bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Risk for Noncervical Anogenital Cancer in Women with Previously Diagnosed High-Grade Cervical Intraepithelial Neoplasia: A Danish Nationwide Cohort Study
Authors: Sand Freja Lærke , Munk Christian , Jensen Signe Marie , Svahn Malene Frøsig , Frederiksen Kirsten , Kjær Susanne K. 
Published: June 2016

Abstract
Background: High-risk human papillomavirus (HPV) is essential for developing high-grade cervical intraepithelial neoplasia (CIN2 and CIN3) and has also been associated with noncervical anogenital cancers. However, limited knowledge exists about the long-term risk for anal, vulvar, and vaginal cancer following CIN2 or CIN3 diagnosis.
Methods: In a nationwide cohort study, we followed nearly 2.8 million women born in 1918–1990 who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. The cohort was linked to multiple nationwide registers to obtain information on cancer diagnoses and confounders. Follow-up started when the women reached 18 years, date of immigration, or January 1978, and continued until emigration, death, December 31, 2012, or the date of first diagnosis of anogenital or rectal cancer.
Results: Women with a history of CIN2 or CIN3 had higher risks for subsequent anal, vulvar, and vaginal cancer than women with no such history. The relative risks were higher for CIN3 than CIN2. No excess risk was found for rectal cancer. Analyses in which time since first CIN3 was taken into account showed increased relative risks for anal [HR = 4.8; 95% confidence interval (CI), 3.3–7.0], vulvar (HR = 3.2; 95% CI, 2.0–5.3), and vaginal (HR = 5.5; 95% CI, 2.4–12.3) cancers ≥25 years after CIN3 diagnosis.
Conclusion: Women with a history of CIN2 or CIN3 have a long-term increased relative risk for developing anal, vulvar, and vaginal cancer due to an impaired ability to control a persistent HPV infection.
Impact: This finding adds to our understanding of the relation between HPV infection and noncervical anogenital cancer. Cancer Epidemiol Biomarkers Prev; 25(7); 1090–7. ©2016 AACR.
Pet Ownership and Cancer Risk in the Women's Health Initiative
Authors: Garcia David O. , Lander Eric M. , Wertheim Betsy C. , Manson JoAnn E. , Volpe Stella L. , Chlebowski Rowan T. , Stefanick Marcia L. , Lessin Lawrence S. , Kuller Lewis H. , Thomson Cynthia A. 
Published: July 2016

Abstract
Background: Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers.
Methods: This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders.
Results: There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons.
Conclusion: Pet ownership had no association with overall cancer incidence.
Impact: This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311–6. ©2016 AACR.
Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke
Authors: Redfors Petra , Lundberg Linnea , Gils Ann , Declerck Paul J. , Nilsson Staffan , Jood Katarina , Jern Christina , Pedersen Annie 
Published: June 2016

SummaryIschaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18–69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00–1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02–1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23, 1.45–3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes
Authors: Brufau Gemma , Gijbels Marion J. J. , Wolfs Ine M. J. , van der Velden Saskia , Pöttgens Chantal C. H. , Vergouwe Monique N. , Wijnands Erwin , Beckers Linda , Goossens Pieter , Kerksiek Anja , Havinga Rick , Müller Werner , Lütjohann Dieter , Groen Albert K. , Lauran Stöger J. , Boshuizen Marieke C. S. , de Winther Menno P. J. 
Published: June 2016

SummaryInflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis.Supplementary Material to this article is available online at www.thrombosis-online.com.
Anti-apolipoprotein A-1 auto-antibodies as active modulators of atherothrombosis
Authors: Carbone Federico , Burger Fabienne , Roth Aline , Bertolotto Maria , Pane Bianca , Spinella Giovanni , Palombo Domenico , Pende Aldo , Dallegri Franco , Satta Nathalie , Virzi Julien , Fontana Pierre , Mach François , Montecucco Fabrizio , Vuilleumier Nicolas , Pagano Sabrina 
Published: June 2016

