bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability-based topology optimization design of a linear piezoelectric micromotor using an optimum finite element method
Authors: Sadeghbeigi Olyaie Mohsen , Razfar Mohammad Reza , Wang Semyung
Published: July 2013

This article presents reliability-based topology optimization design of a linear micromotor, including multitude cantilever piezoelectric microbimorphs. This design is considered for quasi-static and linear conditions, and a relatively new computational approach called the smoothed finite element method is applied. Since microfabrication methods are used for manufacturing this type of actuator, the uncertainty variables become very important. Hence, these variables are considered as constraints during our topology optimization design process and reliability-based topology optimization is conducted. To avoid the overly-stiff behavior in finite element method modeling, the cell-based smoothed finite element method (as a branch of smoothed finite element method) has been conducted for this problem. Here, after finding the most effective random design variables using the performance measure approach and first-order reliability approximation, the topology optimization procedure is implemented in order to find an optimum piezoelectric volume fraction (as an unknown constraint for the first step) using piezoelectric material with penalization and polarization model and method of moving asymptotes optimizer. After determining problem constraints, topology optimization design is followed. This algorithm is called reliability-based design optimization using independent approach. Numerical tests show that final characters of the optimized model using cell-based smoothed finite element methods are improved compared with standard finite element methods.
Modeling systems with mobile components: a comparison between AltaRica and PEPA nets
Authors: Kloul Leila , Prosvirnova Tatiana , Rauzy Antoine
Published: July 2013

Assessing the reliability of systems with mobile components, that is components whose locations and interactions change during the mission of the system, raises a number of specific modeling issues. In this article, we compare two candidate modeling formalisms to do so: AltaRica and PEPA nets. We study their respective advantages and drawbacks and we show benefits of a cross fertilization.
Compliance versus risk assessment: when have we done enough?
Authors: Parkinson Howard J
Published: July 2013

In the UK railway it is necessary to show that risks relating to any design solutions are as-low-as-reasonably-practicable. It is a legal requirement and in certain instances complying with a standard may be enough. However, in other circumstances we may have to perform a formal risk assessment. It seems clear that there is a continuum between the two positions but how do we know what to do and if that is enough? This article seeks to address the question. The UK risk acceptance approach, including the as-low-as-reasonably-practicable principle, is explored and the recent initiative of the common safety method is discussed. An example of a compliance safety process against standards is given using a case study based upon changes to rolling stock. A further example where risk assessment and a cost benefit analysis have been employed to support a safety argument for a non-compliant gradient is then presented, followed by concluding remarks.
Keeping a finger on the pulse: Cardiovascular disease rate as a measure of sustainable development
Authors: Hasan Nazeeha
Published: July 2013

Non-communicable diseases have been somewhat neglected as a public health issue in the past, but there is now growing international consensus that they present a significant obstacle to economic development for both high- and low-income countries. Cardiovascular disease accounts for more than half of all non-communicable disease deaths, and presents a promising target for curbing the non-communicable disease epidemic. This article explains the pressing need for non-communicable disease prevention, focusing on strategies that can be employed to decrease cardiovascular disease risk at an individual and population level, and outlines the UK’s approaches to cardiovascular disease prevention in particular. Given the mounting burden of non-communicable diseases, responsible health governance and a balanced economic policy could consider the use of low cardiovascular disease rates as a measure of positive and sustainable economic development.
Is the Pro-Network Bias Justified?
Authors: Pardo Rafael , Rama Ruth
Published: July 2013

The academic literature, policy makers, and international organizations often emphasize the value of networks that, allegedly, may contribute to subcontractor upgrading, innovation, and economic welfare. By contrast, it is difficult to assess whether engagement in production outsourcing networks also accrues some advantages to outsourcers (contractors). To research differences between these organizations and vertically integrated organizations, we analyzed a sample of 1,031 industrial plants, statistically representative of firms with more than 50 employees in Spain’s manufacturing industry. We used t-tests, nonparametric tests, and chi-square tests, and hypotheses were tested for three subsets of companies, classified by the R&D intensity of the industry. In each set of industries, subcontracting is systematically associated with small batch production. By contrast, vertically integrated plants are more inclined to use mass production. In every type of industry, subcontracting is a form of governance especially efficient for the diffusion of new technology. Plants that subcontract production are more likely than integrated plants to adopt advanced manufacturing technology, whatever the R&D intensity of the industry. We conclude that outsourcers seem better prepared than vertically integrated organizations to meet customers’ requirements but employment of subcontracting do not lower necessarily their technology needs—a widespread “pro-network” argument.
Salter Harris Fractures of the Distal Femur
Authors: McKenna Sean M. , Hamilton Steven W. , Barker Simon L.
Published: July 2013

