bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon
Authors: Hamilton Kathryn E. , Chatterji Priya , Lundsmith Emma T. , Andres Sarah F. , Giroux Veronique , Hicks Philip D. , Noubissi Felicite K. , Spiegelman Vladimir S. , Rustgi Anil K. 
Published: July 2015

Abstract
The colon tumor microenvironment is becoming increasingly recognized as a complex but central player in the development of many cancers. Previously, we identified an oncogenic role for the mRNA-binding protein IMP1 (IGF2BP1) in the epithelium during colon tumorigenesis. In the current study, we reveal the contribution of stromal IMP1 in the context of colitis-associated colon tumorigenesis. Interestingly, stromal deletion of Imp1 (Dermo1Cre;Imp1LoxP/LoxP, or Imp1ΔMes) in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated cancer resulted in increased tumor numbers of larger size and more advanced histologic grade than controls. In addition, Imp1ΔMes mice exhibited a global increase in protumorigenic microenvironment factors, including enhanced inflammation and stromal components. Evaluation of purified mesenchyme from AOM/DSS-treated Imp1ΔMes mice demonstrated an increase in hepatocyte growth factor (HGF), which has not been associated with regulation via IMP1. Genetic knockdown of Imp1 in human primary fibroblasts confirmed an increase in HGF with Imp1 loss, demonstrating a specific, cell-autonomous role for Imp1 loss to increase HGF expression. Taken together, these data demonstrate a novel tumor-suppressive role for IMP1 in colon stromal cells and underscore an exquisite, context-specific function for mRNA-binding proteins, such as IMP1, in disease states.
Implications: The tumor-suppressive role of stromal IMP1 and its ability to modulate protumorigenic factors suggest that IMP1 status is important for the initiation and growth of epithelial tumors. Mol Cancer Res; 13(11); 1478–86. ©2015 AACR.
See related article by Koltsova and Grivennikov, p. 1452
Canadian RCM Projected Transient Changes to Precipitation Occurrence, Intensity, and Return Level over North America
Authors: Jalbert Jonathan , Favre Anne-Catherine , Bélisle Claude , Angers Jean-François , Paquin Dominique 
Published: July 2015

Abstract
As a consequence of the increase in atmospheric greenhouse gas concentrations, potential changes in both precipitation occurrence and intensity may lead to several consequences for Earth’s environment. It is therefore relevant to estimate these changes in order to anticipate their consequences. Many studies have been published on precipitation changes based on climate simulations. These studies are almost always based on time slices; precipitation changes are estimated by comparing two 30-yr windows. To this extent, it is commonly assumed that nonstationary processes are not significant for such a 30-yr slice. Thus, it frees the investigator to statistically model nonstationary processes. However, using transient runs instead of time slices surely leads to more accurate analysis since more data are taken into account. Therefore, the aim of the present study was to develop a transient probabilistic model for describing simulated daily precipitation from the Canadian Regional Climate Model (CRCM) in order to investigate precipitation evolution over North America. Changes to both the occurrence and intensity of precipitation are then assessed from a continuous time period. Extreme values are also investigated with the transient run; a new methodology using the models for precipitation occurrence and intensity was developed for achieving nonstationary frequency analysis. The results herein show an increase in both precipitation occurrence and intensity for most parts of Canada while a decrease is expected over Mexico. For the continental United States, a decrease in both occurrence and intensity is expected in summer but an increase is expected in winter.
Cyclones and Anticyclones in Seismic Imaging
Authors: Barbosa Aguiar A. C. , Ménesguen C. , Le Gentil S. , Schopp R. , Carton X. 
Published: July 2015

