bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rb1 Haploinsufficiency Promotes Telomere Attrition and Radiation-Induced Genomic Instability
Authors: Gonzalez-Vasconcellos Iria , Anastasov Natasa , Sanli-Bonazzi Bahar , Klymenko Olena , Atkinson Michael J. , Rosemann Michael 
Published: May 2013

Abstract
Germline mutations of the retinoblastoma gene (RB1) predispose to both sporadic and radiation-induced osteosarcoma, tumors characterized by high levels of genomic instability, and activation of alternative lengthening of telomeres. Mice with haploinsufficiency of the Rb1 gene in the osteoblastic lineage reiterate the radiation susceptibility to osteosarcoma seen in patients with germline RB1 mutations. We show that the susceptibility is accompanied by an increase in genomic instability, resulting from Rb1-dependent telomere erosion. Radiation exposure did not accelerate the rate of telomere loss but amplified the genomic instability resulting from the dysfunctional telomeres. These findings suggest that telomere maintenance is a noncanonical caretaker function of the retinoblastoma protein, such that its deficiency in cancer may potentiate DNA damage-induced carcinogenesis by promoting formation of chromosomal aberrations, rather than simply by affecting cell-cycle control. Cancer Res; 73(14); 4247–55. ©2013 AACR.
How Long Will It Take to Reduce Gastric Cancer Incidence by Eradicating Helicobacter Pylori Infection?
Authors: Osborn John F. , Cattaruzza Maria S. , Ferri Anna M. , De Angelis Flora , Renzi Davide , Marani Alessandra , Vaira Dino 
Published: May 2013

Abstract
Helicobacter pylori (H. pylori) is the most important risk factor for the development of gastric cancer. The objective of this article is to estimate how the number of clinically diagnosed cases caused by H. pylori would reduce in the years after the eradication of the infection from a population. It is assumed that the eradication of H. pylori will prevent the start of some new gastric tumors, but those that have passed the “point of no return” will continue to develop until diagnosed clinically. The observed reduction in the number of clinically diagnosed cases of gastric cancer will depend on the form and parameters of the distribution of the time t taken for tumor to develop into a clinical case after passing the “point of no return.” This analysis assumes that the time t follows normal and log-normal distributions with means 5, 10, and 15 years. If the mean value of time t were 5 years, H. pylori caused cases should be almost eliminated after 10 years, whereas if the mean were 10 years, the number of cases should be halved. If the mean were 15 years, the reduction would only be about 15% after 10 years. The eradication of H. pylori from a population will reduce the incidence of gastric cancer, but the follow-up time needed to show and evaluate the reduction may be longer than that that has been used in studies published so far. Cancer Prev Res; 6(7); 695–700. ©2013 AACR.
Progesterone Enhances Calcitriol Antitumor Activity by Upregulating Vitamin D Receptor Expression and Promoting Apoptosis in Endometrial Cancer Cells
Authors: Lee Laura R. , Teng Pang-Ning , Nguyen Huyen , Hood Brian L. , Kavandi Leyla , Wang Guisong , Turbov Jane M. , Thaete Larry G. , Hamilton Chad A. , Maxwell George L. , Rodriguez Gustavo C. , Conrads Thomas P. , Syed Viqar 
Published: May 2013

AbstractHuman studies suggest that progesterone and calcitriol may prove beneficial in preventing or inhibiting oncogenesis, but the underlying mechanism is not fully understood. The current study investigates the effects of progesterone, calcitriol, and their combination on immortalized human endometrial epithelial cells and endometrial cancer cells and identifies their targets of action. Combination treatment with both agents enhanced vitamin D receptor expression and inhibited cell proliferation through caspase-3 activation and induction of G0–G1 cell-cycle arrest with associated downregulation of cyclins D1 and D3 and p27 induction. We used mass spectrometry–based proteomics to measure protein abundance differences between calcitriol-, progesterone-, or combination-exposed endometrial cells. A total of 117 proteins showed differential expression among these three treatments. Four proteins were then selected for validation studies: histone H1.4 (HIST1H1E), histidine triad nucleotide-binding protein 2 (HINT2), IFN-induced, double-stranded RNA-activated protein kinase (EIF2AK2), and Bcl-2–associated X protein (BAX). Abundance levels of selected candidates were low in endometrial cancer cell lines versus the immortalized endometrial epithelial cell line. All four proteins displayed elevated expression in cancer cells upon exposure to calcitriol, progesterone, or the combination. Further BAX analysis through gain- or loss-of-function experiments revealed that upregulation of BAX decreased cell proliferation by changing the BAX:BCL-2 ratio. Knockdown of BAX attenuated progesterone- and calcitriol-induced cell growth inhibition. Our results showed that progesterone and calcitriol upregulate the expression of BAX along with other apoptosis-related proteins, which induce inhibition of endometrial cancer cell growth by apoptosis and cell-cycle arrest. Cancer Prev Res; 6(7); 731–43. ©2013 AACR.
Hepatic Steatosis Is Associated With Aortic Valve Sclerosis in the General Population
Authors: Markus Marcello Ricardo Paulista , Baumeister Sebastian Edgar , Stritzke Jan , Dörr Marcus , Wallaschofski Henri , Völzke Henry , Lieb Wolfgang 
Published: May 2013

