bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans
Authors: Colpitts Che C. , Schang Luis M. 
Published: May 2014

ABSTRACTPrimary attachment to cellular glycans is a critical entry step for most human viruses. Some viruses, such as herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV), bind to heparan sulfate, whereas others, such as influenza A virus (IAV), bind to sialic acid. Receptor mimetics that interfere with these interactions are active against viruses that bind to either heparan sulfate or to sialic acid. However, no molecule that inhibits the attachment of viruses in both groups has yet been identified. Epigallocatechin gallate (EGCG), a green tea catechin, is active against many unrelated viruses, including several that bind to heparan sulfate or to sialic acid. We sought to identify the basis for the broad-spectrum activity of EGCG. Here, we show that EGCG inhibits the infectivity of a diverse group of enveloped and nonenveloped human viruses. EGCG acts directly on the virions, without affecting the fluidity or integrity of the virion envelopes. Instead, EGCG interacts with virion surface proteins to inhibit the attachment of HSV-1, HCV, IAV, vaccinia virus, adenovirus, reovirus, and vesicular stomatitis virus (VSV) virions. We further show that EGCG competes with heparan sulfate for binding of HSV-1 and HCV virions and with sialic acid for binding of IAV virions. Therefore, EGCG inhibits unrelated viruses by a common mechanism. Most importantly, we have identified EGCG as the first broad-spectrum attachment inhibitor. Our results open the possibility for the development of small molecule broad-spectrum antivirals targeting virion attachment.IMPORTANCEThis study shows that it is possible to develop a small molecule antiviral or microbicide active against the two largest groups of human viruses: those that bind to glycosaminoglycans and those that bind to sialoglycans. This group includes the vast majority of human viruses, including herpes simplex viruses, cytomegalovirus, influenza virus, poxvirus, hepatitis C virus, HIV, and many others.
Frequency and Abundance of Alphaherpesvirus DNA in Human Thoracic Sympathetic Ganglia
Authors: Nagel Maria A. , Rempel April , Huntington Jonathon , Kim Forrest , Choe Alexander , Gilden Don 
Published: May 2014

ABSTRACT
Alphaherpesvirus reactivation from thoracic sympathetic ganglia (TSG) and transaxonal spread to target organs cause human visceral disease. Yet alphaherpesvirus latency in TSG has not been well characterized. In this study, quantitative PCR detected varicella-zoster virus (VZV), herpes simplex virus 1 (HSV-1), and HSV-2 DNA in 117 fresh TSG obtained postmortem from 15 subjects. VZV DNA was found in 76 (65%) ganglia from all subjects, HSV-1 DNA was found in 5 (4%) ganglia from 3 subjects, and no HSV-2 was found.
A Community Jury on PSA screening: what do well-informed men want the government to do about prostate cancer screening—a qualitative analysis
Authors: Rychetnik Lucie , Doust Jenny , Thomas Rae , Gardiner Robert , MacKenzie Geraldine , Glasziou Paul 
Published: May 2014

ObjectiveCancer screening policies and programmes should take account of public values and concerns. This study sought to determine the priorities, values and concerns of men who were ‘fully informed’ about the benefits and harms of prostate-specific antigen (PSA) screening; and empirically examine the value of a community jury in eliciting public values on PSA screening.SettingCommunity jury was convened on the Gold Coast, Queensland (Australia) to consider PSA screening benefits and harms, and whether government campaigns on PSA screening should be conducted.Participants27 men (volunteers) aged 50–70 with no personal history of prostate cancer and willing to attend jury 6–7 April 2013: 12 were randomly allocated to jury (11 attended).Outcome measuresA qualitative analysis was conducted of the jury deliberations (audio-recorded and transcribed) to elicit the jury's views and recommendations. A survey determined the impact of the jury process on participants’ individual testing decisions compared with control group.ResultsThe jury concluded governments should not invest in programmes focused on PSA screening directed at the public because the PSA test did not offer sufficient reassurance or benefit and could raise unnecessary alarm. It recommended an alternative programme to support general practitioners to provide patients with better quality and more consistent information about PSA screening. After the jury, participants were less likely to be tested in the future compared with the controls, but around half said they would still consider doing so.ConclusionsThe jury's unanimous verdict about government programmes was notable in the light of their divergent views on whether or not they would be screened themselves in the future. Community juries provide valuable insights into the priorities and concerns of men weighing up the benefits and harms of PSA screening. It will be important to assess the degree to which the findings are generalisable to other settings.
ABSTRACTS FROM THE TRI-SERVICE EMERGENCY MEDICINE CONFERENCE, 2013
Authors: Smith Jason E 
Published: May 2014

