bluuebunny/crossref_metadata_2025_split huggingface dataset:
A three-stage approach for genome-wide association studies with family data for quantitative traits
Authors: Chen Ming-Huei , Larson Martin G , Hsu Yi-Hsiang , Peloso Gina M , Guo Chao-Yu , Fox Caroline S , Atwood Larry D , Yang Qiong 
Published: May 2010

Abstract

Background
Genome-wide association (GWA) studies that use population-based association approaches may identify spurious associations in the presence of population admixture. In this paper, we propose a novel three-stage approach that is computationally efficient and robust to population admixture and more powerful than the family-based association test (FBAT) for GWA studies with family data.
We propose a three-stage approach for GWA studies with family data. The first stage is to perform linear regression ignoring phenotypic correlations among family members. SNPs with a first stage p-value below a liberal cut-off (e.g. 0.1) are then analyzed in the second stage that employs a linear mixed effects (LME) model that accounts for within family correlations. Next, SNPs that reach genome-wide significance (e.g. 10-6 for 34,625 genotyped SNPs in this paper) are analyzed in the third stage using FBAT, with correction of multiple testing only for SNPs that enter the third stage. Simulations are performed to evaluate type I error and power of the proposed method compared to LME adjusting for 10 principal components (PC) of the genotype data. We also apply the three-stage approach to the GWA analyses of uric acid in Framingham Heart Study's SNP Health Association Resource (SHARe) project.

Results
Our simulations show that whether or not population admixture is present, the three-stage approach has no inflated type I error. In terms of power, using LME adjusting PC is only slightly more powerful than the three-stage approach. When applied to the GWA analyses of uric acid in the SHARe project of FHS, the three-stage approach successfully identified and confirmed three SNPs previously reported as genome-wide significant signals.

Conclusions
For GWA analyses of quantitative traits with family data, our three-stage approach provides another appealing solution to population admixture, in addition to LME adjusting for genetic PC.
Identification of Mycobacterium tuberculosis clinical isolates in Bangladesh by a species distinguishable multiplex PCR
Authors: Nakajima Chie , Rahim Zeaur , Fukushima Yukari , Sugawara Isamu , van der Zanden Adri GM , Tamaru Aki , Suzuki Yasuhiko 
Published: May 2010

Abstract

Background
Species identification of isolates belonging to the Mycobacterium tuberculosis complex (MTC) seems to be important for the appropriate treatment of patients, since M. bovis is naturally resistant to a first line anti-tuberculosis (TB) drug, pyrazinamide, while most of the other MTC members are susceptible to this antimicrobial agent. A simple and low-cost differentiation method was needed in higher TB burden countries, such as Bangladesh, where the prevalence of M. bovis among people or cattle has not been investigated.

Methods
Genetic regions cfp32, RD9 and RD12 were chosen as targets for a species distinguishable multiplex PCR and the system was evaluated with twenty reference strains of mycobacterial species including non-tubercular mycobacteria (NTM). A total of 350 clinical MTC isolates obtained in Bangladesh were then analyzed with this multiplex PCR.

Results
All of the MTC reference strains gave expected banding patterns and no non-specific amplifications were observed in the NTM strains. Out of 350 clinical isolates examined by this method, 347 (99.1%) were positive for all of the cfp32, RD9 and RD12 and determined as M. tuberculosis. Two isolates lacked cfp32 PCR product and one lacked RD12, however, those three samples were further examined and identified as M. tuberculosis by the sequence analyses of hsp65 and gyrB.

Conclusions
The MTC-discrimination multiplex PCR (MTCD-MPCR) developed in this study showed high specificity and was thought to be very useful as a routine test because of its simplicity. In the current survey, all the 350 MTC isolates obtained from Bangladesh TB patients were determined as M. tuberculosis and no other MTC were detected. This result suggested the general TB treatment regimen including pyrazinamide to be the first choice in Bangladesh.
Common polymorphisms of calpain-10 and the risk of Type 2 Diabetes in a Tunisian Arab population: a case-control study
Authors: Ezzidi Intissar , Turki Amira , Messaoudi Safia , Chaieb Molka , Kacem Maha , Al-Khateeb Ghada M , Mahjoub Touhami , Almawi Wassim Y , Mtiraoui Nabil 
Published: May 2010

Abstract

Background
Genetic variations in the calpain-10 gene (CAPN10), in particular the at-risk diplotype (112/121), were previously implicated with increased risk of type 2 diabetes (T2D).

