bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACPA: automated cluster plot analysis of genotype data
Authors: Schillert Arne , Schwarz Daniel F , Vens Maren , Szymczak Silke , König Inke R , Ziegler Andreas 
Published: December 2009

Abstract
Genome-wide association studies have become standard in genetic epidemiology. Analyzing hundreds of thousands of markers simultaneously imposes some challenges for statisticians. One issue is the problem of multiplicity, which has been compared with the search for the needle in a haystack. To reduce the number of false-positive findings, a number of quality filters such as exclusion of single-nucleotide polymorphisms (SNPs) with a high missing fraction are employed. Another filter is exclusion of SNPs for which the calling algorithm had difficulties in assigning the genotypes. The only way to do this is the visual inspection of the cluster plots, also termed signal intensity plots, but this approach is often neglected. We developed an algorithm ACPA (automated cluster plot analysis), which performs this task automatically for autosomal SNPs. It is based on counting samples that lie too close to the cluster of a different genotype; SNPs are excluded when a certain threshold is exceeded. We evaluated ACPA using 1,000 randomly selected quality controlled SNPs from the Framingham Heart Study data that were provided for the Genetic Analysis Workshop 16. We compared the decision of ACPA with the decision made by two independent readers. We achieved a sensitivity of 88% (95% CI: 81%-93%) and a specificity of 86% (95% CI: 83%-89%). In a screening setting in which one aims at not losing any good SNP, we achieved 99% (95% CI: 98%-100%) specificity and still detected every second low-quality SNP.
Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis candidate genes
Authors: Huang Chien-Hsun , Cong Lei , Xie Jun , Qiao Bo , Lo Shaw-Hwa , Zheng Tian 
Published: December 2009

Abstract
Rheumatoid arthritis (RA, MIM 180300) is a chronic and complex autoimmune disease. Using the North American Rheumatoid Arthritis Consortium (NARAC) data set provided in Genetic Analysis Workshop 16 (GAW16), we used the genotype-trait distortion (GTD) scores and proposed analysis procedures to capture the gene-gene interaction effects of multiple susceptibility gene regions on RA. In this paper, we focused on 27 RA candidate gene regions (531 SNPs) based on a literature search. Statistical significance was evaluated using 1000 permutations. HLADRB1 was found to have strong marginal association with RA. We identified 14 significant interactions (p < 0.01), which were aggregated into an association network among 12 selected candidate genes PADI4, FCGR3, TNFRSF1B, ITGAV, BTLA, SLC22A4, IL3, VEGF, TNF, NFKBIL1, TRAF1-C5, and MIF. Based on our and other contributors' findings during the GAW16 conference, we further studied 24 candidate regions with 336 SNPs. We found 23 significant interactions (p-value < 0.01), nine interactions in addition to our initial findings, and the association network was extended to include candidate genes HLA-A, HLA-B, HLA-C, CTLA4, and IL6. As we will discuss in this paper, the reported possible interactions between genes may suggest potential biological activities of RA.
Genome-wide association study of rheumatoid arthritis by a score test based on wavelet transformation
Authors: Jiang Renfang , Dong Jianping , Dai Yilin 
Published: December 2009

Abstract

Background
We have conducted a genome-wide association study on the Genetic Analysis Workshop (GAW) 16 rheumatoid arthritis data using a multilocus score test based on wavelet transform proposed recently by the authors. The wavelet-based test automatically adjusts for the amount of noise suppressed from the data. The power of the test is also increased by using the genetic information contained in the spatial ordering of single-nucleotide polymorphisms on a chromosome.

Results
After adjusting for the effect of population stratification, the test identified some previously discovered rheumatoid arthritis susceptibility loci (HLA-DRB1 and rs3761847) as well as some loci (rs2076530 and rs3130340) known to have association with sarcoidosis and bone mineral density. It was previously reported that patients with rheumatoid arthritis have elevated prevalence of sarcoidosis and have reduced bone mass.

Conclusion
This new test provides a useful tool in genome-wide association studies.
A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival
Authors: Moulos Panagiotis , Papadodima Olga , Chatziioannou Aristotelis , Loutrari Heleni , Roussos Charis , Kolisis Fragiskos N 
Published: December 2009

Abstract

Background
Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level.

Methods
To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h). Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562). PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects.

Results
In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation) and NOD1 (down-regulation) indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar expression profile. Promoter analysis in a representative cluster revealed shared putative cis-elements suggesting a common regulatory transcription mechanism.

