bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Biomarkers and Endpoints in Oral Cancer Chemoprevention Trials
Authors: William William N. , Papadimitrakopoulou Vassiliki A. 
Published: May 2013

Abstract
Chemoprevention, defined as the use of natural, synthetic, or biologic compounds to halt, reverse, or prevent the initial phases of carcinogenesis or the progression of neoplastic cells to cancer, has produced successes, but progress has been slow. Notably, in the field of oral cancer prevention and despite extensive clinical investigations, a standard systemic therapy for patients with oral premalignant lesions is yet to be developed. In view of safety concerns surrounding the use of pharmaceuticals, the use of phytochemicals derived from the diet has been considered but has not yet translated into clinical success. The Bowman Birk Inhibitor (BBI) is a serine protease inhibitor isolated from soybeans possessing domains with trypsin and chymotrypsin inhibitory activity. Encouraging results were previously reported in a phase IIa trial of BBI complex in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. In this issue of the journal, the less promising results of the randomized, placebo-controlled phase IIb trial are presented.
In this commentary, the complexities involved in defining optimal biomarkers and endpoints for oral cancer prevention trials and the development of dietary chemoprevention agents are discussed. Cancer Prev Res; 6(5); 375–8. ©2013 AACR.
Platelets and neurovascular inflammation
Authors: Chavakis Triantafyllos , Langer Harald F. 
Published: May 2013

SummaryPlatelets participate in haemostasis and in thrombus formation in health and disease. Moreover, they contribute to inflammation and cooperate with immune cells in a magnitude of inflammatory/immune responses. Although the inflammatory response has been recognised to be critical in neuronal diseases such as Alzheimer´s disease or multiple sclerosis and its mouse counterpart, experimental autoimmune encephalomyelitis, the participation of platelets in these diseases is poorly investigated so far. Emerging studies, however, point to an interesting crosstalk between platelets and neuroinflammation. For instance, when the integrity of the blood brain barrier is compromised, platelets may be relevant for endothelial inflammation, as well as recruitment and activation of inflammatory cells, thereby potentially contributing to central nervous tissue pathogenesis. This review summarises recent insights in the role of platelets for neurovascular inflammation and addresses potential underlying mechanisms, by which platelets may affect the pathophysiology of neurovascular diseases.
Endothelial CSN5 impairs NF-κB activation and monocyte adhesion to endothelial cells and is highly expressed in human atherosclerotic lesions
Authors: Asare Yaw , Shagdarsuren Erdenechimeg , Schmid Johannes , Tilstam Pathricia , Grommes Jochen , El Bounkari Omar , Schütz Anke , Weber Christian , de Winther Menno , Noels Heidi , Bernhagen Jürgen 
Published: May 2013

SummaryThe COP9 signalosome (CSN), a multifunctional protein complex involved in the regulation of cullin-RING-E3 ubiquitin ligases (CRLs), has emerged as a regulator of NF-κB signalling. As NF-κB drives the expression of pro-inflammatory and pro-atherosclerotic genes, we probed the yet unknown role of the CSN, in particular CSN5, on NF-KB-mediated atherogenic responses in endothelial cells. Co-immunoprecipitation in human umbilical vein endothelial cells (HUVECs) revealed the presence of a super-complex between IKK and CSN, which dissociates upon TNF-α stimulation. Furthermore, CSN5 silencing enhanced TNF-α-induced IKB-α degradation and NF-κB activity in luci-ferase reporter assays. This was paralleled by an increased NF-KB-driven upregulation of atherogenic chemokines and adhesion molecules, as measured by qPCR and flow cytometry, and translated into an enhanced arrest of THP-1 monocytes on TNF-α-stimulated, CSN5-depleted HUVECs. Reverse effects on NF-κB activity and THP-1 arrest were seen upon CSN5 overexpression. Finally, double-immunostaining confirmed the expression of CSN subunits in the endothelium of human atherosclerotic lesions, and revealed an increased expression of CSN5 which correlated with atheroprogression. In conclusion, endothelial CSN5 attenuates NF-KB-dependent pro-inflammatory gene expression and monocyte arrest on stimulated endothelial cells in vitro, suggesting that CSN5 might serve as a negative regulator of atherogenesis.Note: The review process for this manuscript was fully handled by G. Y. H. Lip, Editor in Chief.
Percutaneous Mitral Valve Repair in the Initial EVEREST Cohort
Authors: Foster Elyse , Kwan Damon , Feldman Ted , Weissman Neil J. , Grayburn Paul A. , Schwartz Allan , Rogers Jason H. , Kar Saibal , Rinaldi Michael J. , Fail Peter S. , Hermiller James , Whitlow Patrick L. , Herrmann Howard C. , Lim D. Scott , Glower Donald D. 
Published: May 2013