Salter Harris–type injuries of the distal femur should be treated as a dislocation of the knee and therefore as a medical emergency. Senior medical staff should be involved early, ankle–brachial index ratio should be measured in all patients and the clinician should have a high index of suspicion for a vascular injury. Ideally reduction, stabilization, and vascular repair, if necessary, should be carried out within 6 hours of the initial event. There should be a low threshold for fasciotomies. These 2 cases demonstrate the importance of having a high index of suspicion for vascular injury and the need for continued reassessment.
The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment
Authors: Gotlib Jason , Maxson Julia E. , George Tracy I. , Tyner Jeffrey W.
Published: July 2013

Although activation of tyrosine kinase pathways is a shared theme among myeloproliferative neoplasms, the pathogenetic basis of chronic neutrophilic leukemia (CNL) has remained elusive. Recently, we identified high-frequency oncogenic mutations in the granulocyte-colony stimulating factor receptor (CSF3R) in CNL and in some patients with atypical chronic myeloid leukemia. Inhibition of Janus kinase 2 or SRC kinase signaling downstream of mutated CSF3R is feasible and should be explored therapeutically. Herein, we discuss the potential impact of these findings for the classification and treatment of these disorders.
Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer
Authors: Han Lin-Lin , Hou Lin , Zhou Ming-Jin , Ma Zhong-liang , Lin Dong-Liang , Wu Li , Ge Yin-lin
Published: July 2013

Background

Cancer cell differentiation is an important characteristic of malignant tumor and has a great impact on prognosis and therapeutic decision for patients. The N-myc downstream regulated gene 1 (NDRG1), a putative tumor suppression gene, is involved in the regulation of human cell differentiation and metastasis in various cancers. Changes in the status of methylation of the NDRG1 gene have not been studied in detail in human breast cancer.

Results

The MDA-MB-231 breast tumor cell line could express NDRG1. However, it was only expressed after treatment with 5-Aza-2'-deoxycytidine (AZA) in T47D cell line, which revealed that NDRG1 expression could modulated by DNA methylation. Therefore, the fragment surrounding the transcript start site of NDRG1 gene promoter was cloned after sodium bisulfite DNA treatment. A high density (66%) of methylation for human NDRG1 gene promoter was detected in T47D; however, there was only 16% of methylated CpG dinucleotides in the NDRG1 gene promoter in MDA-MB-231. DNA methylation in the NDRG1 promoter was detected in 31.1% of primary breast cancer samples. Furthermore, the NDRG1 promoter methylation correlated with the Tumor Node Metastasis (TNM) at stage III/IV, metastasis, lymph invasion, moderate and poor histological grade in the breast cancer patients.

Conclusion

These findings suggest that the DNA methylation status of NDRG1 gene may play an important role in the pathogenesis and/or development of breast cancer, and the expression could be regulated by aberrant DNA methylation.
Data-mining the FlyAtlas online resource to identify core functional motifs across transporting epithelia
Authors: Chintapalli Venkateswara R , Wang Jing , Herzyk Pawel , Davies Shireen A , Dow Julian AT
Published: July 2013

Background

Comparative analysis of tissue-specific transcriptomes is a powerful technique to uncover tissue functions. Our FlyAtlas.org provides authoritative gene expression levels for multiple tissues of Drosophila melanogaster (1). Although the main use of such resources is single gene lookup, there is the potential for powerful meta-analysis to address questions that could not easily be framed otherwise. Here, we illustrate the power of data-mining of FlyAtlas data by comparing epithelial transcriptomes to identify a core set of highly-expressed genes, across the four major epithelial tissues (salivary glands, Malpighian tubules, midgut and hindgut) of both adults and larvae.

Method

Parallel hypothesis-led and hypothesis-free approaches were adopted to identify core genes that underpin insect epithelial function. In the former, gene lists were created from transport processes identified in the literature, and their expression profiles mapped from the flyatlas.org online dataset. In the latter, gene enrichment lists were prepared for each epithelium, and genes (both transport related and unrelated) consistently enriched in transporting epithelia identified.

Results

A key set of transport genes, comprising V-ATPases, cation exchangers, aquaporins, potassium and chloride channels, and carbonic anhydrase, was found to be highly enriched across the epithelial tissues, compared with the whole fly. Additionally, a further set of genes that had not been predicted to have epithelial roles, were co-expressed with the core transporters, extending our view of what makes a transporting epithelium work. Further insights were obtained by studying the genes uniquely overexpressed in each epithelium; for example, the salivary gland expresses lipases, the midgut organic solute transporters, the tubules specialize for purine metabolism and the hindgut overexpresses still unknown genes.