Conclusions
Present results provide novel evidence on the molecular basis of tumor growth inhibition mediated by mastic oil and set a rational basis for application of genomics and bioinformatic methodologies in the screening of natural compounds with potential cancer chemopreventive activities.
Mucosa associated lymphoid tissue lymphoma of the colon: a case report
Authors: Gezen Cem , Kement Metin , Oncel Mustafa , Tuncay Erhan , Sahlepci Taflan , Alkan Serdar 
Published: December 2009

Abstract
A 65-year-old man had suffered from rectal bleeding during defecation for a few weeks, admitted to our department. Laboratory findings were normal except a slight elevation in the level of alkaline phosphatase. Multiple polypoid lesions were observed in colonoscopic examination. The histological and immunochemical evaluation showed atypical lymphoid cell proliferation and lymphoepithelial lesions on the colonic mucosa, staining with CD20 (CD20 × 100). After the diagnosis had been confirmed as low grade mucosa associated lymphoid tissue lymphoma. Abdominal computed tomography revealed polypoid lesions throughout the colon and multiple milimetrics lymphadenopathies in the mesentery. The patient was treated with a chemotherapy regimen. During the follow-up, colonoscopic examination and blind biopsies were repeated in every 6 months, revealed endoscopically and pathologically normal mucosa each time. The patient is still alive without any recurrence of the disease 36 months after the diagnosis.
Pathologic Complete Response Rates in Young Women With BRCA1-Positive Breast Cancers After Neoadjuvant Chemotherapy
Authors: Byrski Tomasz , Gronwald Jacek , Huzarski Tomasz , Grzybowska Ewa , Budryk Magdalena , Stawicka Malgorzata , Mierzwa Tomasz , Szwiec Marek , Wiśniowski Rafal , Siolek Monika , Dent Rebecca , Lubinski Jan , Narod Steven 
Published: December 2009

Purpose To estimate the rate of pathologic complete response (pCR) to neoadjuvant chemotherapy in BRCA1 mutation carriers according to chemotherapy regimen. Patients and Methods From a registry of 6,903 patients, we identified 102 women who carried a BRCA1 founder mutation and who had been treated for breast cancer with neoadjuvant chemotherapy. Pathologic complete response was evaluated using standard criteria. Results Twenty-four (24%) of the 102 BRCA1 mutation carriers experienced a pCR. The response rate varied widely with treatment: a pCR was observed in one (7%) of 14 women treated with cyclophosphamide, methotrexate, and fluorouracil (CMF); in two (8%) of 25 women treated with doxorubicin and docetaxel (AT); in 11 (22%) of 51 women treated with doxorubicin and cyclophosphamide (AC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC), and in 10 (83%) of 12 women treated with cisplatin. Conclusion A low rate of pCR was observed in women with breast cancer and a BRCA1 mutation who were treated with AT or CMF. A high rate of pCR was seen after treatment with cisplatin. An intermediate rate of PCR was associated with AC or FAC. The relative benefits of AC and platinum therapy need to be confirmed through follow-up of this and other cohorts.
Prognostic Role of KRAS and BRAF in Stage II and III Resected Colon Cancer: Results of the Translational Study on the PETACC-3, EORTC 40993, SAKK 60-00 Trial
Authors: Roth Arnaud D. , Tejpar Sabine , Delorenzi Mauro , Yan Pu , Fiocca Roberto , Klingbiel Dirk , Dietrich Daniel , Biesmans Bart , Bodoky György , Barone Carlo , Aranda Enrique , Nordlinger Bernard , Cisar Laura , Labianca Roberto , Cunningham David , Van Cutsem Eric , Bosman Fred 
Published: December 2009

Purpose Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting. Patients and Methods Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models. Results KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10−4). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003). Conclusion In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.
Provision of Spiritual Care to Patients With Advanced Cancer: Associations With Medical Care and Quality of Life Near Death
Authors: Balboni Tracy Anne , Paulk Mary Elizabeth , Balboni Michael J. , Phelps Andrea C. , Loggers Elizabeth Trice , Wright Alexi A. , Block Susan D. , Lewis Eldrin F. , Peteet John R. , Prigerson Holly Gwen 
Published: December 2009