AbstractNearly all the subsurface eddies detected in seismic imaging of sections in the northeast Atlantic have been assumed to be anticyclones containing Mediterranean Water (MW). Fewer MW cyclones have been observed and studied. In this study, the work of previous numerical studies is extended to investigate some characteristics of layering surrounding MW cyclones, using a primitive equation model with equal diffusivities for salinity and temperature to suppress the effects of double diffusion. It is shown that, after a stable state is reached, both anticyclones and cyclones display similar patterns of layering: stacked thin layers of high acoustic reflectivity located above and below the core of each vortex, which do not match isopycnals. The authors conclude that it should not be possible to distinguish between MW cyclones and anticyclones based on their signature in seismic imaging alone. Complementary information is needed to determine the sense of rotation.
A novel high-throughput method for supported liquid extraction of retinol and alpha-tocopherol from human serum and simultaneous quantitation by liquid chromatography tandem mass spectrometry
Authors: Hinchliffe Edward , Rudge James , Reed Paul 
Published: July 2015

Background Measurement of vitamin A (retinol) and E (alpha-tocopherol) in UK clinical laboratories is currently performed exclusively by high-performance liquid chromatography with ultraviolet detection. We investigated whether retinol and alpha-tocopherol could be measured simultaneously by liquid chromatography tandem mass spectrometry. Methods Serum samples (100  μL) were extracted using Isolute + Supported Liquid Extraction plates. Chromatography was performed on a Phenomenex Kinetex Biphenyl 2.6  μm, 50 × 2.1 mm column, and liquid chromatography tandem mass spectrometry on a Waters Acquity TQD. Injection-to-injection time was 4.3 min. The assay was validated according to published guidelines. Patient samples were used to compare liquid chromatography tandem mass spectrometry and high-performance liquid chromatography with ultraviolet detection methods. Results For retinol and alpha-tocopherol, respectively, the assay was linear up to 6.0 and 80.0  μmol/L, and lower limit of quantification was 0.07 and 0.26  μmol/L. Intra and interassay imprecision were within desirable analytical specifications. Analysis of quality control material aligned to NIST SRM 968e, and relative spiked recovery from human serum, both yielded results within 15% of target values. Method comparison with high-performance liquid chromatography with ultraviolet detection methodology demonstrated a negative bias for retinol and alpha-tocopherol by the liquid chromatography tandem mass spectrometry method. Analysis of United Kingdom National External Quality Assurance Scheme samples yielded mean bias from the target value of +3.0% for retinol and −11.2% for alpha-tocopherol. Conclusions We have developed a novel, high-throughput method for extraction of retinol and alpha-tocopherol from human serum followed by simultaneous quantitation by liquid chromatography tandem mass spectrometry. The method offers a rapid, sensitive, specific and cost-effective alternative to high-performance liquid chromatography with ultraviolet detection methodology, and is suitable for routine clinical monitoring of patients predisposed to fat-soluble vitamin malabsorption.
‘In wealth and in poverty?’ The changing role of Spanish municipalities in implementing childcare policies
Authors: Navarro Carmen , Velasco Francisco 
Published: July 2015

In the context of more than a decade of economic expansion that ended in 2008, Spanish municipalities were active in expanding their functions through vigorous policy-making in numerous areas. The crisis meant that town halls had difficulty in providing these services and, in 2013, the central government approved a re-centralization policy driven by the belief that local governments had brought about unsustainable patterns of expenditure. Using a neo-institutionalist theoretical perspective, this article analyses the phenomena of expansion of municipal involvement in childcare policies and the impact of these processes on the functioning of local governments. We observe, as an unintended positive effect of the reallocation of tasks, that local governments have legitimized themselves through action in fields not initially foreseen in the formal decentralization arrangements, and are highly valued by citizens as welfare providers. However, they have not overcome the structural lack of autonomy in which the legal system places them and, so far, they have been able to meet citizens’ expectations only when economic conditions have been favourable. Points for practitioners The study may be taken to show that we can only understand the decentralization dynamics if we pay attention not only to the implementation of formal rules, but also to other aspects of the functioning of communities such as general favourable financial circumstances, particular citizens’ demands at one point in time and strategic behaviour of political actors. Furthermore, the outputs of decentralization are not only changes in the reallocation of tasks but also in legitimacy of local governments that can be strengthened with good performance.
Is it the twilight of decentralization? Testing the limits of functional reforms in the era of austerity
Authors: Hlepas Nikolaos-Komninos 
Published: July 2015

