bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying transcription factors and microRNAs as key regulators of pathways using Bayesian inference on known pathway structures
Authors: Roqueiro Damian , Huang Lei , Dai Yang 
Published: June 2012

Abstract

Background
Transcription factors and microRNAs act in concert to regulate gene expression in eukaryotes. Numerous computational methods based on sequence information are available for the prediction of target genes of transcription factors and microRNAs. Although these methods provide a static snapshot of how genes may be regulated, they are not effective for the identification of condition-specific regulators.

Results
We propose a new method that combines: a) transcription factors and microRNAs that are predicted to target genes in pathways, with b) microarray expression profiles of microRNAs and mRNAs, in conjunction with c) the known structure of molecular pathways. These elements are integrated into a Bayesian network derived from each pathway that, through probability inference, allows for the prediction of the key regulators in the pathway. We demonstrate 1) the steps to discretize the expression data for the computation of conditional probabilities in a Bayesian network, 2) the procedure to construct a Bayesian network using the structure of a known pathway and the transcription factors and microRNAs predicted to target genes in that pathway, and 3) the inference results as potential regulators of three signaling pathways using microarray expression profiles of microRNA and mRNA in estrogen receptor positive and estrogen receptor negative tumors.

Conclusions
We displayed the ability of our framework to integrate multiple sets of microRNA and mRNA expression data, from two phenotypes, with curated molecular pathway structures by creating Bayesian networks. Moreover, by performing inference on the network using known evidence, e.g., status of differentially expressed genes, or by entering hypotheses to be tested, we obtain a list of potential regulators of the pathways. This, in turn, will help increase our understanding about the regulatory mechanisms relevant to the two phenotypes.
Predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using short polypeptide clusters
Authors: Zhang Yuehua , Li Bo , Srimani Pradip K , Chen Xuewen , Luo Feng 
Published: June 2012

Abstract

Background
Protein synthetic lethal genetic interactions are useful to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions remains unclear.

Results
In this study we used the clusters of short polypeptide sequences, which are typically shorter than the classically defined protein domains, to characterize the functionalities of proteins. We developed a framework to identify significant short polypeptide clusters from yeast protein sequences, and then used these short polypeptide clusters as features to predict yeast synthetic lethal genetic interactions. The short polypeptide clusters based approach provides much higher coverage for predicting yeast synthetic lethal genetic interactions. Evaluation using experimental data sets showed that the short polypeptide clusters based approach is superior to the previous protein domain based one.

Conclusion
We were able to achieve higher performance in yeast synthetic lethal genetic interactions prediction using short polypeptide clusters as features. Our study suggests that the short polypeptide cluster may help better understand the functionalities of proteins.
Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins
Authors: Wang Quan , Jiang Jing , Wang Chao , Lian Guodong , Jin Mei-Shan , Cao Xueyuan 
Published: June 2012

Abstract
Leiomyosarcoma of the inferior vena cava (IVCL) is a rare retroperitoneal tumor. We report two cases of level II (middle level, renal veins to hepatic veins) IVCL, who underwent en bloc resection with reconstruction of bilateral or left renal venous return using prosthetic grafts. In our cases, IVCL is documented to be occluded preoperatively, therefore, radical resection of tumor and/or right kidney was performed and the distal end of inferior vena cava was resected and without caval reconstruction. None of the patients developed edema or acute renal failure postoperatively. After surgical resection, adjuvant radiation therapy was administrated. The patients have been free of recurrence 2 years and 3 months, 9 months after surgery, respectively, indicating the complete surgical resection and radiotherapy contribute to the better survival. The reconstruction of inferior vena cava was not considered mandatory in level II IVCL, if the retroperitoneal venous collateral pathways have been established. In addition to the curative resection of IVCL, the renal vascular reconstruction minimized the risks of procedure-related acute renal failure, and was more physiologically preferable. This concept was reflected in the treatment of the two patients reported on.
Diffusion-weighted imaging and FDG PET/CT: predicting the prognoses with apparent diffusion coefficient values and maximum standardized uptake values in patients with invasive ductal carcinoma
Authors: Choi Bo Bae , Kim Sung Hun , Kang Bong Joo , Lee Ji Hye , Song Byung Joo , Jeong Seung Hee , Yim Hyeon Woo 
Published: June 2012

Abstract

Background
FDG PET/CT and DWI are both functional modalities that indirectly represent the biological characteristics of cancer, but there are few studies exploring the association between the two modalities and prognostic factors. Our study attempted to evaluate the mutual association by comparing the prognostic factors, SUVmax value of PET/CT, and ADC values associated with diffusion imaging in invasive ductal carcinoma (IDC) patients.

