bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Markov multistate analysis of the relationship between performance status and death among an ambulatory population of cancer patients
Authors: Sutradhar Rinku , Barbera Lisa 
Published: August 2013

Background: The relationship between performance status and death among cancer patients has been of increasing interest over the past years. However, few studies have implemented statistical models that adequately capture the longitudinal nature of performance status assessments collected under intermittent observation. Aim: The main research aims were to examine the association between performance status and death and to determine the probability of deterioration in performance status over time. Design: This was a population-based longitudinal study among adult outpatients diagnosed with cancer. Throughout their observation period, all patients were repeatedly assessed for performance status using an 11-point scale with a score of 100 being the best, 10 being the worst and 0 representing death. A Markov multistate model accounting for intermittent observation was implemented in which each score represented a distinct state in the model. Results: The cohort consisted of 27,739 patients with over 157,000 assessments. The rate of transition to death increases with a quadratic trend as performance status declines. The 1-month and 3-month probability of deterioration also increases with a quadratic trend as performance status declines. The relative rate of transition to death decreases as we compare lower scores (relative rate = 2.20 for comparing scores 90 vs 100 and relative rate = 1.23 for comparing scores 10 vs 20). Conclusion: There is a significant relationship between performance status and rate of transition to death. The Markov multistate model provides a comprehensive understanding of the shape of this relationship, which facilitates the interpretation of performance status and provides strength in its use as a prognostic tool in a clinical setting.
Effects of CD40 ligation combined with chemotherapy drugs on human breast cancer cell lines
Authors: Wang Zhi-Qing , Wang Jun , Ling Wei-Hua , Zhang Xue-Guang , Shi Qin 
Published: August 2013

Objective To investigate the influence of recombinant human CD40 ligand (rhCD40L) on the biological behaviour of breast cancer cells. Methods MDA-MB-23l and MDA-MB-435 treated with rhCD40L were observed for changes in the cell cycle, in membrane proteins, and in mRNA levels of B cell lymphoma-extra-large (Bcl-xl), Bcl-2 associated X protein (Bax) and regulated upon activation, normal T cell expressed and secreted (RANTES). Effects of rhCD40L on cell proliferation in the presence or absence of interferon (IFN)-γ (500 IU/ml) and/or doxorubicin (20 ng/ml) were also determined. Results rhCD40L dose-dependently inhibited cell proliferation. Combination of rhCD40L with IFN-γ or doxorubicin potentiated the inhibitory activity. After treatment, an increase in cells entering the G1 phase of the cell cycle was observed, with a significant decrease in the number entering the S phase. Levels of several membrane proteins including CD95L and CD120a were also increased. Reverse transcription–polymerase chain reaction revealed an increase in the Bax/Bcl-xl mRNA ratio and an increase in RANTES. Conclusion rhCD40L treatment of breast cancer cells mediates a variety of anti-tumour effects, not only by direct cytotoxic activity but also by upregulation of adhesion molecules, co-stimulators and cytokines to rectify T cell immunity.
Systemic lupus erythematosus (SLE) in the eastern region of Saudi Arabia. A comparative study
Authors: Abid N , Khan A Sattar , Otaibi F Huzam Al 
Published: August 2013