The 2013 Tri-Service Emergency Medicine Conference was held in the Defence CBRN Centre, Winterbourne Gunner, from 14–16 October 2013. Abstracts were invited from military trainees in emergency medicine, and subjected to standardised assessment and scoring. The authors of the four highest scoring abstracts were invited to present their abstracts orally in the final conference session.The top four scoring abstracts, that were included in the oral presentation session, are included below.
Coxiella burnetii seroprevalence and risk factors on commercial sheep farms in The Netherlands
Authors: Schimmer B. , de Lange M. M. A. , Hautvast J. L. A. , Vellema P. , van Duynhoven Y. T. H. P. 
Published: May 2014

Coxiella burnetii seroprevalence was assessed on Dutch dairy and non‐dairy sheep farms using ELISA. Risk factors for seropositivity on non‐dairy sheep farms were identified at farm and sheep level by univariate and multivariate multilevel analyses. Based on 953 dairy and 5671 non‐dairy serum samples, sheep seroprevalences were 18.7 per cent and 2.0 per cent, respectively, and 78.6 per cent and 30.5 per cent at farm level. Significant risk factors for non‐dairy sheep farms were farm location in the south of the country, sheep kept on marginal grounds, one or several supply addresses for ewes during 2007–2009 and wearing farm boots and/or outfit by professional visitors. On sheep level, risk factors included among others farm location in the south of the country, lamb breeding as main farm purpose, goat density within 10 km farm radius, use of windbreak curtain or windshields, and presence of ≥6 stillborn lambs in 2009. Farm location in the south of the country and goat density suggests that infected goats have played a role in the transmission to non‐dairy sheep. Other risk factors suggest introduction of the bacterium through sheep supply and professional visitors. Biosecurity measures should be strengthened, including avoiding infection during handling of stillborn lambs and birth products in the lambing period.
Characterization of excavated claystone and claystone–bentonite mixtures as backfill/seal material
Authors: Zhang Chun-Liang 
Published: May 2014

Abstract
Crushed claystone produced by excavation of repository openings has been investigated as backfill/seal material. The raw coarse-grained claystone can be used for backfilling repository openings and, in mixture with bentonite, for sealing boreholes, drifts and shafts. The investigation programme focused on characterizing the thermo-hydro-mechanical properties of the excavated Callovo-Oxfordian claystone and the compacted claystone–bentonite mixtures, including (1) mechanical compaction, (2) gas and water permeability as a function of porosity, (3) water retention and saturation, (4) swelling capacity and (5) thermal properties of the materials. The major results are presented in this paper.
The Natural History of Cervical Cancer in Chinese Women: Results from an 11-Year Follow-Up Study in China Using a Multistate Model
Authors: Zhang Shao-Kai , Kang Le-Ni , Chang Irene J. , Zhao Fang-Hui , Hu Shang-Ying , Chen Wen , Shi Ju-Fang , Zhang Xun , Pan Qin-Jing , Li Shu-Min , Qiao You-Lin 
Published: May 2014

Abstract
Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China.
Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively.
Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subject's transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74.
Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China.
Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.
One-Carbon Metabolism Dietary Factors and Distal Gastric Cancer Risk in Chinese Women
Authors: Kweon Sun-Seog , Shu Xiao-Ou , Xiang Yongbing , Yang Gong , Ji Bu-Tian , Li Honglan , Gao Yu-Tang , Zheng Wei , Shrubsole Martha J. 
Published: May 2014

Abstract
Background: Previous studies on the association between one-carbon dietary factors and gastric cancer risk have been inconsistent.
Methods: We investigated this association using data from a prospective study, the Shanghai Women's Health Study (1997–2010), including 323 distal gastric cancer cases identified from 73,009 Chinese women. HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression after adjusting for confounders.
Results: Overall, no statistically significant association of gastric cancer was observed with dietary intake of folate, methionine, or B vitamins. However, when stratified by menopausal status, higher intake of riboflavin was associated with decreased gastric cancer risk in premenopausal women with HR of 0.35 (95% CI, 0.17–0.73), 0.48 (0.24–0.97), 0.28 (0.12–0.65), and 0.23 (0.07–0.91), respectively, for the quintiles 2 to 5 intake groups compared with the lowest quintile intake (P for trend = 0.02). Among premenopausal women, highest intake of folate was associated with increased gastric cancer risk (HR, 2.62; 95% CI, 1.04–6.59). There were no statistically significant associations observed among postmenopausal women.
Conclusions: These results suggest that dietary factors involved in one-carbon metabolism are associated with gastric cancer risk among premenopausal women.
Impact: Riboflavin may be a protective factor and folate may be a risk factor for premenopausal gastric cancer. Cancer Epidemiol Biomarkers Prev; 23(7); 1374–82. ©2014 AACR.
FANCD2 Is a Potential Therapeutic Target and Biomarker in Alveolar Rhabdomyosarcoma Harboring the PAX3–FOXO1 Fusion Gene
Authors: Singh Mamata , Leasure Justin M. , Chronowski Christopher , Geier Brian , Bondra Kathryn , Duan Wenrui , Hensley Lauren A. , Villalona-Calero Miguel , Li Ning , Vergis Anthony M. , Kurmasheva Raushan T. , Shen Changxian , Woods Gary , Sebastian Nikhil , Fabian Denise , Kaplon Rita , Hammond Sue , Palanichamy Kamalakannan , Chakravarti Arnab , Houghton Peter J. 
Published: May 2014

