bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation
Authors: Piccini Jonathan P. , Stevens Susanna R. , Chang YuChiao , Singer Daniel E. , Lokhnygina Yuliya , Go Alan S. , Patel Manesh R. , Mahaffey Kenneth W. , Halperin Jonathan L. , Breithardt Günter , Hankey Graeme J. , Hacke Werner , Becker Richard C. , Nessel Christopher C. , Fox Keith A.A. , Califf Robert M. 
Published: December 2012

Background—
We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial.

Methods and Results—

In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non–central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R
2
CHADS
2
) improved net reclassification index by 6.2% compared with CHA
2
DS
2
VASc (C statistic=0.578) and by 8.2% compared with CHADS
2
(C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R
2
CHADS
2
in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%–22.5%) relative to CHADS
2
.

Conclusions—
In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function.

Clinical Trial Registration—

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00403767.
Observed Coherent Trends of Surface and Upper-Air Wind Speed over China since 1960
Authors: Lin Changgui , Yang Kun , Qin Jun , Fu Rong 
Published: December 2012

AbstractPrevious studies indicated that surface wind speed over China declined during past decades, and several explanations exist in the literature. This study presents long-term (1960–2009) changes of both surface and upper-air wind speeds over China and addresses observed evidence to interpret these changes. It is found that surface wind over China underwent a three-phase change over the past 50 yr: (i) it step changed to a strong wind level at the end of the 1960s, (ii) it declined until the beginning of the 2000s, and (iii) it seemed to be steady and even recovering during the very recent years. The variability of surface wind speed is greater at higher elevations and less at lower elevations. In particular, surface wind speed over the elevated Tibetan Plateau has changed more significantly. Changes in upper-air wind speed observed from rawinsonde are similar to surface wind changes. The NCEP–NCAR reanalysis indicates that wind speed changes correspond to changes in geopotential height gradient at 500 hPa. The latter are further correlated with the changes of latitudinal surface temperature gradient, with a correlation coefficient of 0.88 for the past 50 yr over China. This strongly suggests that the spatial gradient of surface global warming or cooling may significantly change surface wind speed at a regional scale through atmospheric thermal adaption. The recovery of wind speed since the beginning of the 2000s over the Tibetan Plateau might be a precursor of the reversal of wind speed trends over China, as wind over high elevations can respond more rapidly to the warming gradient and atmospheric circulation adjustment.
Serum levels of IL-17A in patients with relapsing–remitting multiple sclerosis treated with interferon-β
Authors: Bălaşa Rodica , Bajko Zoltan , Huţanu Adina 
Published: December 2012

Background: Interleukin-17 (IL-17), which is secreted by Th17 cells, is a proinflammatory cytokine that is implicated in the pathogenesis of multiple sclerosis (MS) and plays a role in nonresponse of MS patients to interferon-β (IFN-β) therapy. Objectives: The purpose of this study was to establish a correlation between nonresponders (NR) and IL-17A serum titers and binding antibodies (BAbs) to IFN-β, as well as to find a correlation between IL-17A serum levels and other features of MS patients. Methods: Our prospective study included 72 inactive relapsing–remitting multiple sclerosis (RRMS) patients that had been treated for at least 18 months with IFN-β and 15 healthy subjects. We determined the serum levels of IL-17A and of BAbs. IL-17A levels were considered elevated (IL-17A+) if the recorded value was greater than 1.6 pg/ml. Results: Twenty-seven patients (37.5%) were NR and had a significantly higher serum IL-17A level compared to the responders group. Nineteen patients (26.4%) were IL-17A+ and had had a significantly higher number of relapses in the previous year and a higher Expanded Disability Status Score. The majority of IL-17A+ patients were NR and had a shorter MS duration. Conclusions: RRMS patients with high serum IL-17A levels do not respond well to IFN-β therapy and have shorter MS duration compared to patients with low IL-17A levels. This response is not influenced by the presence of BAbs.
Langerhans cell homeostasis in mice is dependent on mTORC1 but not mTORC2 function
Authors: Kellersch Bettina , Brocker Thomas 
Published: December 2012

