bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting HLA genotypes using unphased and flanking single-nucleotide polymorphisms in Han Chinese population
Authors: Hsieh Ai-Ru , Chang Su-Wei , Chen Pei-Lung , Chu Chen-Chung , Hsiao Ching-Lin , Yang Wei-Shiung , Chang Chien-Ching , Wu Jer-Yuarn , Chen Yuan-Tsong , Chang Tien-Chun , Fann Cathy SJ 
Published: January 2014

Abstract

Background
Genetic variation associated with human leukocyte antigen (HLA) genes has immunological functions and is associated with autoimmune diseases. To date, large-scale studies involving classical HLA genes have been limited by time-consuming and expensive HLA-typing technologies. To reduce these costs, single-nucleotide polymorphisms (SNPs) have been used to predict HLA-allele types. Although HLA allelic distributions differ among populations, most prediction model of HLA genes are based on Caucasian samples, with few reported studies involving non-Caucasians.

Results
Our sample consisted of 437 Han Chinese with Affymetrix 5.0 and Illumina 550 K SNPs, of whom 214 also had data on Affymetrix 6.0 SNPs. All individuals had HLA typings at a 4-digit resolution. Using these data, we have built prediction model of HLA genes that are specific for a Han Chinese population. To optimize our prediction model of HLA genes, we analyzed a number of critical parameters, including flanking-region size, genotyping platform, and imputation. Predictive accuracies generally increased both with sample size and SNP density.

Conclusions
SNP data from the HapMap Project are about five times more dense than commercially available genotype chip data. Using chips to genotype our samples, however, only reduced the accuracy of our HLA predictions by only ~3%, while saving a great deal of time and expense. We demonstrated that classical HLA alleles can be predicted from SNP genotype data with a high level of accuracy (80.37% (HLA-B) ~95.79% (HLA-DQB1)) in a Han Chinese population. This finding offers new opportunities for researchers in obtaining HLA genotypes via prediction using their already existing chip datasets. Since the genetic variation structure (e.g. SNP, HLA, Linkage disequilibrium) is different between Han Chinese and Caucasians, and has strong impact in building prediction models for HLA genes, our findings emphasize the importance of building ethnic-specific models when analyzing human populations.
Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens
Authors: Cai Haoyang , Kumar Nitin , Bagheri Homayoun C , von Mering Christian , Robinson Mark D , Baudis Michael 
Published: January 2014

AbstractBackgroundChromothripsis is a recently discovered phenomenon of genomic rearrangement, possibly arising during a single genome-shattering event. This could provide an alternative paradigm in cancer development, replacing the gradual accumulation of genomic changes with a “one-off” catastrophic event. However, the term has been used with varying operational definitions, with the minimal consensus being a large number of locally clustered copy number aberrations. The mechanisms underlying these chromothripsis-like patterns (CTLP) and their specific impact on tumorigenesis are still poorly understood.ResultsHere, we identified CTLP in 918 cancer samples, from a dataset of more than 22,000 oncogenomic arrays covering 132 cancer types. Fragmentation hotspots were found to be located on chromosome 8, 11, 12 and 17. Among the various cancer types, soft-tissue tumors exhibited particularly high CTLP frequencies. Genomic context analysis revealed that CTLP rearrangements frequently occurred in genomes that additionally harbored multiple copy number aberrations (CNAs). An investigation into the affected chromosomal regions showed a large proportion of arm-level pulverization and telomere related events, which would be compatible to a number of underlying mechanisms. We also report evidence that these genomic events may be correlated with patient age, stage and survival rate.ConclusionsThrough a large-scale analysis of oncogenomic array data sets, this study characterized features associated with genomic aberrations patterns, compatible to the spectrum of “chromothripsis”-definitions as previously used. While quantifying clustered genomic copy number aberrations in cancer samples, our data indicates an underlying biological heterogeneity behind these chromothripsis-like patterns, beyond a well defined “chromthripsis” phenomenon.
Evaluation of chromID strepto B as a screening media for Streptococcus agalactiae
Authors: Morita Toyohisa , Feng Dongyun , Kamio Yoko , Kanno Isao , Somaya Teruo , Imai Kazuhito , Inoue Misaki , Fujiwara Mutsunori , Miyauchi Akihito 
Published: January 2014

