bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of MC1R Genotype and Novel Common Genomic Variants to Melanoma Risk Prediction
Authors: Cust AE , Bui M , Goumas C , Jenkins MA ,   Australian Melanoma Family Study Investigators
Published: March 2014

Abstract
Genome-wide association studies have identified numerous common genomic variants associated with increased susceptibility to melanoma, but there is limited knowledge about the utility of adding them to risk prediction models for melanoma. Individuals diagnosed at a young age might have an underlying genetic susceptibility to melanoma, and young adulthood is a key age period for targeting primary prevention strategies for melanoma. Aim: To evaluate the contribution of melanocortin-1 receptor (MC1R) gene variants and novel common genomic variants to melanoma risk prediction, among young Australian adults. Methods: The sample included 552 cases with invasive cutaneous melanoma diagnosed between ages 18–39 years and 405 controls from an Australian population-based, case-control-family study. MC1R genotype was sequenced, and through a genome-wide association study we obtained genotype data for single nucleotide polymorphisms from 18 selected gene regions. Measures of discriminatory accuracy included the area under receiver operating characteristic curves (AUC) and net reclassification improvement (NRI), calculated based on predicted probabilities of melanoma from unconditional logistic regression models. We used 10-fold cross-validation and bootstrap methods to assess internal validation. Results: The AUC increased from 0.76 (95% CI 0.73–0.79) for the non-genetic multivariate model containing demographic and self-reported risk factors (UV exposure, phenotype, nevi, etc), to 0.81 (95% CI 0.78–0.84) for the genetic model that additionally included MC1R genotype and novel common genomic variants. The combined contribution to the AUC of the novel common genomic variants identified through genome-wide association studies was similar to that contributed from the known common variants in MC1R and CDKN2A. Inclusion of genomic variants in the multivariate model improved the quartile classification of predicted risk (NRI) by a net 17% (95% CI 9–24) compared to the non-genetic model. Conclusions: Our results suggest that MC1R and other common genomic variants could considerably improve risk prediction models for early-onset melanoma, and may have a role in primary prevention of melanoma.
Quality of Life and Comorbidities Impact Education and Employment for Survivors of Adolescent and Young Adult Cancers
Authors: Kirchhoff AC , McFadden M , Warner EL , Kinney AY 
Published: March 2014

Abstract
Survivors of adolescent and young adult (AYA) cancers have a high risk of chronic conditions such as cardiovascular disease and asthma. These conditions may affect their ability to attend school or to work. We examined the impact of quality of life (QOL) and comorbidities on educational attainment and employment status for survivors of AYA cancers relative to a non-cancer comparison group. Methods: Using data from the 2009 Behavioral Risk Factor Surveillance System (BRFSS), we identified 7,471 individuals who were diagnosed with cancer between ages 15 and 39 and were ≥5 years from diagnosis and 326,821 controls without a history of cancer. Participants were ≥25 years of age. QOL was measured by a general health measure (excellent/very good/good/fair/poor). Comorbidities included self-reported cardiovascular disease, hypertension, asthma, and diabetes. Multivariable regressions using BRFSS survey weights were adjusted for sex, race/ethnicity and age, and compared the effects of QOL and comorbidities on educational attainment (college graduate or more vs. less education) and being employed or unable to work (compared to out of work or not in labor force) among the survivor and control groups. Results: Compared to controls, survivors in fair-poor health were less likely to be college graduates or more (survivors 18.5% vs. controls 37.9%, p &lt; 0.01) and less likely to be employed (survivors 31.7% vs. controls 61.6%, p &lt; 0.001), whereas survivors in good-excellent health did not differ from controls for either outcome. In addition, survivors in fair-poor health self-reported being unable to work more often than controls (31.4% vs. 5.4%, respectively; p &lt; 0.001). For comorbidities, inability to work ranged from 14.9% of survivors with hypertension to 27.9% of survivors with cardiovascular conditions compared to 5.4% of controls (all p &lt; 0.001), while survivors with no comorbidities did not differ from controls. Conclusions: AYA cancer survivors with ongoing health problems may face educational or work-related limitations. Early detection and management of health problems could help AYA cancer survivors control health problems before their ability to attend school or employment is disrupted.
Anatomic Pattern of Intracerebral Hemorrhage Expansion
Authors: Boulouis Grégoire , Dumas Andrew , Betensky Rebecca A. , Brouwers H. Bart , Fotiadis Panagiotis , Vashkevich Anastasia , Ayres Alison , Schwab Kristin , Romero Javier M. , Smith Eric E. , Viswanathan Anand , Goldstein Joshua N. , Rosand Jonathan , Gurol M. Edip , Greenberg Steven M. 
Published: March 2014

