bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-17 Promotes Formation and Growth of Prostate Adenocarcinoma in Mouse Models
Authors: Zhang Qiuyang , Liu Sen , Ge Dongxia , Zhang Qingsong , Xue Yun , Xiong Zhenggang , Abdel-Mageed Asim B. , Myers Leann , Hill Steven M. , Rowan Brian G. , Sartor Oliver , Melamed Jonathan , Chen Zhenbang , You Zongbing 
Published: March 2012

AbstractThe contributions of interleukin (IL)-17 to cancer remain unclear and somewhat controversial. We took a genetic approach to explore its role in prostate cancers by interbreeding IL-17 receptor C (IL-17RC)–deficient mice with mice that are conditionally mutant for PTEN, one established preclinical model for prostate cancer. Mice that were IL-17RC–deficient (IL-17RC−) displayed prostates that were smaller than mice that maintained IL-17RC expression (IL-17RC+). In addition, IL-17RC− mice developed a reduced number of invasive prostate adenocarcinomas with lower rates of cellular proliferation and higher apoptosis than IL-17RC+ mice. Moreover, the fibromuscular stroma surrounding prostatic glands was relatively thicker in IL-17RC− mice and was associated with decreased matrix metalloproteinase (Mmp)7 expression and increased Timp1, 2, and 4 expression, whereas administration of recombinant mouse IL-17 induced prostatic expression of Mmp7. Taken together, our results suggested that IL-17 promotes the formation and growth of prostate adenocarcinoma, and that an IL-17–MMP7 signaling axis is required for the transition of prostatic intraepithelial neoplasia to frank adenocarcinoma. Cancer Res; 72(10); 2589–99. ©2012 AACR.
IGF-1R/MDM2 Relationship Confers Enhanced Sensitivity to RITA in Ewing Sarcoma Cells
Authors: Di Conza Giusy , Buttarelli Marianna , Monti Olimpia , Pellegrino Marsha , Mancini Francesca , Pontecorvi Alfredo , Scotlandi Katia , Moretti Fabiola 
Published: March 2012

Abstract
Ewing sarcoma is one of the most frequent bone cancers in adolescence. Although multidisciplinary therapy has improved the survival rate for localized tumors, a critical step is the development of new drugs to improve the long-term outcome of recurrent and metastatic disease and to reduce side effects of conventional therapy. Here, we show that the small molecule reactivation of p53 and induction of tumor cell apoptosis (RITA, NSC652287) is highly effective in reducing growth and tumorigenic potential of Ewing sarcoma cell lines. These effects occur both in the presence of wt-p53 as well as of mutant or truncated forms of p53, or in its absence, suggesting the presence of additional targets in this tumor histotype. Further experiments provided evidence that RITA modulates an important oncogenic mark of these cell lines, insulin-like growth factor receptor 1 (IGF-1R). Particularly, RITA causes downregulation of IGF-1R protein levels. MDM2 degradative activity is involved in this phenomenon. Indeed, inhibition of MDM2 function by genetic or pharmacologic approaches reduces RITA sensitivity of Ewing sarcoma cell lines. Overall, these data suggest that in the cell context of Ewing sarcoma, RITA may adopt additional mechanism of action besides targeting p53, expanding its field of application. Noteworthy, these results envisage the promising utilization of RITA or its derivative as a potential treatment for Ewing sarcomas. Mol Cancer Ther; 11(6); 1247–56. ©2012 AACR.
Common and Low-Frequency Genetic Variants in the
PCSK9
Locus Influence Circulating
PCSK9
Levels
Authors: Chernogubova Ekaterina , Strawbridge Rona , Mahdessian Hovsep , Mälarstig Anders , Krapivner Sergey , Gigante Bruna , Hellénius Mai-Lis , de Faire Ulf , Franco-Cereceda Anders , Syvänen Ann-Christine , Troutt Jason S. , Konrad Robert J. , Eriksson Per , Hamsten Anders , van ’t Hooft Ferdinand M. 
Published: March 2012

Objective —
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that influences plasma low-density lipoprotein concentration and susceptibility to coronary heart disease. Circulating PCSK9 levels show considerable interindividual differences, but the factors responsible for this variation are largely unknown.