AbstractThe PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding of the epidermis with LCs is not affected, the lack of mTORC1 activity in DCs by conditional deletion of Raptor leads to a progressive loss of LCs in the skin of mice. Ablation of mTORC2 function by deletion of Rictor results in a modest reduction of LCs in skin draining lymph nodes. In young mice Raptor-deficient LCs show an increased tendency to leave the skin, leading to a higher frequency of migratory DCs in skin draining lymph nodes, indicating that the loss of LCs results from enhanced migration. LCs lacking Raptor are smaller and display reduced expression of Langerin, E-cadherin, β-catenin, and CCR7 but unchanged levels of MHC-II, ruling out enhanced spontaneous maturation. Ki-67 and annexin V stainings revealed a faster turnover rate and increased apoptosis of Raptor-deficient LCs, which might additionally affect the preservation of the LC network. Taken together our results show that the homeostasis of LCs strictly depends on mTORC1.
Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease
Authors: Franco Melanie , Collec Emmanuel , Connes Philippe , van den Akker Emile , Billette de Villemeur Thierry , Belmatoug Nadia , von Lindern Marieke , Ameziane Nejma , Hermine Olivier , Colin Yves , Le Van Kim Caroline , Mignot Cyril 
Published: December 2012

AbstractGaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase deficiency. It is notably characterized by splenomegaly, complex skeletal involvement, ischemic events of the spleen and bones, and the accumulation of Gaucher cells in several organs. We hypothesized that red blood cells (RBCs) might be involved in some features of GD and studied the adhesive and hemorheologic properties of RBCs from GD patients. Hemorheologic analyses revealed enhanced blood viscosity, increased aggregation, and disaggregation threshold of GD RBCs compared with control (CTR) RBCs. GD RBCs also exhibited frequent morphologic abnormalities and lower deformability. Under physiologic flow conditions, GD RBCs adhered more strongly to human microvascular endothelial cells and to laminin than CTR. We showed that Lu/BCAM, the unique erythroid laminin receptor, is overexpressed and highly phosphorylated in GD RBCs, and may play a major role in the adhesion process. The demonstration that GD RBCs have abnormal rheologic and adhesion properties suggests that they may trigger ischemic events in GD, and possibly phagocytosis by macrophages, leading to the appearance of pathogenic Gaucher cells.
Acute pressure on the sciatic nerve results in rapid inhibition of the wide dynamic range neuronal response
Authors: Wang Wenxue , Tan Wei , Luo Danping , Lin Jianhua , Yu Yaoqing , Wang Qun , Zhao Wangyeng , Wu Buling , Chen Jun , He Jiman 
Published: December 2012

Abstract

Background
Acute pressure on the sciatic nerve has recently been reported to provide rapid short-term relief of pain in patients with various pathologies. Wide dynamic range (WDR) neurons transmit nociceptive information from the dorsal horn to higher brain centers. In the present study, we examined the effect of a 2-min application of sciatic nerve pressure on WDR neuronal activity in anesthetized male Sprague–Dawley rats.

Results
Experiments were carried out on 41 male Sprague–Dawley albino rats weighing 160–280 grams. Dorsal horn WDR neurons were identified on the basis of characteristic responses to mechanical stimuli applied to the cutaneous receptive field. Acute pressure was applied for 2 min to the sciatic nerve using a small vascular clip. The responses of WDR neurons to three mechanical stimuli applied to the cutaneous receptive field were recorded before, and 2, 5 and 20 min after cessation of the 2-min pressure application on the sciatic nerve. Two-min pressure applied to the sciatic nerve caused rapid attenuation of the WDR response to pinching, pressure and brushing stimuli applied to the cutaneous receptive field. Maximal attenuation of the WDR response to pinching and pressure was noted 5 min after release of the 2-min pressure on the sciatic nerve. The mean firing rate decreased from 31.7±1.7 Hz to 13±1.4 Hz upon pinching (p < 0.001), from 31.2±2.3 Hz to 10.9±1.4 Hz (p < 0.001) when pressure was applied, and from 18.9±1.2 Hz to 7.6±1.1 Hz (p < 0.001) upon brushing. Thereafter, the mean firing rates gradually recovered.

Conclusions
Our results indicate that acute pressure applied to the sciatic nerve exerts a rapid inhibitory effect on the WDR response to both noxious and innocuous stimuli. Our results may partially explain the rapid analgesic effect of acute sciatic nerve pressure noted in clinical studies, and also suggest a new model for the study of pain.
Peroxiredoxin 6 promotes upregulation of the prion protein (PrP) in neuronal cells of prion-infected mice
Authors: Wagner Wibke , Reuter Andreas , Hüller Petra , Löwer Johannes , Wessler Silja 
Published: December 2012

Abstract

Background
It has been widely established that the conversion of the cellular prion protein (PrPC) into its abnormal isoform (PrPSc) is responsible for the development of transmissible spongiform encephalopathies (TSEs). However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis.