Background and Purpose—
We sought to identify baseline determinants of the anatomic pattern of hematoma expansion in patients with intracerebral hemorrhage and spot sign.

Methods—
We coregistered baseline and follow-up CT scans from 15 intracerebral hemorrhage patients and measured growth at each surface node from baseline to follow-up hematoma. We analyzed the effects of proximity to the spot sign or hematoma center on distance of expansion, controlling for covariates.

Results—

There was substantial node-to-node variation in the extent of expansion around each hematoma surface (mean coefficient of variation for expansion distance, 0.43; 95% confidence interval, 0.39–0.48), indicating nonuniform expansion. Closer proximity to the hematoma center was independently associated with increased expansion (0.185 mm greater expansion for each 1 mm closer to the center;
P
<0.0001). Closer proximity to the spot sign was not independently associated with increased expansion in models including both terms.

Conclusions—
Hemorrhages expand nonuniformly around their surface with a tendency for greater expansion closer to their center. These findings provide a novel framework for analyzing mechanisms underlying hemorrhage growth and response to treatment.
Plato on Pure Pleasure and the Best Life
Authors: Fletcher Emily 
Published: March 2014

AbstractIn thePhilebus, Socrates maintains two theses about the relationship between pleasure and the good life: (1) the mixed life of pleasure and intelligence is better than the unmixed life of intelligence, and: (2) the unmixed life of intelligence is the most divine. Taken together, these two claims lead to the paradoxical conclusion that the best human life is better than the life of a god. A popular strategy for avoiding this conclusion is to distinguish human from divine goods; on such a reading, pleasure has merely instrumental value, and it benefits human beings only as a result of their imperfect nature. I argue that certain ‘pure’ pleasures are full-fledged, intrinsic goods in thePhilebus, which are even worthy of the gods (thus Socrates ultimately rejects thesis 2). This positive evaluation of pure pleasure results from a detailed examination of pleasure, which reveals that different types of pleasures have fundamentally different natures.
Metformin decreases glycated albumin to glycated haemoglobin ratio in patients with newly diagnosed type 2 diabetes
Authors: Sumitani Satoru , Morita Shinya , Deguchi Reiko , Hirai Koichi , Mukai Kosuke , Utsu Yoshihiko , Miki Shunji , Sato Bunzo , Nakamura Hideji , Kasayama Soji , Koga Masafumi 
Published: March 2014