This retrospective study aimed to collect data related to the clinical manifestations and laboratory investigations of systemic lupus erythematosus (SLE) patients in the eastern part of Saudi Arabia, in one of the tertiary-care centers, King Fahd Hospital Al-Hasa, and to compare it with other regions of Saudi Arabia. Forty-six patients fulfilling the American College of Rheumatology 1997 criteria (ACR) were collected over a period from January 2004 to December 2008. The results showed an average age of onset of 26.17 ( ±9.17). The most common clinical features were nonspecific constitutional symptoms (fever, fatigue and malaise) seen in 44 patients (95.7%). Musculoskeletal features seen were mostly arthralgias (91.3%) and arthritis (76.1%). Nephritis was seen in 58.7% and hypertension in 52.2%. Mucocutaneous involvement included oral ulcers (71.7%), hair loss (65.2%), butterfly rashes (67.4%), photosensitivity (47.8%) and discoid lupus (13%). Neurologic manifestations showed psychosis in 17.4%, depression in 15.2% and headache in 28.3%. The most common hematologic presentation was leukopenia (58.7%) followed by hemolytic anemia and anemia of chronic disease (47.8%). Antinuclear antibodies were positive in 44 (95.7%), anti-dsDNA in 38 (42.6%), anti-Ro SSA and La SSB in 38 (82.6%). Anticardiolipin antibodies and lupus anticoagulant were positive in eight (17.4%). Low complement levels (C3 and C4) were seen in 41 (89.1%) of the patients with active disease. The drugs used in treatment were NSAIDs (100%), antimalarials (97.8%), steroids (100%), intermittent cyclophosphamide and other immunosuppressive drugs (71.7%). We found that the age of onset and sex distributions were different from other areas of Saudi Arabia, while clinical manifestations were the same as in other areas. The prognosis of lupus was good overall despite the multi-organ involvement. However, further studies based on larger number of patients are needed.
An audit strategy for time-to-event outcomes measured with error: Application to five randomized controlled trials in oncology
Authors: Dodd Lori E , Korn Edward L , Freidlin Boris , Gu Wenjuan , Abrams Jeffrey S , Bushnell William D , Canetta Renzo , Doroshow James H , Gray Robert J , Sridhara Rajeshwari 
Published: August 2013

Background Measurement error in time-to-event end points complicates interpretation of treatment effects in clinical trials. Non-differential measurement error is unlikely to produce large bias [1]. When error depends on treatment arm, bias is of greater concern. Blinded-independent central review (BICR) of all images from a trial is commonly undertaken to mitigate differential measurement-error bias that may be present in hazard ratios (HRs) based on local evaluations. Similar BICR and local evaluation HRs may provide reassurance about the treatment effect, but BICR adds considerable time and expense to trials. Methods We describe a BICR audit strategy [2] and apply it to five randomized controlled trials to evaluate its use and to provide practical guidelines. The strategy requires BICR on a subset of study subjects, rather than a complete-case BICR, and makes use of an auxiliary-variable estimator. Results When the effect size is relatively large, the method provides a substantial reduction in the size of the BICRs. In a trial with 722 participants and a HR of 0.48, an average audit of 28% of the data was needed and always confirmed the treatment effect as assessed by local evaluations. More moderate effect sizes and/or smaller trial sizes required larger proportions of audited images, ranging from 57% to 100% for HRs ranging from 0.55 to 0.77 and sample sizes between 209 and 737. Limitations The method is developed for a simple random sample of study subjects. In studies with low event rates, more efficient estimation may result from sampling individuals with events at a higher rate. Conclusion The proposed strategy can greatly decrease the costs and time associated with BICR, by reducing the number of images undergoing review. The savings will depend on the underlying treatment effect and trial size, with larger treatment effects and larger trials requiring smaller proportions of audited data.
Feasibility trial of a Spanish-language multimedia educational intervention
Authors: Wells Kristen J , McIntyre Jessica , Gonzalez Luis E , Lee Ji-Hyun , Fisher Kate J , Jacobsen Paul B , Meade Cathy , Muñoz-Antonia Teresita , Quinn Gwendolyn P 
Published: August 2013

Background Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Purpose Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. Methods A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute’s Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Results Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Limitations Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. Conclusion In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.
Mucosal and systemic T cell response in mice intragastrically infected with Neospora caninum tachyzoites
Authors: Correia Alexandra , Ferreirinha Pedro , Costa Amanda A , Dias Joana , Melo Joana , Costa Rita , Ribeiro Adília , Faustino Augusto , Teixeira Luzia , Rocha António , Vilanova Manuel 
Published: August 2013