Abstract

Background

Streptococcus agalactiae (Group B Streptococcus, GBS), a leading cause of sepsis and meningitis in infants, can be transmitted vertically from mother to infant during passage through the birth canal. Detection of GBS colonization in perinatal women is a major strategy for the prevention of postpartum neonatal disease. The U.S. Centers for Disease Control and Prevention recommends that all women undergo vaginal-rectal screening for GBS colonization at 35-37 weeks of gestation. ChromID Strepto B (STRB) is a chromogenic GBS screening media on which GBS colonies appear pink or red, while other bacteria are either inhibited or form colonies in other colors. In this study, we compared STRB with a conventional GBS detection method using 5% sheep blood agar (BA) followed by a selective enrichment broth.

Methods
Anovaginal swabs were collected from 1425 women during weeks 35 to 37 of their pregnancies. The swabs were used to inoculate both STRB and BA plates after enrichment with selective Todd Hewitt Broth (THB). A GBS latex agglutination test was used to confirm the identity of isolates from each plate.

Results
GBS was recovered from 319 (22.4%) samples with one or both media: 318 on STRB compared to 299 using BA. One false negative was observed on STRB, and 20 false negatives were observed on BA. In addition, non-hemolytic GBS was recovered from 19 (6.0%) samples using STRB.

Conclusions
STRB offers effectiveness and convenience over BA for GBS screening in clinical laboratories. STRB produces fewer false negatives, has a higher detection rate and uses a simple color screen that is ideal for technician-level applications. We recommend STRB as the media of choice for GBS screening.
The Nightingale study: rationale, study design and baseline characteristics of a prospective cohort study on shift work and breast cancer risk among nurses
Authors: Pijpe Anouk , Slottje Pauline , van Pelt Cres , Stehmann Floor , Kromhout Hans , van Leeuwen Flora E , Vermeulen Roel CH , Rookus Matti A 
Published: January 2014

AbstractBackgroundEvidence for the carcinogenicity of shift work in humans is limited because of significant heterogeneity of the results, thus more in-depth research in needed. The Nightingale Study is a nationwide prospective cohort study on occupational exposures and risks of chronic diseases among female nurses and focuses on the potential association between shift work and risk of breast cancer. The study design, methods, and baseline characteristics of the cohort are described.Methods/DesignThe source population for the cohort comprised 18 to 65 year old women who were registered as having completed training to be a nurse in the nationwide register for healthcare professionals in the Netherlands. Eligible women were invited to complete a web-based questionnaire including full job history, a detailed section on all domains of shift work (shift system, cumulative exposure, and shift intensity) and potential confounding factors, and an informed consent form for linkage with national (disease) registries. Women were also asked to donate toenail clippings as a source of DNA for genetic analyses. Between October 6, 2011 and February 1, 2012, 31% of the 192,931 women who were invited to participate completed the questionnaire, yielding a sample size of 59,947 cohort members. The mean age of the participants was 46.9 year (standard deviation 11.0 years). Toenail clippings were provided by 23,439 participants (39%).DiscussionResults from the Nightingale Study will contribute to the scientific evidence of potential shift work-related health risks among nurses and will help develop preventive measures and policy aimed at reducing these risks.
Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines
Authors: Cui Hai , Cheng Ying , Piao Su-Zhou , Xu Yun-Jie , Sun Hong-Hua , Cui Xian , Li Xiang-Zi , Zhang Song-Nan , Piao Long-Zhen , Jin Yong-Min , Lin Zhen-hua , Shen Xiong-Hu 
Published: January 2014

Abstract

Introduction
Although advanced gastric cancer has many limitations and response rate is marginal in chemotherapy. Overexpression of human epidermal growth factor receptor 2(HER-2/neu) gene and its protein are associated with increased cell division and a high rate of tumor growth and have been reported in several malignancies. Especially, approximately 30% of breast cancer patients have overexpression of HER-2/neu protein and the overexpression metastasize faster, induces resistance of the chemotherapy and down-regulate function of estrogen receptor. Recombinant humanized anti-HER2 antibody (Herceptin) inhibits proliferation of HER-2/neu overexpressing tumor cells and the use of that in combination in metastatic breast cancer have increased cytotoxicity of chemotherapeutic agents.