Economic crisis and rigid austerity seem to have brought a long-lasting period of decentralization to an end. The comeback of centralist patterns offers the rapid implementation of austerity measures, while the lack of resources is challenging the sustainability of decentralized services. There is an obvious inconsistency between European decentralization policies, on the one side, and European austerity policies, on the other. Empirical evidence shows that local authorities were more responsive to citizens’ demands for social services, but now municipalities without resources repulse decentralization. In spite of centralist patterns, case studies of fiscal consolidation have revealed a remarkable deviation of municipal responses to top-down fiscal policies. Visionary leadership, active citizenry and inclusive decision-making processes predict good performance, while reproductive leadership and a passive citizenry predetermine unproductive central–local conflicts over burden-sharing and blame-shifting. Points for practitioners Our results show that both decentralization and centralization policies are highly dependent on the attitudes and actions of local authorities. In the case of social services, the responsiveness of local authorities brings obvious performance gains. Attempts at burden-shifting to municipalities in times of crisis will, however, most probably face blockades. In the case of austerity policies, top-down unitary strategies with rigid norms and mechanisms cannot rule out performance disparities among the addressees of these policies. The responsiveness of municipalities is highly dependent on local leadership, actors’ constellations and the attributes of the community involved. In case of functional reforms, the prior consultation and ongoing assistance of local authorities and involved communities should be a standard practice.
Bidirectional triggering association between migraine and restless legs syndrome: A diary study
Authors: Chen Ping-Kun , Fuh Jong-Ling , Wang Shuu-Jiun 
Published: July 2015

Objective Migraine is comorbid with restless legs syndrome (RLS). However, the temporal association between these two episodic disorders remains elusive. The current study investigated the temporal relationship between migraine and RLS attacks. Methods Migraine patients with RLS were recruited from a headache clinic. Patients with symptomatic RLS, RLS mimics, daily headaches, or daily RLS attacks were excluded. The patients recorded their headaches and RLS attacks for two weeks in a diary. The severity of each headache or RLS attack was rated on a four-point (0−3) Likert scale. Logit-normal, random-effects models were employed to estimate the odds ratios (ORs) for the temporal association between migraine and RLS attacks. Results Thirty migraine patients with RLS (28 F/2 M, mean age 35.5 ± 9.0 years) completed the study. On the basis of 420 daily diary records, migraine attacks were associated with subsequent RLS attacks occurring on the same and next nights (OR = 6.94, 95% confidence interval (CI) = 4.39–11.0 and OR = 3.00, CI = 1.92–4.68; both p < 0.001). RLS attacks were associated with subsequent migraine attacks only on Day 1 (OR = 1.97 (CI = 1.3–2.98; p = 0.01). Overall, the frequencies of migraine and RLS attacks in two weeks were correlated (Spearman’s correlation = 0.56, p = 0.001). Conclusions Our study results showed a bidirectional triggering association between migraine and RLS attacks. The association was stronger and lasted longer for migraine triggering subsequent RLS than that for vice versa.
Population-based analysis of hospitalizations in a West-European region revealed major changes in hospital utilization for patients with systemic lupus erythematosus over the period 2001–2012
Authors: Piga M , Casula L , Perra D , Sanna S , Floris A , Antonelli A , Cauli A , Mathieu A 
Published: July 2015