AbstractThe murine model has been widely used to study the host immune response toNeospora caninum. However, in most studies, the intraperitoneal route was preferentially used to establish infection. Here, C57BL/6 mice were infected withN. caninumtachyzoites by the intragastric route, as it more closely resembles the natural route of infection through the gastrointestinal tract. The elicited T-cell mediated immune response was evaluated in the intestinal epithelium and mesenteric lymph nodes (MLN). Early upon the parasitic challenge, IL-12 production by conventional and plasmacytoid dendritic cells was increased in MLN. Accordingly, increased proportions and numbers of TCRαβ+CD8+IFN-γ+lymphocytes were detected, not only in the intestinal epithelium and MLN, but also in the spleen of the infected mice. In this organ, IFN-γ-producing TCRαβ+CD4+T cells were also found to increase in the infected mice, however later than CD8+T cells. Interestingly, splenic and MLN CD4+CD25+T cells sorted from infected mice presented a suppressive activity on in vitro T cell proliferation and cytokine production above that of control counterparts. These results altogether indicate that, by producing IFN-γ, TCRαβ+CD8+cells contribute for local and systemic host protection in the earliest days upon infection established through the gastrointestinal tract. Nevertheless, they also provide substantial evidence for a parasite-driven reinforcement of T regulatory cell function which may contribute for parasite persistence in the host and might represent an additional barrier to overcome towards effective vaccination.
Group sparse canonical correlation analysis for genomic data integration
Authors: Lin Dongdong , Zhang Jigang , Li Jingyao , Calhoun Vince D , Deng Hong-Wen , Wang Yu-Ping 
Published: August 2013

Abstract

Background
The emergence of high-throughput genomic datasets from different sources and platforms (e.g., gene expression, single nucleotide polymorphisms (SNP), and copy number variation (CNV)) has greatly enhanced our understandings of the interplay of these genomic factors as well as their influences on the complex diseases. It is challenging to explore the relationship between these different types of genomic data sets. In this paper, we focus on a multivariate statistical method, canonical correlation analysis (CCA) method for this problem. Conventional CCA method does not work effectively if the number of data samples is significantly less than that of biomarkers, which is a typical case for genomic data (e.g., SNPs). Sparse CCA (sCCA) methods were introduced to overcome such difficulty, mostly using penalizations with l-1 norm (CCA-l1) or the combination of l-1and l-2 norm (CCA-elastic net). However, they overlook the structural or group effect within genomic data in the analysis, which often exist and are important (e.g., SNPs spanning a gene interact and work together as a group).

Results
We propose a new group sparse CCA method (CCA-sparse group) along with an effective numerical algorithm to study the mutual relationship between two different types of genomic data (i.e., SNP and gene expression). We then extend the model to a more general formulation that can include the existing sCCA models. We apply the model to feature/variable selection from two data sets and compare our group sparse CCA method with existing sCCA methods on both simulation and two real datasets (human gliomas data and NCI60 data). We use a graphical representation of the samples with a pair of canonical variates to demonstrate the discriminating characteristic of the selected features. Pathway analysis is further performed for biological interpretation of those features.

Conclusions
The CCA-sparse group method incorporates group effects of features into the correlation analysis while performs individual feature selection simultaneously. It outperforms the two sCCA methods (CCA-l1 and CCA-group) by identifying the correlated features with more true positives while controlling total discordance at a lower level on the simulated data, even if the group effect does not exist or there are irrelevant features grouped with true correlated features. Compared with our proposed CCA-group sparse models, CCA-l1 tends to select less true correlated features while CCA-group inclines to select more redundant features.
Modeling of 2D diffusion processes based on microscopy data: parameter estimation and practical identifiability analysis
Authors: Hock Sabrina , Hasenauer Jan , Theis Fabian J 
Published: August 2013

Abstract

Background
Diffusion is a key component of many biological processes such as chemotaxis, developmental differentiation and tissue morphogenesis. Since recently, the spatial gradients caused by diffusion can be assessed in-vitro and in-vivo using microscopy based imaging techniques. The resulting time-series of two dimensional, high-resolutions images in combination with mechanistic models enable the quantitative analysis of the underlying mechanisms. However, such a model-based analysis is still challenging due to measurement noise and sparse observations, which result in uncertainties of the model parameters.

Methods
We introduce a likelihood function for image-based measurements with log-normal distributed noise. Based upon this likelihood function we formulate the maximum likelihood estimation problem, which is solved using PDE-constrained optimization methods. To assess the uncertainty and practical identifiability of the parameters we introduce profile likelihoods for diffusion processes.