SummaryHumoral autoimmune-mediated inflammation plays a role in atherogenesis, and potentially in arterial thrombosis. Anti-apolipoprotein A-1 (apoA-1) IgG have been reported to represent emergent mediators of atherogenesis through Toll-like receptors (TLR) 2, 4 and CD14 signalling. We investigated the role of anti-apoA-1 IgG on tissue factor (TF) expression and activation, a key coagulation regulator underlying atherothrombosis. Atherothrombosis features were determined by immunohistochemical TF staining of human carotid biopsies derived from patients with severe carotid stenosis undergoing elective surgery (n=176), and on aortic roots of different genetic backgrounds mice (ApoE-/-; TLR2-/-ApoE-/- and TLR4-/-ApoE-/-) exposed to passive immunisation with anti-apoA-1 IgG. Human serum levels of anti-apoA-1 IgG were measured by ELISA. In vitro, on human-monocyte-derived-macrophages (HMDM) the anti-apoA-1 IgG increased TF expression and activity were analysed by FACS and chromogenic assays in presence of different pharmacological inhibitors. Human serum anti-apoA-1 IgG levels significantly correlated to intraplaque TF expression in carotid biopsies (r=0.31, p<0.001), which was predictive of clinically symptomatic lesions. On HMDM, anti-apoA-1 IgG induced a TLR2, 4 and CD14-dependent increase in TF expression and activity, involving NF-kappaB and a c-Jun N-terminal kinase-dependent AP-1 transcription factors. In ApoE-/- mice, anti-apoA-1 IgG passive immunisation significantly enhanced intraplaque TF expression when compared to control IgG. This effect was lost in both TLR2-/-ApoE-/- and TLR4-/-ApoE-/- mice. These results demonstrate that anti-apoA-1 IgG are associated with TF expression in human atherosclerotic plaques, induce TF expression in vitro and in vivo through TLR2 and 4 signalling, supporting a possible causal relationship between anti-apoA-1 IgG and atherothrombosis.
Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway
Authors: Wu Hongxian , Cheng Xian Wu , Hu Lina , Takeshita Kyosuke , Hu Chen , Du Qiuna , Li Xiang , Zhu Enbo , Huang Zhe , Yisireyili Maimaiti , Zhao Guangxian , Piao Limei , Inoue Aiko , Jiang Haiying , Lei Yanna , Zhang Xiaohong , Liu Shaowen , Dai Qiuyan , Kuzuya Masafumi , Shi Guo-Ping , Murohara Toyoaki 
Published: July 2016

Objective—
Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely to contribute to stem cell development. Histone deacetylase 6 (HDAC6) is required in modulating the proliferation and migration of various types of cancer cells. Here, we investigated the cross talk between CatS and HADC6 in injury-related vascular repair in mice.

Approach and Results—
Ligation injury to the carotid artery in mice increased the CatS expression, and CatS-deficient mice showed reduced neointimal formation in injured arteries. CatS deficiency decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and toll-like receptor 2 expression in ligated arteries. The genetic or pharmacological inhibition of CatS also alleviated the increased phosphorylation of p38 mitogen-activated protein kinase, Akt, and HDAC6 induced by platelet-derived growth factor BB in cultured vascular smooth muscle cells (VSMCs), and p38 mitogen-activated protein kinase inhibition and Akt inhibition decreased the phospho-HDAC6 levels. Moreover, CatS inhibition caused decrease in the levels of the HDAC6 activity in VSMCs in response to platelet-derived growth factor BB. The HDAC6 inhibitor tubastatin A downregulated platelet-derived growth factor–induced VSMC proliferation and migration, whereas HDAC6 overexpression exerted the opposite effect. Tubastatin A also decreased the intimal VSMC proliferation and neointimal hyperplasia in response to injury. Toll-like receptor 2 silencing decreased the phosphorylation levels of p38 mitogen-activated protein kinase, Akt, and HDAC6 and VSMC migration and proliferation.