Methods
We evaluated the expression of HER-2/neu protein in gastric cell lines by FACS and then comparing the cytotoxicity in chemotherapeutics (doxorubicin, cisplatin, paclitaxel, 5-FU) alone and in combination with Herceptin according to the expression of HER-2/neu protein by MTT assay.

Results
1. NCI-N87 (88%) gastric cancer cell line and SK-BR-3 (89%) breast cancer cell line with strong positivity of HER-2/neu expression. YBC-2 (55%) and YBC-3 (48%) gastric cancer cell line with intermediated, weak positivity respectively. Negative control U-87 MG (6%) brain cancer cell line were showed low expression of HER-2/neu. 2. Cell growth was dose-dependently inhibited in HER-2/neu positive, control cell line SK-BR-3 by Herceptin treatment but not observed in HER-2/neu negative control cell line U-87 MG. Effective growth inhibition was not observed in gastric cancer cell lines with single treatment of Herceptin, all cell lines observed the dose-dependent growth inhibition to chemotherapeutic agents (doxorubicin, cisplatin, paclitaxel and 5-FU). 3. Combination of Herceptin with doxorubicin observed synergistic effects in all cancer cell lines except YBC-3, combination of Herceptin with cisplatin observed NCI-N87 and SK-BR-3 and combination of Herceptin with paclitaxel observed synergistic effects in YBC-2. Combination of Herceptin with 5-FU observed antagonistic effects in all cancer cell lines.

Conclusions
According to HER-2/neu expression level, effect of anti-cancer agents was observed differently in combination of Herceptin with chemotherapeutic agents. This suggests that HER-2/neu expression level can be applied standard of combination drug selection in combination of Herceptin With chemotherapeutic agents in gastric cancer.
Effects of a standard provision versus an autonomy supportive exercise referral programme on physical activity, quality of life and well-being indicators: a cluster randomised controlled trial
Authors: Duda Joan L , Williams Geoffrey C , Ntoumanis Nikos , Daley Amanda , Eves Frank F , Mutrie Nanette , Rouse Peter C , Lodhia Rekha , Blamey Ruth V , Jolly Kate 
Published: January 2014

Abstract

Background
The National Institute for Health and Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the feasibility and impact of a Self Determination Theory-based (SDT) exercise referral consultation.

Methods
An exploratory cluster randomised controlled trial comparing standard provision exercise referral with an exercise referral intervention grounded in Self Determination Theory. Individuals (N = 347) referred to an exercise referral scheme were recruited into the trial from 13 centres.
Outcomes and processes of change measured at baseline, 3 and 6-months: Minutes of self-reported moderate or vigorous physical activity (PA) per week (primary outcome), health status, positive and negative indicators of emotional well-being, anxiety, depression, quality of life (QOL), vitality, and perceptions of autonomy support from the advisor, need satisfaction (3 and 6 months only), intentions to be active, and motivational regulations for exercise.
Blood pressure and weight were assessed at baseline and 6 months.

Results
Perceptions of the autonomy support provided by the health and fitness advisor (HFA) did not differ by arm. Between group changes over the 6-months revealed significant differences for reported anxiety only. Within arm contrasts revealed significant improvements in anxiety and most of the Dartmouth CO-OP domains in the SDT arm at 6 months, which were not seen in the standard exercise referral group. A process model depicting hypothesized relationships between advisor autonomy support, need satisfaction and more autonomous motivation, enhanced well being and PA engagement at follow up was supported.

