bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?
Authors: Gallamini Andrea , Kostakoglu Lale 
Published: August 2012

AbstractDespite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria. A final remark on the appropriate use of interim PET is also provided.
How I treat anticoagulated patients undergoing an elective procedure or surgery
Authors: Spyropoulos Alex C. , Douketis James D. 
Published: August 2012

AbstractThe periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.
Multi-scale agent-based brain cancer modeling and prediction of TKI treatment response: Incorporating EGFR signaling pathway and angiogenesis
Authors: Sun Xiaoqiang , Zhang Le , Tan Hua , Bao Jiguang , Strouthos Costas , Zhou Xiaobo 
Published: August 2012

Abstract

Background
The epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in brain cancer act as an engine for tumor initiation, expansion and response to therapy. Since the existing literature does not have any models that investigate the impact of both angiogenesis and molecular signaling pathways on treatment, we propose a novel multi-scale, agent-based computational model that includes both angiogenesis and EGFR modules to study the response of brain cancer under tyrosine kinase inhibitors (TKIs) treatment.

Results
The novel angiogenesis module integrated into the agent-based tumor model is based on a set of reaction–diffusion equations that describe the spatio-temporal evolution of the distributions of micro-environmental factors such as glucose, oxygen, TGFα, VEGF and fibronectin. These molecular species regulate tumor growth during angiogenesis. Each tumor cell is equipped with an EGFR signaling pathway linked to a cell-cycle pathway to determine its phenotype. EGFR TKIs are delivered through the blood vessels of tumor microvasculature and the response to treatment is studied.

Conclusions
Our simulations demonstrated that entire tumor growth profile is a collective behaviour of cells regulated by the EGFR signaling pathway and the cell cycle. We also found that angiogenesis has a dual effect under TKI treatment: on one hand, through neo-vasculature TKIs are delivered to decrease tumor invasion; on the other hand, the neo-vasculature can transport glucose and oxygen to tumor cells to maintain their metabolism, which results in an increase of cell survival rate in the late simulation stages.
The impact of random frequency-dependent mutations on the average population fitness
Authors: Huang Weini , Werner Benjamin , Traulsen Arne 
Published: August 2012

Abstract

Background
In addition to selection, the process of evolution is accompanied by stochastic effects, such as changing environmental conditions, genetic drift and mutations. Commonly it is believed that without genetic drift, advantageous mutations quickly fixate in a halpoid population due to strong selection and lead to a continuous increase of the average fitness. This conclusion is based on the assumption of constant fitness. However, for frequency dependent fitness, where the fitness of an individual depends on the interactions with other individuals in the population, this does not hold.

Results
We propose a mathematical model that allows to understand the consequences of random frequency dependent mutations on the dynamics of an infinite large population. The frequencies of different types change according to the replicator equations and the fitness of a mutant is random and frequency dependent. To capture the interactions of different types, we employ a payoff matrix of variable size and thus are able to accommodate an arbitrary number of mutations. We assume that at most one mutant type arises at a time. The payoff entries to describe the mutant type are random variables obeying a probability distribution which is related to the fitness of the parent type.

Conclusions
We show that a random mutant can decrease the average fitness under frequency dependent selection, based on analytical results for two types and simulations for n types. Interestingly, in the case of at most two types the probabilities to increase or decrease the average fitness are independent of the concrete probability density function. Instead, they only depend on the probability that the payoff entries of the mutant are larger than the payoff entries of the parent type.
Coevolution between simple sequence repeats (SSRs) and virus genome size
Authors: Zhao Xiangyan , Tian Yonglei , Yang Ronghua , Feng Haiping , Ouyang Qingjian , Tian You , Tan Zhongyang , Li Mingfu , Niu Yile , Jiang Jianhui , Shen Guoli , Yu Ruqin 
Published: August 2012

AbstractBackgroundRelationship between the level of repetitiveness in genomic sequence and genome size has been investigated by making use of complete prokaryotic and eukaryotic genomes, but relevant studies have been rarely made in virus genomes.ResultsIn this study, a total of 257 viruses were examined, which cover 90% of genera. The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size. Certain repeat class is distributed in a certain range of genome sequence length. Mono-, di- and tri- repeats are widely distributed in all virus genomes, tetra- SSRs as a common component consist in genomes which more than 100 kb in size; in the range of genome < 100 kb, genomes containing penta- and hexa- SSRs are not more than 50%. Principal components analysis (PCA) indicated that dinucleotide repeat affects the differences of SSRs most strongly among virus genomes. Results showed that SSRs tend to accumulate in larger virus genomes; and the longer genome sequence, the longer repeat units.ConclusionsWe conducted this research standing on the height of the whole virus. We concluded that genome size is an important factor in affecting the occurrence of SSRs; hosts are also responsible for the variances of SSRs content to a certain degree.
Normalization of a chromosomal contact map
Authors: Cournac Axel , Marie-Nelly Hervé , Marbouty Martial , Koszul Romain , Mozziconacci Julien 
Published: August 2012

