; however, they also exhibited a degree of compromise in voice quality.
Recalcitrant Rhinosinusitis, Innate Immunity, and Mannose-Binding Lectin
Authors: Justice Jeb M. , Sleasman John W. , Lanza Donald C. 
Published: July 2014

Background: Mannose-binding lectin (MBL) is a protein produced by the liver that participates in innate immunity by tagging the surface of microbes for opsonization. Mannose-binding lectin deficiency is present in 7% of the population and has been implicated in recurrent respiratory tract infections in children. Mannose-binding lectin deficiency has not been explored in rhinosinusitis but is associated with increased mortality in adult pneumococcal infection. The purpose of this report is to describe a tertiary rhinology patient experience with MBL deficiency and recalcitrant rhinosinusitis. Methods: This retrospective case series report characterizes predominantly adult patients with low MBL levels from January 2010 to June 2012. Indications for MBL testing, sinus culture data, immunological testing results, and treatments used to control rhinosinusitis are described. Results: Mannose-binding lectin levels were deficient in 12 of 36 patients (33.3%) tested. IgG subclasses were abnormally low in 5 of 12 patients; IgA was normal in 11 of 12 patients; and IgM was normal in 11 of 12 patients. Staphylococcus aureus, coagulase-negative Staphylococcus species, and Pseudomonas aeruginosa, known to be “tagged” by MBL, were the most common organisms grown on culture. Treatments included culture directed systemic antimicrobial therapy and topical steroids/antibiotics. Conclusion: Mannose-binding lectin, an important component of the lectin complement pathway and innate immunity, is possibly associated with recalcitrant adult rhinosinusitis. Steroid/antibiotic irrigations appear to benefit patients with recalcitrant rhinosinusitis and possibly those with MBL deficiency. Given that the prevalence of MBL deficiency in this case series is 4 times that seen in the normal population, additional investigations are warranted to further elucidate the role of MBL deficiency in rhinosinusitis.
PREDICT: a diagnostic accuracy study of a tool for predicting mortality within one year: Who should have an advance healthcare directive?
Authors: Richardson Philip , Greenslade Jaimi , Shanmugathasan Sulochana , Doucet Katherine , Widdicombe Neil , Chu Kevin , Brown Anthony 
Published: July 2014

Background: CARING is a screening tool developed to identify patients who have a high likelihood of death in 1 year. Aim: This study sought to validate a modified CARING tool (termed PREDICT) using a population of patients presenting to the Emergency Department. Setting/participants: In total, 1000 patients aged over 55 years who were admitted to hospital via the Emergency Department between January and June 2009 were eligible for inclusion in this study. Design: Data on the six prognostic indicators comprising PREDICT were obtained retrospectively from patient records. One-year mortality data were obtained from the State Death Registry. Weights were applied to each PREDICT criterion, and its final score ranged from 0 to 44. Receiver operator characteristic analyses and diagnostic accuracy statistics were used to assess the accuracy of PREDICT in identifying 1-year mortality. Results: The sample comprised 976 patients with a median (interquartile range) age of 71 years (62–81 years) and a 1-year mortality of 23.4%. In total, 50% had ≥1 PREDICT criteria with a 1-year mortality of 40.4%. Receiver operator characteristic analysis gave an area under the curve of 0.86 (95% confidence interval: 0.83–0.89). Using a cut-off of 13 points, PREDICT had a 95.3% (95% confidence interval: 93.6–96.6) specificity and 53.9% (95% confidence interval: 47.5–60.3) sensitivity for predicting 1-year mortality. PREDICT was simpler than the CARING criteria and identified 158 patients per 1000 admitted who could benefit from advance care planning. Conclusion: PREDICT was successfully applied to the Australian healthcare system with findings similar to the original CARING study conducted in the United States. This tool could improve end-of-life care by identifying who should have advance care planning or an advance healthcare directive.
The IMF and the policy of low inflation: A review of Article IV consultations for selected Asian developing countries
Authors: Muzaffar Ahmed Taneem , Chowdhury Anis 
Published: July 2014

AbstractSpearheaded by the International Monetary Fund (IMF), there has been a rethinking of macroeconomic policies, in particular with regard to targeting inflation at a very low level in the wake of 2008–2009 global economic crisis. We provide a content analysis of the IMF Staff Reports on Article IV consultation of 12 Asian developing countries during the period 2009–2010 in order to see whether that rethinking has been reflected in the IMF’s advice. The findings of this study reveal that the IMF continues with its prescription of achieving low inflationary environment irrespective of country-specific circumstances.
The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma
Authors: Spencer Andrew , Yoon Sung-Soo , Harrison Simon J. , Morris Shannon R. , Smith Deborah A. , Brigandi Richard A. , Gauvin Jennifer , Kumar Rakesh , Opalinska Joanna B. , Chen Christine 
Published: July 2014

Key Points
Afuresertib has a favorable safety profile with manageable side effects and demonstrates single-agent activity against hematologic malignancies. Inhibition of AKT with afuresertib may provide a novel therapeutic strategy for hematologic malignancies, especially for multiple myeloma.
All-age relationship between arm span and height in different ethnic groups
Authors: Quanjer Philip H. , Capderou André , Mazicioglu Mumtaz M. , Aggarwal Ashutosh N. , Banik Sudip Datta , Popovic Stevo , Tayie Francis A.K. , Golshan Mohammad , Ip Mary S.M. , Zelter Marc 
Published: July 2014

The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females.The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5–99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1503 patients were calculated using measured height and height calculated from arm span and age.ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV1, FVC and FEV1/FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV1, 5.0% for FVC and 0.3% for FEV1/FVC. The percentages of disparate findings for a low FEV1, FVC and FEV1/FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings.Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful.
Factors associated with low fitness in adolescents – A mixed methods study
Authors: Charlton Richard , Gravenor Michael B , Rees Anwen , Knox Gareth , Hill Rebecca , Rahman Muhammad A , Jones Kerina , Christian Danielle , Baker Julien S , Stratton Gareth , Brophy Sinead 
Published: July 2014

AbstractBackgroundFitness and physical activity are important for cardiovascular and mental health but activity and fitness levels are declining especially in adolescents and among girls. This study examines clustering of factors associated with low fitness in adolescents in order to best target public health interventions for young people.Methods1147 children were assessed for fitness, had blood samples, anthropometric measures and all data were linked with routine electronic data to examine educational achievement, deprivation and health service usage. Factors associated with fitness were examined using logistic regression, conditional trees and data mining cluster analysis. Focus groups were conducted with children in a deprived school to examine barriers and facilitators to activity for children in a deprived community.ResultsUnfit adolescents are more likely to be deprived, female, have obesity in the family and not achieve in education. There were 3 main clusters for risk of future heart disease/diabetes (high cholesterol/insulin); children at low risk (not obese, fit, achieving in education), children ‘visibly at risk’ (overweight, unfit, many hospital/GP visits) and ‘invisibly at risk’ (unfit but not overweight, failing in academic achievement). Qualitative findings show barriers to physical activity include cost, poor access to activity, lack of core physical literacy skills and limited family support.ConclusionsLow fitness in the non-obese child can reveal a hidden group who have high risk factors for heart disease and diabetes but may not be identified as they are normal weight. In deprived communities low fitness is associated with non-achievement in education but in non-deprived communities low fitness is associated with female gender. Interventions need to target deprived families and schools in deprived areas with community wide campaigns.