Background—
Percutaneous repair of mitral regurgitation (MR) permits examination of the effect of MR reduction without surgery and cardiopulmonary bypass on left ventricular (LV) dimensions and function. The goal of this analysis was to determine the extent of reverse remodeling at 12 months after successful percutaneous reduction of MR with the MitraClip device.

Methods and Results—
Of 64 patients with 3 and 4+ MR who achieved acute procedural success after treatment with the MitraClip device, 49 patients had moderate or less MR at 12-month follow-up. Their baseline and 12-month echocardiograms were compared between the group with and without LV dysfunction. In patients with persistent MR reduction and pre-existing LV dysfunction, there was a reduction in LV wall stress, reduced LV end-diastolic volume, LV end-systolic volume and increase in LV ejection fraction in contrast to those with normal baseline LV function, who showed reduction in LV end-diastolic volume, LV wall stress, no change in LV end-systolic volume, and a fall in LV ejection fraction.

Conclusions—
Patients with pre-existing LV dysfunction demonstrate reverse remodeling and improved LV ejection fraction after percutaneous mitral valve repair.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00209339, NCT00209274.
From Colors and Guns to Caps and Gowns? The Effects of Gang Membership on Educational Attainment
Authors: Pyrooz David C. 
Published: May 2013

Objectives: This study examined the effects of adolescent gang membership on educational attainment over a 12-year period. A broader conceptualization of gang membership—as a snare in the life course—is used to study its noncriminal consequences. Method: Data from the National Longitudinal Survey of Youth 1997 and propensity score matching were used to assess the cumulative and longitudinal effects of gang membership on seven educational outcomes, including educational attainment in years and six educational milestones. After adjusting for nonrandom selection into gangs, youths who joined a gang were compared annually to their matched counterparts from 1998 to 2009. Results: Selection-adjusted estimates revealed disparities between gang and nongang youth in education attainment. Youth who joined gangs were 30 percent less likely to graduate from high school and 58 percent less likely to earn a four-year degree than their matched counterparts. The effects of gang membership on educational attainment were statistically observable within one year of joining, and accumulated in magnitude over time to reach −0.62 years (ES=0.25) by the final point of observation. Conclusion: The snare-like forces linked to the onset of gang membership have consequences that spill into a range of life domains, including education. These findings take on added significance because of a historical context where education has a prominent role in social stratification.
Dynamic imaging reveals promiscuous crosspresentation of blood-borne antigens to naïve CD8+ T cells in the bone marrow
Authors: Milo Idan , Sapoznikov Anita , Kalchenko Vyacheslav , Tal Orna , Krauthgamer Rita , van Rooijen Nico , Dudziak Diana , Jung Steffen , Shakhar Guy 
Published: May 2013

Key PointsSoluble blood-borne antigens are crosspresented in the BM, triggering T-cell arrest, clustering, and in situ proliferation. In the BM, not only DCs but also other mononuclear phagocytes participate in crosspresentation.
Stability of genomic imprinting in human induced pluripotent stem cells
Authors: Hiura Hitoshi , Toyoda Masashi , Okae Hiroaki , Sakurai Masahiro , Miyauchi Naoko , Sato Akiko , Kiyokawa Nobutaka , Okita Hajime , Miyagawa Yoshitaka , Akutsu Hidenori , Nishino Koichiro , Umezawa Akihiro , Arima Takahiro 
Published: May 2013

Abstract

Background
hiPSCs are generated through epigenetic reprogramming of somatic tissue. Genomic imprinting is an epigenetic phenomenon through which monoallelic gene expression is regulated in a parent-of-origin-specific manner. Reprogramming relies on the successful erasure of marks of differentiation while maintaining those required for genomic imprinting. Loss of imprinting (LOI), which occurs in many types of malignant tumors, would hinder the clinical application of hiPSCs.