Methods
Patients with pathologically confirmed IDC were recruited. There were 118 patients who underwent MRI, including DWI, FDG PET/CT, and immunohistochemical staining of the surgical specimen. Histologic analysis was done on tumor size, lymph node metastasis, expression of estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, and epidermal growth factor receptors (EGFR). The relationship among ADC values, SUVmax and prognostic factors were evaluated.

Results
There was significant association between the ADC value and ER-positive and HER2-negative expression. Significant associations were noted between SUVmax and tumor size, lymph node metastasis, histologic grade, ER and PR expression, EGFR and Ki-67. However, there was no significant correlation between the ADC value and SUVmax.

Conclusions
Even though there was no correlation between ADC and SUVmax, both indexes are useful for predicting the prognosis of IDC.
Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro
Authors: Guo You-feng , Wang Xiao-bing , Tian Xiao-ying , Li Yang , Li Bin , Huang Quan , Zhang Meng , Li Zhi 
Published: June 2012

Abstract

Background
We examined the association of tumor-derived hepatocyte growth factor (HGF) with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients.

Methods
Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI) and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si)-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro.

Results
Both high HGF expression in tumor cells (59.2%, 45/76) and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P < 0.05). However, only histological grading (P = 0.004) and high-expression of HGF (P = 0.008) emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin.

Conclusion
This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.
The existence of solutions for nonlinear fractional multipoint boundary value problems at resonance
Authors: Xu Na , Liu Wenbin , Xiao Lishun 
Published: June 2012

Abstract
A class of nonlinear fractional multipoint boundary value problems at resonance is considered in this article. The existence results are obtained by the method of the coincidence degree theory of Mawhin. An example is given to illustrate the results.

MSC:34A08.
Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury
Authors: Cho Newton , Nguyen Dung H , Satkunendrarajah Kajana , Branch Donald R , Fehlings Michael G 
Published: June 2012

AbstractBackgroundSpinal cord injury (SCI) is a devastating condition with substantial functional and social morbidity. Previous research has established that the neuroinflammatory response plays a significant role in cord damage post-SCI. However, global immunosuppressive therapies have demonstrated mixed results. As a result, more specific therapies modulating inflammation after injury are needed. In this regard, research into cytokine signaling has demonstrated that cytokines of the gp130 family including IL-6 and leukemia inhibitory factor (LIF) play key roles in mediating damage to the spinal cord. Since members of the gp130 family all share a common signal transduction pathway via the JAK/STAT system, we performed the first study of a relatively new member of the gp130 family, IL-11, in SCI.MethodsA validated clip-compression mouse model of SCI was used to assess for temporal changes in expression of IL-11 and its receptor, IL-11Rα, post-SCI. To elucidate the role of IL-II in the pathophysiology of SCI, we compared differences in locomotor recovery (Basso Mouse Score; CatWalk), electrophysiological spinal cord signaling, histopathology, and the acute inflammatory neutrophil response in IL-11Rα knockouts with littermate wild-type C57BL/6 mice.ResultsWe found an increase in gene expression of IL-11 in the spinal cord to a peak at twenty-four hours post-SCI with increases in IL-11Rα gene expression, peaking at seven days post-SCI. In spite of clear changes in the temporal expression of both IL-11 and its receptor, we found that there were no significant differences in motor function, electrophysiological signaling, histopathology, or neutrophil infiltration into the spinal cord between wild-type and knockout mice.ConclusionsThis is the first study to address IL-11 in SCI. This study provides evidence that IL-11 signaling may not play as significant a role in SCI as other gp130 cytokines, which will ideally guide future therapy design and the signaling pathways those therapies target.
Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers
Authors: Adamcakova-Dodd Andrea , Stebounova Larissa V , O’Shaughnessy Patrick T , Kim Jong Sung , Grassian Vicki H , Thorne Peter S 
Published: June 2012

Abstract

Background
Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols.

Methods
Primary dimensions of AO nanowhiskers specified by manufacturer were 2–4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics.

Results
Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 μg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice.