Findings
Apolipoprotein E and peroxiredoxin 6 (PRDX6) were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells.

Conclusions
Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.
Inactivation of Chikungunya virus by 1,5 iodonapthyl azide
Authors: Sharma Anuj , Gupta Paridhi , Maheshwari Radha K 
Published: December 2012

Abstract

Background
Chikungunya virus (CHIKV) is an arthropod borne alphavirus of the family Togaviridae. CHIKV is a reemerging virus for which there is no safe prophylactic vaccine. A live attenuated strain of CHIKV, CHIK181/25, was previously demonstrated to be highly immunogenic in humans, however, it showed residual virulence causing transient arthralgia.

Findings
In this study, we demonstrate the complete inactivation of CHIKV181/25 by 1,5 iodonapthyl azide (INA). No cytopathic effect and virus replication was observed in cells infected with the INA-inactivated CHIKV. However, a reduction in the INA-inactivated CHIK virus-antibody binding capacity was observed by western blot analysis.

Conclusion
INA completely inactivated CHIKV and can further be explored for developing an inactivated-CHIKV vaccine.
Comparative study of sulfite pretreatments for robust enzymatic saccharification of corn cob residue
Authors: Bu Lingxi , Xing Yang , Yu Hailong , Gao Yuxia , Jiang Jianxin 
Published: December 2012

Abstract

Background
Corn cob residue (CCR) is a kind of waste lignocellulosic material with enormous potential for bioethanol production. The moderated sulphite processes were used to enhance the hydrophily of the material by sulfonation and hydrolysis. The composition, FT-IR spectra, and conductometric titrations of the pretreated materials were measured to characterize variations of the CCR in different sulfite pretreated environments. And the objective of this study is to compare the saccharification rate and yield of the samples caused by these variations.

Results
It was found that the lignin in the CCR (43.2%) had reduced to 37.8%, 38.0%, 35.9%, and 35.5% after the sulfite pretreatment in neutral, acidic, alkaline, and ethanol environments, respectively. The sulfite pretreatments enhanced the glucose yield of the CCR. Moreover, the ethanol sulfite sample had the highest glucose yield (81.2%, based on the cellulose in the treated sample) among the saccharification samples, which was over 10% higher than that of the raw material (70.6%). More sulfonic groups and weak acid groups were produced during the sulfite pretreatments. Meanwhile, the ethanol sulfite treated sample had the highest sulfonic group (0.103 mmol/g) and weak acid groups (1.85 mmol/g) in all sulfite treated samples. In FT-IR spectra, the variation of bands at 1168 and 1190 cm-1 confirmed lignin sulfonation during sulfite pretreatment. The disappearance of the band at 1458 cm-1 implied the methoxyl on lignin had been removed during the sulfite pretreatments.

Conclusions
It can be concluded that the lignin in the CCR can be degraded and sulfonated during the sulfite pretreatments. The pretreatments improve the hydrophility of the samples because of the increase in sulfonic group and weak acid groups, which enhances the glucose yield of the material. The ethanol sulfite pretreatment is the best method for lignin removal and with the highest glucose yield.
Disease activity and cognition in rheumatoid arthritis: an open label pilot study
Authors: Raftery Graham , He Jiabao , Pearce Ruth , Birchall Daniel , Newton Julia L , Blamire Andrew M , Isaacs John D 
Published: December 2012

Abstract
Introduction
We hypothesised that fatigue in rheumatoid arthritis (RA) is related to TNF-alpha induced dysregulation of cerebral blood flow. Our objectives were to assess fatigue, cognitive function and cerebral blood flow before and after initiation of anti-TNF treatment.

Methods
In a pilot study, 15 patients initiating treatment with adalimumab were assessed for fatigue using a visual analogue scale (FACIT-F), cognitive function using a panel of psychometric tests and regional cerebral blood flow using MR perfusion imaging.

Results
Patients improved clinically after anti-TNF therapy in terms of DAS28 and FACIT-F. Furthermore significant improvements were documented in full scale, verbal and performance IQ following therapy. There was a non-significant trend towards reduced cerebral perfusion in both grey and white matter, and fatigue at 3 months correlated with cerebral blood flow in white (p = 0.014) and grey (p = 0.005) matter.