Results
We examined the imprinting status, expression levels and DNA methylation status of eight imprinted genes in five independently generated hiPSCs. We found a low frequency of LOI in some lines. Where LOI was identified in an early passage cell line, we found that this was maintained through subsequent passages of the cells. Just as normal imprints are maintained in long-term culture, this work suggests that abnormal imprints are also stable in culture.

Conclusions
Analysis of genomic imprints in hiPSCs is a necessary safety step in regenerative medicine, with relevance both to the differentiation potential of these stem cells and also their potential tumorigenic properties.
Whole genome scanning and association mapping identified a significant association between growth and a SNP in the IFABP-a gene of the Asian seabass
Authors: Xia Jun Hong , Lin Grace , He Xiaoping , Liu Peng , Liu Feng , Sun Fei , Tu Rongjian , Yue Gen Hua 
Published: May 2013

AbstractBackgroundAquaculture is the quickest growing sector in agriculture. However, QTL for important traits have been only identified in a few aquaculture species. We conducted QTL mapping for growth traits in an Asian seabass F2family with 359 individuals using 123 microsatellites and 22 SNPs, and performed association mapping in four populations with 881 individuals.ResultsTwelve and nine significant QTL, as well as 14 and 10 suggestive QTL were detected for growth traits at six and nine months post hatch, respectively. These QTL explained 0.9-12.0% of the phenotypic variance. For body weight, two QTL intervals at two stages were overlapped while the others were mapped onto different positions. The IFABP-a gene located in a significant QTL interval for growth on LG5 was cloned and characterized. A SNP in exon 3 of the gene was significantly associated with growth traits in different populations.ConclusionsThe results of QTL mapping for growth traits suggest that growth at different stages was controlled by some common QTL and some different QTL. Positional candidate genes and association mapping suggest that the IFABP-a is a strong candidate gene for growth. Our data supply a basis for fine mapping QTL, marker-assisted selection and further detailed analysis of the functions of the IFABP-a gene in fish growth.
Association between HLA genes and American cutaneous leishmaniasis in endemic regions of Southern Brazil
Authors: Ribas-Silva Rejane C , Ribas Adriana D , dos Santos Maria CG , da Silva Waldir V , Lonardoni Maria VC , Borelli Sueli D , Silveira Thaís GV 
Published: May 2013

AbstractBackgroundThe present study sought to investigate the association between HLA-A, HLA-B and HLA-DRB1 genes and susceptibility or resistance to the different clinical manifestations of American cutaneous leishmaniasis (ACL) in southern Brazil.MethodsThe sample consisted of 169 patients with a diagnosis of ACL and 270 healthy subjects for comparison. HLA-A, HLA-B and HLA-DRB1 were typed by PCR-SSO reverse dot blot.ResultsResults showed a trend towards susceptibility to cutaneous lesions for alleles HLA-DRB1*13 (P=0.0228;Pc=0.3420; OR=1.66; 95%CI=1.08 – 2.56), HLA-B*35 (P=0.0218;Pc=0.6758; OR=1.67; 95%CI=1.08 – 2.29) and HLA-B*44 (P=0.0290;Pc=0.8990; OR=1.67; 95%CI=1.05 – 2.64). Subjects with allele HLA-B*27 (P=0.0180;Pc=0.5580; OR=7.1111; 95%CI=1.7850 – 28.3286) tended towards susceptibility to mucocutaneous lesions, those with HLA-B*49 (P=0.0101;Pc=0.3131; OR=6.4000; 95%CI=1.8472 – 22.1743) to recurrent ACL, and HLA-B*52 (P=0.0044;Pc=0.1360; OR=12.61; 95%CI=3.08 – 51.66), to re-infection. Presence of HLA-B*45 (P=0.0107;Pc=0.3317) tended to provide protection against the cutaneous form of ACL. The most frequent haplotypes that may be associated with susceptibility to ACL were A*02 B*44 DRB1*07 (P= 0.0236) and A*24 B*35 DRB1*01 (P= 0.0236).ConclusionSome Class I and Class II HLA genes appear to contribute towards susceptibility to and protection against different clinical manifestations of ACL. Other genetic marker studies may contribute toward future prophylactic and therapeutic interventions in ACL.
Autosomal dominant hereditary ataxia in Sri Lanka
Authors: Sumathipala Dulika S , Abeysekera Gayan S , Jayasekara Rohan W , Tallaksen Chantal ME , Dissanayake Vajira HW 
Published: May 2013

Abstract

Background
Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype.