Background To know whether metformin improves postprandial hyperglycaemia, we examined the effect of metformin on the glycated albumin (GA) to glycated haemoglobin (HbA1c) ratio (GA/HbA1c ratio) in patients with newly diagnosed type 2 diabetes. Methods Metformin and lifestyle interventions were initiated in 18 patients with newly diagnosed type 2 diabetes. Metformin was titrated to 1500 mg/day or maximum-tolerated dose. HbA1c and GA were measured every four weeks up to 24 weeks. Results HbA1c decreased significantly from 9.0 ± 2.1% at baseline to 6.5 ± 0.9% at week 24, and GA decreased significantly from 24.3 ± 8.2% to 16.2 ± 3.1%. The GA/HbA1c ratio decreased significantly from 2.66 ± 0.37 at baseline to 2.47 ± 0.29 at week 24 ( P < 0.01), despite that the GA/HbA1c ratio reached a plateau value at week 16. The change in the GA/HbA1c ratio during 24 weeks (ΔGA/HbA1c ratio) was significantly correlated with both baseline HbA1c and GA. Moreover, the ΔGA/HbA1c ratio was significantly correlated with the change in GA during 24 weeks but not with the change in HbA1c. Conclusions Metformin decreased the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes. This suggests that metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes.
Anatomic Variations of the Lateral Intercondylar Ridge
Authors: Tsukada Sachiyuki , Fujishiro Hitomi , Watanabe Kentaro , Nimura Akimoto , Mochizuki Tomoyuki , Mahakkanukrauh Pasuk , Yasuda Kazunori , Akita Keiichi 
Published: March 2014

Background: The lateral intercondylar ridge (LIR) has been recognized as an important landmark to create an appropriate femoral tunnel in single-bundle anterior cruciate ligament (ACL) reconstruction. However, because of variations in the distal part of the LIR or because the relationship between the LIR and the anterior margin of the ACL attachment has not been sufficiently clarified, the utility of the LIR for anatomic single- and double-bundle reconstruction remains controversial. Hypotheses: (1) There is a large degree of positional and dimensional variation in the LIR, specifically concerning the distal part. (2) There may be significant differences between sexes in the LIR. (3) The anterior margin of the ACL attachment may be located anterior to the distal part of the LIR. Study Design: Descriptive laboratory study. Methods: A total of 318 femora, which were collected with the donors’ demographic data, were examined to determine anatomic variations of the LIR. In addition, 20 cadaveric knees, in which the anterior margin was marked by radiopaque silicon markers, were examined with micro–computed tomography to evaluate the positional relationship between the LIR and the anterior margin of the ACL attachment. Results: Although the LIR was identified in 94.0% of the 318 femora, the distal half of the LIR was not visible in 18.4% of these femora. Moreover, the LIR was located in an extremely anterior part of the lateral condyle surface in 8.8% in comparison with the common location, and in an extremely posterior part in 8.5%. The length–height ratio (69.9% in men, 63.6% in women) and the length between the inlet of the notch roof and the proximal part of the LIR (19.9 mm in men, 17.9 mm in women) were significantly greater in males than in females ( P = .0028 and P < .0001, respectively). The anterior margin of the ACL attachment was commonly located anterior to the middle and distal part of the LIR, having the mean marker-ridge distance of 4.2 mm. Conclusion: There were large positional and dimensional variations in the LIR, specifically concerning the distal part. There are slight but significant differences between the male and female femora. The anterior margin of the ACL attachment is commonly located anterior to the middle and distal parts of the LIR. Clinical Relevance: Utility of the LIR as an osseous landmark for femoral tunnel creation is limited in anatomic reconstruction of the posterolateral bundle and anatomic single-bundle reconstruction.
Increasing Asian American participation in clinical trials by addressing community concerns
Authors: Ma Grace X , Seals Brenda , Tan Yin , Wang Sylvia Y , Lee Richard , Fang Carolyn Y 
Published: March 2014

