bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive risk algorithms in a population setting: an overview
Authors: Manuel Douglas G , Rosella Laura C , Hennessy Deirdre , Sanmartin Claudia , Wilson Kumanan 
Published: August 2012

BackgroundThe widespread use of risk algorithms in clinical medicine is testimony to how they have helped transform clinical decision-making. Risk algorithms have a similar but underdeveloped potential to support decision-making for population health.ObjectiveTo describe the role of predictive risk algorithms in a population setting.MethodsFirst, predictive risk algorithms and how clinicians use them are described. Second, the population uses of risk algorithms are described, highlighting the strengths of risk algorithms for health planning. Lastly, the way in which predictive risk algorithms are developed is discussed briefly and a guide for algorithm assessment in population health presented.ConclusionFor the past 20 years, absolute and baseline risk has been a cornerstone of population health planning. The most accurate and discriminating method to generate such estimates is the use of multivariable risk algorithms. Routinely collected data can be used to develop algorithms with characteristics that are well suited to health planning and such data are increasingly available. The widespread use of risk algorithms in clinical medicine is testimony to how they have helped transform clinical decision-making. Risk algorithms have a similar but underdeveloped potential to support decision-making for population health.
Early clinical implications of microalbuminuria in patients with acute ischaemic stroke
Authors: Cho Bang-Hoon , Kim Joon-Tae , Chang Jane , Choi Kang-Ho , Nam Tai-Seung , Choi Seong-Min , Lee Seung-Han , Park Man-Seok , Kim Byeong-Chae , Kim Myeong-Kyu , Cho Ki-Hyun 
Published: August 2012

Abstract

Background
Microalbuminuria is thought to be independently associated with an increased risk of, and mortality from, stroke. However, no studies have shown whether microalbuminuria is associated with the early clinical outcomes of acute ischaemic stroke. Therefore we investigated whether this. We also looked at radiological outcomes in stroke patients with microalbuminuria.

Methods
This was a retrospective study of patients with ischaemic stroke (within 72 h of symptom onset) who had been consecutively admitted to the Cerebrovascular Center at Chonnam National University Hospital between May 2010 and February 2011. Early clinical outcomes were assessed by early neurological deterioration (END) and modified Rankin Scale score &gt;2 at discharge. In addition, early radiological outcomes were assessed from haemorrhagic transformation (HT) and lesion changes on follow-up diffusion-weighted imaging. We categorised a urine albumin/creatinine ratio of ≤30 mg albumin/g creatinine as normal and 30–300 mg albumin/g creatinine as microalbuminuria.

Results
139 of 361 patients (38.5%) had microalbuminuria. In multivariate analysis, microalbuminuria was independently associated with END and HT. Furthermore, there were significant relationships between urinary albumin/creatinine ratio and white matter hyperintensity (WMH) grades (31.78 mg albumin/g creatinine for no WMH, 48.41 for grade 1, 64.29 for grade 2, and 44.16 for grade 3; p=0.004) and the types of HT (37.43 mg albumin/g creatinine for no HT, 71.41 for HI, and 131.63 for PH; p&lt;0.001).

Conclusion
In the early phase of ischaemic stroke, patients with microalbuminuria were associated with worse clinical and radiological outcomes (END, HT and lesion changes on follow-up diffusion-weighted imaging) than those without.
Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review
Authors: Yaphe Sean , Bozinoff Nikki , Kyle Rachel , Shivkumar Sushmita , Pai Nitika Pant , Klein Marina 
Published: August 2012