Methods
Thirty four patients with autosomal dominant ataxia were recruited. For every patient the following was done: recording of clinical details and genotyping for SCA 1, 2, 3, 6, 7, 8, 12, and 17.

Results
Sixty one per cent of the subjects were identified as SCA1. One subject had SCA2, 12 remain unidentified. Mean age at onset was 34.8 ± 10years for SCA1 and 32.7 ± 9.8 for non SCA1. 76% of SCA1 patients and 50% of non SCA1 were using walking aids. Quantification of symptoms and signs were similar in the SCA1 and non SCA1 groups. Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients. Mean CAG repeat length in SCA1 patients was 52.0 ± 3.8, with greater anticipation seen with paternal inheritance.

Conclusion
SCA1 was the predominant subtype and showed similar phenotype to previous reports. However, disease severity was higher and depression more prevalent in this population than previously described.
Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors
Authors: Ludwig Kirsten , Tse Edison S , Wang Jean YJ 
Published: May 2013

Abstract

Background
The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal growth factor (EGF). In human colorectal cancer, the Wnt pathway is constitutively activated through genetic and epigenetic alterations in as many as 11 genes encoding components of this crypt stem-cell maintenance mechanism. Although the proliferation of colon cancer cells does not require Wnt, it is possible that colon cancer cells can still respond to the crypt growth factors in the colonic microenvironment. A number of studies have shown that epithelial cells behave differently in 3-D versus 2-D cultures. Because the 3-D conditions more closely mimic the in vivo environment, we examined the effects of Wnt and other crypt growth factors on colon cancer cell growth in 3-D culture.

Methods
Colon cancer cells were grown in 3-D matrigel supplemented with different combinations of crypt growth factors and colonies were examined for morphology and pathways.

Results
When colon cancer cells were cultured in 3-D with EGF, they grew as round spheroid colonies. However, colon cancer cells also grew as flat, disc-like colonies when cultured with EGF plus Wnt, R-Spondin1 and Noggin. Disc colonies were found to have comparable levels of E-cadherin as the spheroid colonies, but showed decreased E-cadherin at the cell-matrix contact sites. Disc colonies also elaborated F-actin rich protrusions (FRP) at the cell-matrix edge, reminiscent of an invasive phenotype but without the expression of vimentin. These E-cadherin and F-actin alterations were not induced by the four growth factors in 2-D culture. Formation of the disc colonies was inhibited by the knockdown of β-catenin and by protein kinase inhibitors such as gefitinib, imatinib and MK-2206. Furthermore, withdrawal of the crypt growth factors was able to revert the disc colonies to spheroid growth, showing that the invasive phenotype was reversible dependent on the availability of growth factors.

Conclusions
These findings show that colon cancer cells remain responsive to the growth factors in the crypt microenvironment and can be induced to undergo morphological transformation in the more physiologically relevant 3-D culture.
Hydration status of underground miners in a temperate Australian region
Authors: Polkinghorne Benjamin G , Gopaldasani Vinodkumar , Furber Susan , Davies Brian , Flood Victoria M 
Published: May 2013

Abstract

Background
Dehydration is a health risk for miners in tropical regions of Australia. However, it is not known whether dehydration poses a health risk to miners working in temperate regions of Australia.

Methods
A cross-sectional study of 88 miners from two underground mines was undertaken in south-eastern New South Wales, Australia. Participants had their height, weight, waist circumference and hydration status measured and completed a self-administered questionnaire on fluid intake, access to water, and socio-demographic characteristics. Health and Safety managers were surveyed about guidelines relating to healthy work and lifestyle behaviours which impact/influence hydration.

Results
Hydration tests indicated that more than half of the miners (approximately 58%) were dehydrated (Urinary Specific Gravity (USG) >1.020) both before and after their shift, with three workers pre-shift and four workers post-shift displaying clinical dehydration (USG>1.030). Overall, 54.0% of participants were overweight and 36.8% were obese. Miners who commenced the shift with poor hydration status were 2.6 times more likely to end the shift with poor hydration, compared to those who commenced the shift with good hydration (OR 2.6, 95% CI 1.06, 6.44). Miners who had a mean USG result for the entire shift indicating dehydration were more likely to be obese (42.9%) and have a waist measurement in the high risk range for metabolic complications (40.8%) than those workers that were adequately hydrated for their entire shift (29.4% and 14.7% respectively). Some guidelines promoting healthy lifestyles and supportive work environments were in place, but there were limited guidelines on healthy weight and hydration.