Methods and Results—

We analyzed circulating PCSK9 levels in 4 cohorts of healthy, middle-aged Swedes (n=5722) and found that PCSK9 levels varied over ≈50-fold range, showed a positive relationship with plasma low-density lipoprotein–cholesterol concentration, and were associated with plasma triglyceride, fibrinogen, insulin, and glucose concentrations. A genome-wide association study conducted in 2 cohorts (n=1215) failed to uncover common genetic variants robustly associated with variation in circulating PCSK9 level. As expected, the minor allele of the
PCSK9
R46L variant was in all cohorts associated with reduced PCSK9 levels and decreased plasma low-density lipoprotein–cholesterol concentrations, but no relationship was observed with the plasma triglyceride concentration. Further mapping of the
PCSK9
locus revealed a common polymorphism (rs2479415, minor allele frequency 43.9%), located ≈6 kb upstream from
PCSK9
, which is independently associated with increased circulating PCSK9 levels.

Conclusion—

Common and low-frequency genetic variants in the
PCSK9
locus influence the pronounced interindividual variation in circulating PCSK9 levels in healthy, middle-aged white (predominantly Swedish) subjects.
Potential Role of Upstream Stimulatory Factor 1 Gene Variant in Familial Combined Hyperlipidemia and Related Disorders
Authors: Auer Simon , Hahne Penelope , Soyal Selma M. , Felder Thomas , Miller Karl , Paulmichl Markus , Krempler Franz , Oberkofler Hannes , Patsch Wolfgang 
Published: March 2012

Objective—
Genetic studies implicated upstream stimulatory factor 1 (USF1) in familial combined hyperlipidemia because the rs2073658 minor allele was associated with reduced risk of familial combined hyperlipidemia and related disorders. The molecular mechanisms whereby rs2073658 influences trait expression have remained elusive.

Methods and Results—

Plasma lipids, rs2073658 genotypes (N=372), and hepatic transcript levels (N=96) of
USF1
and genes involved in hepatic lipoprotein production were determined in obese subjects. The rs2073658 minor allele was associated with reduced plasma triglycerides (TGs) (
P
<0.001), hepatic
USF1
(
P
<0.01), and microsomal TG transfer protein transcript levels (
P
<0.05). Functional studies in human hepatocellular carcinoma cells showed that rs2073658 is located in a forkhead box A2 (FOXA2) binding site and that major allele constructs displayed higher transcriptional activity than minor allele constructs. Knockdown of FOXA2 reduced the activity of major, but not minor allele constructs. Furthermore, an interaction between hepatic FOXA2 transcript levels and rs2073658 minor allele carrier status on hepatic
USF1
transcript levels was observed in vivo (
P
<0.05).
USF1
activated the transcription of FOXA2 and FOXA2 strongly activated the transcription of microsomal TG transfer protein.

Conclusion—

A feed-forward loop comprising activation of
USF1
transcription by FOXA2 and activation of FOXA2 transcription by
USF1
, driving microsomal TG transfer protein expression, is modulated by rs2073658. Hence, rs2073658 likely influences hepatic TG secretion.
Depression and Antidepressant Use After Stroke and Transient Ischemic Attack
Authors: El Husseini Nada , Goldstein Larry B. , Peterson Eric D. , Zhao Xin , Pan Wenqin , Olson DaiWai M. , Zimmer Louise O. , Williams John W. , Bushnell Cheryl , Laskowitz Daniel T. 
Published: March 2012

Background and Purpose—
Patients with stroke and transient ischemic attack (TIA) often have comparable comorbidities, but it is unclear whether they have similar rates of depression or antidepressant use.

Methods—
This study was a secondary analysis of a prospective cohort registry that enrolled subjects from 2006 to 2008 in the United States. Depression (defined by the Patient Health Questionnaire-8 score ≥10) and medication use were prospectively assessed 3 and 12 months after hospitalization in 1450 subjects with ischemic stroke and 397 subjects with TIA.

Results—

The proportional frequency of depression after stroke and TIA was similar at 3 months (17.9% versus 14.3%,
P
=0.09) and at 12 months (16.4% versus 12.8%,
P
=0.08). The rates of newly identified depression between 3 and 12 months were also similar (8.7% versus 6.2%,
P
=0.12). Persistent depression (defined as Patient Health Questionnaire-8 score ≥10 at both 3 and 12 months) was present in 134 (9.2%) of those with stroke and in 30 (7.6%) of those with TIA. Younger age, greater stroke-related disability, and inability to work at 3 months were associated with persistent depression in subjects with stroke. Among subjects with persistent depression, 67.9% of those with stroke and 70.0% of those with TIA were not using antidepressants at either time point (
P
=0.920).