BackgroundA recent increase in reports of acute hepatitis C virus infection (HCV) in HIV-infected and HIV-uninfected men who have sex with men (MSM), with the sole risk factor being sexual exposure, has led to routine screening and targeted prevention requests for this population; current evidence for this necessity is unclear.ObjectiveA systematic review was conducted to assess the incidence of HCV infection among studies conducted in HIV-positive and/or HIV-negative MSM to explore the implications for routine HCV screening.Data sourcesThe MEDLINE, EMBASE and BIOSYS databases were searched for the period January 2000 to May 2012, yielding 21 studies. Six conferences were hand-searched for the same period yielding four abstracts.Study selectionOnly studies in English presenting incidence rates of HCV and specifying HIV status were included.Data abstractionData were abstracted by two authors using predefined data fields. The STROBE checklist was used to assess study quality.Data synthesisData were divided into HIV-negative MSM and HIV-positive MSM subgroups, and HCV incidence density measurements were pooled. Using a DerSimonian–Laird random effects model, pooled incidence was 1.48/1000 person-years (95% CI 0.75 to 2.21) for the HIV-negative MSM subgroup. The HIV-positive MSM subgroup was at 4.1 times higher risk of acquiring HCV at 6.08/1000 person-years (95% CI 5.18 to 6.99). Studies directly comparing subgroups estimated a pooled risk difference of 3.45/1000 person-years (95% CI 1.63 to 5.27).ConclusionHIV-positive MSM were at higher risk for acute HCV infection than HIV-negative MSM, substantiating the need for routine screening initiatives. Insufficient evidence exists to warrant routine screening of HIV-negative MSM, except on a case-by-case basis, such as high-risk sexual behaviour.
Serum and urinary adiponectin in dogs with renal disease from leishmaniasis
Authors: Tvarijonaviciute A. , Ceron J. J. , García‐Martinez J. D. 
Published: August 2012

The objective of this study was to perform an analytical validation of a commercially available ELISA kit (human adiponectin) for urinary adiponectin determination in dogs, and to evaluate urinary adiponectin in dogs with glomerular injury. For this purpose, urine samples from three healthy dogs and three dogs with diagnosed kidney disease were used for analytical validation of the method. In order to evaluate possible influence of kidney damage on urinary adiponectin, serum and urine samples from six healthy and 58 dogs with leishmaniasis were included. The diseased dogs were allocated to three groups according to their urine protein/creatinine (UPC) ratio as non‐proteinuric (NP), borderline proteinuric (BP), and proteinuric (P). Intra‐ and inter‐assay coefficients of variation (CV) were lower than 10 per cent and 12 per cent, respectively. Dilutions of canine urine samples resulted in linear regression equations close to 1. Mean recovery was of 112 per cent. The detection limit was 0.75 ng/ml. Urinary adiponectin and urinary adiponectin/creatinine (UAC) ratio showed significantly higher values in urine of P group dogs compared with healthy, NP and BP dogs. In conclusion, an ELISA kit can be used for precise and accurate urinary adiponectin measurement in dogs. Urinary adiponectin is increased in dogs with proteinuria suggesting its possible use as a marker of kidney damage.
A comparison between longitudinal shedding patterns of Salmonella Typhimurium and Salmonella Dublin on dairy farms
Authors: Kirchner M. , McLaren I. , Clifton‐Hadley F. A. , Liebana E. , Wales A. D. , Davies R. H. 
Published: August 2012

Salmonellain cattle herds may behave as epidemic or endemic infections. An intensive longitudinal sampling study across all management groups and ages on six dairy farms in the UK was used to examine patterns of Salmonella shedding, following the prior identification of either Salmonella Dublin (SD) (three farms) or Salmonella Typhimurium (ST) (three farms) on the premises in the context of clinical salmonellosis. Individual faeces, pooled faeces and environmental samples (total 5711 samples), taken approximately every six weeks for 15–24 weeks, were cultured for Salmonella. SD was detected at low frequency (on any visit, 0.5–18.3 per cent of samples positive) and most consistently in calves. By contrast, ST was isolated at higher frequency (on any visit, 6.8–75 per cent of samples positive), and in higher numbers, up to 107 cfu/g faeces. Significantly more samples from calves were positive for ST than were positive for SD (50.6 per cent v 3.1 per cent; P < 0.001), which was also true for milking cows (46.3 per cent v 4.4 per cent; P < 0.001). The differences could help to explain the different patterns of bovine infection classically associated with these two serovars in the UK. No consistent effect upon shedding was seen among the ST‐infected herds following vaccination.
UNIFORM ASYMPTOTIC APPROXIMATIONS FOR THE MEIXNER–SOBOLEV POLYNOMIALS
Authors: KHWAJA S. FARID , OLDE DAALHUIS A. B. 
Published: August 2012

