bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative
Authors: He Dengming , Guo Shimin , Chen Wen , Chen Xianli , Yan Guohua , Wang Jie , Li Maoshi , Zhu Peng , Huang Hongfei , Wang Yuming
Published: October 2013

Background

Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study.

Methods

A total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart.

Results

The time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12–24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96–168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12–48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients.

Conclusions

NUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response.
Potentially modifiable factors associated with non-adherence to phosphate binder use in patients on hemodialysis
Authors: Martins Maria Tereza Silveira , Silva Luciana Ferreira , Kraychete Angiolina , Reis Dandara , Dias Lidiane , Schnitman Gabriel , Oliveira Lívia , Lopes Gildete Barreto , Lopes Antonio Alberto
Published: October 2013

Background

Despite the evidence that phosphate binder (PB) is associated with improved outcomes many hemodialysis patients do not adhere to prescribed PB regimen. Therefore, barriers to PB adherence should be identified and eliminated. The purpose of this study was to evaluate PB adherence among hemodialysis patients and to explore potentially modifiable factors associated with low PB adherence.

Methods

A cross-sectional study (502 patients) was performed in four dialysis units in Salvador, Brazil, using data from the second phase of the Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO). Patients were categorized as adherent or non-adherent to PB based on their responses to a semi-structured questionnaire.

Results

Non-adherence to PB was observed for 65.7% of the patients. After adjustments for numerous covariates, cerebrovascular disease (odds ratio (OR), 3.30; 95% confidence interval (CI), 1.03-10.61), higher PTH (OR per each 300 pg/mL, 1.14; 95% CI, 1.01-1.28), lack of comprehension of the appropriate time to use PB (OR, 7.09; 95% CI, 2.10-23.95) and stopping PB use after feeling better (OR, 4.54; 95% CI, 1.45-14.25) or feeling worse (OR, 11.04; 95% CI, 1.79- 68.03) were significantly associated with PB non-adherence. By contrast, the adjusted odds of PB non-adherence were lower for patients with more years on dialysis (OR by each 2 years, 0.87; 95% CI, 0.80-0.95), with serum phosphorus above 5.5 mg/dL (OR, 0.53; 95% CI 0.34-0.82), who referred that were encouraged by the dialysis staff to be independent (OR, 0.52; 95% CI 0.30-0.90), and reported that the nephrologist explained how PB should be used (OR, 0.20; 95% CI 0.05-0.73).

Conclusion

The results of the present study are encouraging by showing evidence that improvement in the care provided by the dialysis staff and the attending nephrologist may play an important role in reducing the high prevalence of non-adherence to PB in maintenance hemodialysis patients. A new questionnaire is presented and may help to evaluate systematically the patients regarding PB adherence in hemodialysis setting.
Identification of genetic contribution to ischemic stroke by screening of single nucleotide polymorphisms in stroke patients by using a case control study design
Authors: Kumar Amit , Sagar Ram , Kumar Pradeep , Sahu Jitendra K , Grover Ashoo , Srivastava Achal K , Vivekanandhan S , Prasad Kameshwar
Published: October 2013

Background

Stroke is the second most common cause of death and disability worldwide. It is a multi-factorial disease influenced by both environmental and genetic factors. Studies from the different ethnic regions of world have reported variable results on association of Apolioprotein E (APOE), Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), beta-fibrinogen and Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence from the European descent genetic studies showing that genetic risk of stroke varies as per specific subtypes of ischemic stroke.

This study aims to test the hypothesis that above mentioned encoding gene polymorphisms are associated with stroke and to determine whether risk varies as per specific subtypes of stroke.

Methods/Design

The study design would be case–control study. Six hundred cases with diagnosis of stroke and 600 age and sex matched controls will be recruited. Controls will be matched in 1:1 ratio. Baseline and demographic data will be collected in standardized data collection form. Four ml of blood will be collected in EDTA coated vial and will be used for DNA isolation. Genotyping will be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR product of each genotype in triplet for all the selected polymorphism will be sent for DNA sequencing. Data will be analyzed using conditional logistic regression to determine odds ratio associated with the above genes.

Discussion

This protocol will assess the association of above mentioned gene polymorphisms with ischemic stroke in North Indian Population. This study will also helpful to determine genetic component of stroke and whether variation in genetic risk as per different subtypes of stroke.
A method for cell type marker discovery by high-throughput gene expression analysis of mixed cell populations
Authors: Andrade-Navarro Miguel A , Kanji Femina , Palii Carmen G , Brand Marjorie , Atkins Harold , Perez-Iratxeta Carol
Published: October 2013

Background

Gene transcripts specifically expressed in a particular cell type (cell-type specific gene markers) are useful for its detection and isolation from a tissue or other cell mixtures. However, finding informative marker genes can be problematic when working with a poorly characterized cell type, as markers can only be unequivocally determined once the cell type has been isolated. We propose a method that could identify marker genes of an uncharacterized cell type within a mixed cell population, provided that the proportion of the cell type of interest in the mixture can be estimated by some indirect method, such as a functional assay.