Conclusions—
Stroke and TIA subjects had a similar frequency of depression at 3 and 12 months after hospitalization and similar rates of newly identified depression between 3 and 12 months. A high proportion of those with persistent depression was untreated.
Comparison of 2 Extended Activities of Daily Living Scales With the Barthel Index and Predictors of Their Outcomes
Authors: Sarker Shah-Jalal , Rudd Anthony G. , Douiri Abdel , Wolfe Charles D.A. 
Published: March 2012

Background and Purpose—
Basic activities of daily living measures are often supplemented by extended activities of daily living. We compared the Frenchay Activities Index (FAI) and Nottingham Extended Activities of Daily Living (NEADL) with the Barthel Index (BI) in terms of distribution of scores, concurrent validity, reliability, and their agreement and investigated the predictors of scales outcomes.

Methods—
Two hundred thirty-eight patients from the population-based South London Stroke Register were assessed with the BI, FAI, and NEADL 3 months after a first-ever stroke. The pairwise relationship was studied using correlations, fractional polynomial regression, and Bland and Altman plot; the baseline predictors, for example, sociodemography, case severity: National Institutes of Health Stroke Scale, and 7-day Abbreviated Memory Test, comorbidities, and acute treatments by negative binomial regression.

Results—

The BI was highly affected by a ceiling effect (33% had the highest score), FAI was only affected by floor effect (19%), but NEADL was symmetrical with only 4% highest and lowest score. Despite high concurrent validity of the scales (
r
≥0.80,
P
<0.001), they agreed poorly only for the highest and the lowest level of activities. The association and agreement of NEADL with BI was higher than that of FAI with BI. Severe stroke patients (National Institutes of Health Stroke Scale >13) had 28% lower BI (79% lower FAI and 62% lower NEADL) score than nonsevere patients (
P
≤0.001). Cognitively intact patients (Abbreviated Memory Test: 8–10) had 2.3 times greater FAI values (65% higher NEADL) compared with impaired patients (
P
<0.001).

Conclusions—
The NEADL scale was symmetrical, concurrently valid with no floor and ceiling effects. It corresponded better with BI than FAI did confirming its basic activities of daily living properties, yet it is a more sensitive tool for extended activities of daily living without the floor and ceiling effects. Future functional status could be predicted by the acute stage National Institutes of Health Stroke Scale score, whereas only extended activities of daily living status could be predicted by the Abbreviated Memory Test score. Predicting future functional status at the acute stage may decrease unnecessary length of stay in acute care settings.
An Approach for Improving Cirrus Cloud-Top Pressure/Height Estimation by Merging High-Spatial-Resolution Infrared-Window Imager Data with High-Spectral-Resolution Sounder Data
Authors: Weisz Elisabeth , Menzel W. Paul , Smith Nadia , Frey Richard , Borbas Eva E. , Baum Bryan A. 
Published: March 2012

AbstractThe next-generation Visible and Infrared Imaging Radiometer Suite (VIIRS) offers infrared (IR)-window measurements with a horizontal spatial resolution of at least 1 km, but it lacks IR spectral bands that are sensitive to absorption by carbon dioxide (CO2) or water vapor (H2O). The CO2 and H2O absorption bands have high sensitivity for the inference of cloud-top pressure (CTP), especially for semitransparent ice clouds. To account for the lack of vertical resolution, the “merging gradient” (MG) approach is introduced, wherein the high spatial resolution of an imager is combined with the high vertical resolution of a sounder for improved CTP retrievals. The Cross-Track Infrared Sounder (CrIS) is on the same payload as VIIRS. In this paper Moderate Resolution Imaging Spectroradiometer (MODIS) and Atmospheric Infrared Sounder (AIRS) data are used as proxies for VIIRS and CrIS, respectively, although the approach can be applied to any imager–sounder pair. The MG method establishes a regression relationship between gradients in both the sounder radiances convolved to imager bands and the sounder CTP retrievals. This relationship is then applied to the imager radiance measurements to obtain CTP retrievals at imager spatial resolution. Comparisons with Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) cloud altitudes are presented for a variety of cloud scenes. Results demonstrate the ability of the MG algorithm to add spatial definition to the sounder retrievals with a higher accuracy and precision than those obtained solely from the imager.
Some Counterintuitive Dependencies of Tropical Cyclone Frequency on Parameters in a GCM
Authors: Zhao Ming , Held Isaac M. , Lin Shian-Jiann 
Published: March 2012