We obtain uniform asymptotic approximations for the monic Meixner–Sobolev polynomials Sn(x). These approximations for n → ∞, are uniformly valid for x/n restricted to certain intervals, and are in terms of Airy functions. We also give asymptotic approximations for the location of the zeros of Sn(x), especially the small and the large zeros are discussed. As a limit case, we also give a new asymptotic approximation for the large zeros of the classical Meixner polynomials. The method is based on an integral representation in which a hypergeometric function appears in the integrand. After a transformation, the hypergeometric functions can be uniformly approximated by unity, and all that remains are simple integrals for which standard asymptotic methods are used. As far as we are aware, this is the first time that standard uniform asymptotic methods have been used for the Sobolev-class of orthogonal polynomials.
Chemopreventive and Chemotherapeutic Actions of mTOR Inhibitor in Genetically Defined Head and Neck Squamous Cell Carcinoma Mouse Model
Authors: Sun Zhi-Jun , Zhang Lu , Hall Bradford , Bian Yansong , Gutkind J. Silvio , Kulkarni Ashok B. 
Published: August 2012

Abstract
Purpose: To assess the efficacy of rapamycin treatment in chemoprevention and chemotherapy of tumorigenesis in a genetically defined mouse model of head and neck squamous cell carcinoma (HNSCC).
Experimental design: Knockdown of Tgfbr1 and/or Pten using siRNA-mediated RNA interference was carried out in human HNSCC cell lines to analyze molecular changes in the mTOR pathway. Tgfbr1flox/flox; Ptenflox/flox; K14-CreERtam mice were treated with oral gavage of tamoxifen for the conditional deletion of Tgfbr1 and Pten in oral mucosa, resulting in HNSCC. Tgfbr1 and Pten conditonal deletion (2cKO) mice were treated with rapamycin before or after the onset of HNSCC, and the efficacy of this treatment was assessed by determining tumor burden, longevity, and molecular analysis of the mTOR pathway. Molecular changes observed in human HNSCC cell lines and 2cKO mice were compared to identify key alterations in the mTOR pathway.
Results: Knockdown of Tgfbr1 and/or Pten in human HNSCC cell lines resulted in activation of mTOR activity complex 1 and increased levels of survivin. Furthermore, we observed similar changes in HNSCC of the 2cKO mouse. In the human HNSCC tissue array, a loss of Tgfbr1 expression correlated with increased survivin levels. Chemopreventive rapamycin treatment significantly delayed the onset of the HNSCC tumors and prolonged survival in 2cKO mice. In addition, we also found that rapamycin had a therapeutic effect on squamous cell carcinomas in these mice. In 2cKO HNSCC tongue tumors, rapamycin treatment induced apoptosis, inhibited cell proliferation and phosphorylation of Akt and S6, and decreased survivin expression.
Conclusions: These findings indicate that tumorigenesis in 2cKO HNSCC is associated with activation of the Akt/mTOR/survivin pathway, and inhibition of this pathway by rapamycin treatment successfully ameliorates the onset and progression of tumorigenesis. Clin Cancer Res; 18(19); 5304–13. ©2012 AACR.
Zeroing in on ROS1 Rearrangements in Non–Small Cell Lung Cancer
Authors: Stumpfova Magda , Jänne Pasi A. 
Published: August 2012

Abstract
Rimkunas and colleagues report on the development and validation of an immunohistochemical assay evaluating non–small cell lung cancers (NSCLC) for the presence of ROS1 fusions. The diagnostic was validated in a screen of 556 NSCLCs, identifying 9 (1.6%) tumors with oncogenic ROS1 rearrangements. These patients are candidates for ROS1-targeted therapies. Clin Cancer Res; 18(16); 4222–4. ©2012 AACR.
Hepatocyte Growth Factor Enhances Alternative Splicing of the Krüppel-like Factor 6 (KLF6) Tumor Suppressor to Promote Growth through SRSF1
Authors: Muñoz Úrsula , Puche Juan E. , Hannivoort Rebekka , Lang Ursula E. , Cohen-Naftaly Michal , Friedman Scott L. 
Published: August 2012