Abstract
Purpose: Alveolar rhabdomyosarcoma that harbors the PAX3–FOXO1 fusion gene (t-ARMS) is a common and lethal subtype of this childhood malignancy. Improvement in clinical outcomes in this disease is predicated upon the identification of novel therapeutic targets.
Experimental Design: Robust mouse models were used for in vivo analysis, and molecular studies were performed on xenografts treated in parallel. Two independent patient sets (n = 101 and 124) of clinically annotated tumor specimens were used for analysis of FANCD2 levels and its association with clinical and molecular characteristics and outcomes.
Results: Our xenograft studies reveal a selective suppression of FANCD2 by m-TOR kinase inhibition and radiosensitization of the t-ARMS line only. In the initial patient set, we show that FANCD2 transcript levels are prognostic in univariate analysis, and are significantly associated with metastatic disease and that the copresence of the translocation and high expression of FANCD2 is independently prognostic. We also demonstrate a significant and nonrandom enrichment of mTOR-associated genes that correlate with FANCD2 gene expression within the t-ARMS samples, but not within other cases. In the second patient set, we show that on a protein level, FANCD2 expression correlates with PAX3–FOXO1 fusion gene and is strongly associated with phospho-P70S6K expression in cases with the fusion gene.
Conclusions: Our data demonstrate that FANCD2 may have a significant role in the radiation resistance and virulence of t-ARMS. Indirectly targeting this DNA repair protein, through mTOR inhibition, may represent a novel and selective treatment strategy. Clin Cancer Res; 20(14); 3884–95. ©2014 AACR.
Vitamin D Deficiency Predicts Prostate Biopsy Outcomes
Authors: Murphy Adam B. , Nyame Yaw , Martin Iman K. , Catalona William J. , Hollowell Courtney M.P. , Nadler Robert B. , Kozlowski James M. , Perry Kent T. , Kajdacsy-Balla Andre , Kittles Rick 
Published: May 2014

Abstract
Purpose: The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination.
Experimental Design: Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage.
Results: Among European American (EA) men, there was an association of 25-OH D &lt;12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41–9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14–5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D &lt; 20 ng/mL [OR, 2.43 (1.20–4.94); P = 0.01]. AA men demonstrated an association between 25-OH D &lt; 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59–15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52–11.74); P = 0.003].
Conclusions: In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage. Clin Cancer Res; 20(9); 2289–99. ©2014 AACR.
Vitamin D Status: Ready for Guiding Prostate Cancer Diagnosis and Treatment?
Authors: Grant William B. 
Published: May 2014

Abstract
Vitamin D deficiency is associated with increased risk of prostate cancer for those with elevated prostate-specific antigen (PSA) level or abnormal digital rectal examination. Vitamin D deficiency is also associated with aggressive prostate cancer. Vitamin D level could be added as an additional factor to consider before ordering a biopsy. Clin Cancer Res; 20(9); 2241–3. ©2014 AACR.
Preferential Estrogen Receptor β Ligands Reduce Bcl-2 Expression in Hormone-Resistant Breast Cancer Cells to Increase Autophagy
Authors: Ruddy Samantha C. , Lau Rosanna , Cabrita Miguel A. , McGregor Chelsea , McKay Bruce C. , Murphy Leigh C. , Wright James S. , Durst Tony , Pratt M.A. Christine 
Published: May 2014