Purpose To determine whether spiritual care from the medical team impacts medical care received and quality of life (QoL) at the end of life (EoL) and to examine these relationships according to patient religious coping. Patients and Methods Prospective, multisite study of patients with advanced cancer from September 2002 through August 2008. We interviewed 343 patients at baseline and observed them (median, 116 days) until death. Spiritual care was defined by patient-rated support of spiritual needs by the medical team and receipt of pastoral care services. The Brief Religious Coping Scale (RCOPE) assessed positive religious coping. EoL outcomes included patient QoL and receipt of hospice and any aggressive care (eg, resuscitation). Analyses were adjusted for potential confounders and repeated according to median-split religious coping. Results Patients whose spiritual needs were largely or completely supported by the medical team received more hospice care in comparison with those not supported (adjusted odds ratio [AOR] = 3.53; 95% CI, 1.53 to 8.12, P = .003). High religious coping patients whose spiritual needs were largely or completely supported were more likely to receive hospice (AOR = 4.93; 95% CI, 1.64 to 14.80; P = .004) and less likely to receive aggressive care (AOR = 0.18; 95% CI, 0.04 to 0.79; P = .02) in comparison with those not supported. Spiritual support from the medical team and pastoral care visits were associated with higher QOL scores near death (20.0 [95% CI, 18.9 to 21.1] v 17.3 [95% CI, 15.9 to 18.8], P = .007; and 20.4 [95% CI, 19.2 to 21.1] v 17.7 [95% CI, 16.5 to 18.9], P = .003, respectively). Conclusion Support of terminally ill patients' spiritual needs by the medical team is associated with greater hospice utilization and, among high religious copers, less aggressive care at EoL. Spiritual care is associated with better patient QoL near death.
Nilotinib As Front-Line Treatment for Patients With Chronic Myeloid Leukemia in Early Chronic Phase
Authors: Cortes Jorge E. , Jones Dan , O'Brien Susan , Jabbour Elias , Konopleva Marina , Ferrajoli Alessandra , Kadia Tapan , Borthakur Gautam , Stigliano Denise , Shan Jianqin , Kantarjian Hagop 
Published: December 2009

Purpose Although most patients with chronic myeloid leukemia (CML) in chronic phase respond well to front-line therapy with imatinib, some patients do not achieve the desirable end point, and others may eventually lose response or are intolerant. Patients and Methods Patients with newly diagnosed CML in chronic phase were treated with nilotinib 400 mg twice daily on an empty stomach as initial therapy. Results Among 51 patients in chronic phase observed for at least 3 months, 50 (98%) achieved a complete cytogenetic remission (CCyR), and 39 (76%) achieved a major molecular response (MMR). Responses occurred rapidly, with 96% of patients achieving CCyR by 3 months and 98% achieving CCyR by 6 months. The projected event-free survival at 24 months is 90%, and all patients are alive after a median follow-up time of 17 months. Grade ≥ 3 neutropenia occurred in 12% of patients, and thrombocytopenia in occurred 11%. Nonhematologic toxicity was usually grade 1 to 2 and manageable. The actual median dose at 12 months was 800 mg (range, 200 to 800 mg). Conclusion Nilotinib is an effective option for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR, with most patients reaching these responses early during their therapy.
Investigation of the potential for vascular bubble formation in a repetitively diving dolphin
Authors: Houser D. S. , Dankiewicz-Talmadge L. A. , Stockard T. K. , Ponganis P. J. 
Published: December 2009

SUMMARYThe production of venous gas emboli (VGE) resulting from altered dive behavior is postulated as contributing to the stranding of beaked whales exposed to mid-frequency active sonar. To test whether nitrogen gas uptake during repetitive breath-hold diving is sufficient for asymptomatic VGE formation in odontocetes, a bottlenose dolphin (Tursiops truncatus Montagu) was trained to perform 10–12 serial dives with 60 s surface intervals to depths of 30, 50, 70 or 100 m. The dolphin remained at the bottom depth for 90 s on each dive. Doppler and/or two-dimensional imaging ultrasound did not detect VGE in the portal and brachiocephalic veins following a dive series. Van Slyke analyses of serial, post-dive blood samples drawn from the fluke yielded blood nitrogen partial pressure (PN2) values that were negligibly different from control samples. Mean heart rate (HR; ±1 s.d.) recorded during diving was 50±3 beats min–1 and was not significantly different between the 50, 70 and 100 m dive sessions. The absence of VGE and elevated blood PN2 during post-dive periods do not support the hypothesis that N2 supersaturation during repetitive dives contributes to VGE formation in the dolphin. The diving HR pattern and the presumed rapid N2 washout during the surface-interval tachycardia probably minimized N2 accumulation in the blood during dive sessions.
Fibre type-specific expression patterns of myosin heavy chain genes in adult torafugu Takifugu rubripes muscles
Authors: Akolkar D. B. , Kinoshita S. , Yasmin L. , Ono Y. , Ikeda D. , Yamaguchi H. , Nakaya M. , Erdogan O. , Watabe S. 
Published: December 2009