Background Asian Americans are underrepresented in clinical trials, but little is known about the factors that contribute to clinical trial participation in this population. Purpose The purpose of this study was to identify knowledge, barriers, facilitators, and cultural influences on participating in clinical trials among three Asian American ethnic groups. Concurrently, we sought to identify mechanisms and messages to facilitate dissemination of information and to identify strategies to promote clinical trial participation in this population. Methods Eight focus groups were conducted (n = 103) with Chinese (four groups), Korean (two groups), and Vietnamese (two groups) Americans. Each group was conducted with a moderator and a translator using a standardized guide. Results Participants discuss the benefits of contributing to science, future generations, and their families by being in clinical trials. Some participants think clinical trials would give hope to those with terminal illnesses. A doctor’s recommendation, being sick, and needing more options for treatment are motivators for Asian Americans. Having some guarantee of treatment effectiveness and lack of side effects facilitates participation. Cultural or religious beliefs are not believed to prevent clinical trial participation. Limitations This qualitative, two-site study included three Asian American ethnic groups and is not meant to establish prevalence of beliefs. Conclusion Asian Americans need more information about clinical trials and their benefits to science and the larger community. Health-care providers can play pivotal roles in enhancing recruitment of Asian Americans. Basing recruitment goals on percentage representation in most US geographic areas does not provide sufficient numbers to allow for analysis of minorities like Asian American groups. The discovery of important group-specific harms and benefits depends on greater participation of racial/ethnic subgroups.
Predicting the size of pulmonary arteriovenous malformations on chest computed tomography: a role for transthoracic contrast echocardiography
Authors: Velthuis Sebastiaan , Buscarini Elisabetta , Mager Johannes J. , Vorselaars Veronique M.M. , van Gent Marco W.F. , Gazzaniga Pietro , Manfredi Guido , Danesino Cesare , Diederik Arjen L. , Vos Jan A. , Gandolfi Silvia , Snijder Repke J. , Westermann Cornelis J.J. , Post Martijn C. 
Published: March 2014

This study aimed to investigate whether pulmonary shunt grade on transthoracic contrast echocardiography (TTCE) predicts the size of pulmonary arteriovenous malformations (PAVMs) on chest computed tomography (CT) and subsequent feasibility for transcatheter embolotherapy.We prospectively included 772 persons with possible or definite hereditary haemorrhagic telangiectasia, who underwent both TTCE and chest CT for screening of PAVMs. A quantitative three-point grading scale was used to classify the pulmonary shunt size on TTCE (grade 1–3). Transcatheter embolotherapy was performed for PAVMs deemed large enough for endovascular closure on chest CT.TTCE documented pulmonary shunting in 510 (66.1%) patients. The positive predictive value of a pulmonary shunt grade 1, 2 and 3 on TTCE for presence of PAVMs on chest CT was 13.4%, 45.3% and 92.5%, respectively (p<0.001). None of the 201 persons with a pulmonary shunt grade 1 on TTCE had PAVMs on chest CT large enough for transcatheter embolotherapy, while 38 (25.3%) and 123 (77.4%) individuals with a pulmonary shunt grade 2 and 3 on TTCE, respectively, underwent endovascular closure of PAVMs.Pulmonary shunt grade on TTCE predicts the size of PAVMs on chest CT and their feasibility for subsequent transcatheter embolotherapy. Chest CT can be safely withheld from all persons with a pulmonary shunt grade 1 on TTCE, as any PAVM found in these subjects will be too small for transcatheter embolotherapy.
Prevalence and correlates of airflow obstruction in ∼317 000 never-smokers in China
Authors: Smith Margaret , Li Liming , Augustyn Mareli , Kurmi Om , Chen Junshi , Collins Rory , Guo Yu , Han Yabin , Qin Jingxin , Xu Guanqun , Wang Jian , Bian Zheng , Zhou Gang , Peto Richard , Chen Zhengming 
Published: March 2014