Conclusion

Taken together, these data provide a unique insight into epithelial function in this key model insect, and a framework for comparison with other species. They also provide a methodology for function-led datamining of FlyAtlas.org and other multi-tissue expression datasets.
Directional RNA-seq reveals highly complex condition-dependent transcriptomes in E. coli K12 through accurate full-length transcripts assembling
Authors: Li Shan , Dong Xia , Su Zhengchang
Published: July 2013

Background

Although prokaryotic gene transcription has been studied over decades, many aspects of the process remain poorly understood. Particularly, recent studies have revealed that transcriptomes in many prokaryotes are far more complex than previously thought. Genes in an operon are often alternatively and dynamically transcribed under different conditions, and a large portion of genes and intergenic regions have antisense RNA (asRNA) and non-coding RNA (ncRNA) transcripts, respectively. Ironically, similar studies have not been conducted in the model bacterium E coli K12, thus it is unknown whether or not the bacterium possesses similar complex transcriptomes. Furthermore, although RNA-seq becomes the major method for analyzing the complexity of prokaryotic transcriptome, it is still a challenging task to accurately assemble full length transcripts using short RNA-seq reads.

Results

To fill these gaps, we have profiled the transcriptomes of E. coli K12 under different culture conditions and growth phases using a highly specific directional RNA-seq technique that can capture various types of transcripts in the bacterial cells, combined with a highly accurate and robust algorithm and tool TruHMM (http://bioinfolab.uncc.edu/TruHmm_package/) for assembling full length transcripts. We found that 46.9 ~ 63.4% of expressed operons were utilized in their putative alternative forms, 72.23 ~ 89.54% genes had putative asRNA transcripts and 51.37 ~ 72.74% intergenic regions had putative ncRNA transcripts under different culture conditions and growth phases.

Conclusions

As has been demonstrated in many other prokaryotes, E. coli K12 also has a highly complex and dynamic transcriptomes under different culture conditions and growth phases. Such complex and dynamic transcriptomes might play important roles in the physiology of the bacterium. TruHMM is a highly accurate and robust algorithm for assembling full-length transcripts in prokaryotes using directional RNA-seq short reads.
Staphylococcus aureus but not Listeria monocytogenes adapt to triclosan and adaptation correlates with increased fabI expression and agr deficiency
Authors: Nielsen Lene Nørby , Larsen Marianne Halberg , Skovgaard Sissel , Kastbjerg Vicky , Westh Henrik , Gram Lone , Ingmer Hanne
Published: July 2013

Background

The ability of pathogens to adapt to the widely used biocide, triclosan, varies substantially. The purpose of the study was to examine bacterial adaptation over an extended period of time to low increments of triclosan concentrations. Focus was two human pathogens, S. aureus and L. monocytogenes that previously have displayed inherent high and low adaptability, respectively.

Results

Three strains of L. monocytogenes and two strains of S. aureus including the community-acquired USA300 were exposed to increasing, sub-lethal concentrations of triclosan in triclosan-containing agar gradients. Following 25 days of exposure on agar plates to sub-lethal concentrations of triclosan with a twofold concentration increase every second day, minimum inhibitory concentration (MIC) for S. aureus increased from 0.125 (8325–4) and 0.0625 (USA 300) mg/L to 4 mg/L. The MIC of all three L. monocytogenes strains was initially 4 mg/L and remained unaltered by the exposure. The adapted S. aureus isolates retained normal colony size but displayed increased expression of fabI encoding an essential enzyme in bacterial fatty acid synthesis. Also, they displayed decreased or no expression of the virulence associated agrC of the agr quorum sensing system. While most adapted strains of USA300 carried mutations in fabI, none of the adapted strains of 8325–4 did.

Conclusions

Adaptability to triclosan varies substantially between Gram positive human pathogens. S. aureus displayed an intrinsically lower MIC for triclosan compared to L. monocytogenes but was easily adapted leading to the same MIC as L. monocytogenes. Even though all adapted S. aureus strains over-expressed fabI and eliminated expression of the agr quorum sensing system, adaptation in USA300 involved fabI mutations whereas this was not the case for 8325–4. Thus, adaptation to triclosan by S. aureus appears to involve multiple genetic pathways.
Herbal-drug interaction induced rhabdomyolysis in a liposarcoma patient receiving trabectedin
Authors: Strippoli Sabino , Lorusso Vito , Albano Anna , Guida Michele
Published: July 2013

Background

Rhabdomyolysis is an uncommon side effect of trabectedin which is used for the second line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. This side effect may be due to pharmacokinetic interactions caused by shared mechanisms of metabolism involving the cytochrome P450 (CYP) system in the liver. Here, for the first time in literature, we describe the unexpected onset of heavy toxicity, including rhabdomyolysis, after the fourth course of trabectedin in a patient with retroperitoneal liposarcoma who at the same time was taking an alternative herbal medicine suspected of triggering this adverse event.