Results

We show that cell-type specific gene markers can be identified from the global gene expression of several cell mixtures that contain the cell type of interest in a known proportion by their high correlation to the concentration of the corresponding cell type across the mixtures.

Conclusions

Genes detected using this high-throughput strategy would be candidate markers that may be useful in detecting or purifying a cell type from a particular biological context. We present an experimental proof-of-concept of this method using cell mixtures of various well-characterized hematopoietic cell types, and we evaluate the performance of the method in a benchmark that explores the requirements and range of validity of the approach.
Laboratorial training of examiners for using a visual caries detection system in epidemiological surveys
Authors: Piovesan Chaiana , Moro Bruna LP , Lara Juan S , Ardenghi Thiago M , Guedes Renata S , Haddad Ana E , Braga Mariana M , Mendes Fausto M
Published: October 2013

Background

In epidemiological surveys, a good reliability among the examiners regarding the caries detection method is essential. However, training and calibrating those examiners is an arduous task because it involves several patients who are examined many times. To facilitate this step, we aimed to propose a laboratory methodology to simulate the examinations performed to detect caries lesions using the International Caries Detection and Assessment System (ICDAS) in epidemiological surveys.

Methods

A benchmark examiner conducted all training sessions. A total of 67 exfoliated primary teeth, varying from sound to extensive cavitated, were set in seven arch models to simulate complete mouths in primary dentition. Sixteen examiners (graduate students) evaluated all surfaces of the teeth under illumination using buccal mirrors and ball-ended probe in two occasions, using only coronal primary caries scores of the ICDAS. As reference standard, two different examiners assessed the proximal surfaces by direct visual inspection, classifying them in sound, with non-cavitated or with cavitated lesions. After, teeth were sectioned in the bucco-lingual direction, and the examiners assessed the sections in stereomicroscope, classifying the occlusal and smooth surfaces according to lesion depth. Inter-examiner reproducibility was evaluated using weighted kappa. Sensitivities and specificities were calculated at two thresholds: all lesions and advanced lesions (cavitated lesions in proximal surfaces and lesions reaching the dentine in occlusal and smooth surfaces).

Results

Regarding the reproducibility, the mean (range) of kappa values was 0.781 (0.529–0.927) for occlusal surfaces, 0.568 (0.191–0.881) for smooth surfaces, and 0.844 (0.698–0.971) for proximal surfaces. Considering all lesions, sensitivity and specificity mean values were respectively 0.724 and 0.844 for occlusal, 0.635 and 0.943 for smooth and 0.658 and 0.927 for proximal surfaces. For detecting advanced lesions, sensitivities and specificities were 0.563 and 0.920 for occlusal, 0.670 and 0.985 for smooth, and 0.838 and 0.985 for proximal surfaces.

Conclusion

The methodology purposed for training and calibration of several examiners designated for epidemiological surveys of dental caries in preschool children using the ICDAS is feasible, permitting the assessment of reliability and accuracy of the examiners previously to the survey´s development.
Patient reported outcome instruments used in clinical trials of HIV-infected adults on NNRTI-based therapy: a 10-year review
Authors: Simpson Kit N , Hanson Kristin A , Harding Gale , Haider Seema , Tawadrous Margaret , Khachatryan Alexandra , Pashos Chris L , Wu Albert W
Published: October 2013

Background

Patient-reported outcomes (PROs) may provide valuable information to clinicians and patients when choosing initial antiretroviral therapy.

Objective

To identify and classify PRO instruments used to measure treatment effects in clinical trials evaluating NNRTIs.

Methods

We conducted a structured literature review using PubMed to identify NNRTI trials published from March 2003 to February 2013. Studies identified--based on disease, instrument, PRO, and NNRTI medication terms were reviewed--to identify PRO instruments. Domains measured within each instrument were recorded to understand key areas of interest in NNRTIs.