SUMMARY
Comprehensive in silico studies, based on the total fugu genome database, which was the first to appear in fish, revealed that torafugu Takifugu rubripes contains 20 sarcomeric myosin heavy chain (MYH) genes (MYH genes) (Ikeda et al., 2007). The present study was undertaken to identify MYH genes that would be expressed in adult muscles. In total, seven MYH genes were found by screening cDNA clone libraries constructed from fast, slow and cardiac muscles. Three MYH genes, fast-type MYHM86-1, slow-type MYHM8248 and slow/cardiac-type MYHM880, were cloned exclusively from fast, slow and cardiac muscles, respectively. Northern blot hybridization substantiated their specific expression, with the exception of MYHM880. In contrast, transcripts of fast-type MYHM2528-1 and MYHM1034 were found in both fast and slow muscles as revealed by cDNA clone library and northern blot techniques. This result was supported by in situ hybridization analysis using specific RNA probes, where transcripts of fast-type MYHM2528-1 were expressed in fast fibres with small diameters as well as in fibres of superficial slow muscle with large diameters adjacent to fast muscle. Transcripts of fast-type MYHM86-1 were expressed in all fast fibres with different diameters, whereas transcripts of slow-type MYHM8248 were restricted to fibres with small diameters located in a superficial part of slow muscle. Interestingly, histochemical analyses showed that fast fibres with small diameters and slow fibres with large diameters both contained acid-stable myofibrillar ATPase, suggesting that these fibres have similar functions, possibly in the generation of muscle fibres irrespective of their fibre types.
Gravikinesis inStylonychia mytilusis based on membrane potential changes
Authors: Krause Martin , Bräucker Richard , Hemmersbach Ruth 
Published: December 2009

SUMMARYThe graviperception of the hypotrichous ciliate Stylonychia mytilus was investigated using electrophysiological methods and behavioural analysis. It is shown that Stylonychia can sense gravity and thereby compensates sedimentation rate by a negative gravikinesis. The graviresponse consists of a velocity-regulating physiological component (negative gravikinesis) and an additional orientational component. The latter is largely based on a physical mechanism but might, in addition, be affected by the frequency of ciliary reversals, which is under physiological control. We show that the external stimulus of gravity is transformed to a physiological signal, activating mechanosensitive calcium and potassium channels. Earlier electrophysiological experiments revealed that these ion channels are distributed in the manner of two opposing gradients over the surface membrane. Here, we show, for the first time, records of gravireceptor potentials in Stylonychia that are presumably based on this two-gradient system of ion channels. The gravireceptor potentials had maximum amplitudes of approximately 4 mV and slow activation characteristics (0.03 mV s–1). The presumptive number of involved graviperceptive ion channels was calculated and correlates with the analysis of the locomotive behaviour.
Lateral line diversity among ecologically divergent threespine stickleback populations
Authors: Wark A. R. , Peichel C. L. 
Published: December 2009

SUMMARYThe lateral line is a mechanoreceptive sensory system that allows fish to sense objects and motion in their local environment. Variation in lateral line morphology may allow fish in different habitats to differentially sense and respond to salient cues. Threespine sticklebacks (Gasterosteus aculeatus) occupy a diverse range of aquatic habitats; we therefore hypothesized that populations within the G. aculeatus species complex might show variation in the morphology of the lateral line sensory system. We sampled 16 threespine stickleback populations from marine, stream and lake (including benthic and limnetic) habitats and examined the distribution, type and number of neuromasts on different regions of the body. We found that the threespine stickleback has a reduced lateral line canal system, completely lacking canal neuromasts. Although the arrangement of lines of superficial neuromasts on the body was largely the same in all populations, the number of neuromasts within these lines varied across individuals, populations and habitats. In pairwise comparisons between threespine sticklebacks adapted to divergent habitats, we found significant differences in neuromast number. Stream residents had more neuromasts than marine sticklebacks living downstream in the same watershed. In two independent lakes, benthic sticklebacks had more trunk neuromasts than sympatric limnetic sticklebacks, providing evidence for parallel evolution of the lateral line system. Our data provide the first demonstration that the lateral line sensory system can vary significantly between individuals and among populations within a single species, and suggest that this sensory system may experience different selection regimes in alternative habitats.