Conclusions
Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.
Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer
Authors: Zhang Jian , Peng Feng , Li Na , Liu Yongmei , Xu Yong , Zhou Lin , Wang Jin , Zhu Jiang , Huang Meijuan , Gong Youling 
Published: June 2012

Abstract

Purpose
To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery.

Methods
50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group).

Results
The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study.

Conclusions
For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome.
Quality of life and depression in caregivers of patients with breast cancer
Authors: Heidari Gorji Mohammad Ali , Bouzar Zinnatossadat , Haghshenas Mohsen , Kasaeeyan Ali Akbar , Sadeghi Mohammad Reza , Ardebil Maryam Didehdar 
Published: June 2012

Abstract

Background
Caregivers have a considerable role in caring and recovery of cancer patients. They may experience psychological problems such as depression, anxiety and decreases in quality of life (QOL). Present study aimed to explore depression and quality of life and their relationship among care givers of patients with breast cancer .

Methods
In this cross sectional study, enrolled 63 care givers of women with breast cancer attending IMKH hospital in Iran as outpatients during 2009–2010. In order to assess the QOL and depression, we used Caregiver QOL Index-Cancer (CQOL-C) and Beck Depression Inventory respectively.

Results
We found depression has strong negative correlation with QOL and participants with depression were more likely to have a poorer overall QOL.

Conclusions
Depression has some effects on QOL of breast cancer patients’ care givers. Assistance and giving information through education and intervention from healthcare professionals is the key of improve the ability of caregivers to enhance their QOL.
Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity
Authors: Ardley Melissa , McCorquodale Thomas , Lahooti Hooshang , Champion Bernard , Wall Jack R 
Published: June 2012

Abstract

Background
Ophthalmopathy is a common manifestation of Graves’ disease (GD) occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course.

Objective
We determined the prevalences of eye and eyelid signs and positive thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s thyroiditis.

Design
The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s thyroiditis and hypothyroidism and 12 of their euthyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1) and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R) antibodies as i) TSH-R binding inhibiting immunoglobulin (TBII) and ii) thyroid stimulating immunoglobulin (TSI). Eye signs were classified and quantified using the clinical activity score (CAS), NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD) as a measure of upper eyelid retraction (UER).

Main outcomes
Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies.

Conclusion
Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with thyroid autoimmunity and their euthyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with thyroid autoimmunity.
Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease
Authors: Elguezabal Natalia , Chamorro Susana , Molina Elena , Garrido Joseba M , Izeta Ander , Rodrigo Luis , Juste Ramón A 
Published: June 2012

Abstract

Background
Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD.

Methods
In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes.

Results
As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status.

Conclusions
We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations with IBD.
Effect of pretreatments on chemical compositions of mince from Nile tilapia (Oreochromis niloticus) and fishy odor development in protein hydrolysate
Authors: Yarnpakdee Suthasinee , Benjakul Soottawat , Kristinsson Hordur G 
Published: June 2012

Abstract
Fish protein hydrolysates (FPH) have gained increasing attention as nutritious fish products. Lipid oxidation associated with fishy odor in FPH limits its utility. Thus, an appropriate pretreatment of fish mince prior to hydrolysis by lowering pro-oxidants and lipid substrates could tackle such a problem. Different pretreatments of Nile tilapia minces including (1) washing (W), (2) washing and membrane removal (W-MR), and (3) washing/membrane removal followed by acid or alkaline solubilization (W-MR-Ac or W-MR-Al) were conducted prior to hydrolysis. During the hydrolysis process, degree of hydrolysis (DH) and chemical changes were monitored. Color and sensory properties of milk fortified with hydrolysates prepared from mince without and with pretreatment were also determined. Among the pretreated mince samples, W-MR-Al contained the lowest remaining myoglobin and heme iron contents and also showed the lowest total lipid and phospholipid contents (P < 0.05). When mince and W-MR-Al were hydrolyzed using Alcalase for up to 120 min, higher DH were found in W-MR-Al. Furthermore, lower peroxide values, thiobarbituric acid reactive substances, and non-heme iron contents of hydrolysates from W-MR-Al were also observed (P < 0.05). When FPH powder from mince and W-MR-Al (0.3% to 0.5%) were fortified in milk, the former yielded a lower likeness score (P < 0.05) at all levels used. The addition of the latter up to 0.5% had no effect on likeness of all attributes, compared with control (without FPH). An appropriate pretreatment of mince was a promising approach to lower fishy odor problem, caused by lipid oxidation in FPH.