bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature
Authors: deLeeuw Ronald J. , Kost Sara E. , Kakal Juzer A. , Nelson Brad H. 
Published: April 2012

AbstractCD8+ tumor-infiltrating lymphocytes (TIL) are associated with survival in a variety of cancers. A second subpopulation of TIL, defined by forkhead box protein P3 (FoxP3) expression, has been reported to inhibit tumor immunity, resulting in decreased patient survival. On the basis of this premise, several groups are attempting to deplete FoxP3+ T cells to enhance tumor immunity. However, recent studies have challenged this paradigm by showing that FoxP3+ T cells exhibit heterogeneous phenotypes and, in some cohorts, are associated with favorable prognosis. These discrepant results could arise from differences in study methodologies or the biologic properties of specific cancer types. Here, we conduct the first systematic review of the prognostic significance of FoxP3+ T cells across nonlymphoid cancers (58 studies from 16 cancers). We assessed antibody specificity, cell-scoring strategy, multivariate modeling, use of single compared with multiple markers, and tumor site. Two factors proved important. First, when FoxP3 was combined with one additional marker, double-positive T cells were generally associated with poor prognosis. Second, tumor site had a major influence. FoxP3+ T cells were associated with poor prognosis in hepatocellular cancer and generally good prognosis in colorectal cancer, whereas other cancer types were inconsistent or understudied. We conclude that FoxP3+ T cells have heterogeneous properties that can be discerned by the use of additional markers. Furthermore, the net biologic effects of FoxP3+ T cells seem to depend on the tumor site, perhaps reflecting microenvironmental differences. Thus, depletion of FoxP3+ T cells might enhance tumor immunity in some patient groups but be detrimental in others. Clin Cancer Res; 18(11); 3022–9. ©2012 AACR.
Testosterone Supplementation in Heart Failure
Authors: Toma Mustafa , McAlister Finlay A. , Coglianese Erin E. , Vidi Venkatesan , Vasaiwala Samip , Bakal Jeffrey A. , Armstrong Paul W. , Ezekowitz Justin A. 
Published: April 2012

Background—
Low testosterone is an independent predictor of reduced exercise capacity and poor clinical outcomes in patients with heart failure (HF). We sought to determine whether testosterone therapy improves exercise capacity in patients with stable chronic HF.

Methods and Results—
We searched Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (1980–2010). Eligible studies included randomized controlled trials (RCTs) reporting the effects of testosterone on exercise capacity in patients with HF. Reviewers determined the methodological quality of studies and collected descriptive, quality, and outcome data. Four trials (n=198; men, 84%; mean age, 67 years) were identified that reported the 6-minute walk test (2 RCTs), incremental shuttle walk test (2 RCTs), or peak oxygen consumption (2 RCTs) to assess exercise capacity after up to 52 weeks of treatment. Testosterone therapy was associated with a significant improvement in exercise capacity compared with placebo. The mean increase in the 6-minute walk test, incremental shuttle walk test, and peak oxygen consumption between the testosterone and placebo groups was 54.0 m (95% CI, 43.0–65.0 m), 46.7 m (95% CI, 12.6–80.9 m), and 2.70 mL/kg per min (95% CI, 2.68–2.72 mL/kg per min), respectively. Testosterone therapy was associated with a significant increase in exercise capacity as measured by units of pooled SDs (net effect, 0.52 SD; 95% CI, 0.10–0.94 SD). No significant adverse cardiovascular events were noted.

Conclusions—
Given the unmet clinical needs, testosterone appears to be a promising therapy to improve functional capacity in patients with HF. Adequately powered RCTs are required to assess the benefits of testosterone in this high-risk population with regard to quality of life, clinical events, and safety.
Asiatic Acid Attenuates Infarct Volume, Mitochondrial Dysfunction, and Matrix Metalloproteinase-9 Induction After Focal Cerebral Ischemia
Authors: Lee Ki Yong , Bae Ok-Nam , Serfozo Kelsey , Hejabian Siamk , Moussa Ahmad , Reeves Mathew , Rumbeiha Wilson , Fitzgerald Scott D. , Stein Gary , Baek Seung-Hoon , Goudreau John , Kassab Mounzer , Majid Arshad 
Published: April 2012

Background and Purpose—
Asiatic acid (AA) has been shown to attenuate cerebral infarction in a mouse model of focal ischemia and shows promise as a neuroprotective stroke therapy. To facilitate translation of these findings to clinical studies, we determined pharmacokinetics, a dose–response relationship, the therapeutic time window, and efficacy using multiple stroke models. We also explored potential mechanisms of action.

Methods—
Escalating doses of intravenous AA were administered and serum concentrations were measured at multiple time points for the pharmacokinetic studies. Subsequently, a dose–response relationship was determined followed by administration at different intervals after the onset of ischemia to establish a therapeutic time window for neuroprotection. Outcome measurements included both histological and behavioral. Mitochondrial function and matrix metalloproteinase activity in controls and treated rats were also determined.