Results

Of 189 articles reviewed, 27 validated instruments were administered in 26 unique trials, with a mean of 1.9 instruments (median: 1; range: 1–7) per trial. The Medical Outcomes Study HIV Health Survey (MOS-HIV) was the most commonly used instrument (n = 8 trials). Seventeen trials (65%) included at least one multidimensional health-related quality of life (HRQL) instrument (HIV-targeted, n = 11; general, n = 8). Other validated instruments measured sleep (n = 5), depression (n = 5), anxiety (n = 4), psychiatric symptoms (n = 2), beliefs about HIV medications (n = 2), HIV symptoms (n = 1), and stress (n = 1).

Conclusions

Although review of recent NNRTI trials suggests a lack of consensus on the optimal PRO instruments, a typical battery is comprised of a multidimensional HRQL measure coupled with one or more symptom measures. Further work is needed to clarify advantages and disadvantages of using specific PRO instruments to measure relevant constructs and to identify the most useful batteries of instruments for NNRTI trials.
Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a Smad7- and ERK-dependent manner
Authors: van Rooyen Beverley A , Schäfer Georgia , Leaner Virna D , Parker M Iqbal
Published: October 2013

Background

Recent studies have revealed that interactions between tumour cells and the surrounding stroma play an important role in facilitating tumour growth and invasion. Stromal fibroblasts produce most of the extracellular matrix components found in the stroma. The aim of this study was to investigate mechanisms involved in tumour cell-mediated regulation of extracellular matrix and adhesion molecules in co-cultured fibroblasts. To this end, microarray analysis was performed on CCD-1068SK human fibroblast cells after direct co-culture with MDA-MB-231 human breast tumour cells.

Results

We found that the expression of both connective tissue growth factor (CTGF/CCN2) and type I collagen was negatively regulated in CCD-1068SK fibroblast cells under direct co-culture conditions. Further analysis revealed that Smad7, a known negative regulator of the Smad signalling pathway involved in CCN2 promoter regulation, was increased in directly co-cultured fibroblasts. Inhibition of Smad7 expression in CCD-1068SK fibroblasts resulted in increased CCN2 expression, while Smad7 overexpression had the opposite effect. Silencing CCN2 gene expression in fibroblasts led, in turn, to a decrease in type I collagen mRNA and protein levels. ERK signalling was also shown to be impaired in CCD-1068SK fibroblasts after direct co-culture with MDA-MB-231 tumour cells, with Smad7 overexpression in fibroblasts leading to a similar decrease in ERK activity. These effects were not, however, seen in fibroblasts that were indirectly co-cultured with tumour cells.

Conclusion

We therefore conclude that breast cancer cells require close contact with fibroblasts in order to upregulate Smad7 which, in turn, leads to decreased ERK signalling resulting in diminished expression of the stromal proteins CCN2 and type I collagen.
PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy
Authors: Huang Yi-Teng , Li Fei-Fei , Ke Chen , Li Zhou , Li Zong-Tai , Zou Xiao-Fang , Zheng Xiao-Xuan , Chen Yu-Ping , Zhang Hao
Published: October 2013

Background

Protein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently been in the spotlight as a tumor suppressor, whose encoding gene is frequently methylated in cancers. We examined the methylation status of the PTPRO gene promoter in breast cancer and evaluated the correlation between PTPRO promoter methylation and both clinicopathological parameters and prognosis of breast cancer patients.

Methods

Two hundred twenty-one formalin-fixed, paraffin-embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched plasma samples, collected from primary breast cancer patients, were assessed for PTPRO gene promoter methylation using methylation-specific PCR. Associations of promoter methylation with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect on survival.

Results

175 samples gave identifiable PCR products, of which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation correlated with higher histological grade (P = 0.028), but not other clinical parameters. Multivariate analysis indicated that overall survival (OS) was significantly poorer in HER2-positive, but not ER-positive patients with methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and only observed in plasma from patients whose corresponding primary tumors were also methylated.

Conclusions

PTPRO methylation is a common event in the primary breast cancer and can be reliably detected in peripheral blood samples. PTPRO methylation is associated with poor survival only in HER2-positive patients, suggesting use of PTPRO methylation as a prognostic factor for breast cancer and for optimizing individualized therapy for HER2-positive patients.
Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure
Authors: Zhao Bo , Wang Xue-Qing , Wang Xiao-You , Zhang Hua , Dai Wen-Bing , Wang Jun , Zhong Zhen-Lin , Wu Hou-Nan , Zhang Qiang
Published: October 2013

Background

Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research.

Objectives

Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared.

Methods

In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice.

Results

All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs.