Conclusions—
This is the first report detailing cross-interaction between toll-like receptor 2–mediated CatS and HDAC6 during injury-related vascular repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for the control of vascular diseases that are involved in neointimal lesion formation.
Loss of Macrophage Low-Density Lipoprotein Receptor–Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-α Inhibition
Authors: Zhu Lin , Giunzioni Ilaria , Tavori Hagai , Covarrubias Roman , Ding Lei , Zhang Youmin , Ormseth Michelle , Major Amy S. , Stafford John M. , Linton MacRae F. , Fazio Sergio 
Published: July 2016

Objective—

Antiatherosclerotic effects of tumor necrosis factor-α (TNF-α) blockade in patients with systemic inflammatory states are not conclusively demonstrated, which suggests that effects depend on the cause of inflammation. Macrophage LRP1 (low-density lipoprotein receptor–related protein 1) and apoE contribute to inflammation through different pathways. We studied the antiatherosclerosis effects of TNF-α blockade in hyperlipidemic mice lacking either LRP1 (MΦLRP1
−/−
) or apoE from macrophages.

Approach and Results—

Lethally irradiated low-density lipoprotein receptor (LDLR)
−/−
mice were reconstituted with bone marrow from either wild-type, MΦLRP1
−/−
, apoE
−/−
or apoE
−/−
/MΦLRP1
−/−
(DKO) mice, and then treated with the TNF-α inhibitor adalimumab while fed a Western-type diet. Adalimumab reduced plasma TNF-α concentration, suppressed blood ly6C
hi
monocyte levels and their migration into the lesion, and reduced lesion cellularity and inflammation in both wild-type→LDLR
−/−
and apoE
−/−
→LDLR
−/−
mice. Overall, adalimumab reduced lesion burden by 52% to 57% in these mice. Adalimumab reduced TNF-α and blood ly6C
hi
monocyte levels in MΦLRP1
−/−
→LDLR
−/−
and DKO→LDLR
−/−
mice, but it did not suppress ly6C
hi
monocyte migration into the lesion or atherosclerosis progression.

Conclusions—
Our results show that TNF-α blockade exerts antiatherosclerotic effects that are dependent on the presence of macrophage LRP1.
Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease
Authors: Schutte Elise , de Vos Lisanne C. , Lutgers Helen L. , Lambers Heerspink Hiddo J. , Wolffenbuttel Bruce H.R. , Vart Priya , Zeebregts Clark J. , Gansevoort Ron T. , Lefrandt Joop D. 
Published: July 2016

Objective—
Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease.

Approach and Results—

We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m
2
and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m
2
/y. During a median follow-up of 3 years, the mean change in eGFR per year was −1.8±4.4 mL/min/1.73 m
2
/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (−0.1 mL/min/1.73 m
2
/y; 95% confidence interval, −0.7 to 0.5;
P
=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m
2
(hazard ratio, 1.54; 95% confidence interval, 1.13–2.10;
P
=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20–2.59;
P
=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline.

Conclusions—
In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study.
Smooth Muscle Cell–Derived Interleukin-17C Plays an Atherogenic Role via the Recruitment of Proinflammatory Interleukin-17A
+
T Cells to the Aorta
Authors: Butcher Matthew J. , Waseem Tayab C. , Galkina Elena V. 
Published: July 2016

Objective—
Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. Interleukin-17C (IL-17C) is detectable within atherosclerotic lesions; however, the potential involvement of this cytokine has not been examined. Thus, we sought to investigate the role of IL-17C in atherosclerosis.