Case presentation

This is the case of a 56 year old Caucasian man affected by a relapsed de-differentiated liposarcoma who, after the fourth cycle of second-line chemotherapy with trabectedin, complained of sudden weakness, difficulty walking and diffuse muscle pain necessitating complete bed rest. Upon admission to our ward the patient showed grade (G) 4 pancytopenia and a marked increase in liver lytic enzymes, serum levels of myoglobin, creatine phosphokinase (CPK) and lactate dehydrogenase. No cardiac or kidney function injuries were present. Based on these clinical and laboratory features, our conclusive diagnosis was of rhabdomyolysis induced by trabectedin.

The patient did not report any trauma or muscular overexertion and no co-morbidities were present. He had not received any drugs during treatment with trabectedin, but upon further questioning the patient informed us he had been taking a folk medicine preparation of chokeberry (Aronia melanocarpa) daily during the last course of trabectedin and in the 2 subsequent weeks.

One week after hospitalization and cessation of intake of chokeberry extract, CPK and other markers of myolysis slowly returned to standard range, and the patient noted a progressive recovery of muscle strength.

The patient was discharged on day 14 when a blood transfusion and parenteral hydration gradually lowered general toxicity. Progressive mobilization of the patient was obtained as well as a complete normalization of the laboratory findings.

Conclusions

The level of evidence of drug interaction leading to the adverse event observed in our patient was 2 (probable). Thus our case underlines the importance of understanding rare treatment-related toxicities such as trabectedin-induced rhabdomyolysis and the possible role of the drug-drug interactions in the pathogenesis of this rare side effect. Furthermore, this report draws attention to a potential problem of particular concern, that of nutritional supplements and complementary and alternative drug interactions. These are not widely recognized and can cause treatment failure.
The Burnaby treatment center for mental health and addiction, a novel integrated treatment program for patients with addiction and concurrent disorders: results from a program evaluation
Authors: Schütz Christian , Linden Isabelle Aubé , Torchalla Iris , Li Kathy , Al-Desouki Majid , Krausz Michael
Published: July 2013

Background

Patients with addictions and concurrent disorders constitute the most underserved population in the system of care. There are numerous reasons why this population has so much difficulty accessing services, including behavioural issues, criminal engagement, and non-compliance with outpatient services. To improve services to this population which is marked by multiple morbidities, high mortality and insufficient access to health care, the government of British Columbia, Canada developed a program for people with both substance use disorder and one or more mental disorders who have not benefited from previous therapies.

Method

In July 2008, the Burnaby Treatment Centre for Mental Health and Addiction (BCMHA), a specialized and integrated tertiary care facility, was opened. The current article provides a description of the treatment program and a clinical profile of the population.

Results

The target population is being served, at intake clients present with high rates of psychopathology, childhood and adult trauma, and substance use.

Conclusion

While preliminary, these results indicate, that the novel approach of the Burnaby Centre may constitute a new path towards providing effective recovery for this population.
Dietary nutrient intake and metabolic syndrome risk in Chinese adults: a case–control study
Authors: Bian Shanshan , Gao Yuxia , Zhang Meilin , Wang Xuan , Liu Weiqiao , Zhang Dalong , Huang Guowei
Published: July 2013

Background

Because human diets are composed of a wide variety of nutrients that may work synergistically to prevent or promote disease, assessing dietary nutrient intake status may be informative. The purpose of this study was to assess the dietary nutrient intake status of Chinese adults with metabolic syndrome (MetS) and to evaluate its possible role in MetS.

Methods

This case–control study was conducted from March 2010 to January 2011. A total of 123 patients with MetS and 135 controls participated in this study at the Health Examination Center of Heping District in Tianjin, China. Dietary intake was estimated by 24-h dietary recalls. We used principal component factor analysis to derive nutrient groups from 17 major nutrients. We examined the odds ratios and 95% confidence intervals using logistic regression models to test the relationship between tertiles of dietary nutrient pattern and MetS.

Results

There were 4 major dietary nutrient patterns in this study: “vitamin B group”, “protein and lipids”, “vitamin E and minerals”, and “antioxidant vitamins”. After adjustment for potential confounders, the highest tertile of the nutrient pattern factor score for the “vitamin B group” (odds ratio: 0.16; 95% confidence interval: 0.05–0.47) was negatively associated with MetS compared with the lowest tertiles. No relationships were found between other dietary nutrient patterns and MetS.