Conclusions

These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles.
Digital dermatitis in cattle is associated with an excessive innate immune response triggered by the keratinocytes
Authors: Refaai Walid , Ducatelle Richard , Geldhof Peter , Mihi Belgacem , El-shair Mahasen , Opsomer Geert
Published: October 2013

Background

Digital Dermatitis (DD) is a common disease of dairy cows, the pathogenesis of which is still not clear. This study examined some host responses associated with the typical lesions, in an attempt to further elucidate the pathogenesis of the disease. Twenty four samples representing the 5 different clinical stages of DD (M0-M4) were collected from slaughtered cattle for histopathological and immunological analyses.

Results

Significant increases in total epidermal thickness were found in M2, M3, and M4 when compared with M0 and M1. M3 samples, when compared with M0 and M1, were characterized by a significant increase in the thickness of the keratin layer. Counts of both eosinophils and neutrophils were at a maximum in the M2 stage and decreased in the M3 and M4 stage. A significant increase in IL8 expression was observed in the M2-M3 stages of the disease and immunohistochemical staining showed the source as keratinocytes, suggesting an important role for keratinocyte-derived IL8 in the pathogenesis of DD.

Conclusion

Results of the present study point to a strong stimulation of the innate immune response at the level of the keratinocytes throughout most of the clinical stages, and a delayed response of the adaptive immune reaction.
Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure
Authors: Langereis Eveline J , Borgo Andrea , Crushell Ellen , Harmatz Paul R , van Hasselt Peter M , Jones Simon A , Kelly Paula M , Lampe Christina , van der Lee Johanna H , Odent Thierry , Sakkers Ralph , Scarpa Maurizio , Schafroth Matthias U , Struijs Peter A , Valayannopoulos Vassili , White Klane K , Wijburg Frits A
Published: October 2013

Background

Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder characterized by progressive multi-organ disease. The standard of care for patients with the severe phenotype (Hurler syndrome, MPS I-H) is early hematopoietic stem cell transplantation (HSCT). However, skeletal disease, including hip dysplasia, is almost invariably present in MPS I-H, and appears to be particularly unresponsive to HSCT. Hip dysplasia may lead to pain and loss of ambulation, at least in a subset of patients, if left untreated. However, there is a lack of evidence to guide the development of clinical guidelines for the follow-up and treatment of hip dysplasia in patients with MPS I-H. Therefore, an international Delphi consensus procedure was initiated to construct consensus-based clinical practice guidelines in the absence of available evidence.

Methods

A literature review was conducted, and publications were graded according to their level of evidence. For the development of consensus guidelines, eight metabolic pediatricians and nine orthopedic surgeons with experience in the care of MPS I patients were invited to participate. Eleven case histories were assessed in two written rounds. For each case, the experts were asked if they would perform surgery, and they were asked to provide information on the aspects deemed essential or complicating in the decision-making process. In a subsequent face-to-face meeting, the results were presented and discussed. Draft consensus statements were discussed and adjusted until consensus was reached.

Results

Consensus was reached on seven statements. The panel concluded that early corrective surgery for MPS I-H patients with hip dysplasia should be considered. However, there was no full consensus as to whether such a procedure should be offered to all patients with hip dysplasia to prevent complications or whether a more conservative approach with surgical intervention only in those patients who develop clinically relevant symptoms due to the hip dysplasia is warranted.

Conclusions

This international consensus procedure led to the construction of clinical practice guidelines for hip dysplasia in transplanted MPS I-H patients. Early corrective surgery should be considered, but further research is needed to establish its efficacy and role in the treatment of hip dysplasia as seen in MPS I.
Sunitinib treatment enabling resection of massive liver metastasis: a case report
Authors: Mitomo Shingo , Takahara Takeshi , Nitta Hiroyuki , Fujita Tomohiro , Ito Naoko , Uesugi Noriyuki , Sugai Tamotsu , Wakabayashi Go
Published: October 2013

Introduction

Sunitinib was developed as a molecular-targeted drug to treat advanced renal cell carcinoma. It is not yet known whether liver damage occurs in patients with liver metastases of renal cell carcinoma after sunitinib administration. Here, we report the case of a patient with an inoperable massive liver metastasis of renal cell carcinoma for whom sunitinib administration was dramatically effective with no obvious evidence of liver damage. As a result, the liver metastasis could be resected. We emphasize the dramatic reduction in liver metastasis with sunitinib treatment, and the histopathological effects of sunitinib on the non-tumorous liver parenchyma.