Results—
The pharmacokinetic studies showed that AA (75 mg/kg) has a half-life of 2.0 hours. AA significantly decreased infarct volume and improved neurological outcome even when administration was at time points up to 12 hours after the onset of ischemia. Infarct volume was also significantly decreased in female rats and spontaneously hypertensive rats. AA attenuated mitochondrial dysfunction and reduced matrix metalloproteinase-9 induction.

Conclusions—
Our study shows AA is effective against multiple models of focal ischemia, has a long therapeutic time window, and is also effective in females and hypertensive animals. AA may mediate neuroprotection by protecting mitochondria and inhibiting matrix metalloproteinase-9 induction and activation. Taken together these data suggest that AA is an excellent candidate for development as a stroke therapy.
Developing an Index to Measure Urban Heat Island Effect Using Satellite Land Skin Temperature and Land Cover Observations
Authors: Jin Menglin S. 
Published: April 2012

Abstract
A new index of calculating the intensity of urban heat island effects (UHI) for a city using satellite skin temperature and land cover observations is recommended. UHI, the temperature difference between urban and rural regions, is traditionally identified from the 2-m surface air temperatures (i.e., the screen-level temperature T2m) measured at a pair of weather stations sited in urban and rural locations. However, such screen-level UHI is affected by the location, distance, and geographic conditions of the pair of weather stations. For example, choosing a different pair of rural and city sites leads to a different UHI intensity for the same city, due to the high heterogeneity of the urban surface temperature. To avoid such uncertainty, satellite-observed surface skin temperature measurements (i.e., skin level temperature Tskin) is recommended to record UHI, known as skin-level UHI or UHIskin. This new index has advantages of high spatial resolution and aerial coverage to better record UHI intensity than T2m. An assessment of skin-level UHI from 10 yr of the National Aeronautics and Space Administration (NASA)’s Moderate Resolution Imaging Spectroradiometer (MODIS) observations reveals that skin-level UHI has a strong UHI signal during the day and at night. In addition, there are significant diurnal and seasonal variations in skin-level UHI. Furthermore, the skin-level UHI is stronger during the day and summer (July) than during nighttime and winter. This new index is important for more uniformly assessing UHIs over cities around the globe. Nevertheless, whether the seasonality and diurnal variations revealed in this work using skin-level UHI index are valid over desert cities, such as Phoenix, Arizona, need to be examined.
Measuring a Utility-Scale Turbine Wake Using the TTUKa Mobile Research Radars
Authors: Hirth Brian D. , Schroeder John L. , Gunter W. Scott , Guynes Jerry G. 
Published: April 2012

Abstract
Observations of the wake generated by a single utility-scale turbine and collected by the Texas Tech University Ka-band mobile research radars on 27 October 2011 are introduced. Remotely sensed turbine wake observations using lidar technology have proven effective; however, the presented radar capabilities provide a larger observational footprint and greater along-beam resolution than current scanning lidar systems. Plan-position indicator and range–height indicator scanning techniques are utilized to produce various wake analyses. Preliminary analyses confirm radial velocity and wind speed deficits immediately downwind of the turbine hub to be on the order of 50%. This introduction lays the groundwork for more in-depth analyses of wake structure and evolution using the Texas Tech University Ka-band radar systems, including wake meandering and wake-to-wake interaction in large wind park deployments.
Health behaviours of community-treated patients with psychosis
Authors: Feiler Gabriel , Chen Roger Chih-Yu , Pantelis Christos , Lambert Timothy 
Published: April 2012

Objective: To assess physical health self-reports and health utilization behaviours of community dwelling persons with persistent psychosis. Method: A cross-sectional survey was conducted of 106 patients with persistent psychosis. Using self-reported measures, the prevalence of smoking, alcohol consumption and exercise, and body mass index were determined. Health utilization behaviour, especially with respect to general practice, was assessed. Data was compared with that derived from the general population and longitudinally with a historical cohort. Results: Compared with the general population, those with psychosis were more likely to be smokers, overweight or obese, and less likely to be non/ex-smokers. Compared with previous studies, smoking and obesity persisted as major modifiable risk factors. Over 7 years, some risks such as smoking increased, whereas moderating factors such as light exercise, improved. Three-quarters of patients would visit their GP if they had a physical illness but a third reported not having visited their GP or other doctor in the previous 12 months. Conclusions: Patients with persistent psychosis have increased rates of cardiometabolic risk yet seek medical attention infrequently. These findings have not improved despite an increased awareness of the enhanced risk of developing metabolic disease in this group.
Use of Dual-Energy X-Ray Absorptiometry (DXA) Scans in HIV-Infected Patients
Authors: Dickinson S. A. , Fantry L. E. 
Published: April 2012