AbstractHigh-resolution global climate models (GCMs) have been increasingly utilized for simulations of the global number and distribution of tropical cyclones (TCs), and how they might change with changing climate. In contrast, there is a lack of published studies on the sensitivity of TC genesis to parameterized processes in these GCMs. The uncertainties in these formulations might be an important source of uncertainty in the future projections of TC statistics.This study investigates the sensitivity of the global number of TCs in present-day simulations using the Geophysical Fluid Dynamics Laboratory High Resolution Atmospheric Model (GFDL HIRAM) to alterations in physical parameterizations. Two parameters are identified to be important in TC genesis frequency in this model: the horizontal cumulus mixing rate, which controls the entrainment into convective cores within the convection parameterization, and the strength of the damping of the divergent component of the horizontal flow. The simulated global number of TCs exhibits nonintuitive response to incremental changes of both parameters. As the cumulus mixing rate increases, the model produces nonmonotonic response in global TC frequency with an initial sharp increase and then a decrease. However, storm mean intensity rises monotonically with the mixing rate. As the strength of the divergence damping increases, the model produces a continuous increase of global number of TCs and hurricanes with little change in storm mean intensity. Mechanisms for explaining these nonintuitive responses are discussed.
Thermodynamic Aspects of Tropical Cyclone Formation
Authors: Wang Zhuo 
Published: March 2012

Abstract
The thermodynamic aspects of tropical cyclone (TC) formation near the center of the wave pouch, a region of approximately closed Lagrangian circulation within the wave critical layer, are examined through diagnoses of a high-resolution numerical simulation and dropsonde data from a recent field campaign. It is found that the meso-β area near the pouch center is characterized by high saturation fraction, small difference in equivalent potential temperature θe between the surface and the middle troposphere, and a short incubation time scale. Updrafts tend to be more vigorous in this region, presumably because of reduced dry air entrainment, while downdrafts are not suppressed. The thermodynamic conditions near the pouch center are thus critically important for TC formation.
The balanced responses to convective and stratiform heating at the pregenesis stage are examined using the Sawyer–Eliassen equation. Deep convection is concentrated near the pouch center. The strong radial and vertical gradients of latent heat release effectively force the transverse circulation and spin up a surface protovortex near the pouch center. Stratiform heating induces modest midlevel inflow and very weak low-level outflow, which contributes to the midlevel spinup without substantially spinning down the low-level circulation.
The analysis of dropsonde data shows that the midlevel θe increases significantly near the pouch center one to two days prior to genesis but changes little away from the pouch center. This may indicate convective organization and the impending TC genesis. It also suggests that the critical information of TC genesis near the pouch center may be masked out if a spatial average is taken over the pouch scale.
Tropical Cyclone Climatology of the South Pacific Ocean and Its Relationship to El Niño–Southern Oscillation
Authors: Dowdy Andrew J. , Qi Lixin , Jones David , Ramsay Hamish , Fawcett Robert , Kuleshov Yuri 
Published: March 2012

Abstract
Climatological features of tropical cyclones in the South Pacific Ocean have been analyzed based on a new archive for the Southern Hemisphere. A vortex tracking and statistics package is used to examine features such as climatological maps of system intensity and the change in intensity with time, average tropical cyclone system movement, and system density. An examination is presented of the spatial variability of these features, as well as changes in relation to phase changes of the El Niño–Southern Oscillation phenomenon. A critical line is defined in this study based on maps of cyclone intensity to describe the statistical geographic boundary for cyclone intensification. During El Niño events, the critical line shifts equatorward, while during La Niña events the critical line is generally displaced poleward. Regional variability in tropical cyclone activity associated with El Niño–Southern Oscillation phases is examined in relation to the variability of large-scale atmospheric or oceanic variables associated with tropical cyclone activity. Maps of the difference fields between different phases of El Niño–Southern Oscillation are examined for sea surface temperature, vertical wind shear, lower-tropospheric vorticity, and midtropospheric relative humidity. Results are also examined in relation to the South Pacific convergence zone. The common region where each of the large-scale variables showed favorable conditions for cyclogenesis coincided with the location of maximum observed cyclogenesis for El Niño events as well as for La Niña years.
Expertise in Crime Scene Examination
Authors: Baber Chris , Butler Mark 
Published: March 2012