Objective
We aimed to analyze the association between hepatic steatosis and aortic valve sclerosis in the general population.

Approach and Results

Cross-sectional data of 2212 men and women, aged 45 to 81 years, from the baseline examination of the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Hepatic steatosis was primarily defined as the presence of a hyperechogenic ultrasound pattern of the liver. Aortic valve sclerosis was determined by echocardiography. In our sample, hepatic steatosis was present in 877 (39.7%) individuals. Among participants with hepatic steatosis, aortic valve sclerosis was more common (n=323; 36.8%) compared with participants without hepatic steatosis (n=379; 28.4%;
P
<0.001). After adjustment for potential confounders, individuals with hepatic steatosis had 33% higher odds of aortic valve sclerosis compared with those without hepatic steatosis (95% confidence interval, 6%–66%;
P
=0.014). Additional adjustment for high-sensitive C-reactive protein, serum ferritin levels, and white blood cells slightly reduced the association to 32% (95% confidence interval, 4%–66%;
P
=0.021).

Conclusions
Our findings add evidence that hepatic steatosis and aortic valve sclerosis are interrelated after adjustment for major confounders. The release of proatherogenic substances by the steatotic liver or its contribution to insulin resistance and dyslipidemia may contribute to the development of calcification and sclerosis of the aortic valve.
Dkk1 and Msx2–Wnt7b Signaling Reciprocally Regulate the Endothelial–Mesenchymal Transition in Aortic Endothelial Cells
Authors: Cheng Su-Li , Shao Jian-Su , Behrmann Abraham , Krchma Karen , Towler Dwight A. 
Published: May 2013

Objective—
Endothelial cells (ECs) can undergo an endothelial–mesenchymal transition with tissue fibrosis. Wnt- and Msx2-regulated signals participate in arteriosclerotic fibrosis and calcification. We studied the impact of Wnt7, Msx2, and Dkk1, a Wnt7 antagonist, on endothelial–mesenchymal transition in primary aortic ECs.

Approach and Results—

Transduction of aortic ECs with vectors expressing Dkk1 suppressed EC differentiation and induced a mineralizing myofibroblast phenotype. Dkk1 suppressed
claudin 5, PECAM
,
cadherin 5
(
Cdh5
),
Tie1
, and
Tie2
. Dkk1 converted the cuboidal cell monolayer into a spindle-shaped multilayer and inhibited EC cord formation. Myofibroblast and osteogenic markers,
SM22, type I collagen
,
Osx
,
Runx2
, and
alkaline phosphatase
, were upregulated by Dkk1 via activin-like kinase/Smad pathways. Dkk1 increased fibrotic mineralization of aortic ECs cultured under osteogenic conditions—the opposite of mesenchymal cell responses. Msx2 and Wnt7b maintained morphology and upregulated markers of differentiated ECs. Deleting EC
Wnt7b
with the
Cdh5-Cre
transgene in
Wnt7b(fl/fl);LDLR
−/−
mice upregulated aortic osteogenic genes (
Osx
,
Sox9
,
Runx2
, and
Msx2
) and nuclear phospho-Smad1/5, and increased collagen and calcium accumulation.