Objective The objective of this paper is to evaluate hospital admissions in systemic lupus erythematosus (SLE) patients through a retrospective population-based study analyzing hospitalization data during 2001–2012 in Sardinia, an Italian region with universal health system coverage. Methods Data on the hospital discharge records with the ICD-9-CM code for SLE (710.0) were obtained from the Department of Health and Hygiene and analyzed, mostly focusing on primary and non-primary diagnosis and Diagnosis-Related Group (DRG) code. In order to establish the significance of the annual trend for number and type of primary and non-primary discharge diagnosis, the two-tailed Cochran-Armitage test for trend was applied. In order to estimate SLE prevalence, data from administrative database and medical records were assembled. Results This study included 6222 hospitalizations in 1675 patients (87% women). Hospitalizations with SLE as primary diagnosis were 3782 (58.0%) and significantly decreased during the study period. The annual number of renal, hematologic and neuropsychiatric disorders as non-primary diagnosis associated with SLE remained constant; however, their percentage increased ( p < 0.0001) because of a declining number of admissions for SLE without associated diagnosis and without complications. Hospitalizations with SLE as non-primary diagnosis showed a significant upward trend in number and percentage of cerebrovascular accident ( p = 0.0004), acute coronary syndrome ( p = 0.0004) and chronic renal failure ( p = 0.0003) as underlying primary diagnosis, while complications of pregnancy, labor and childbirth ( p = 0.3375), malignancies ( p = 0.6608) and adverse drug reactions ( p = 0.2456) did not show statistically significant changes. Infections showed an increasing trend between 2001 and 2012 but did not reach statistical significance ( p = 0.0304). After correction for hospitalization (93.8%) and survival (91.1%) rates calculated over the study period, the 2012 SLE prevalence in Sardinia was estimated to be 99.3 per 100,000 inhabitants. Conclusions While overall hospitalizations for SLE patients declined, those for cerebrovascular accident, acute coronary syndrome and chronic renal failure as underlying primary diagnosis increased during the study period.
Noninvasive Arterial Testing in Patients With Diabetes
Authors: Wukich Dane K. , Shen Wei , Raspovic Katherine M. , Suder Natalie C. , Baril Donald T. , Avgerinos Efthymios 
Published: July 2015

Background: This study was designed to compare the findings of noninvasive arterial testing in patients with and without diabetic foot pathology. Methods: The ABI (ankle brachial index), TBI (toe brachial index), and great toe pressures were measured in 207 patients. PAD (peripheral artery disease) was defined as an ABI < 0.91 on either extremity or a TBI < 0.7. Results: PAD was identified in 103 of the 207 patients (49.8%), 80 patients with diabetic foot pathology and 23 patients with nondiabetic foot pathology. Although patients with diabetic foot pathology were 1.4 times more likely to have PAD compared to patients without diabetic pathology, this increased risk was not statistically significant (OR 1.41 [95% CI 0.75-2.64], P = .28). Patients with PAD and diabetic foot pathology were 4.9 times more likely to have ischemia (toe pressure < 60 mm Hg) than patients with PAD and nondiabetic foot pathology (OR 4.93 [95% CI 1.35-17.94], P < .05). Patients on dialysis had a 7.3 times increased likelihood of having PAD compared to patients not on dialysis (OR 7.3 [95% CI 1.6-33.6], P < .01). Patients with absent pedal pulses were 4.9 more likely to have PAD than patients with normal pulses (OR 4.9 [95% CI 2.6-9.4], P < .0001). PAD was identified in 97 of 188 patients (51.6%) with peripheral neuropathy compared to 6 of 19 patients (31.5%) without peripheral neuropathy (OR 2.31 [95% CI 0.84-6.33], P = .10). Conclusions: Combining the ABI with TBI improved the ability to diagnose PAD in diabetic patients because the ABI has high specificity (low false positives) and the TBI has high sensitivity (low false negatives). The TBI was more reliable in patients with noncompressible arteries, medial artery calcinosis and/or neuropathy. Due to the relative incompressibility of calcified distal arteries in patients with DM, the ABI may be within normal limits in patients with PAD. This false negative result may lead surgeons to assume that normal perfusion is present. Level of Evidence: Level III, comparative study.
Possible prevention of dialysis-requiring congestive heart failure by angiotensin-II receptor blockers in non-dialysis Japanese patients with Stage 5 chronic kidney disease
Authors: Ikeda Masato , Nakao Masatsugu , Hirano Keita , Yokoyama Keitaro , Yokoo Takashi , Joki Nobuhiko , Ando Ryoichi , Shinoda Toshio , Inaguma Daijo , Yamaka Toshihiko , Komatsu Yasuhiro , Koiwa Fumihiko , Sakaguchi Toshifumi , Negi Shigeo , Shigematsu Takashi 
Published: July 2015