Conclusions

The “vitamin B group” pattern was inversely associated with MetS in Chinese adults. This finding supports the hypothesis that the “vitamin B group” pattern may have a potentially beneficial effect on the prevention of MetS.
Rs12218 In SAA1 gene was associated with serum lipid levels
Authors: Xu Xiao-Lin , Sun Xiao-Tian , Pang Liewen , Huang Guoqian , Huang Jiechun , Shi Meng , Wang Yi-Qing
Published: July 2013

Background

Serum amyloid A (SAA) is a kind of apolipoprotein. Several studies indicated that SAA genetic polymorphism rs12218 was associated with carotid atherosclerosis, peripheral arterial disease, and serum uric acid levels. However, the relation between rs12218 and lipid levels remains unclear. This study assessed the correlation between SAA1 gene rs12218 polymorphism and lipid levels in a Chinese population.

Methods

A total of 823 participants were selected from the subjects for health check in Shanghai Huashan hospital from Jan. 2013 to Mach. 2013. Correlations between rs12218 polymorphism and lipid levels were investigated through the identification of rs12218 genotypes using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results

We found that the SNP rs12218 was associated with triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels by analyses of a dominant model (P<0.001, P=0.002, P=0.003, respectively), a recessive model (P <0.001, P=0.001, P=0.005, respectively) and an additive model (P < 0.001, P=0.001, P=0.002, respectively), and the difference remained significant after the adjustment of sex, age, alcohol intake, and smoking (All P < 0.01).

Conclusion

Our results indicated that the rs12218 in the SAA1 gene was associated with lipid levels in a Chinese population.
Modification of the fatty acid composition of the erythrocyte membrane in patients with chronic respiratory diseases
Authors: Novgorodtseva Tatyana P. , Denisenko Yulia K. , Zhukova Natalia V. , Antonyuk Marina V. , Knyshova Vera V. , Gvozdenko Tatyana A.
Published: July 2013

Background

Early preclinical diagnosis of COPD is urgent. We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases. Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied. It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients.

Methods

Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic. The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFα, sTNF-RI, bFGF, TGF-β, IL-8). Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography. Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0.

Results

In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established. The amount of the arachidonic acid (20:4n-6) was increased by 13% (р < 0.05) in CB patients and by 41% (р < 0.001) in COPD patients, as compared with healthy persons. The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased. The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (р < 0.05) in CB patients and 2-fold (р < 0.001) in COPD patients. The observed increase in the 20:4n-6/20:5n-3 ratio - 1.5-fold (р < 0.001) in CB patients and 3-fold in COPD patients - can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development.

Conclusions

Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids.
Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling
Authors: Kosla Jan , Paňková Daniela , Plachý Jiří , Tolde Ondřej , Bicanová Kristýna , Dvořák Michal , Rösel Daniel , Brábek Jan
Published: July 2013

Background

Although there is extensive evidence for the amoeboid invasiveness of cancer cells in vitro, much less is known about the role of amoeboid invasiveness in metastasis and the importance of Rho/ROCK/MLC signaling in this process.

Results

We analyzed the dependence of amoeboid invasiveness of rat and chicken sarcoma cells and the metastatic activity of chicken cells on individual elements of the Rho/ROCK/MLC pathway. In both animal models, inhibition of Rho, ROCK or MLC resulted in greatly decreased cell invasiveness in vitro, while inhibition of extracellular proteases using a broad spectrum inhibitor did not have a significant effect. The inhibition of both Rho activity and MLC phosphorylation by dominant negative mutants led to a decreased capability of chicken sarcoma cells to metastasize. Moreover, the overexpression of RhoA in non-metastatic chicken cells resulted in the rescue of both invasiveness and metastatic capability. Rho and ROCK, unlike MLC, appeared to be directly involved in the maintenance of the amoeboid phenotype, as their inhibition resulted in the amoeboid-mesenchymal transition in analyzed cell lines.

Conclusion

Taken together, these results suggest that protease-independent invasion controlled by elements of the Rho/ROCK/MLC pathway can be frequently exploited by metastatic sarcoma cells.
Armigeres subalbatus incriminated as a vector of zoonotic Brugia pahangi filariasis in suburban Kuala Lumpur, Peninsular Malaysia
Authors: Muslim Azdayanti , Fong Mun-Yik , Mahmud Rohela , Lau Yee-Ling , Sivanandam Sinnadurai
Published: July 2013

Background

In 2011, we reported occurrence of natural human infections with Brugia pahangi, a filarial worm of dogs and cats, in a surburb of Kuala Lumpur, the capital city of Malaysia. Our preliminary entomological survey at that time suggested the mosquito species Armigeres subalbatus as the vector of the zoonotic infections. In this present report, we provide biological evidence to confirm our preliminary finding.