Conclusions—
Dkk1 enhances endothelial–mesenchymal transition in aortic ECs, whereas Wnt7b and Msx2 signals preserve EC phenotype. EC responses to Dkk1, Wnt7b, and Msx2 are the opposite of mesenchymal responses, coupling EC phenotypic stability with osteofibrogenic predilection during arteriosclerosis.
Racial and Ethnic Differences in Outcomes in Older Patients With Acute Ischemic Stroke
Authors: Qian Feng , Fonarow Gregg C. , Smith Eric E. , Xian Ying , Pan Wenqin , Hannan Edward L. , Shaw Benjamin A. , Glance Laurent G. , Peterson Eric D. , Eapen Zubin J. , Hernandez Adrian F. , Schwamm Lee H. , Bhatt Deepak L. 
Published: May 2013

Background—
Little is known as to whether long-term outcomes of acute ischemic stroke (AIS) vary by race/ethnicity. Using the American Heart Association Get With The Guidelines–Stroke registry linked with Medicare claims data set, we examined whether 30-day and 1-year outcomes differed by race/ethnicity among older patients with AIS.

Methods and Results—
We analyzed 200 900 patients with AIS >65 years of age (170 694 non-Hispanic whites, 85.0%; 20 514 non-Hispanic blacks, 10.2%; 6632 Hispanics, 3.3%; 3060 non-Hispanic Asian Americans, 1.5%) from 926 US centers participating in the Get With The Guidelines–Stroke program from April 2003 through December 2008. Compared with whites, other racial and ethnic groups were on average younger and had a higher median score on the National Institutes of Health Stroke Scale. Whites had higher 30-day unadjusted mortality than other groups (white versus black versus Hispanic versus Asian=15.0% versus 9.9% versus 11.9% versus 11.1%, respectively). Whites also had higher 1-year unadjusted mortality (31.7% versus 28.6% versus 28.1% versus 23.9%, respectively) but lower 1-year unadjusted all-cause rehospitalization (54.7% versus 62.5% versus 60.0% versus 48.6%, respectively). After risk adjustment, Asian American patients with AIS had lower 30-day and 1-year mortality than white, black, and Hispanic patients. Relative to whites, black and Hispanic patients had higher adjusted 1-year all-cause rehospitalization (black: adjusted odds ratio, 1.28 [95% confidence interval, 1.21–1.37]; Hispanic: adjusted odds ratio, 1.22 [95% confidence interval, 1.11–1.35]), whereas Asian patients had lower odds (adjusted odds ratio, 0.83 [95% confidence interval, 0.74–0.94]).

Conclusions—
Among older Medicare beneficiaries with AIS, there were significant differences in long-term outcomes by race/ethnicity, even after adjustment for stroke severity, other prognostic variables, and hospital characteristics.
Poststroke Outcomes Vary by Pathogenic Stroke Subtype in The Atherosclerosis Risk in Communities Study
Authors: Jones Sara B. , Sen Souvik , Lakshminarayan Kamakshi , Rosamond Wayne D. 
Published: May 2013

Background and Purpose—
Early risk of recurrence and mortality after stroke differs by subtype, but less is known about long-term recurrence and hospital readmissions. These differences have economic implications and will affect long-term disability and stroke survivor quality of life. We examined recurrent stroke, all-cause hospital readmission, and mortality by index pathogenic subtype.

Methods—
We identified 987 Atherosclerosis Risk in Communities Study cohort participants with first-ever stroke and followed them for a median 5.3 years after first stroke. Outcomes were compared across index subtypes (infarction: thrombotic, cardioembolic, and lacunar; hemorrhagic: subarachnoid and intracerebral) using Kaplan–Meier analysis and Cox proportional hazards regression, adjusting for age, sex, and race.

Results—
There were 183 recurrent strokes among 147 participants, 3234 hospitalizations among 746 participants, and 529 deaths; only 14% of participants were event-free over follow-up. The majority of recurrent events were of the same subtype, except for lacunar infarcts, which were followed ≈3 quarters of the time by nonlacunar events. Adjusted mortality was higher for intracerebral hemorrhage (hazard ratio, 2.3; 95% confidence interval, 1.7–3.0) compared with thrombotic stroke and lower for lacunar infarcts. Lacunar infarcts had somewhat higher recurrence compared with thrombotic infarcts (hazard ratio, 1.3; 95% confidence interval, 0.9–1.9), but lower all-cause readmission (hazard ratio, 0.8; 95% confidence interval, 0.7–1.0). Readmission was 40% higher for cardioembolic stroke relative to thrombotic stroke (hazard ratio, 1.4; 95% confidence interval, 1.1–1.7).