Abstract
Alternative splicing of the Krüppel-like factor 6 (KLF6) tumor suppressor into an antagonistic splice variant 1 (SV1) is a pathogenic event in several cancers including hepatocellular carcinoma (HCC) because elevated SV1 is associated with increased tumor metastasis and mortality. Ras activation is one factor that can enhance KLF6 splicing in cancer cells, however pathways driving KLF6 splicing are unknown. Splice site selection is regulated by splice factors that include serine/arginine-rich (SR) proteins such as SRSF1 (ASF-SF2), which in turn is controlled by phosphoinositide 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) signaling pathway. Because signaling pathways downstream of the liver mitogen hepatocyte growth factor (HGF) include Akt, we explored whether HGF induces KLF6 alternative splicing. In HepG2 cells, HGF (25 ng/mL) significantly increases the ratio of SV1/KLF6 full by 40% through phosphorylation of Akt and subsequent downregulation of two splicing regulators, SRSF3 (SRp20) and SRSF1. Decreased SRSF3 levels regulate SRSF1 levels by alternative splicing associated with the nonsense-mediated mRNA decay pathway (AS-NMD), which stimulates cell growth by decreasing p21 levels. Enhanced cell replication through increased KLF6 alternative splicing is a novel growth-promoting pathway of HGF that could contribute to the molecule's mitogenic activity in physiologic liver growth and hepatocellular carcinoma. Mol Cancer Res; 10(9); 1216–27. ©2012 AACR.
The Methyl Xanthine Caffeine Inhibits DNA Damage Signaling and Reactive Species and Reduces Atherosclerosis in ApoE
−/−
Mice
Authors: Mercer John R. , Gray Kelly , Figg Nichola , Kumar Sheetal , Bennett Martin R. 
Published: August 2012

Objective—
Caffeine remains one of the most widely consumed drugs in the world. Caffeine has multiple actions, including inhibition of the DNA damage response, and its metabolites, 1-methylxanthine and 1-methyluric acid, are potent antioxidants. Combined, these properties can exert direct effects on cell proliferation, cell death, inflammation, and DNA repair, all important processes that occur in atherosclerosis.

Methods and Results—

We first examined the effects of caffeine on mouse vascular smooth muscle cells. Caffeine inhibited activation of the DNA damage response regulator ataxia telangiectasia mutated protein and its downstream targets. Caffeine delayed DNA repair, had a concentration-dependent effect on cell proliferation, and protected against apoptosis. In vitro caffeine reduced oxygen consumption and decreased generation of reactive oxygen species. In vivo caffeine reduced DDR activation in vascular and nonvascular tissues, reduced reactive nitrogen species and serum levels of the DNA adduct 8-oxo-guanine, and inhibited atherogenesis in fat−fed ApoE
−/−
mice. Reduction in atherosclerosis was independent of the effects on blood pressure and serum lipids but associated with reduced cell proliferation and ataxia telangiectasia mutated protein activation.

Conclusion—

The Methyl Xanthine caffeine inhibits the DNA damage response in vitro and in vivo, regulates both cell proliferation and apoptosis after DNA damage, inhibits reactive species, and reduces atherogenesis in ApoE
−/−
mice.
Modulation of the Cochaperone AHA1 Regulates Heat-Shock Protein 90 and Endothelial NO Synthase Activation by Vascular Endothelial Growth Factor
Authors: Desjardins Fanny , Delisle Chantal , Gratton Jean-Philippe 
Published: August 2012

Objective—
Vascular endothelial growth factor (VEGF) signaling to endothelial NO synthase (eNOS) plays a central role in angiogenesis. In endothelial cells (ECs), heat-shock protein 90 (Hsp90) is also a regulator of eNOS activity. Our study is designed to determine whether modulation of the activator of Hsp90 ATPase 1 (AHA1) regulates the function of Hsp90 in ECs.