Abstract
Acquired resistance to selective estrogen receptor (ER) modulators (SERM) and downregulators (SERD) is a significant clinical problem in the treatment of estrogen (E2) receptor-positive (ER+) breast cancers. There are two ER subtypes, ERα and ERβ, which promote and inhibit breast cancer cell proliferation, respectively. Although ER+ breast cancers typically express a high ratio of ERα to ERβ, the acquisition of SERM resistance in vitro and in vivo is associated with increased relative expression of the ERβ. On some gene enhancers, ERβ has been shown to function in opposition to the ERα in the presence of E2. Here, we demonstrate that two different ERβ agonists, WAY-20070 and a novel “A-CD” estrogen called L17, produce a marked reduction in G2–M phase correlated with effects on cyclin D1 and cyclin E expression in a SERM/SERD-resistant breast cancer cell line. ERβ agonists recruited both the ERα and ERβ to the Bcl-2 E2-response element strongly reducing Bcl-2 mRNA and protein in an ERβ-dependent manner. L17 recruited RIP140 to the Bcl-2 promoter in cells overexpressing ERβ. Exposure to the ERβ ligands also resulted in increased processing of LC3-I to LC3-II, indicative of enhanced autophagic flux. The coaddition of ERβ agonist and the autophagy inhibitor chloroquine resulted in a significant accumulation of sub-G1 DNA which was completely prevented by the addition of the caspase inhibitor Z-VAD-FMK. We propose that combined therapies with an ERβ agonist and an inhibitor of autophagy may provide the basis for a novel approach to the treatment of SERM/SERD-resistant breast cancers. Mol Cancer Ther; 13(7); 1882–93. ©2014 AACR.
SPSB1 Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling
Authors: Feng Yi , Pan Tien-Chi , Pant Dhruv K. , Chakrabarti Kristi R. , Alvarez James V. , Ruth Jason R. , Chodosh Lewis A. 
Published: May 2014

Abstract
Breast cancer mortality is principally due to tumor recurrence; however, the molecular mechanisms underlying this process are poorly understood. We now demonstrate that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated during mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in genetically engineered mouse models. The recurrence-promoting effects of SPSB1 result from its ability to protect cells from apoptosis induced by HER2/neu pathway inhibition or chemotherapy. This, in turn, is attributable to SPSB1 potentiation of c-MET signaling, such that preexisting SPSB1-overexpressing tumor cells are selected for following HER2/neu downregulation. Consistent with this, SPSB1 expression is positively correlated with c-MET activity in human breast cancers and with an increased risk of relapse in patients with breast cancer in a manner that is dependent upon c-MET activity. Our findings define a novel pathway that contributes to breast cancer recurrence and provide the first evidence implicating SPSB proteins in cancer.
Significance: The principal cause of death from breast cancer is recurrence. This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1–c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression. Cancer Discov; 4(7); 790–803. ©2014 AACR.
See related commentary by Qin and McAllister, p. 760
This article is highlighted in the In This Issue feature, p. 745
Predictors of Spontaneous Reverse Remodeling in Mild Heart Failure Patients With Left Ventricular Dysfunction
Authors: Brenyo Andrew , Barsheshet Alon , Kutyifa Valentina , Ruwald Anne-Christine , Rao Mohan , Zareba Wojciech , Pouleur Anne-Catherine , Knappe Dorit , Solomon Scott D. , McNitt Scott , Huang David T. , Moss Arthur J. , Goldenberg Ilan 
Published: May 2014

Background—
There are limited data regarding factors associated with spontaneous left ventricular reverse remodeling (S-LVRR) among mildly symptomatic heart failure (HF) patients and its prognostic implications on clinical outcomes.

Methods and Results—

Best subsets logistic regression analysis was used to identify factors associated with S-LVRR (defined as ≥15% reduction in left ventricular end-systolic volume at 1-year of follow-up) among 612 patients treated with internal cardioverter defibrillator–only therapy in Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) and to create a score for the prediction of S-LVRR. Cox proportional hazards regression modeling was used to assess the clinical outcome of all internal cardioverter defibrillator–only patients (n=714) with a high S-LVRR score. S-LVRR occurred in 25% of internal cardioverter defibrillator–only patients. Predictors of S-LVRR included systolic blood pressure≥140 mm Hg, serum creatinine<1.0 mg/dL, QRS 130 to 160 ms, and nonischemic cardiomyopathy. Multivariate analysis showed that each 1-point increment in S-LVRR score (range, 0–7) was associated with an 11% (
P
=0.019) reduction in the risk of HF or death. Treatment with cardiac resynchronization therapy was associated with a significant reduction in the risk of HF or death only among internal cardioverter defibrillator–treated patients with a low (Q1–3) S-LVRR score (hazard ratio=0.55;
P
<0.001), but not among those with a higher (Q4) score (hazard ratio=1.06;
P
=0.72).

Conclusions—
Our data suggest that approximately one quarter of mild HF patients eligible for biventricular pacing experience S-LVRR. Combined assessment of clinical factors associated with S-LVRR can be used to identify mild HF patients with a low risk for clinical events without cardiac resynchronization therapy intervention.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00180271.