Objective: The strategies of novice and expert crime scene examiners were compared in searching crime scenes. Background: Previous studies have demonstrated that experts frame a scene through reconstructing the likely actions of a criminal and use contextual cues to develop hypotheses that guide subsequent search for evidence. Method: Novice (first-year undergraduate students of forensic sciences) and expert (experienced crime scene examiners) examined two “simulated” crime scenes. Performance was captured through a combination of concurrent verbal protocol and own-point recording, using head-mounted cameras. Results: Although both groups paid attention to the likely modus operandi of the perpetrator (in terms of possible actions taken), the novices paid more attention to individual objects, whereas the experts paid more attention to objects with “evidential value.” Novices explore the scene in terms of the objects that it contains, whereas experts consider the evidence analysis that can be performed as a consequence of the examination. Conclusion: The suggestion is that the novices are putting effort into detailing the scene in terms of its features, whereas the experts are putting effort into the likely actions that can be performed as a consequence of the examination. Application: The findings have helped in developing the expertise of novice crime scene examiners and approaches to training of expertise within this population.
Clinical evaluation of the Sorin Xtra® autotransfusion system
Authors: Overdevest EP , Lanen PWJ , Feron JCM , van Hees JWH , Tan MESH 
Published: March 2012

The performance of the Sorin Xtra® Autotransfusion System (ATS) was studied in 62 patients undergoing coronary artery bypass grafting. Blood was collected intraoperatively and washed using three different wash sets in 4 groups. Both collected and washed blood were analysed for hemoglobin levels and hematocrit, concentrations of proteins, albumin, heparin and plasma free hemoglobin (PFH) were determined, erythrocytes, platelets and leukocytes were counted. Hematocrit measurements of the Xtra® were compared with laboratory measurements to study the accuracy of the Xtra® hematocrit sensor. In addition, the red blood cell recovery rate and elimination rates were calculated to evaluate the clinical performance of the Xtra®. The Xtra® ATS produced a volume of concentrated red blood cells with an average hematocrit from 58% to 63%, depending on the size of the bowl and the chosen default program. In all bowl sizes and programs, the Xtra® Hct-out measurement underestimated the CELL-DYN measurement by approximately 15%. The calculated recovery rates for red blood cells (RBC) in the 4 groups ranged from 86.7% to 91.6%. Elimination rates were calculated in each group for proteins (96.8-99.2%), albumin (96.4-98.7%), plasma free hemoglobin (83.6–91.2%), heparin (98.8-99.9%), platelets (82.4-94.3%) and white blood cells (28.6-42.3%). The Xtra® ATS can be appealing for its performance by producing high hematocrit levels in the washed RBC volume, while keeping RBC recovery rate at the same high level (≈ 90%) as in its predecessor, the Electa® Autotransfusion System.
The Effects of Lithium on Renal Function in Older Adults—A Systematic Review
Authors: Rej Soham , Herrmann Nathan , Shulman Kenneth 
Published: March 2012

Chronic renal failure (CRF) and nephrogenic diabetes insipidus (NDI) are potential consequences of chronic lithium use, while acute renal failure (ARF) has been described in lithium intoxication. We performed a systematic review of all studies pertaining to the effects of lithium on the kidney in older adults. The ARF incidence was 1.5% per person-year and concurrent loop diuretic and angiotensin-converting enzyme inhibitor use with lithium increased the risk. The CRF prevalence estimates varied from 1.2% to 34%, with risk factors including age, previous lithium intoxication, polyuria, previously impaired renal function, and decreased maximal urine osmolality. The prevalence of NDI varied widely from 1.8% to 85%. Risk factors included lithium duration, dose, level, slow-release formulation, and clinical nonresponse. Except for amiloride use in NDI, there is little evidence for treatment of other lithium-induced adverse renal effects. Currently, there is no compelling evidence to suggest that lithium should be avoided in elderly patients for fear of renal side effects.