Conclusions
Significant gains in physical activity and improvements in quality of life and well-being outcomes emerged in both the standard provision exercise referral and the SDT-based intervention at programme end. At 6-months, observed between arm and within intervention arm differences for indicators of emotional health, and the results of the process model, were in line with SDT. The challenges in optimising recruitment and implementation of SDT-based training in the context of health and leisure services are discussed.

Trial registration
The trial is registered as Current Controlled trials ISRCTN07682833.
RNF14 is a regulator of mitochondrial and immune function in muscle
Authors: Ingham Aaron B , Osborne Simone A , Menzies Moira , Briscoe Suzie , Chen Wei , Kongsuwan Kritaya , Reverter Antonio , Jeanes Angela , Dalrymple Brian P , Wijffels Gene , Seymour Robert , Hudson Nicholas J 
Published: January 2014

Abstract

Background
Muscle development and remodelling, mitochondrial physiology and inflammation are thought to be inter-related and to have implications for metabolism in both health and disease. However, our understanding of their molecular control is incomplete.

Results
In this study we have confirmed that the ring finger 14 protein (RNF14), a poorly understood transcriptional regulator, influences the expression of both mitochondrial and immune-related genes. The prediction was based on a combination of network connectivity and differential connectivity in cattle (a non-model organism) and mice data sets, with a focus on skeletal muscle. They assigned similar probability to mammalian RNF14 playing a regulatory role in mitochondrial and immune gene expression. To try and resolve this apparent ambiguity we performed a genome-wide microarray expression analysis on mouse C2C12 myoblasts transiently transfected with two Rnf14 transcript variants that encode 2 naturally occurring but different RNF14 protein isoforms. The effect of both constructs was significantly different to the control samples (untransfected cells and cells transfected with an empty vector). Cluster analyses revealed that transfection with the two Rnf14 constructs yielded discrete expression signatures from each other, but in both cases a substantial set of genes annotated as encoding proteins related to immune function were perturbed. These included cytokines and interferon regulatory factors. Additionally, transfection of the longer transcript variant 1 coordinately increased the expression of 12 (of the total 13) mitochondrial proteins encoded by the mitochondrial genome, 3 of which were significant in isolated pair-wise comparisons (Mt-coxII, Mt-nd2 and mt-nd4l). This apparent additional mitochondrial function may be attributable to the RWD protein domain that is present only in the longer RNF14 isoform.

Conclusions
RNF14 influences the expression of both mitochondrial and immune related genes in a skeletal muscle context, and has likely implications for the inter-relationship between bioenergetic status and inflammation.
A case of metastatic cancer with markedly elevated PSA level that was not detected by repeat prostate biopsy
Authors: Iwamura Hiromichi , Hatakeyama Shingo , Tanaka Yoshimi , Tanaka Toshikazu , Tokui Noriko , Yamamoto Hayato , Imai Atsushi , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Yoshikawa Kazuaki , Ohyama Chikara 
Published: January 2014

Abstract

Background
Prostate-specific antigen (PSA) is a widely used specific tumor marker for prostate cancer. We experienced a case of metastatic prostate cancer that was difficult to detect by repeat prostate biopsy despite a markedly elevated serum PSA level.

Case presentation
A 64-year-old man was referred to our hospital with lumbar back pain and an elevated serum PSA level of 2036 ng/mL. Computed tomography, bone scintigraphy, and magnetic resonance imaging showed systemic lymph node and osteoblastic bone metastases. Digital rectal examination revealed a small, soft prostate without nodules. Ten-core transrectal prostate biopsy yielded negative results. Androgen deprivation therapy (ADT) was started because of the patient’s severe symptoms. Twelve-core repeat transrectal prostate biopsy performed 2 months later, and transurethral resection biopsy performed 5 months later, both yielded negative results. The patient refused further cancer screening because ADT effectively relieved his symptoms. His PSA level initially decreased to 4.8 ng/mL, but he developed castration-resistant prostate cancer 7 months after starting ADT. He died 21 months after the initial prostate biopsy from disseminated intravascular coagulation.