Background: Preventive medications for dialysis-requiring congestive heart failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney disease (CKD) are unknown. Our aim was to explore which CKD medication was associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. Methods: The present multicenter, retrospective, cross-sectional study examined the association between CKD medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. Results: There were 1536 Japanese Stage 5 CKD patients who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our multivariate analysis, only ARB use was significantly associated with a lower risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516–0.897; p = 0.0064), of the CKD treatments examined in this study. Conclusions: We found that ARB use during the pre-dialysis period is associated with a lower prevalence of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese patients with Stage 5 CKD.
Angiotensin type 1 receptor mediates renal production and conversion of prostaglandins E2 to F2α in conscious diabetic rats
Authors: Abadir Peter M , Siragy Helmy M 
Published: July 2015

Introduction: Previous studies demonstrated that stimulation of angiotensin subtype 1 receptor (AT1R) led to increased renal generation of prostaglandins E2 (PGE2) and renal inflammation. In turn, PGE2 increases AT1R activity. The conversion of PGE2 to the less active metabolite prostaglandin F2α (PGF2α) via 9-ketoreductase interrupts this feedback loop. The effects of diabetes on the interface between AT1R, PGE2 and PGF2α are not well established. We hypothesized that in diabetes, an aberrant AT1R activity enhances the biosynthesis of PGE2 and impairs the activity of PGE 9-ketoreductase, leading to accumulation of PGE2. Materials and methods: Using microdialysis technique, we monitored renal interstitial fluid levels of angiotensin II (Ang II), PGE2 and PGF2α in control and AT1R blocker, valsartan, treated diabetic rats ( N=8 each). We utilized the PGF2α to PGE2 ratio as indirect measure of PGE 9-ketoreductase activity. Results: Diabetes increased renal interstitial fluid levels of Ang II, PGE2 and PGF2α. PGF2α/PGE2 ratio increased by the third week, but declined by the sixth week of diabetes. Valsartan reduced PGE2 and PGF2α levels and increased Ang II and the conversion of PGE2 to PGF2α. Conclusion: Our results suggest that in diabetes, AT1R increases PGE2 generation and reduces conversion of PGE2 to PGF2α with the progression of diabetes.
Serum adiponectin levels in patients with acute coronary syndromes: Serial changes and relation to infarct size
Authors: Alkofide Hadeel , Huggins Gordon S , Ruthazer Robin , Beshansky Joni R , Selker Harry P 
Published: July 2015

Background: The role of adiponectin in patients with acute coronary syndromes is incompletely defined. This study investigated adiponectin levels in patients with acute coronary syndromes and the association between adiponectin and 30-day infarct size and 1-year clinical outcomes. Methods: Retrospective analysis of 120 participants with acute coronary syndromes enrolled in the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial. Blood levels were tested three times within 24 h of onset of ischaemic symptoms. Infarct size was measured at 30 days. The 1-year clinical outcome was the composite of all-cause mortality or hospitalization for heart failure. Results: Using linear mixed models, log adiponectin levels decreased by −0.005 µg/mL per hour ( p = 0.035). After stratifying the analysis by gender, there was no decrease in log adiponectin in men; however, levels decreased by −0.01 µg/mL per hour in women ( p = 0.02). Results of multivariable regression models showed no association between log adiponectin and infarct size ( β = −1.1, p = 0.64). Log adiponectin levels did not predict 1-year outcomes using Cox-proportional hazard models. Conclusion: There was a small decrease in plasma adiponectin shortly after symptoms of ischaemia, more noticeable in women. No relationship was found between adiponectin and infarct size or clinical outcomes. This adds to evidence showing no clear association between adiponectin and adverse outcomes in patients with acute coronary syndromes.