Methods and Results—
We show that eNOS phosphorylation on Ser-1179 after VEGF stimulation is significantly reduced in ECs transfected with a small interfering RNA against AHA1. Accordingly, VEGF-stimulated NO production, endothelial permeability, cell migration, and EC invasion in Matrigel implants in mice are reduced in small interfering RNA against AHA1-treated conditions. Furthermore, the induction of eNOS association with Hsp90 after VEGF stimulation is decreased in AHA1-downregulated cells. We also demonstrate that modulation of Hsp90 activity by AHA1 regulates phosphorylation of Hsp90 on Tyr-300. Interestingly, the association of AHA1 with Hsp90 is increased after c-Src–mediated phosphorylation of Hsp90 on Tyr-300. Finally, we show that overexpression of AHA1 in ECs promotes association of eNOS and Hsp90, phosphorylation of Ser-1179 of eNOS, increases NO production, and cell migration.

Conclusion—
These results reveal that modulation of Hsp90 activity by AHA1 regulates VEGF signaling to eNOS and angiogenesis.
IL1B
and
VWF
Variants Are Associated With Fibrinolytic Early Recanalization in Patients With Ischemic Stroke
Authors: Fernández-Cadenas Israel , del Río-Espínola Alberto , Giralt Dolors , Domingues-Montanari Sophie , Quiroga Adoracion , Mendióroz Maite , Ruíz Agustin , Ribó Marc , Serena Joaquin , Obach Victor , Freijo Mari Mar , Martí-Fábregas Joan , Delgado Pilar , Montaner Joan 
Published: August 2012

Background and Purpose—
There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration.

Methods—
A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity.

Results—

After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in
IL1B
gene (CC: 53.1% of recanalization, A-carriers: 32.7%;
P
=0.022; replication cohort:
P
=0.046), rs16944 in
IL1B
gene (AA: 50% of recanalization, G-carriers: 32%;
P
=0.038; replication cohort:
P
=0.049), and rs1063856 in the
vWF
gene (GG: 53.8% of recanalization, A-carriers: 31.5%;
P
=0.006; replication cohort:
P
=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in
vWF
and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%;
P
=0.005).

Conclusions—
Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.
Comparison of Computed Tomography Perfusion and Magnetic Resonance Imaging Perfusion-Diffusion Mismatch in Ischemic Stroke
Authors: Campbell Bruce C.V. , Christensen Søren , Levi Christopher R. , Desmond Patricia M. , Donnan Geoffrey A. , Davis Stephen M. , Parsons Mark W. 
Published: August 2012

Background and Purpose—
Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with contemporaneous perfusion-diffusion magnetic resonance imaging (MRI).

Methods—
Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6 seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio >1.2, absolute mismatch >10 mL, infarct core <70 mL).

Results—

In analysis of 49 patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining relCBF <31% within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL (
P
<0.001). The optimal CT-Tmax threshold to match MR-Tmax >6 seconds was 6.2 seconds (95% confidence interval, 5.6–7.3 seconds; sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6 seconds “penumbra” and relTTP-constrained relCBF “core,” CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80).

Conclusions—
Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
Turbulence and Diapycnal Mixing in Drake Passage
Authors: St. Laurent L. , Naveira Garabato A. C. , Ledwell J. R. , Thurnherr A. M. , Toole J. M. , Watson A. J. 
Published: August 2012

Abstract
Direct measurements of turbulence levels in the Drake Passage region of the Southern Ocean show a marked enhancement over the Phoenix Ridge. At this site, the Antarctic Circumpolar Current (ACC) is constricted in its flow between the southern tip of South America and the northern tip of the Antarctic Peninsula. Observed turbulent kinetic energy dissipation rates are enhanced in the regions corresponding to the ACC frontal zones where strong flow reaches the bottom. In these areas, turbulent dissipation levels reach 10−8 W kg−1 at abyssal and middepths. The mixing enhancement in the frontal regions is sufficient to elevate the diapycnal turbulent diffusivity acting in the deep water above the axis of the ridge to 1 × 10−4 m2 s−1. This level is an order of magnitude larger than the mixing levels observed upstream in the ACC above smoother bathymetry. Outside of the frontal regions, dissipation rates are O(10−10) W kg−1, comparable to the background levels of turbulence found throughout most mid- and low-latitude regions of the global ocean.