Conclusion
CUP remains a considerable challenge in clinical oncology. Biopsies of metastatic lesions and multimodal approaches were helpful in this case.
Effect of garlic on lipid profile and expression of LXR alpha in intestine and liver of hypercholesterolemic mice
Authors: Mohammadi Abbas , Oshaghi Ebrahim Abbasi 
Published: January 2014

Abstract
Background
Garlic is one of the medicinal plants which has showed beneficial effects on atherosclerosis risk factors. The liver X receptor α (LXRα) is an important regulator of cholesterol, triglyceride and glucose homeostasis that belongs to the nuclear receptor superfamily. In this study we investigated the effect of garlic on lipid profile, glucose as well as LXRα expression in intestine and liver of mice.

Methods
Forty male N-Mary mice were randomly divided into 3 groups (n = 8): group1 received chow + 2% cholesterol + 0.5% cholic acid, group 2: chow + 4% (w/w) garlic extract + 2% cholesterol + 0.5% cholic acid, and group 3: chow only. After one month of treatment, mice were anesthetized, blood was collected from their heart, and the first 10 cm of the small intestine and liver were removed. Glucose was measured by a glucometer; other biochemical factors were measured by enzymatic methods. LXR expression was checked by RT-PCR and western blotting.

Results
Compared with hypercholesterolemic mice, treatment with garlic extract significantly decreased total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, very low density lipoprotein-cholesterol (VLDL-C), atherogenic index, alanine aminotranferease (ALT) and aspartate aminotransferase (AST) (all of them P < 0.05). Change in HDL-C levels was not significant in garlic-extract treated animals compared with hypercholesterolemic group. LXR protein and mRNA in the intestine were increased in garlic-extract treated group compared with chow group (P < 0.05), while in the liver, only mRNA of LXR was increased in hypercholesterolemic control mice (P < 0.05).

Conclusions
The present study demonstrated that garlic extract reduced LXRα expression in the liver and increased its expression in the intestine. These effects probably have an important role in reducing serum triglyceride and cholesterol.
DMARD non-use in low-income, elderly rheumatoid arthritis patients: results of 86 structured interviews
Authors: Brown Erika M , Garneau Katie L , Tsao Hsun , Solomon Daniel H 
Published: January 2014

Abstract
Introduction
Disease-modifying antirheumatic drugs (DMARDs) have become the treatment standard for patients with rheumatoid arthritis (RA). Although several general-population studies document that a large population of patients diagnosed with RA do not use DMARDs, little is known about this group. We explored the characteristics, experiences, and knowledge of a low-income, elderly RA population not currently using DMARDs, or receiving care from a rheumatologist.

Methods
We administered structured telephone interviews to participants enrolled in a large pharmacy benefits program for the elderly who had two diagnoses of RA ≥7 days apart and no DMARD prescriptions or rheumatologist visits in the prior year. The interview contained questions concerning each participant’s sociodemographic information, disease activity, DMARD experiences, and the Modified Health Assessment Questionnaire (MHAQ). We described responses and compared prior users with never users.

Results
A total of 86 people completed the interview. The mean age was 80 years and 89% were female. On average, disease duration was 20 years. Mean MHAQ score was 0.55 (SD = 0.55). Of 86 participants, 19 had previously used DMARDs, 10 of whom discontinued them because of side effects or safety concerns. Among 67 never-users, 35 (52.2%) reported that their physicians had never offered them DMARDs, 13 (19.4%) described fear of side effects, and 49 (73.1%) knew nothing about them. Prior-users reported experiencing more-severe RA symptoms than never-users.

Conclusions
We found that side effects or safety concerns were the primary cause for DMARD cessation among prior-users. Among never-users, most reported never discussing or being offered DMARDs, suggesting that an educational gap may deter patients with RA from using them.