Conclusions
Dehydration, being overweight and obesity were linked issues in this cohort of miners. Strategies are needed to: adapt the workplace environment to increase water accessibility; encourage appropriate consumption of water both at work and at home; and to promote physical activity and good nutrition to maintain healthy weight.
Dental caries among children visiting a mobile dental clinic in South Central Kentucky: a pooled cross-sectional study
Authors: Dawkins Erika , Michimi Akihiko , Ellis-Griffith Gregory , Peterson Tina , Carter Daniel , English Gary 
Published: May 2013

Abstract

Background
Dental caries is one of the most common chronic childhood diseases affecting a large portion of children in the United States. The prevalence of childhood dental caries in Kentucky is among the highest in the nation. The purposes of this study are to (1) compare sociodemographic differences between caries and no caries groups and (2) investigate factors associated with untreated dental caries among children who visited a mobile dental clinic in South Central Kentucky.

Methods
Study subjects were children aged 6 to 15 years who participated in the school-based dental sealant program through the mobile dental clinic operated by the Institute for Rural Health at Western Kentucky University between September 2006 and May 2011 (n = 2,453). Descriptive statistics were calculated for sociodemographic factors (age, gender, race/ethnicity, insurance status, and urban versus rural residential location) and caries status. We used chi-square tests to compare sociodemographic differences of children stratified by caries and no caries status as well as three levels of caries severity. We developed a logistic regression model to investigate factors associated with untreated dental caries while controlling for sociodemographic characteristics.

Results
The proportion of children having untreated dental caries was 49.7% and the mean number of untreated dental caries was 2.0. The proportion of untreated dental caries was higher in older children, children with no insurance and living in rural residential locations, and caries severity was also higher in these groups. Odds ratio indicated that older ages, not having private insurance (having only public, government-sponsored insurance or no insurance at all) and rural residential location were associated with having untreated dental caries after controlling for sociodemographic characteristics of children.

Conclusions
Untreated dental caries was more likely to be present in older children living in rural areas without insurance. Health interventionists may use this information and target rural children without having proper insurance in order to reduce geographic disparities in untreated dental caries in South Central Kentucky.
Effects of Ginkgo biloba on chemically-induced mammary tumors in rats receiving tamoxifen
Authors: Dias Marcos Correa , Furtado Kelly Silva , Rodrigues Maria Aparecida Marchesan , Barbisan Luís Fernando 
Published: May 2013

Abstract

Background

Ginkgo biloba extract (GbE) is used extensively by breast cancer patients undergoing treatment with Tamoxifen (TAM). Thus, the present study investigated the effects of GbE in female Sprague–Dawley (SD) rats bearing chemically-induced mammary tumors and receiving TAM.

Methods
Animals bearing mammary tumors (≥1 cm in diameter) were divided into four groups: TAM [10 mg/kg, intragastrically (i.g.)], TAM plus GbE [50 and 100 mg/kg, intraperitoneally (i.p.)] or an untreated control group. After 4 weeks, the therapeutic efficacy of the different treatments was evaluated by measuring the tumor volume (cm3) and the proportions of each tumor that were alive, necrotic or degenerative (mm2). In addition, labeling indexes (LI%) were calculated for cell proliferation (PCNA LI%) and apoptosis (cleaved caspase-3 LI%), expression of estrogen receptor-alpha (ER-α) and p63 biomarkers.

Results
Overall, the tumor volume and the PCNA LI% within live tumor areas were reduced by 83% and 99%, respectively, in all TAM-treated groups when compared to the untreated control group. GbE treatment (100 mg/kg) reduced the proportions of live (24.8%) and necrotic areas (2.9%) (p = 0.046 and p = 0.038, respectively) and significantly increased the proportion of degenerative areas (72.9%) (p = 0.004) in mammary tumors when compared to the group treated only with TAM. The expression of ER-α, p63 and cleaved caspase-3 in live tumor tissues was not modified by GbE treatment.

Conclusions
Co-treatment with 100 mg/kg GbE presented a slightly beneficial effect on the therapeutic efficacy of TAM in female SD rats bearing mammary tumors.