Findings

A total of 1798 adult female Ar. subalbatus mosquitoes was caught in the vicinity of the suburb, and 1599 were dissected for the presence of filarial larvae. Sixty-two mosquitoes were positive, and 27 of these were infected with L3 larvae. The L3 were inoculated into male gerbils. Microfilariae could be detected in the gerbils 92 days post-infection. Post-mortem on the gerbils recovered adult worms in the peritoneal cavity, heart, lungs, tail and testis. Male adult worms were confirmed to be B. pahangi by the ratio length of their spicules (left spicule: right spicule). Female adult worms were confirmed by the absence of minute cuticular bosses in the tail region. The worms were further confirmed to be B. pahangi by PCR.

Conclusions

Our results showed that Ar. subalbatus was the vector for the zoonotic Brugia pahangi infections. This mosquito species should now be categorised as a medically important mosquito species in Malaysia. Its role in the transmission of zoonotic B. pahangi must therefore be considered in future studies on filarial infections.
Overexpression of WDR62 is associated with centrosome amplification in human ovarian cancer
Authors: Zhang Yu , Tian Yan , Yu Jing-Jing , He Jie , Luo Jia , Zhang Sai , Tang Cen-E , Tao Yi-ming
Published: July 2013

Purpose

To assess the clinical significance of WD40 repeat containing 62 (WDR62), a novel centrosome abnormalities-associated gene, in ovarian cancer.

Materials and methods

In this study, WDR62 expression was assessed by western blot (6 ovarian cancer cell lines) and immunohistochemistry (primary epithelial ovarian cancer clinical specimens), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence staining in ovarian cancer cell lines, and by immunohistochemistry staining in ovarian cancer samples.

Results

Six ovarian cancer cell lines exhibited significant WDR62 protein overexpression, and amplification of centrosome. High-grade ovarian cancer specimens exhibited significantly stronger nuclear staining of WDR62 than low-grade ovarian carcinoma specimens (80.4% vs 41.3%; P<0.012). High WDR62 expression was strongly associated with supernumerary centrosome count in tumor cells (P < 0.001).

Conclusion

Our findings suggest that WDR62 overexpression is related to centrosome amplification in ovarian cancer. It may be a novel useful differentiation biomarker and a potential therapy target for OC. Further assessment of WDR62 expression is highly warranted in large, prospective studies.
Geospatial variability in the autumn community structure of epipelagic zooplankton in the upper layer of the northern South China Sea
Authors: Tseng Li-Chun , Dahms Hans-Uwe , Chen Qing-Chao , Hwang Jiang-Shiou
Published: July 2013

Background

For the present study, we collected mesozooplankton in the upper layer (above 100 m in depth) of four stations in the northern South China Sea (SCS) to determine the influence of different water masses on their distribution and abundance from 27 September to 2 October 1999.

Results

In total, 18 major zooplankton taxa were recovered from the samples. Calanoid copepods, Noctilucales, and chaetognaths were dominant and together comprised 65.90% of the overall zooplankton counts. Zooplankton densities ranged from 102.19 to 1,285.24 individuals per cubic meters (ind./m3) (average, 306.38 ± 435.71). Noctilucales were abundant at stations located in the Kuroshio Current (KC) intrusion area. Integrating all samples, 32 copepod species were identified consisting of 23 genera belonging to 16 families. Total copepod abundances ranged from 30.24 to 311.17 ind./m3(average, 99.14 ± 97.84). Numerically,Pleuromamma gracilis,Nannocalanus minor, andLucicutia flavicorniswere the most dominant species. The most frequently occurring species in all samples wereAcartia(Acartia)negligensandCorycaeus(Farranula)gibbula. Results of a cluster analysis indicated that community structures of zooplankton and copepods of the northern SCS varied at geospatial scales during the sampling period.

Conclusions

Results of the present study suggest that the composition and community structure of zooplankton and copepods were influenced by intrusion of the KC in the shallow layer above 100 m in depth in the northern SCS. Some indicator species characteristic of the KC indicated that the study area received water masses from the northern SCS and the KC.
Systemic dysregulation of TDP-43 binding microRNAs in amyotrophic lateral sclerosis
Authors: Freischmidt Axel , Müller Kathrin , Ludolph Albert C , Weishaupt Jochen H
Published: July 2013

Background

A pathological hallmark of most amyotrophic lateral sclerosis (ALS) cases are intracellular aggregates of the protein TDP-43. The pathophysiological relevance of TDP-43 is underlined by familial ALS cases caused by TDP-43 mutations. TDP-43 is involved in processing of both coding RNAs and microRNAs, which are key epigenetic regulators of transcriptome plasticity and suspected to contribute to neurological diseases. We therefore asked whether the TDP-43 binding microRNAs recently identified in cell lines are also dysregulated in ALS patients. We compared their abundance in cerebrospinal fluid (CSF), serum and immortalized lymphoblast cell lines (LCLs) derived from ALS patients and healthy controls.