Methods
We examined the association of CAPN10 UCSNP-43 (rs3792267), UCSNP-19 (rs3842570), and UCSNP-63 (rs5030952) SNPs with T2D in 917 Tunisian T2D patients and 748 non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.

Results
Enrichment of UCSNP-19 2R (minor) allele and 2R/2R genotype was found in T2D patients; the allele and genotype distribution of UCSNP-43 and UCSNP-63 alleles and genotypes were not significantly different between patient groups and non-diabetic control subjects. Regression analysis demonstrated progressive increases in T2D risk in 3R/2R [OR (95% CI) = 1.35 (1.08 - 1.68)] and 2R/2R [OR (95% CI) = 1.61 (1.20 - 2.18)] genotypes. Of the six haplotypes detected, enrichment of haplotype 111 (UCSNP-43/UCSNP-19/UCSNP-63) was seen in patients (Pc = 0.034); the distribution of the other haplotypes was comparable between patients and control subjects; neither haplotype 211 nor haplotype 212 was observed. Furthermore, the frequency of all CAPN10 diplotypes identified, including the "high-risk diplotype (112/121) reported for Mexican-Americans and Northern Europeans, were comparable between patients and controls.

Conclusions

CAPN10 UCSNP-19 variant, and the 111 haplotype contribute to the risk of T2D in Tunisian subjects; no significant associations between CAPN10 diplotypes and T2D were demonstrated for Tunisians.
Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study
Authors: Veronesi Andrea , Miolo GianMaria , Magri Maria D , Crivellari Diana , Scalone Simona , Bidoli Ettore , Lombardi Davide 
Published: May 2010

Abstract

Background
A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients.

Methods
From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients.

Results
Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients.

Conclusions
This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far.
Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin
Authors: Stubbert Lawton J , Smith Jennifer M , McKay Bruce C 
Published: May 2010

Abstract

Background
One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity.

Methods
RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined.

Results
These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines.

Conclusion
The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic.
Comparison of group counseling with individual counseling in the comprehension of informed consent: a randomized controlled trial
Authors: Sarkar Rajiv , Sowmyanarayanan Thuppal V , Samuel Prasanna , Singh Azara S , Bose Anuradha , Muliyil Jayaprakash , Kang Gagandeep 
Published: May 2010

Abstract

Background
Studies on different methods to supplement the traditional informed consent process have generated conflicting results. This study was designed to evaluate whether participants who received group counseling prior to administration of informed consent understood the key components of the study and the consent better than those who received individual counseling, based on the hypothesis that group counseling would foster discussion among potential participants and enhance their understanding of the informed consent.

Methods
Parents of children participating in a trial of nutritional supplementation were randomized to receive either group counseling or individual counseling prior to administration of the informed consent. To assess the participant's comprehension, a structured questionnaire was administered approximately 48-72 hours afterwards by interviewers who were blinded to the allocation group of the respondents.

Results
A total of 128 parents were recruited and follow up was established with 118 (90.2%) for the study. All respondents were aware of their child's participation in a research study and the details of sample collection. However, their understanding of study purpose, randomization and withdrawal was poor. There was no difference in comprehension of key elements of the informed consent between the intervention and control arm.

Conclusions
The results suggest that the group counseling might not influence the overall comprehension of the informed consent process. Further research is required to devise better ways of improving participants' understanding of randomization in clinical trials.