Approach and Results—

The expression of IL-17 cytokines was profiled within aortas of apolipoprotein E double knockout (
Apoe
−/−
) mice, and
Il17c
expression was elevated. Flow cytometry experiments revealed a major population of aortic IL-17C–producing smooth muscle cells. Next, we generated
Il17c
−/−
Apoe
−/−
mice and demonstrated that atherosclerotic lesion and collagen content was diminished within Western diet–fed
Il17c
−/−
Apoe
−/−
aortas and aortic roots in comparison to
Apoe
−/−
controls. Smooth muscle cells and fibroblasts were mainly responsible for the reduced
Col1A1
expression in the aorta of
Il17c
−/−
Apoe
−/−
mice. Importantly, IL-17C–treated
Apoe
−/−
aortas showed upregulated
Col1A1
expression ex vivo.
Il17c
−/−
Apoe
−/−
mice displayed a proportional reduction in aortic macrophages, neutrophils, T cells, T helper 1 cells, and T regulatory cells, without corresponding changes in the peripheral immune composition. Examination of aortic IL-17A
+
T-cell receptor γδ T cells and Th17 cells demonstrated a stark reduction in the percentage and number of these subsets within
Il17c
−/−
Apoe
−/−
versus
Apoe
−/−
mice. Explanted 12-week Western diet–fed
Apoe
−/−
aortas treated with IL-17C resulted in the induction of multiple vascular chemokines and cytokines. Th17 cells demonstrated attenuated migration toward supernatants from cultures of
Il17c
−/−
Apoe
−/−
smooth muscle cells, and short-term homing experiments revealed diminished recruitment of Th17 cells to the aorta of
Il17c
−/−
Apoe
−/−
recipients.

Conclusions—
Smooth muscle cell–derived IL-17C plays a proatherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.
Natural History of Dilated Cardiomyopathy in Children
Authors: Puggia Ilaria , Merlo Marco , Barbati Giulia , Rowland Teisha J. , Stolfo Davide , Gigli Marta , Ramani Federica , Di Lenarda Andrea , Mestroni Luisa , Sinagra Gianfranco 
Published: July 2016

Background

The long‐term progression of idiopathic dilated cardiomyopathy (
DCM
) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long‐term progression of pediatric and adult
DCM
populations.

Methods and Results

Between 1988 and 2014, 927
DCM
patients were consecutively enrolled. The pediatric population (aged <18 years at enrollment) included 47 participants (5.1%). At presentation, the pediatric population compared with adult patients had a significantly increased occurrence of familial forms (
P
=0.03), shorter duration of heart failure (
P
=0.04), lower systolic blood pressure (
P
=0.01), decreased presence of left bundle‐branch block (
P
=0.001), and increased left ventricular ejection fraction (
P
=0.03). Despite these baseline differences, long‐term longitudinal trends of New York Heart Association class
III
to
IV
, left ventricular dimensions, left ventricular ejection fraction, and restrictive filling pattern were similar between the 2 populations. Regarding survival analysis, because of the size difference between the 2 populations, we compared the pediatric population with a sample of adult patients randomly matched using the above‐mentioned baseline differences in a 3:1 ratio (141 adult versus 47 pediatric patients). During a median follow‐up of 110 months, survival free from heart transplantation was significantly lower among pediatric patients compared with adults (
P
<0.001). Furthermore, pediatric age (ie, <18 years) was found to be associated with an increasing risk of both death from pump failure and life‐threatening arrhythmias.

Conclusions

Despite the pediatric
DCM
population having higher baseline left ventricular ejection fraction and similar long‐term echocardiographic progression compared with the adult
DCM
population, the pediatric
DCM
patients had worse cardiovascular prognosis.
Language Mixture, Contact and Semiotic Dynamics: Some Thoughts in Counterpoint to Schuchardt’s Approach
Authors: Nicolaï Robert 
Published: June 2016

This paper compares the conceptual framework of Schuchardt’s perspective on language mixing (or at least my representation of it) with that of ‘semiotic dynamics’ as presented in several of my earlier works (Nicolaï, 2011, 2012a). These two approaches entail a same interest in the activities of individuals and groups (communication actors, etc.) who, in their ordinary usage, produce and transform languages. Thus the framework of semiotic dynamics introduces conceptualizations, obviously developed independently of the process which « Slawo-deutsches und Slawo-italienisches » exemplifies, but which, despite differing trajectories, intersects with it. This intersection justifies my assertion as to the work’s modernity and the usefulness of reviewing it. At the same time, this review broadens the scope of research and reflections in this field.
In counterpoint, I will look into the justified (or not) propensity of scholars and documenters to consider a priori the objects-languages with which they work as constitutively homogeneous entities, albeit subject to modification and transformation by a (contingent) contact situation.