In China, the burden of chronic obstructive disease (COPD) is high in never-smokers but little is known about its causes in this group.We analysed data on 287 000 female and 30 000 male never-smokers aged 30–79 years from 10 regions in China, who participated in the China Kadoorie Biobank baseline survey (2004–2008). Prevalence of airflow obstruction (AFO) (pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and below the lower limit of normal (LLN)) was estimated, by age and region. Cross-sectional associations of AFO (FEV1/FVC <0.7), adjusted for confounding, were examined.AFO prevalence defined as FEV1/FVC <0.7 was 4.0% in females and 5.1% in males (mean ages 51 and 54 years, respectively). AFO prevalence defined as FEV1/FVC <LLN was 5.9% and 5.2%, respectively. In females, odds ratios of AFO were positively associated with lower household income (1.63, 95% CI 1.55–1.72 for lowestversushighest income groups), prior tuberculosis (2.36, 95% CI 2.06–2.71), less education (1.17, 95% CI 1.12–1.23 for no schoolingversuscollege education), rural region and lower body mass index. AFO was positively associated with cooking with coal but not with other sources of household air pollution. Associations were similar for males.AFO is prevalent in Chinese never-smokers, particularly among those with low socioeconomic status or prior tuberculosis, and in rural males.
Cyr61 Expression is associated with prognosis in patients with colorectal cancer
Authors: Jeong Dongjun , Heo Suhak , Sung Ahn Tae , Lee Sookyoung , Park Soyoung , Kim Hyungjoo , Park Doosan , Byung Bae Sang , Lee Sung Soo , Soo Lee Moon , Kim Chang-Jin , Jun Baek Moo 
Published: March 2014

Abstract

Background
Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up.

Methods
We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis.

Results
We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer.

Conclusions
Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers.
Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1
Authors: Wei Jinrong , Zhou Yong , Jiang Guo-Qin , Xiao Dong 
Published: March 2014

AbstractBackgroundClinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cell lines. In this study, we investigated the effects of ETS1 on adriamycin resistance in MCF-7/ADR cells.MethodssiRNAs against ETS1 or negative control siRNAs was transfected to MCF-7/ADR breast cancer cells. Reverse transcription-PCR and Western blotting were used to determine the mRNA and protein expression of ETS1 and MDR1. The cytotoxicity of adriamycin was assessed using the MTT assay. Drug efflux was investigated by flow cytometry using the Rhodamine 123 intracellular accumulation assay.ResultsETS1 mRNA and protein was significantly overexpressed in MCF-7/ADR cells, compared to MCF-7 cells. ETS1 siRNA successfully silenced ETS1 mRNA and protein expression. Silencing of ETS1 also significantly reduced the mRNA and protein expression levels of MDR1 (multidrug resistance 1; also known asABCB1, P-glycoprotein/P-gp), which is a major ATP-binding cassette (ABC) transporter linked to multi-drug resistance in cancer cells. Silencing of ETS1 significantly increased the sensitivity of MCF-7/ADR cells to adriamycin, compared to cells transfected with negative control siRNA. In addition, intracellular accumulation of Rhodamine 123 significantly increased in MCF-7/ADR cells transfected with ETS1 siRNA, indicating that silencing of ETS1 may reduce drug efflux.ConclusionsThis study demonstrates that drug resistance can be effectively reversed in adriamycin-resistant breast carcinoma cells through delivery of siRNAs targeting ETS1.
Facile synthesis and optical properties of polymer-laced ZnO-Au hybrid nanoparticles
Authors: Wang XianHong , Zhang XiaoYan , Cheng WenZheng , Shao HongQin , Liu Xiao , Li XueMei , Liu HongLing , Wu JunHua 
Published: March 2014

Abstract
Bi-phase dispersible ZnO-Au hybrid nanoparticles were synthesized via one-pot non-aqueous nanoemulsion using the triblock copolymer poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) as the surfactant. The characterization shows that the polymer-laced ZnO-Au nanoparticles are monosized and of high crystallinity and demonstrate excellent dispersibility and optical performance in both organic and aqueous medium, revealing the effects of quantum confinement and medium. The findings show two well-behaved absorption bands locating at approximately 360 nm from ZnO and between 520 and 550 nm from the surface plasmon resonance of the nanosized Au and multiple visible fingerprint photoluminescent emissions. Consequently, the wide optical absorbance and fluorescent activity in different solvents could be promising for biosensing, photocatalysis, photodegradation, and optoelectronic devices.