Conclusions
We demonstrate for the first time a significant improvement in cognitive function following effective treatment of RA. Although we observed minor reductions in cerebral blood flow, and a correlation between cerebral blood flow and fatigue, a larger, controlled study would be required to affirm a causal relationship.
Positron Emission Tomography/Computed Tomography Identification of Clear Cell Renal Cell Carcinoma: Results From the REDECT Trial
Authors: Divgi Chaitanya R. , Uzzo Robert G. , Gatsonis Constantine , Bartz Roman , Treutner Silke , Yu Jian Qin , Chen David , Carrasquillo Jorge A. , Larson Steven , Bevan Paul , Russo Paul 
Published: December 2012

Purpose A clinical study to characterize renal masses with positron emission tomography/computed tomography (PET/CT) was undertaken. Patients and Methods This was an open-label multicenter study of iodine-124 (124I) -girentuximab PET/CT in patients with renal masses who were scheduled for resection. PET/CT and contrast-enhanced CT (CECT) of the abdomen were performed 2 to 6 days after intravenous 124I-girentuximab administration and before resection of the renal mass(es). Images were interpreted centrally by three blinded readers for each imaging modality. Tumor histology was determined by a blinded central pathologist. The primary end points—average sensitivity and specificity for clear cell renal cell carcinoma (ccRCC)—were compared between the two modalities. Agreement between and within readers was assessed. Results 124I-girentuximab was well tolerated. In all, 195 patients had complete data sets (histopathologic diagnosis and PET/CT and CECT results) available. The average sensitivity was 86.2% (95% CI, 75.3% to 97.1%) for PET/CT and 75.5% (95% CI, 62.6% to 88.4%) for CECT (P = .023). The average specificity was 85.9% (95% CI, 69.4% to 99.9%) for PET/CT and 46.8% (95% CI, 18.8% to 74.7%) for CECT (P = .005). Inter-reader agreement was high (κ range, 0.87 to 0.92 for PET/CT; 0.67 to 0.76 for CECT), as was intrareader agreement (range, 87% to 100% for PET/CT; 73.7% to 91.3% for CECT). Conclusion This study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy. 124I-girentuximab PET/CT can accurately and noninvasively identify ccRCC, with potential utility for designing best management approaches for patients with renal masses.
Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma
Authors: Choueiri Toni K. , Vaishampayan Ulka , Rosenberg Jonathan E. , Logan Theodore F. , Harzstark Andrea L. , Bukowski Ronald M. , Rini Brian I. , Srinivas Sandy , Stein Mark N. , Adams Laurel M. , Ottesen Lone H. , Laubscher Kevin H. , Sherman Laurie , McDermott David F. , Haas Naomi B. , Flaherty Keith T. , Ross Robert , Eisenberg Peter , Meltzer Paul S. , Merino Maria J. , Bottaro Donald P. , Linehan W. Marston , Srinivasan Ramaprasad 
Published: December 2012

Purpose Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC. Patients and Methods Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR). Results Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli. Conclusion Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations.
Heterotopic ossificans in chronic venous insufficiency: a new consideration for clinical, aetiology, anatomy and pathophysiology staging
Authors: Cafasso D E , Bowen D K , Kinkennon S A , Stanbro M D , Kellicut D C 
Published: December 2012

Objectives: Heterotopic ossification is defined as the abnormal formation of true bone within extraskeletal soft tissues. It may be associated with a variety of clinical conditions, but is most frequently seen with musculoskeletal trauma, neurologic injury or genetic abnormalities. It has also been described in patients with chronic venous insufficiency; however, it often goes underdiagnosed due to chronic ulceration that masks exam findings. To date, few reports of heterotopic ossification due to chronic venous disease exist within the literature with the most recent dating back to the 1970s. Methods: We present a case study of a man presenting with extensive leg ulceration and a history of chronic venous insufficency. He had a large non-healing venous stasis ulcer of the left lower extremity with extensive heterotopic ossification discovered intraoperatively. Results: The patient was managed with serial wound debridement, innovative woundcare and eventual split thickness skin grafting that achieved limb salvage despite the complexity of his wound. Conclusions: Our discussion focuses on the epidemiology, pathophysiology, diagnostic work-up and management of heterotopic ossification in the setting of chronic venous insufficiency. We propose that heterotopic ossification be included in any future modifications of the clinical, aetiology, anatomy and pathophysiology system classification as a complication of chronic venous disease.