Results

We found that expression levels of 5 out of 9 TDP-43 binding microRNAs were altered in the CSF and serum of sporadic ALS cases. The differentially regulated serum microRNAs together with a poor correlation between CSF and serum levels indicate a systemic dysregulation of microRNA abundance independent from the CSF compartment, in line with the ubiquitous expression of TDP-43. The most strongly regulated microRNAs could be confirmed in LCLs from genetically defined ALS patients. While dysregulation of miR-143-5p/3p seems to be a common feature of ALS pathology, downregulation of miR-132-5p/3p and miR-574-5p/3p was evident in sporadic, TARDBP, FUS and C9ORF72, but not SOD1 mutant patients. This parallels the TDP-43 pathology found in most ALS cases, but usually not in patients with SOD1 mutation.

Conclusions

We thus report a systemic and genotype-dependent dysregulation of TDP-43 binding microRNAs in human biomaterial that might reflect an easily accessible biological measure of TDP-43 dysfunction. Furthermore we suggest an independent regulation of TDP-43 binding microRNAs in the serum and CSF compartment as well as a generally low transition of microRNAs across the blood-cerebrospinal fluid barrier.
Autoimmune diseases and hypersensitivities improve the prognosis in ER-negative breast cancer
Authors: Einefors Rickard , Kogler Ulrika , Ellberg Carolina , Olsson Håkan
Published: July 2013

Introduction

Breast cancer (BC) is one of the leading causes of death among women worldwide. Immunostimulatory treatment has increasingly been used as adjuvant therapy in the last few years, in patients with melanoma and other cancer forms, often with an induction of autoimmunity as a consequence of a successful treatment. We aimed at investigating if coexisting autoimmune diseases (AD) or hypersensitivities (HS) similarly to the side effects of immunostimulatory treatment resulted in a better overall survival, compared to patients without these disorders.

Material and methods

The patient material used was a consecutive clinical material consisting of 1705 patients diagnosed with BC between 1980 and 2010 in Sweden. The patients were stratified according to coexisting AD, HS or lack of both. Overall survival was calculated using Kaplan-Meier and the Cox proportional hazard model.

Results

Our main finding was that BC patients with estrogen receptor (ER) negative tumors together with preexisting AD or HS had a statistically significant better overall survival (HR=0.53; 95% CI= 0.30-0.96) compared to patients without. Premenopausal BC patients with a coexistence of AD or HS had a better overall survival, but this was not statistically significant.

Discussion

For patients with premenopausal or ER-negative BC, coexistence with AD or HS was associated with a better overall survival. Although these findings require validation, and the mechanisms responsible need to be found, they hint to possible new treatment strategies for BC, especially for those with ER-negative tumors and potentially for premenopausal patients.
Randomized, Phase II, Placebo-Controlled, Double-Blind Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin As First-Line Treatment Followed by Maintenance Treatment in Advanced Ovarian Cancer
Authors: Vergote Ignace B. , Chekerov Radoslav , Amant Frederic , Harter Philipp , Casado Antonio , Emerich Janusz , Bauknecht Thomas , Mansouri Kambiz , Myrand Scott P. , Nguyen Tuan S. , Shi Peipei , Sehouli Jalid
Published: July 2013

Purpose

Enzastaurin is an oral serine/threonine kinase inhibitor antitumor agent. Our phase II trial tested the efficacy and safety of enzastaurin added to a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly diagnosed advanced ovarian cancer.

Patients and Methods

This was a randomized, placebo-controlled study in patients with International Federation of Gynecology and Obstetrics stage IIB to IV ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin ± enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo). Primary end point was progression-free survival (PFS). Secondary measures included response rate, safety assessment, and translational research.

Results

A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n = 73). Patients in the PCE group had a 3.7-month longer median PFS compared with patients in the PC group; this was not statistically significant (hazard ratio [HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms were comparable. Frequency of discontinuation because of adverse events was similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51; 95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40). Translational research of immunohistochemistry protein assays did not identify any markers significantly associated with treatment difference regarding PFS.

Conclusion

The PCE combination increased PFS, but it was not significantly superior to PC in this phase II study.
Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma
Authors: Smith Sonali M. , Burns Linda J. , van Besien Koen , LeRademacher Jennifer , He Wensheng , Fenske Timothy S. , Suzuki Ritsuro , Hsu Jack W. , Schouten Harry C. , Hale Gregory A. , Holmberg Leona A. , Sureda Anna , Freytes Cesar O. , Maziarz Richard Thomas , Inwards David J. , Gale Robert Peter , Gross Thomas G. , Cairo Mitchell S. , Costa Luciano J. , Lazarus Hillard M. , Wiernik Peter H. , Maharaj Dipnarine , Laport Ginna G. , Montoto Silvia , Hari Parameswaran N.
Published: July 2013

Purpose

To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma.