Case presentation

A 54-year-old Japanese woman was diagnosed with right renal cell carcinoma and underwent right nephrectomy 12 years earlier. She presented to a local clinic with right abdominal pain. A computed tomography scan showed a massive liver metastasis occupying her right hepatic lobe, and she was referred to our hospital for treatment. The diagnosis was not only liver metastasis, but also left renal metastasis. Oral administration of tyrosine kinase inhibitor sunitinib was started. Adverse events due to sunitinib included liver dysfunction, thrombocytopenia, and decreased hemoglobin, but she completed eight courses with the help of drug holidays and dose adjustments. Post-treatment computed tomography showed a dramatic reduction in size of her liver metastasis, enabling right lobectomy of her liver. Histopathological findings showed no obvious liver damage due to chemotherapy in non-cancerous parenchymal areas.

Conclusions

With the availability of sunitinib, some patients with potentially unresectable massive liver metastases of renal cell carcinoma may be able to undergo major hepatectomy curatively and safely with little histopathological damage to non-tumorous liver parenchyma, thus improving their prognosis.
SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs)
Authors: Abrahams Brett S , Arking Dan E , Campbell Daniel B , Mefford Heather C , Morrow Eric M , Weiss Lauren A , Menashe Idan , Wadkins Tim , Banerjee-Basu Sharmila , Packer Alan
Published: October 2013

New technologies enabling genome-wide interrogation have led to a large and rapidly growing number of autism spectrum disorder (ASD) candidate genes. Although encouraging, the volume and complexity of these data make it challenging for scientists, particularly non-geneticists, to comprehensively evaluate available evidence for individual genes. Described here is the Gene Scoring module within SFARI Gene 2.0 (https://gene.sfari.org/autdb/GS_Home.do), a platform developed to enable systematic community driven assessment of genetic evidence for individual genes with regard to ASD.
SCLpredT: Ab initio and homology-based prediction of subcellular localization by N-to-1 neural networks
Authors: Adelfio Alessandro , Volpato Viola , Pollastri Gianluca
Published: October 2013

The prediction of protein subcellular localization is a important step towards the prediction of protein function, and considerable effort has gone over the last decade into the development of computational predictors of protein localization. In this article we design a new predictor of protein subcellular localization, based on a Machine Learning model (N-to-1 Neural Networks) which we have recently developed. This system, in three versions specialised, respectively, on Plants, Fungi and Animals, has a rich output which incorporates the class “organelle” alongside cytoplasm, nucleus, mitochondria and extracellular, and, additionally, chloroplast in the case of Plants. We investigate the information gain of introducing additional inputs, including predicted secondary structure, and localization information from homologous sequences. To accommodate the latter we design a new algorithm which we present here for the first time. While we do not observe any improvement when including predicted secondary structure, we measure significant overall gains when adding homology information. The final predictor including homology information correctly predicts 74%, 79% and 60% of all proteins in the case of Fungi, Animals and Plants, respectively, and outperforms our previous, state-of-the-art predictor SCLpred, and the popular predictor BaCelLo. We also observe that the contribution of homology information becomes dominant over sequence information for sequence identity values exceeding 50% for Animals and Fungi, and 60% for Plants, confirming that subcellular localization is less conserved than structure.

SCLpredT is publicly available at http://distillf.ucd.ie/sclpredt/. Sequence- or template-based predictions can be obtained, and up to 32kbytes of input can be processed in a single submission.
Phytochemical analysis, antimicrobial and radical-scavenging properties of Acalypha manniana leaves
Authors: Noumedem Jaures AK , Tamokou Jean de Dieu , Teke Gerald Ngo , Momo Rosine CD , Kuete Victor , Kuiate Jules Roger
Published: October 2013

Acalypha manniana (Euphorbiaceae) is a plant popularly used in Cameroon and in several parts of Africa for the treatment of various microbial diseases like diarrhea and skin infections.

The present study was designed to evaluate the phytochemical composition, antimicrobial and radical-scavenging activities of A. manniana methanol leaf extract and its fractions.

The methanol extract was partitioned into hexane, ethyl acetate and residual fractions and phytochemical analysis was conducted using standard methods. The broth microdilution method was used to evaluate the antimicrobial activity against nine bacterial species and four dermatophyte species. The free radical scavenging activities of the methanol extract and its fractions were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.

The results obtained showed that A. manniana contains alkaloids, tannins, anthocyanins, flavonoids, phenols and steroids. The methanol extract as well as the hexane, ethyl acetate and residual fractions exhibited both antibacterial and antidermatophytic activities that varied between the microbial species (MIC = 0.12 – 2.04 mg/mL). These tested samples also showed high radical-scavenging activities (RaS50 = 3.34 – 4.80 μg/mL) when compared with vitamin C used as reference antioxidant (RaS50 = 1.74 μg/mL).

