bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human hair melanins: what we have learned and have not learned from mouse coat color pigmentation
Authors: Ito Shosuke , Wakamatsu Kazumasa 
Published: August 2010

SummaryHair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur‐containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase‐related proteins are involved in eumelanogenesis, while only the additional presence of cysteine is necessary for pheomelanogenesis. Other important proteins involved in melanogenesis include P protein, MATP protein, α‐MSH, agouti signaling protein (ASIP), MC1R (the receptor for MSH and ASIP), and SLC7A11, a cystine transporter. Many studies have examined the effects of loss‐of‐function mutations of those proteins on mouse coat color pigmentation. In contrast, much less is known regarding the effects of mutations of the corresponding proteins on human hair pigmentation except for MC1R polymorphisms that lead to pheomelanogenesis. This perspective will discuss what we have/have not learned from mouse coat color pigmentation, with special emphasis on the significant roles of pH and the level of cysteine in melanosomes in controlling melanogenesis. Based on these data, a hypothesis is proposed to explain the diversity of human hair pigmentation.
Cancer stem cells versus phenotype‐switching in melanoma
Authors: Hoek Keith S. , Goding Colin R. 
Published: August 2010

SummaryTumours comprise multiple phenotypically distinct subpopulations of cells, some of which are proposed to possess stem cell‐like properties, being able to self‐renew, seed and maintain tumours, and provide a reservoir of therapeutically resistant cells. Here, we use melanoma as a model to explore the validity of the cancer stem cell hypothesis in the light of accumulating evidence that melanoma progression may instead be driven by phenotype‐switching triggered by genetic lesions that impose an increased sensitivity to changes in the tumour microenvironment. Although at any given moment cells within a tumour may exhibit differentiated, proliferative or invasive phenotypes, an ability to switch phenotypes implies that most cells will have the potential to adopt a stem cell‐like identity. Insights into the molecular events underpinning phenotype‐switching in melanoma highlight the close relationship between signalling pathways that generate, maintain and activate melanocyte stem cells as well as the inverse correlation between proliferation and invasive potentials. An understanding of phenotype‐switching in melanoma, and in particular the signalling events that regulate the expression of the microphthalmia‐associated transcription factor Mitf, points to new therapeutic opportunities aimed at eradicating therapeutically resistant stem cell‐like melanoma cells.
Latanoprost versus timolol as first choice therapy in patients with ocular hypertension. A cost‐effectiveness analysis
Authors: Peeters Andrea , Schouten Jan S.A.G. , Severens Johan L. , Hendrikse Fred , Prins Martin H. , Webers Carroll A.B. 
Published: August 2010

Abstract.Purpose: To determine the cost‐effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol.Methods: Two strategies for OH therapy are modelled, (1) ‘starting with timolol’ and (2) ‘starting with latanoprost’. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side‐effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow‐up with IOP‐dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP‐lowering effect of drugs is based on meta‐analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients.Results: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (±0.017) mm Hg (strategy 1) and to 16.5 (±0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were € 367 and € 469, respectively. Lifetime blindness and costs were 0.0334 years and € 3 514 (strategy 1) and 0.0318 years and € 4 397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately € 537 000.Conclusion: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high.
Evaluation of a Chromogenic Culture Medium for Isolation of
Clostridium difficile
within 24 Hours
Authors: Perry John D. , Asir Kerry , Halimi Diane , Orenga Sylvain , Dale Joanne , Payne Michelle , Carlton Ruth , Evans Jim , Gould F. Kate 
Published: August 2010