Conclusions—
Although the highest mortality was observed for intracerebral hemorrhage, there was significant burden of recurrent stroke and hospital readmissions for lacunar and cardioembolic strokes, respectively. There may be opportunities to reduce the relatively high rate of poststroke readmissions.
Depression and Risk of Stroke in Midaged Women
Authors: Jackson Caroline A. , Mishra Gita D. 
Published: May 2013

Background and Purpose—
Depression is known to increase stroke risk. Although limited, there is some evidence for age differences, with a suggestion for a stronger association in younger groups. We investigated the effect of depression on stroke incidence in a large cohort of midaged women.

Methods—
We included 10 547 women without a history of stroke aged 47 to 52 years from the Australian Longitudinal Study on Women’s Health, surveyed every 3 years from 1998 to 2010. Depression was defined at each survey using the Center for Epidemiological Studies Depression Scale (shortened version) and antidepressant use in the past month. Stroke was ascertained through self-report and mortality data. We determined the association between depression and stroke at the subsequent survey, using generalized estimating equation analysis, adjusting for time-varying covariates.

Results—
At each survey, ≈24% were defined as having depression. During follow-up, 177 strokes occurred. Depression was associated with a >2-fold increased odds of stroke (odds ratio, 2.41; 95% confidence interval, 1.78–3.27), which attenuated after adjusting for age, socioeconomic status, lifestyle, and physiological factors (odds ratio, 1.94; 95% confidence interval, 1.37–2.74). Findings were robust to sensitivity analyses addressing methodological issues, including definition of depression, antidepressant use, and missing covariate data.

Conclusions—
Depression is a strong risk factor for stroke in midaged women, with the association partially explained by lifestyle and physiological factors. Further studies of midaged and older women from the same population are needed to confirm whether depression is particularly important in younger women and to inform targeted intervention approaches.
Understanding Religious Disaffiliation: Parental Values and Religious Transmission over Two Generations of Dutch Parents
Authors: Groen Sanne , Vermeer Paul 
Published: May 2013

Abstract
Religious disaffiliation, a major phenomenon in the Netherlands, is predominantly a generational matter. Each successive birth cohort is less involved in institutional religion than the previous one. Parents do not seem to pass on a lasting religious commitment to their offspring, which might indicate an overall shift in parental values from conformity to autonomy. In this article we use panel data to test the assumption and to compare parenting goals and their effects on the offspring’s church attendance over two generations of parents. Our research question is: To what extent is the intergenerational transmission of religious commitment affected by a change in parental values from an emphasis on conformity to an emphasis on autonomy? Results show that while there is indeed a shift in parental values from conformity to autonomy, this barely affects the offspring’s church attendance — which is determined, rather, by the parents’ church attendance, irrespective of the goals they pursue.
A Case of the Chinese (Dis)order? The Haoqiu zhuan and Competing Forms of Knowledge in European and Japanese Readings
Authors: Lam Ling Hon 
Published: May 2013

Abstract
For mid-eighteenth- and early nineteenth-century European readers, the Haoqiu zhuan epitomized China’s “whole system of manners,” showing at one and the same time the orderly civility and the disorderly excess of the Chinese. These notions of wholeness and reversibility of order constitute the “anthropological” turn of Western knowledge, which was predicated on the finitude and perversion of humanity. Against the grain of such order-disorder totality, I read along with late Edo writers, whose rewriting of the Haoqiu zhuan focused on ninkyō/renxia (knight-errantry), a course of action presenting itself as an extreme case in which the norm is overextended to the point that it is no longer recognizable. The two competitive forms of knowledge—anthropology and case thinking—articulate the two sides of theatricality across the globe under the sway of commerce and print.
Mammographic and ultrasonographic features of triple-negative breast cancer: a comparison with other breast cancer subtypes
Authors: Kim Mi Young , Choi Nami 
Published: May 2013