Patients and Methods

Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes.

Results

AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival.

Conclusion

These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology.
Sorafenib in Combination With Intensive Chemotherapy in Elderly Patients With Acute Myeloid Leukemia: Results From a Randomized, Placebo-Controlled Trial
Authors: Serve Hubert , Krug Utz , Wagner Ruth , Sauerland M. Cristina , Heinecke Achim , Brunnberg Uta , Schaich Markus , Ottmann Oliver , Duyster Justus , Wandt Hannes , Fischer Thomas , Giagounidis Aristoteles , Neubauer Andreas , Reichle Albrecht , Aulitzky Walter , Noppeney Richard , Blau Igor , Kunzmann Volker , Stuhlmann Reingard , Krämer Alwin , Kreuzer Karl-Anton , Brandts Christian , Steffen Björn , Thiede Christian , Müller-Tidow Carsten , Ehninger Gerhard , Berdel Wolfgang E.
Published: July 2013

Purpose

The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML.

Patients and Methods

All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives.

Results

Age, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity.

Conclusion

In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
Prevalence and Co-Occurrence of Actionable Genomic Alterations in High-Grade Bladder Cancer
Authors: Iyer Gopa , Al-Ahmadie Hikmat , Schultz Nikolaus , Hanrahan Aphrothiti J. , Ostrovnaya Irina , Balar Arjun V. , Kim Philip H. , Lin Oscar , Weinhold Nils , Sander Chris , Zabor Emily C. , Janakiraman Manickam , Garcia-Grossman Ilana R. , Heguy Adriana , Viale Agnes , Bochner Bernard H. , Reuter Victor E. , Bajorin Dean F. , Milowsky Matthew I. , Taylor Barry S. , Solit David B.
Published: July 2013

Purpose

We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with high-grade bladder cancer to serve as a platform for therapeutic drug discovery.

Patients and Methods

An integrative analysis of 97 high-grade bladder tumors was conducted to identify actionable drug targets, which are defined as genomic alterations that have been clinically validated in another cancer type (eg, BRAF mutation) or alterations for which a selective inhibitor of the target or pathway is under clinical investigation. DNA copy number alterations (CNAs) were defined by using array comparative genomic hybridization. Mutation profiling was performed by using both mass spectroscopy-based genotyping and Sanger sequencing.

Results

Sixty-one percent of tumors harbored potentially actionable genomic alterations. A core pathway analysis of the integrated data set revealed a nonoverlapping pattern of mutations in the RTK-RAS-RAF and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways and regulators of G1-S cell cycle progression. Unsupervised clustering of CNAs defined two distinct classes of bladder tumors that differed in the degree of their CNA burden. Integration of mutation and copy number analyses revealed that mutations in TP53 and RB1 were significantly more common in tumors with a high CNA burden (P < .001 and P < .003, respectively).

Conclusion

High-grade bladder cancer possesses substantial genomic heterogeneity. The majority of tumors harbor potentially tractable genomic alterations that may predict for response to target-selective agents. Given the genomic diversity of bladder cancers, optimal development of target-specific agents will require pretreatment genomic characterization.
Can You Help Me Feel Less Exhausted All the Time?
Authors: de Raaf Pleun J. , van der Rijt Carin C.D.
Published: July 2013

A 64-year-old woman with metastatic rectal cancer is admitted to the acute palliative care unit of our cancer center because of debilitating fatigue. She had been diagnosed with metastatic disease in 2009, when liver metastases were found 1 year after the primary treatment of her rectal cancer with preoperative radiotherapy and low anterior resection. Since then, she had been treated with resection of liver metastases in 2009 and 2010, palliative combination chemotherapy (oxaliplatin plus capecitabine) after the diagnosis of new liver and lung metastases in 2010, irinotecan in 2011, and then cetuximab until progression. She declined participation in a phase I clinical trial because she was afraid of experiencing adverse effects; she felt relatively well at the time. She had functioned without hindering symptoms until 2 weeks before admission. Her condition had deteriorated markedly since then. At admission, she is bedridden because of progressive fatigue. Furthermore, she complains of dyspnea and nausea and vomits approximately twice per day. She also suffers from pain in the upper abdomen, especially when rising from the bed. She is no longer able to care for her 84-year-old husband or her 40-year-old mentally disabled son, who lives with them. She is aware of her poor prognosis but is not able to share her sorrows with her family.