Trial Registration
Clinical Trial Registry - India (CTRI): CTRI/2009/091/000612
The associated factors to endometrial cavity fluid and the relevant impact on the IVF-ET outcome
Authors: He Rong-Huan , Gao Hui-Juan , Li Ya-Qiong , Zhu Xiao-Ming 
Published: May 2010

Abstract

Background
Endometrial cavity fluid (ECF) is a fluid accumulation within the endometrial cavity. The significance of ECF remains unclear during the program of in vitro fertilization-embryo transfer (IVF-ET). The aim of the present study was to investigate the associated factors to ECF, visualized through ultrasound at the day of oocyte retrieval, and the relevant impact on the outcome of IVF-ET.

Methods
From the clinical data of 1557 infertility patients for IVF-ET program, 46 ECF patients were retrospectively selected as the ECF group; and another 134 patients with a bilateral salpingectomy and without ECF, selected as the control group. The demographics and the outcome of IVF-ET were compared between the two groups.

Results
The incidence of ECF was 2.95% (46/1557). Over half (28/46, 60.87%) of ECF patients had tubal infertility. Only 12 Of 46 ECF patients (26.09%) had visible hydrosalpinx on ultrasonography before ovarian stimulation. The cycle cancellation rate (4/46, 8.69%) of ECF group was not significantly higher than that of the control group (6/134, 4.48%; P > 0.05). Reasons for cycle cancellation in both groups were all the high risk of ovarian hyperstimulation syndrome (OHSS). No significant difference was found in clinical pregnancy rate between the patients with their ECF <3.5 mm in the anterior-posterior diameter (APD) and the control group (35.48% versus 30.47%; P > 0.05). No clinical pregnancy was found among those patients with their ECF equal or higher 3.5 mm in APD.

Conclusions
It was tubal infertility, not hydrosalpinx, which was related to the development of ECF. Excessive ECF (equal or higher 3.5 mm in APD) at the day of oocyte retrieval would have a negative impact on the outcome of IVF-ET.
Rapid effects of progesterone on ciliary beat frequency in the mouse fallopian tube
Authors: Bylander Anna , Nutu Magdalena , Wellander Rikard , Goksör Mattias , Billig Håkan , Larsson DG Joakim 
Published: May 2010

Abstract

Background
The physiological regulation of ciliary beat frequency (CBF) within the fallopian tube is important for controlling the transport of gametes and the fertilized ovum. Progesterone influences gamete transport in the fallopian tube of several mammalian species. In fallopian tubes isolated from cows, treatment with 20 micromolar progesterone caused a rapid reduction of the tubal CBF. The aims of this study were to establish methodology for studying fallopian tube CBF in the mouse, as it is an important model species, and to investigate if progesterone rapidly affects the CBF of mice at nM concentrations.

Methods
A method to assess tubal CBF of mice was developed. Fallopian tubes were dissected and the tissue was cut in small pieces. Tissue samples with moving cilia were located under an inverted bright field microscope and held still against the bottom of a petri dish by a motorized needle system. Images were acquired over 90 minutes at 35 degrees C with a high-speed camera and used for assessing changes in the CBF in response to the addition of hormone.

Results
The baseline CBF of the mouse fallopian tube was 23.3 +/- 3.8 Hz. The CBF was stable over at least 90 minutes allowing establishment of a baseline frequency, addition of hormone and subsequent recordings. Progesterone at concentrations of 20 micromolar and 100 nM significantly reduced the CBF by 10% and 15% respectively after 30 minutes compared with controls.

Conclusions
The present study demonstrates that the mouse, despite its small size, is a useful model for studying the fallopian tube CBF ex vivo. The rapid reduction in CBF by 100 nM progesterone suggests that gamete transport in the fallopian tube could be mediated by progesterone via a non-genomic receptor mechanism.
Testing bias in clinical databases: methodological considerations
Authors: Velthove Karin J , Leufkens Hubert GM , Souverein Patrick C , Schweizer René C , van Solinge Wouter W 
Published: May 2010

Abstract
Background
Laboratory testing in clinical practice is never a random process. In this study we evaluated testing bias for neutrophil counts in clinical practice by using results from requested and non-requested hematological blood tests.

