bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundGene 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.ResultsWe 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.ConclusionsGenes 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

Abstract

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

AbstractBackgroundPatient-reported outcomes (PROs) may provide valuable information to clinicians and patients when choosing initial antiretroviral therapy.ObjectiveTo identify and classify PRO instruments used to measure treatment effects in clinical trials evaluating NNRTIs.MethodsWe 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.ResultsOf 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).ConclusionsAlthough 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract

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.