Background Triple-negative breast cancer (TNBC) is known to be associated with aggressive biologic features and a poor clinical outcome. Therefore, early detection of TNBC without missing cancer is mandatory to improve prognosis. Purpose To retrospectively evaluate the mammographic and sonographic features of TNBC compared to ER (+) cancers and HER2 (+) cancers. Material and Methods From June 2011 through June 2012, mammographic and sonographic features of 281 surgically confirmed ER (+) cancers ( n = 153), HER2 (+) cancers ( n = 83), and TNBC ( n = 45) were retrospectively reviewed by two radiologists in consensus. The clinicopathological features were also compared between the three subtypes. Additionally the 45 TNBC cases were analyzed using morphologic criteria of ACR BI-RADS lexicon. Results Most TNBC (93.3%, 42 of 45) were mammographically seen and presented with mass or focal asymmetry without microcalcifications ( P < 0.001). Ultrasonographically TNBC were presented as hypoechoic nodule without microcalcifications ( P < 0.001). Palpable symptom ( P < 0.001), a lower incidence of ductal carcinoma in situ ( P < 0.001), invasive tumor size that is >2 cm ( P = 0.028) and high histologic grade ( P < 0.001) were significantly associated with TNBC. With regard to morphologic features of 45 TNBC cases, TNBC were most likely to be hyperdense mass (89.3%) with oval (68.9%) or lobular shape (28.6%) and indistinct (42.9%) or circumscribed margin (32.1%) on mammogram. Ultrasonographically TNBC were most likely to be a hypoechoic mass (82.2%) with irregular (68.9%) or oval (28.9%) shape and microlobulated (46.7%), circumscribed (17.8%) or indistinct margin (17.8%) and parallel orientation (68.9%). Conclusion Being familiar with combined mammographic and ultrasonographic features of TNBC may be useful to avoid false-negative cases of TNBC.
Quantitative computed tomography assessment of bone mineral density after 2 years’ oral bisphosphonate treatment in postmenopausal osteoarthritis patients who underwent total knee arthroplasty
Authors: Lee Jin Kyu , Choi Choong H , Kang Chang-Nam 
Published: May 2013

Objectives To identify the effects of two years’ oral bisphosphonate (alendronate) treatment in patients who underwent total knee arthroplasty (TKA); to determine whether significant responses seen after the first year of treatment changed during the second year. Additionally, the study tried to identify factors relating to bone mineral density (BMD) changes. Methods This was a prospective 2-year follow-up study of a previous 1-year report of postmenopausal women with knee osteoarthritis who underwent primary unilateral or staged bilateral TKA, after which they received 70 mg alendronate orally once-weekly. BMD was measured using quantitative computed tomography (QCT) on lumbar vertebrae at baseline (pre-TKA) and at 12 and 24 months. Factors associated with BMD changes were determined by regression analysis. Results Sixty-one patients entered the second year and continued treatment for ≥24 months. Mean vertebral QCT BMDs at baseline and after 12 and 24 months’ alendronate treatment were 71.8 mg/ml (41.9–97.5 mg/ml), 69.3 mg/ml (31.4–103.9 mg/ml), and 72.7 mg/ml (33.1–136.1 mg/ml), respectively. Patients undergoing bilateral TKA and who had more severe OA at baseline (bilateral severe [grade 4] OA) had a lower BMD response after 2 years’ bisphosphonate treatment, compared with patients with less severe unilateral knee OA who underwent unilateral TKA. Improvements were, however, seen compared with year 1 levels. Low BMI was associated with BMD nonresponse. Conclusions Patients with bilateral severe OA (grade 4) requiring bilateral knee replacement are at greater risk of nonresponse after 2 years’ oral alendronate treatment. A longer duration of treatment may be necessary in these patients.
Membrane and capillary components of lung diffusion and pro-angiogenic cells in infants
Authors: Chang Daniel V. , Tiller Christina J. , Kisling Jeffrey A. , Case Jamie , Mund Julie A. , Haneline Laura S. , Ingram David A. , Tepper Robert S. 
Published: May 2013

Angiogenesis is a critical determinant of alveolarisation, which increases alveolar surface area and pulmonary capillary blood volume in infants; however, our understanding of this process is very limited. The purpose of our study was to measure the pulmonary membrane diffusion capacity (DM) and pulmonary capillary blood volume (VC) components of the diffusing capacity of the lung for carbon monoxide (DLCO) in healthy infants and toddlers, and evaluate whether these components were associated with pro-angiogenic circulating haematopoietic stem/progenitor cells (pCHSPCs) early in life.21 healthy subjects (11 males), 3–25 months of age, were evaluated.DLCOwas measured under normoxic and hyperoxic conditions, andDMandVCwere calculated. From 1 mL venous blood, pCHSPCs were quantified by multiparametric flow cytometry.DMandVCincreased with increasing body length; however, membrane resistance as a fraction of total resistance to pulmonary diffusion remained constant with somatic size. In addition,DLCOandVC, but notDM, increased with an increasing percentage of pCHSPCs.The parallel increase in the membrane and vascular components of pulmonary diffusion is consistent with alveolarisation during this period of rapid lung growth. In addition, the relationship between pCHSPCs andVCsuggest that pro-angiogenic cells may contribute to this vascular process.