Methods
This study was conducted using data from the Utrecht Patient Oriented Database. This clinical database is unique, as it contains physician requested data, but also data that are not requested by the physician, but measured as result of requesting other hematological parameters. We identified adult patients, hospitalized in 2005 with at least two blood tests during admission, where requests for general blood profiles and specifically for neutrophil counts were contrasted in scenario analyses. Possible effect modifiers were diagnosis and glucocorticoid use.

Results
A total of 567 patients with requested neutrophil counts and 1,439 patients with non-requested neutrophil counts were analyzed. The absolute neutrophil count at admission differed with a mean of 7.4 × 109/l for requested counts and 8.3 × 109/l for non-requested counts (p-value < 0.001). This difference could be explained for 83.2% by the occurrence of cardiovascular disease as underlying disease and for 4.5% by glucocorticoid use.

Conclusion
Requests for neutrophil counts in clinical databases are associated with underlying disease and with cardiovascular disease in particular. The results from our study show the importance of evaluating testing bias in epidemiological studies obtaining data from clinical databases.
Intensity modulated radiotherapy with concurrent chemotherapy for larynx preservation of advanced resectable hypopharyngeal cancer
Authors: Huang Wen-Yen , Jen Yee-Min , Chen Chang-Ming , Su Yu-Fu , Lin Chun-Shu , Lin Yaoh-Shiang , Chang Ying-Nan , Chao Hsing-Lung , Lin Kuen-Tze , Chang Li-Ping 
Published: May 2010

Abstract

Background
To analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy, and compare the results with patients treated with primary surgery.

Methods
Between January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT) using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method.

Results
The median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788). The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2) and pharyngitis (≥ grade 3) were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival.

Conclusions
IMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential.
Sequence embedding for fast construction of guide trees for multiple sequence alignment
Authors: Blackshields Gordon , Sievers Fabian , Shi Weifeng , Wilm Andreas , Higgins Desmond G 
Published: May 2010

Abstract

Background
The most widely used multiple sequence alignment methods require sequences to be clustered as an initial step. Most sequence clustering methods require a full distance matrix to be computed between all pairs of sequences. This requires memory and time proportional to N
2 for N sequences. When N grows larger than 10,000 or so, this becomes increasingly prohibitive and can form a significant barrier to carrying out very large multiple alignments.

Results
In this paper, we have tested variations on a class of embedding methods that have been designed for clustering large numbers of complex objects where the individual distance calculations are expensive. These methods involve embedding the sequences in a space where the similarities within a set of sequences can be closely approximated without having to compute all pair-wise distances.

Conclusions
We show how this approach greatly reduces computation time and memory requirements for clustering large numbers of sequences and demonstrate the quality of the clusterings by benchmarking them as guide trees for multiple alignment. Source code is available for download from http://www.clustal.org/mbed.tgz.
Up-regulation of fas reverses cisplatin resistance of human small cell lung cancer cells
Authors: Wu Wei , Wang Hai-dong , Guo Wei , Yang Kang , Zhao Yun-ping , Jiang Yao-guang , He Ping 
Published: May 2010

AbstractBackground/AimFas/FasL system is a major regulator of apoptosis. The mechanisms by which Fas mediates cisplatin resistance remain unclear. The aim of this study is to explore the effect of Fas over-expression on cisplatin resistance of small cell lung cancer cells and its possible mechanisms.Materials and methodsFas was over-expressed in H446/CDDP cells by infection with the adenoviruses containing Fas. Sensitivity of Fas-overexpressed H446/CDDP cells to cisplatin was evaluated using MTT assay. Expressions of Fas, GST-π and ERCC1 were detected by RT-PCR and Western blot analysis. Apoptosis rate was examined by FACS.ResultsOver-expression of Fas in H446/CDDP cells significantly decreased the expressions of GST-π and ERCC1 at mRNA and protein levels, and increased the cell apoptosis. Furthermore, up-regulation of Fas significantly decreased the tolerance of H446/CDDP cells to cisplatin.ConclusionOver-expression of Fas reverses drug resistance of H446/CDDP cells, possibly due to the increased cell sensitivity to apoptosis and the decreased expressions of GST-π and ERCC1.