Results and conclusion
As proof of concept, we model certain aspects of the guidance of dendritic cells towards lymphatic vessels, an example for haptotaxis. Using a realistic set of artificial measurement data, we estimate the five kinetic parameters of this model and compute profile likelihoods. Our novel approach for the estimation of model parameters from image data as well as the proposed identifiability analysis approach is widely applicable to diffusion processes. The profile likelihood based method provides more rigorous uncertainty bounds in contrast to local approximation methods.
miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability
Authors: Qiao Ying , Badduke Chansonette , Mercier Eloi , Lewis Suzanne ME , Pavlidis Paul , Rajcan-Separovic Evica 
Published: August 2013

AbstractBackgroundMicroRNAs (miRNAs) are a family of short, non-coding RNAs modulating expression of human protein coding genes (miRNA target genes). Their dysfunction is associated with many human diseases, including neurodevelopmental disorders. It has been recently shown that genomic copy number variations (CNVs) can cause aberrant expression of integral miRNAs and their target genes, and contribute to intellectual disability (ID).ResultsTo better understand the CNV-miRNA relationship in ID, we investigated the prevalence and function of miRNAs and miRNA target genes in five groups of CNVs. Three groups of CNVs were from 213 probands with ID (24de novoCNVs, 46 familial and 216 common CNVs), one group of CNVs was from a cohort of 32 cognitively normal subjects (67 CNVs) and one group of CNVs represented 40 ID related syndromic regions listed in DECIPHER (30 CNVs) which served as positive controls for CNVs causing or predisposing to ID. Our results show that 1). The number of miRNAs is significantly higher inde novoor DECIPHER CNVs than in familial or common CNV subgroups (P < 0.01). 2). miRNAs with brain related functions are more prevalent inde novoCNV groups compared to common CNV groups. 3). More miRNA target genes are found inde novo, familial and DECIPHER CNVs than in the common CNV subgroup (P < 0.05). 4). The MAPK signaling cascade is found to be enriched among the miRNA target genes fromde novoand DECIPHER CNV subgroups.ConclusionsOur findings reveal an increase in miRNA and miRNA target gene content inde novoversus common CNVs in subjects with ID. Their expression profile and participation in pathways support a possible role of miRNA copy number change in cognition and/or CNV-mediated developmental delay. Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.
Lactobacillus plantarum MYL26 induces endotoxin tolerance phenotype in Caco-2 cells
Authors: Chiu Yi-Heng , Lu Ying-Chen , Ou Chu-Chyn , Lin Shiao-Lin , Tsai Chin-Chi , Huang Chien-Tsai , Lin Meei-Yn 
Published: August 2013

Abstract

Background
Crohn's disease and ulcerative colitis are the major types of chronic inflammatory bowel disease occurring in the colon and small intestine. A growing body of research has proposed that probiotics are able to attenuate the inflammatory symptoms of these diseases in vitro and in vivo. However, the mechanism of probiotic actions remains unclear.

Results
Our results suggested Lactobacillus plantarum MYL26 inhibited inflammation in Caco-2 cells through regulation of gene expressions of TOLLIP, SOCS1, SOCS3, and IκBα, rather than SHIP-1 and IRAK-3.

Conclusions
We proposed that live/ heat-killed Lactobacillus plantarum MYL26 and bacterial cell wall extract treatments impaired TLR4-NFκb signal transduction through Tollip, SOCS-1 and SOCS-3 activation, thus inducing LPS tolerance. Our findings suggest that either heat-killed probiotics or probiotic cell wall extracts are able to attenuate inflammation through pathways similar to that of live bacteria.
Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors
Authors: Juliachs Mercè , Vidal August , del Muro Xavier Garcia , Piulats Josep M , Condom Enric , Casanovas Oriol , Graupera Mariona , Germà Jose R , Villanueva Alberto , Viñals Francesc 
Published: August 2013

Abstract

Background
Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs.

Methods
We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated.

Results
TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth.

Conclusions
We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies.