GenEpi: gene-based epistasis discovery using machine learning.

BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future

Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

<p>Abstract</p> <p>Background</p> <p>To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer.</p> <p>Methods</p> <p>Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m²intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0).</p> <p>Results</p> <p>The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully.</p> <p>Conclusion</p> <p>HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted.</p

Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan

Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms

The Association of Thyrotropin and Autoimmune Thyroid Disease in Developing Papillary Thyroid Cancer

Background. Papillary thyroid carcinoma (PTC) is the most common type of malignant thyroid neoplasm. However, the incidence of PTC with autoimmune thyroid disease (AITD) varies between studies. This study aims to investigate whether patients with AITD have increased incidence of PTC. We also analyzed the relationship of serum thyroid-stimulating hormone (TSH) levels and PTC in relation to AITD based on histopathological data. Methods. A total of 533 participants who underwent thyroidectomy were enrolled in this retrospective study based on clinicohistopathological data and known thyroid autoantibodies. Patients were divided into PTC and benign groups according to histopathologic diagnosis. Age, gender, body mass index, and serum TSH level before thyroidectomy were recorded. Results. Of the 533 enrolled patients, 159 (29.8%) were diagnosed with PTC, of which 38 (35.5%) had Hashimoto’s thyroiditis (HT). More patients with HT were female, and patients with HT, Graves’ disease, and thyroid nodules with higher TSH level had a higher incidence of PTC. Conclusions. A high proportion of the patients with PTC had HT. There was a trend that a higher serum TSH level was associated with a greater risk of thyroid cancer

18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters

<p>Abstract</p> <p>Background</p> <p>To define a suitable threshold setting for gross tumor volume (GTV) when using ¹⁸Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC).</p> <p>Methods</p> <p>Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax.</p> <p>Results</p> <p>Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R²= 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R²= 0.89). The sTL was not associated with the value of C-pGTVs.</p> <p>Conclusion</p> <p>In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.</p

Transgenic Expression of Decoy Receptor 3 Protects Islets from Spontaneous and Chemical-induced Autoimmune Destruction in Nonobese Diabetic Mice

Decoy receptor 3 (DCR3) halts both Fas ligand– and LIGHT-induced cell deaths, which are required for pancreatic β cell damage in autoimmune diabetes. To directly investigate the therapeutic potential of DCR3 in preventing this disease, we generated transgenic nonobese diabetic mice, which overexpressed DCR3 in β cells. Transgenic DCR3 protected mice from autoimmune and cyclophosphamide-induced diabetes in a dose-dependent manner and significantly reduced the severity of insulitis. Local expression of the transgene did not alter the diabetogenic properties of systemic lymphocytes or the development of T helper 1 or T regulatory cells. The transgenic islets had a higher transplantation success rate and survived for longer than wild-type islets. We have demonstrated for the first time that the immune-evasion function of DCR3 inhibits autoimmunity and that genetic manipulation of grafts may improve the success and survival of islet transplants

Resveratrol Impedes the Stemness, Epithelial-Mesenchymal Transition, and Metabolic Reprogramming of Cancer Stem Cells in Nasopharyngeal Carcinoma through p53 Activation

Cancer stem cells (CSCs) are able to self-renew and are refractory to cancer treatment. To investigate the effects of resveratrol on CSCs of nasopharyngeal carcinoma (NPC), we employed a behavior selection strategy to isolate CSCs based on radioresistance, chemoresistance, and tumor sphere formation ability. These NPC CSCs displayed stem cell properties and underwent metabolic shift to predominately rely on glycolysis for energy supply. Intriguingly, we found that resveratrol turned off the metabolic switch, increased the reactive oxygen species (ROS) level, and depolarized mitochondrial membranes. These alterations in metabolism occurred concomitantly with the suppression of CSC properties including resistance to therapy, self-renewal capacity, tumor initiation capacity, and metastatic potential in NPC CSCs. We found that resveratrol impeded CSC properties through the activation of p53 and this effect could be reversed by knockdown of p53. Furthermore, resveratrol suppressed the stemness and EMT through reactivating p53 and inducing miR-145 and miR-200c, which were downregulated in NPC CSCs. In conclusion, we demonstrated that resveratrol employed the p53 pathway in regulating stemness, EMT, and metabolic reprogramming. Further investigation of the molecular mechanism of p53 activation by resveratrol may provide useful information for the development of novel therapies for cancer treatment through targeting to CSCs

Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report

<p>Abstract</p> <p>Background</p> <p>Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously.</p> <p>Case Presentation</p> <p>A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected.</p> <p>Conclusions</p> <p>Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.</p