These findings provide evidence that the studied plant possesses antimicrobial and antioxidant properties and may act as potential antioxidant for biological systems susceptible to free radical-mediated reactions.
Marital status and its effect on lung cancer survival
Authors: Tannenbaum Stacey L , Zhao Wei , Koru-Sengul Tulay , Miao Feng , Lee David , Byrne Margaret M
Published: October 2013

Purpose

The purpose of this study was to determine if marital status, including specific types of single status categories, is associated with length of survival in lung cancer patients.

Methods

Data from the 1996–2007 Florida Cancer Data System were linked with Agency for Health Care Administration data and U.S. Census data. Patients with both small cell and non-small cell lung cancer were identified (n = 161,228). Marital status was characterized by married, widowed, separated/divorced, and never married. We compared median survival time and 1, 3, and 5-year post diagnosis survival rates.

Results

Overall, 54.6% were married, 19.1% were widowed, 13.5% were separated/divorced, and 12.7% had never married. Median survival in months was longest for married (9.9) and widowed (7.7) patients, and shortest for never married (4.9) and separated/divorced (4.1) patients. Five-year survival rates were 14.2% for married, 10.7% for widowed, 8.9% for separated/divorced, and 8.4% for never married. In univariate Cox regression, marital status was a significant predictor of better survival for married (HR = 0.70; p < 0.001) and widowed (HR = 0.81; p < 0.001) patients compared with never married patients, but worse for separated/divorced patients (HR = 1.03; p = 0.003). Multivariate models demonstrated sustained survival benefits for married (HR = 0.86; p < 0.001) and widowed (HR = 0.88; p < 0.001) patients, and detriments for separated/divorced patients (HR = 1.05; p < 0.001) after adjusting for extensive confounders including demographics; tumor stage, grade, and morphology; comorbidities; treatment; and smoking status.

Conclusions

Our study demonstrated that married or widowed lung cancer patients have better survival compared to patients who were never married or separated/divorced. Research to understand the mechanism of this effect, and how the beneficial effect can be extended to those who have never married or have had the marital relationship severed through divorce or separation is needed.
Variability in protocols on donation after circulatory death in Europe
Authors: Wind Jentina , Faut Marloes , van Smaalen Tim C , van Heurn Ernest LW
Published: October 2013

Introduction

Organ donation after circulatory death (DCD) has become an accepted strategy to reduce the shortage of organs for transplantation in many European countries. The use and number of DCD donors varies between countries. The purpose of this study was to evaluate the available protocols for DCD in Europe.

Methods

We contacted national transplant societies and responsible transplant co-ordinators in the countries that perform DCD to obtain DCD protocols. We compared information on the protocols and additional data including: inclusion and exclusion criteria for donation, legislation, determination of death and preservation methods.

Results

In ten European countries DCD is performed, eight of which describe the methods in protocols. There are large differences in used DCD categories, legislation and the way death is determined. Protocols differ in the detail in which DCD procedures are described and the way methods are supported by additional consensus statements and ethical frameworks.

Conclusions

Although DCD is an established strategy to enlarge the donor pool and to contribute to the reduction of the waiting list for transplantation, its potential has not been fully utilized yet. To further promote DCD transplantation, it is important to share expertise and obtain consensus, so that this can be translated into more uniform and solid protocols supported by the competent authorities, transplant and intensive care professionals, which may eventually result in a further promotion of DCD transplantation in Europe.
Direct interaction between two actin nucleators is required in Drosophila oogenesis
Authors: Quinlan Margot E.
Published: October 2013

Controlled actin assembly is crucial to a wide variety of cellular processes, including polarity establishment during early development. The recently discovered actin mesh, a structure that traverses the Drosophila oocyte during mid-oogenesis, is essential for proper establishment of the major body axes. Genetic experiments indicate that at least two proteins, Spire (Spir) and Cappuccino (Capu), are required to build this mesh. The spire and cappuccino genetic loci were first identified as maternal effect genes in Drosophila. Mutation in either locus results in the same phenotypes, including absence of the mesh, linking them functionally. Both proteins nucleate actin filaments. Spir and Capu also interact directly with each other in vitro, suggesting a novel synergistic mode of regulating actin. In order to understand how and why proteins with similar biochemical activity would be required in the same biological pathway, genetic experiments were designed to test whether a direct interaction between Spir and Capu is required during oogenesis. Indeed, data in this study indicate that Spir and Capu must interact directly with one another and then separate to function properly. Furthermore, these actin regulators are controlled by a combination of mechanisms, including interaction with one another, functional inhibition and regulation of their protein levels. Finally, this work demonstrates for the first time in a multicellular organism that the ability of a formin to assemble actin filaments is required for a specific structure.
A new zebrafish model produced by TILLING of SOD1-related amyotrophic lateral sclerosis replicates key features of the disease and represents a tool for in vivo therapeutic screening
Authors: Da Costa Marc M. J. , Allen Claire E. , Higginbottom Adrian , Ramesh Tennore , Shaw Pamela J. , McDermott Christopher J.
Published: October 2013