Abstract

Background
Chromatin organization has been increasingly studied in relation with its important influence on DNA-related metabolic processes such as replication or regulation of gene expression. Since its original design ten years ago, capture of chromosome conformation (3C) has become an essential tool to investigate the overall conformation of chromosomes. It relies on the capture of long-range trans and cis interactions of chromosomal segments whose relative proportions in the final bank reflect their frequencies of interactions, hence their spatial proximity in a population of cells. The recent coupling of 3C with deep sequencing approaches now allows the generation of high resolution genome-wide chromosomal contact maps. Different protocols have been used to generate such maps in various organisms. This includes mammals, drosophila and yeast. The massive amount of raw data generated by the genomic 3C has to be carefully processed to alleviate the various biases and byproducts generated by the experiments. Our study aims at proposing a simple normalization procedure to minimize the influence of these unwanted but inevitable events on the final results.

Results
Careful analysis of the raw data generated previously for budding yeast S. cerevisiae led to the identification of three main biases affecting the final datasets, including a previously unknown bias resulting from the circularization of DNA molecules. We then developed a simple normalization procedure to process the data and allow the generation of a normalized, highly contrasted, chromosomal contact map for S. cerevisiae. The same method was then extended to the first human genome contact map. Using the normalized data, we revisited the preferential interactions originally described between subsets of discrete chromosomal features. Notably, the detection of preferential interactions between tRNA in yeast and CTCF, PolII binding sites in human can vary with the normalization procedure used.

Conclusions
We quantitatively reanalyzed the genomic 3C data obtained for S. cerevisiae, identified some of the biases inherent to the technique and proposed a simple normalization procedure to analyse them. Such an approach can be easily generalized for genomic 3C experiments in other organisms. More experiments and analysis will be necessary to reach optimal resolution and accuracies of the maps generated through these approaches. Working with cell population presenting highest levels of homogeneity will prove useful in this regards.
A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy
Authors: Chang Yi-Ping , Huang San-Kuei , Tao Ping , Chien Ching-Wen 
Published: August 2012

Abstract

Background
Because of the rapid growth in elderly population, polypharmacy has become a serious public health issue worldwide. Although acute renal failure (ARF) is one negative consequence of polypharmacy, the association between the duration of polypharmacy and ARF remains unclear. We therefore assessed this association using a population-based database.

Methods
Data were collected from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 through 2006. The case group included patients hospitalized for ARF during 2006, but not admitted due to trauma, surgery, burn trauma, car accident, transplantation, or infectious diseases; the control group included patients hospitalized without ARF. The cumulative number of days of polypharmacy (defined as more than 5 prescriptions per day) for 1 year prior to admission was determined, with patients further subdivided into 4 categories: less than 30 days, 31–90 days, 91–180 days, and over 181 days. The dependent variable was ARF, and the control variables were age, gender, comorbidities in patients hospitalized for ARF, stay in ICUs during ARF hospitalization and site of operation for prior admissions within one month of ARF hospitalization.

Results
Of 20,790 patients who were admitted to hospitals for ARF in 2006, 12,314 (59.23 %) were male and more than 60 % were older than 65 years. Of patients with and without ARF, 16.14 % and 10.61 %, respectively, received polypharmacy for 91–180 days and 50.22 % and 24.12 %, respectively, for over 181 days. A statistical model indicated that, relative to patients who received polypharmacy for less than 30 days, those who received polypharmacy for 31–90, 91–180 and over 181 days had odds ratios of developing ARF of 1.33 (p<0.001), 1.65 (p<0.001) and 1.74 (p<0.001), respectively.

Conclusions
We observed statistically significant associations between the duration of polypharmacy and the occurrence of ARF.
Association of response to hepatitis B vaccination and survival in dialysis patients
Authors: Lin Shih-Yi , Liu Jiung-Hsiun , Wang Shu-Ming , Wang I-Kuan , Tsai Chen-An , Liu Yao-lung , Lin Hsin-Hung , Chang Chiz-Chung , Huang Chiu-Ching 
Published: August 2012

Abstract

Background
The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients.

Methods
A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response.

Results
The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937).