Multiple studies have demonstrated increased rates of osteopenia and osteoporosis in HIV-infected patients but there have been no published studies on current screening practices. We conducted a retrospective chart review of 2924 patients attending an urban HIV clinic. Thirty patients (1%) had dual-energy x-ray absorptiometry (DXA) scans. Patients undergoing DXA scans were more likely to be older, women, and have nondetectable HIV viral load and CD4 count ≥200. The most frequently cited indications for screening were perimenopausal or postmenopausal status and HIV infection. Of the patients screened, 96% had osteopenia or osteoporosis with a median T-score of −1.9 and a median of 3.8 osteoporosis risk factors in addition to HIV. Of the 20 practitioners in the clinic, only 7 had patients with screening DXA scans. DXA scans are underutilized in the HIV population given the high rate of osteopenia and osteoporosis detected in this study.
Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1
Authors: Romano Emanuela , Cotari Jesse W. , Barreira da Silva Rosa , Betts Brian C. , Chung David J. , Avogadri Francesca , Fink Mitsu J. , St Angelo Erin T. , Mehrara Babak , Heller Glenn , Münz Christian , Altan-Bonnet Gregoire , Young James W. 
Published: April 2012

AbstractHuman CD34+ progenitor-derived Langerhans-type dendritic cells (LCs) are more potent stimulators of T-cell immunity against tumor and viral antigens in vitro than are monocyte-derived DCs (moDCs). The exact mechanisms have remained elusive until now, however. LCs synthesize the highest amounts of IL-15R-α mRNA and protein, which binds IL-15 for presentation to responder lymphocytes, thereby signaling the phosphorylation of signal transducer and activator of transcription 5 (pSTAT5). LCs electroporated with Wilms tumor 1 (WT1) mRNA achieve sufficiently sustained presentation of antigenic peptides, which together with IL-15R-α/IL-15, break tolerance against WT1 by stimulating robust autologous, WT1-specific cytolytic T-lymphocytes (CTLs). These CTLs develop from healthy persons after only 7 days' stimulation without exogenous cytokines and lyse MHC-restricted tumor targets, which include primary WT1+ leukemic blasts. In contrast, moDCs require exogenous rhuIL-15 to phosphorylate STAT5 and attain stimulatory capacity comparable to LCs. LCs therefore provide a more potent costimulatory cytokine milieu for T-cell activation than do moDCs, thus accounting for their superior stimulation of MHC-restricted Ag-specific CTLs without need for exogenous cytokines. These data support the use of mRNA-electroporated LCs, or moDCs supplemented with exogenous rhuIL-15, as vaccines for cancer immunotherapy to break tolerance against self-differentiation antigens shared by tumors.
Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease
Authors: Tanabe Naoya , Muro Shigeo , Tanaka Shiro , Sato Susumu , Oguma Tsuyoshi , Kiyokawa Hirofumi , Takahashi Tamaki , Kinose Daisuke , Hoshino Yuma , Kubo Takeshi , Ogawa Emiko , Hirai Toyohiro , Mishima Michiaki 
Published: April 2012

Abstract

Background
The progression of chronic obstructive pulmonary disease (COPD) considerably varies among patients. Those with emphysema identified by quantitative computed tomography (CT) are associated with the rapid progression assessed by forced expiratory volume in one second (FEV1). However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear.

Methods
We followed up 131 male patients with COPD for a median of 3.7 years. We measured wall area percent (WA%) in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%), and the standard deviation (SD) of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal emphysema heterogeneity. Annual changes in FEV1 were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV1 were examined.

Results
The mean (SD) annual change in FEV1 was −44.4 (10.8) mL. Multivariate random coefficient model showed that higher baseline FEV1, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV1, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity.

Conclusions
A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV1 independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status. In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted strategy with which to prevent disease progression.
The prevalence and identity of Chlamydia -specific IgE in children with asthma and other chronic respiratory symptoms
Authors: Patel Katir K , Anderson Erica , Salva Paul S , Webley Wilmore C 
Published: April 2012

Abstract

Background
Recent studies have confirmed the presence of viable Chlamydia in the bronchoalveolar lavage (BAL) fluid of pediatric patients with airway hyperresponsiveness. While specific IgG and IgM responses to C. pneumoniae are well described, the response and potential contribution of Ag-specific IgE are not known. The current study sought to determine if infection with Chlamydia triggers the production of pathogen-specific IgE in children with chronic respiratory diseases which might contribute to inflammation and pathology.

Methods
We obtained BAL fluid and serum from pediatric respiratory disease patients who were generally unresponsive to corticosteroid treatment as well as sera from age-matched control patients who saw their doctor for wellness checkups. Chlamydia-specific IgE was isolated from BAL and serum samples and their specificity determined by Western blot techniques. The presence of Chlamydia was confirmed by species-specific PCR and BAL culture assays.