Mutations in the superoxide dismutase gene (SOD1) are one cause of familial amyotrophic lateral sclerosis [ALS; also known as motor neuron disase (MND)] in humans. ALS is a relentlessly progressive neurodegenerative disease and, to date, there are no neuroprotective therapies with significant impact on the disease course. Current transgenic murine models of the disease, which overexpress mutant SOD1, have so far been ineffective in the identification of new therapies beneficial in the human disease. Because the human and the zebrafish (Danio rerio) SOD1 protein share 76% identity, TILLING ('targeting induced local lesions in genomes') was carried out in collaboration with the Sanger Institute in order to identify mutations in the zebrafish sod1 gene. A T70I mutant zebrafish line was characterised using oxidative stress assays, neuromuscular junction analysis and motor function studies. A T70I mutant zebrafish line was characterised using oxidative stress assays, neuromuscular junction (NMJ) analysis and motor function studies. The T70I sod1 zebrafish model offers the advantage over current murine models of expressing the mutant Sod1 protein at a physiological level, as occurs in humans with ALS. The T70I sod1 zebrafish demonstrates key features of ALS; an early NMJ phenotype, a susceptibility to oxidative stress and an adult-onset motor neuron disease phenotype. We have demonstrated that the susceptibility of T70I sod1 embryos to oxidative stress can be used in a drug screening assay, to identify compounds that merit further investigation as potential therapies for ALS.
Transcriptional changes and developmental abnormalities in a zebrafish model of myotonic dystrophy type 1
Authors: Todd Peter K. , Ackall Feras Y. , Hur Junguk , Sharma Kush , Paulson Henry L. , Dowling James J.
Published: October 2013

Myotonic dystrophy type I (DM1) is a multi-system, autosomal dominant disorder caused by expansion of a CTG repeat sequence in the 3′UTR of the DMPK gene. The size of the repeat sequence correlates with age at onset and disease severity, with large repeats leading to congenital forms of DM1 associated with hypotonia and intellectual disability. In models of adult DM1, expanded CUG repeats lead to an RNA toxic gain of function, mediated at least in part by sequestering specific RNA splicing proteins, most notably muscleblind-related (MBNL) proteins. However, the impact of CUG RNA repeat expression on early developmental processes is not well understood. To better understand early developmental processes in DM1, we utilized the zebrafish, Danio rerio, as a model system. Direct injection of (CUG)91 repeat-containing mRNA into single-cell embryos induces toxicity in the nervous system and muscle during early development. These effects manifest as abnormal morphology, behavioral abnormalities and broad transcriptional changes, as shown by cDNA microarray analysis. Co-injection of zebrafish mbnl2 RNA suppresses (CUG)91 RNA toxicity and reverses the associated behavioral and transcriptional abnormalities. Taken together, these findings suggest that early expression of exogenously transcribed CUG repeat RNA can disrupt normal muscle and nervous system development and provides a new model for DM1 research that is amenable to small-molecule therapeutic development.
Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models
Authors: Demontis Fabio , Piccirillo Rosanna , Goldberg Alfred L. , Perrimon Norbert
Published: October 2013

A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.
Oncogenic mutations in adenomatous polyposis coli (Apc) activate mechanistic target of rapamycin complex 1 (mTORC1)in mice and zebrafish
Authors: Valvezan Alexander J. , Huang Jian , Lengner Christopher J. , Pack Michael , Klein Peter S.
Published: October 2013