Conclusion
There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.
The comparative effectiveness of statin therapy in selected chronic diseases compared with the remaining population
Authors: Sheng Xia , Murphy Michael J , MacDonald Thomas M , Wei Li 
Published: August 2012

Abstract

Background
Total cholesterol (TC) concentration is the most commonly used measure of statin efficacy in the UK. This study aimed to evaluate the effectiveness of statins in lowering TC, cardiovascular events (CV) and mortality five common chronic diseases (chronic obstructive pulmonary disease (COPD), osteoarthritis (OA), rheumatoid arthritis (RA), chronic kidney disease (CKD), and diabetes mellitus (DM)) and to compare effectiveness with the rest of the population not recorded as having these diseases.

Methods
A population-based cohort study was conducted in Tayside population who had at least two TC measurements between 1993 and 2007. There were 12,140 patients with chronic diseases and 9,481 patients in the rest of the population not recorded as having these chronic diseases. The main outcomes were TC change from baseline, CV events and all-cause mortality.

Results
Statin-associated TC reductions varied from 15% to 28% with baseline value of between 5.1 and 5.9 mmol/L in the primary prevention (PP) and from 7% to 23% with baseline value of 4.5 to 5.2 mmol/L in the secondary prevention (SP) among chronic diseases patients. In the rest of the population, TC reductions with statins were 31% in PP and 28% in SP with baselines of 6.3 mmol/L and 5.3 mmol/L, respectively (test of heterogeneity with chronic disease groups: p < 0.001). A notional reduction of 0.5 mmol/L in TC predicted variable reductions in incident CV events of 30% in RA, 19% in CKD, and 20% in DM, and recurrent CV events by 62% in COPD, 16% in CKD, and 19% in DM. The corresponding figures for the rest of population were 12% for incident CV events and 17% for the recurrent CV events, respectively. Risk reductions for all-cause mortality varied from 20% to 36% in PP and from 18% to 40% in SP, except in OA or RA patients in the chronic diseases and 11% in PP and 16% in the rest of population (test of heterogeneity: p > 0.05).

Conclusions
The effectiveness of statins in common chronic diseases varied. With the exception of diabetes, statins tends to be less effective in patients with the chronic diseases compared with the rest of the study population. Changes in TC with statins appear not to correlate well with the changes in cardiovascular events and all-cause mortality.
Throughput and delay analysis of network coded ALOHA in wireless networks
Authors: Lee Hyun-kwan , Hwang June , Kim Seong-Lyun , Jäntti Riku 
Published: August 2012

Abstract
The purpose of this article is to analyze the impact of network coding in wireless networks. We consider a network coded ALOHA that performs bi-directional network coding over the ALOHA MAC protocol in a star topology network. The transmission probabilities of each outer node and the center node, and the target signal-to-interference-plus-noise ratio (SINR) are jointly optimized to achieve the maximum throughput of coded ALOHA. We analyze and compare the optimal performance of slotted and coded ALOHA. Under the unsaturated traffic condition at the center node, we derive practical throughput and delay, considering the network coding opportunity and the maximum queue length of the center node. Under the saturated traffic condition, we obtain a throughput upper bound of coded ALOHA to judge the ideal gain of network coding. The impact of asymmetric topology is evaluated with simulations.
Pavement crack characteristic detection based on sparse representation
Authors: Sun Xiaoming , Huang Jianping , Liu Wanyu , Xu Mantao 
Published: August 2012

Abstract
Pavement crack detection plays an important role in pavement maintaining and management. The three-dimensional (3D) pavement crack detection technique based on laser is a recent trend due to its ability of discriminating dark areas, which are not caused by pavement distress such as tire marks, oil spills and shadows. In the field of 3D pavement crack detection, the most important thing is the accurate extraction of cracks in individual pavement profile without destroying pavement profile. So after analyzing the pavement profile signal characteristics and the changeability of pavement crack characteristics, a new method based on the sparse representation is developed to decompose pavement profile signal into a summation of the mainly pavement profile and cracks. Based on the characteristics of the pavement profile signal and crack, the mixed dictionary is constructed with an over-complete exponential function and an over-complete trapezoidal membership function, and the signal is separated by learning in this mixed dictionary with a matching pursuit algorithm. Some experiments were conducted and promising results were obtained, showing that we can detect the pavement crack efficiently and achieve a good separation of crack from pavement profile without destroying pavement profile.
Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines
Authors: Kan Anne A , de Jager Wilco , de Wit Marina , Heijnen Cobi , van Zuiden Mirjam , Ferrier Cyrill , van Rijen Peter , Gosselaar Peter , Hessel Ellen , van Nieuwenhuizen Onno , de Graan Pierre N E 
Published: August 2012

AbstractMesial temporal lobe epilepsy (mTLE) is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25). Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25) showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7) showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7) could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I) and CCL4 IR (pattern II) were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.