Results
Chlamydial DNA was detected in the BAL fluid of 134/197 (68%) patients. Total IgE increased with age until 15 years old and then decreased. Chlamydia-specific IgE was detected in the serum and/or BAL of 107/197 (54%) patients suffering from chronic respiratory disease, but in none of the 35 healthy control sera (p < 0.0001). Of the 74 BAL culture-positive patients, 68 (91.9%, p = 0.0001) tested positive for Chlamydia-specific IgE. Asthmatic patients had significantly higher IgE levels compared to non-asthmatics (p = 0.0001). Patients who were positive for Chlamydia DNA or culture had significantly higher levels of serum IgE compared to negative patients (p = 0.0071 and p = 0.0001 respectively). Only 6 chlamydial antigens induced Chlamydia-specific IgE and patients with C. pneumoniae-specific IgE had significantly greater levels of total IgE compared to C. pneumoniae-specific IgE negative ones (p = 0.0001).

Conclusions
IgE antibodies play a central role in allergic inflammation; therefore production of Chlamydia-specific IgE may prove significant in the exacerbation of chronic, allergic airway diseases, thus highlighting a direct role for Chlamydia in asthma pathogenesis.
Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis
Authors: Chang William YC , Cane Jennifer L , Blakey John D , Kumaran Maruti , Pointon Kate S , Johnson Simon R 
Published: April 2012

Abstract

Background
Lymphangioleiomyomatosis is a rare disease occurring almost exclusively in women. Diagnosis often requires surgical biopsy and the clinical course varies between patients with no predictors of progression. We evaluated recent diagnostic guidelines, clinical features and serum biomarkers as diagnostic and prognostic tools.

Methods
Serum vascular endothelial growth factor-D (VEGF-D), angiotensin converting enzyme (ACE), matrix metalloproteinases (MMP) -2 and -9, clinical phenotype, thoracic and abdominal computerised tomography, lung function and quality of life were examined in a cohort of 58 patients. 32 healthy female controls had serum biomarkers measured.

Results
Serum VEGF-D, ACE and total MMP-2 levels were elevated in patients. VEGF-D was the strongest discriminator between patients and controls (median = 1174 vs. 332 pg/ml p < 0.0001 with an area under the receiver operating characteristic curve of 0.967, 95% CI 0.93-1.01). Application of European Respiratory Society criteria allowed a definite diagnosis without biopsy in 69%. Adding VEGF-D measurement to ERS criteria further reduced the need for biopsy by 10%. VEGF-D was associated with lymphatic involvement (p = 0.017) but not the presence of angiomyolipomas.

Conclusions
Combining ERS criteria and serum VEGF-D reduces the need for lung biopsy in LAM. VEGF-D was associated with lymphatic disease but not lung function.
Hierarchical cluster analysis of labour market regulations and population health: a taxonomy of low- and middle-income countries
Authors: Muntaner Carles , Chung Haejoo , Benach Joan , Ng Edwin 
Published: April 2012

AbstractBackgroundAn important contribution of the social determinants of health perspective has been to inquire about non-medical determinants of population health. Among these, labour market regulations are of vital significance. In this study, we investigate the labour market regulations among low- and middle-income countries (LMICs) and propose a labour market taxonomy to further understand population health in a global context.MethodsUsing Gross National Product per capita, we classify 113 countries into either low-income (n = 71) or middle-income (n = 42) strata. Principal component analysis of three standardized indicators of labour market inequality and poverty is used to construct 2 factor scores. Factor score reliability is evaluated with Cronbach's alpha. Using these scores, we conduct a hierarchical cluster analysis to produce a labour market taxonomy, conduct zero-order correlations, and create box plots to test their associations with adult mortality, healthy life expectancy, infant mortality, maternal mortality, neonatal mortality, under-5 mortality, and years of life lost to communicable and non-communicable diseases. Labour market and health data are retrieved from the International Labour Organization's Key Indicators of Labour Markets and World Health Organization's Statistical Information System.ResultsSix labour market clusters emerged: Residual (n = 16), Emerging (n = 16), Informal (n = 10), Post-Communist (n = 18), Less Successful Informal (n = 22), and Insecure (n = 31). Primary findings indicate: (i) labour market poverty and population health is correlated in both LMICs; (ii) association between labour market inequality and health indicators is significant only in low-income countries; (iii) Emerging (e.g., East Asian and Eastern European countries) and Insecure (e.g., sub-Saharan African nations) clusters are the most advantaged and disadvantaged, respectively, with the remaining clusters experiencing levels of population health consistent with their labour market characteristics.ConclusionsThe labour market regulations of LMICs appear to be important social determinant of population health. This study demonstrates the heuristic value of understanding the labour markets of LMICs and their health effects using exploratory taxonomy approaches.