Truncating mutations in adenomatous polyposis coli (Apc) are strongly linked to colorectal cancers. APC is a negative regulator of the Wnt pathway and constitutive Wnt activation mediated by enhanced Wnt-β-catenin target gene activation is believed to be the predominant mechanism responsible for Apc mutant phenotypes. However, recent evidence suggests that additional downstream effectors contribute to Apc mutant phenotypes. We previously identified a mechanism in cultured human cells by which APC, acting through glycogen synthase kinase-3 (GSK-3), suppresses mTORC1, a nutrient sensor that regulates cell growth and proliferation. We hypothesized that truncating Apc mutations should activate mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes. We find mTORC1 is strongly activated in apc mutant zebrafish and in intestinal polyps in Apc mutant mice. Furthermore, mTORC1 activation is essential downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes including early lethality, reduced circulation and liver hyperplasia. Importantly, combining mTORC1 and Wnt inhibition rescues defects in morphogenesis of the anterior-posterior axis that are not rescued by inhibition of either pathway alone. These data establish mTORC1 as a crucial, β-catenin independent effector of oncogenic Apc mutations and highlight the importance of mTORC1 regulation by APC during embryonic development. Our findings also suggest a new model of colorectal cancer pathogenesis in which mTORC1 is activated in parallel with Wnt/β-catenin signaling.
Improvement in Photovoltaic Performance of Dye-sensitized Solar Cells by Cosensitization with an Organometal Halide Perovskite
Authors: Kakiage Kenji , Kyomen Toru , Hanaya Minoru
Published: October 2013

The possibility of an organometal halide perovskite, CH3NH3PbBr3, was investigated as a cosensitizer to a Ru-complex dye and an alkoxysilylcoumarin dye in dye-sensitized solar cells. The perovskite was found to work as the cosensitizer effectively, and the light-to-electric energy conversion efficiencies of the cells were improved more than 10% by the cosensitization under the present test conditions.
The Wrong Shape of Insurance? What Cross-Sectional Distributions Tell Us about Models of Consumption Smoothing
Authors: Broer Tobias
Published: October 2013

This paper shows how two standard models of consumption risk-sharing—self-insurance through borrowing and saving and limited commitment to insurance contracts—replicate similarly well the standard, second-moment measures of insurance observed in US micro data. A nonparametric analysis, however, reveals strongly contrasting and counterfactual joint distributions of consumption, income and wealth. Method of moments estimation shows how measurement error in consumption eliminates excessive skewness and smoothness of consumption growth. Moreover, counterfactual nonlinearities disappear at high-estimated risk aversion under self-insurance, but are a robust feature of limited commitment. Its “shape of insurance” thus argues in favor of the self-insurance model. (JEL D14, D81, D91, G22, E21)
Democracy and Reforms: Evidence from a New Dataset
Authors: Giuliano Paola , Mishra Prachi , Spilimbergo Antonio
Published: October 2013

Empirical evidence on the relationship between democracy and economic reforms is limited to few reforms, countries, and years. This paper studies the effect of democracy on the adoption of economic reforms using a new dataset on reforms in the financial, capital and banking sectors, product markets, agriculture, and trade for 150 countries over the period 1960–2004. Democracy has a positive and significant impact on the adoption of economic reforms, but there is scarce evidence that economic reforms foster democracy. Our results are robust to the inclusion of a large variety of controls and estimation strategies. (JEL D72, E02, E60, L51, O17, O20)
Weak States and Steady States: The Dynamics of Fiscal Capacity
Authors: Besley Timothy , Ilzetzki Ethan , Persson Torsten
Published: October 2013

Investments in fiscal capacity—economic institutions for tax compliance—are an important feature of economic development. This paper develops a dynamic model to study the evolution of fiscal capacity over time. We contrast a social planner's investment path with politically feasible paths. Three types of states emerge in the long run: a common-interest state where public resources are devoted to public goods, a redistributive state where additional fiscal capacity is used for transfers, and a weak state with no transfers and a low level of public goods provision. We also present some preliminary evidence consistent with the theory. (JEL E23, E62, H23, H26, H41)
Safety Traps
Authors: Benhima Kenza , Massenot Baptiste
Published: October 2013

Fear of risk provides a rationale for protracted economic downturns. We develop a real business cycle model where investors with decreasing relative risk aversion choose between a risky and a safe technology that exhibit decreasing returns. Because of a feedback effect from the interest rate to risk aversion, two equilibria can emerge: a standard equilibrium and a “safe” one in which investors invest in safer assets. We refer to the dynamics of this second equilibrium as a safety trap because it is self-reinforcing as investors accumulate more wealth and show it to be consistent with Japan's lost decade. (JEL D14, E13, E21, E22, E23, E32)
Richard L. Epstein, “Critical Thinking”
Authors: Rush Penelope A.
Published: October 2013

Richard L. Epstein with Carolyn Kerbrger, Critical Thinking, 3rd Edition, Advanced Reasoning Forum, 2012, 464 pp., ISBN-10: 1938421000, ISBN-13: 978-1938421006.Richard L. Epstein, The Pocket Guide to Critical Thinking, 4th Edition, Advanced Reasoning Forum, 2011, 162 pp., paperback ISBN-13: 9780981550770, ISBN-10: 0981550770, ebook ISBN-13: 9780981550787.