ABSTRACT

Rapid and effective methods for the isolation of
Clostridium difficile
from stool samples are desirable to obtain isolates for typing or to facilitate accurate diagnosis of
C. difficile
-associated diarrhea. We report on the evaluation of a prototype chromogenic medium (ID
C. difficile
prototype [IDCd]) for isolation of
C. difficile
. The chromogenic medium was compared using (i) 368 untreated stool samples that were also inoculated onto CLO medium, (ii) 339 stool samples that were subjected to alcohol shock and also inoculated onto five distinct selective agars, and (iii) standardized suspensions of 10
C. difficile
ribotypes (untreated and alcohol treated) that were also inoculated onto five distinct selective agars. Two hundred thirty-six isolates of
C. difficile
were recovered from 368 untreated stool samples, and all but 1 of these strains (99.6%) were recovered on IDCd within 24 h, whereas 74.6% of isolates were recovered on CLO medium after 48 h. Of 339 alcohol-treated stool samples cultured onto IDCd and five other selective agars,
C. difficile
was recovered from 218 samples using a combination of all media. The use of IDCd allowed recovery of 96.3% of isolates within 24 h, whereas 51 to 83% of isolates were recovered within 24 h using the five other media. Finally, when they were challenged with pure cultures, all 10 ribotypes of
C. difficile
generated higher colony counts on IDCd irrespective of alcohol pretreatment or duration of incubation. We conclude that IDCd is an effective medium for isolation of
C. difficile
from stool samples within 24 h.
NFX1 Plays a Role in Human Papillomavirus Type 16 E6 Activation of NFκB Activity
Authors: Xu Mei , Katzenellenbogen Rachel A. , Grandori Carla , Galloway Denise A. 
Published: August 2010

ABSTRACTHigh-risk human papillomavirus (HR HPV) requires differentiating epithelial cells to continue to divide in order to replicate the viral DNA. To achieve this, HPV perturbs several regulatory pathways, including cellular apoptosis and senescence signals. HPV E6 has been identified as a regulator of the NFκB signaling pathway, a pathway important in many cellular processes, as well as regulation of virus-host cell interactions. We report here that NFX1-91, an endogenously expressed transcriptional regulator of human telomerase reverse transcriptase (hTERT) that is targeted by HPV type 16 (HPV16) E6/E6-associated protein (E6AP) for degradation, is also critical for regulation of the NFκB pathway by HPV16 E6. Microarray analysis revealed induction of NFκB-responsive genes and reduction of NFκB inhibitors with knockdown of NFX1-91. Knockdown of NFX1-91 induced downregulation of p105, an NFκB inhibitor in both primary human foreskin keratinocytes (HFKs) and HCT116 cells. Chromatin immunoprecipitation assays further confirmed that NFX1-91 bound to the p105 promoter and upregulated its expression. Similarly, in HPV16 E6-positive cells, reduction of p105 expression was observed, paralleling knockdown of NFX1-91 expression. Overall, our data suggest a mechanism for HPV16 E6 activation of the NFκB pathway through NFX1-91. Also, it provides evidence that NFX1-91 can function as a dual regulator, not only a transcriptional repressor, but also a transcriptional activator, when bound to DNA.
NS Reassortment of an H7-Type Highly Pathogenic Avian Influenza Virus Affects Its Propagation by Altering the Regulation of Viral RNA Production and Antiviral Host Response
Authors: Wang Zhongfang , Robb Nicole C. , Lenz Eva , Wolff Thorsten , Fodor Ervin , Pleschka Stephan 
Published: August 2010

ABSTRACT
Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of the A/FPV/Rostock/34 HPAIV (FPV; H7N1) were generated by reverse genetics. Virological characterizations demonstrated that the growth kinetics of the reassortant viruses differed from that of wild-type (wt) FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the antiviral host response but also affected viral genome replication and transcription as well as nuclear ribonucleoprotein (RNP) export. RNP reconstitution experiments demonstrated that the effects on accumulation levels of viral RNA species were dependent on the specific NS segment as well as on the genetic background of the RNA-dependent RNA polymerase (RdRp). Beta interferon (IFN-β) expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype, and nonstructural protein NS1 expression levels showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall, our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral life cycle as a result of the different effects of the NS1 protein on multiple viral and host functions.
Tracking the Evolution of MultipleIn VitroHepatitis C Virus Replicon Variants under Protease Inhibitor Selection Pressure by 454 Deep Sequencing
Authors: Verbinnen Thierry , Van Marck Herwig , Vandenbroucke Ina , Vijgen Leen , Claes Marijke , Lin Tse-I , Simmen Kenneth , Neyts Johan , Fanning Gregory , Lenz Oliver 
Published: August 2010

ABSTRACTResistance to hepatitis C virus (HCV) inhibitors targeting viral enzymes has been observed inin vitroreplicon studies and during clinical trials. The factors determining the emergence of resistance and the changes in the viral quasispecies population under selective pressure are not fully understood. To assess the dynamics of variants emergingin vitrounder various selective pressures with TMC380765, a potent macrocyclic HCV NS3/4A protease inhibitor, HCV genotype 1b replicon-containing cells were cultured in the presence of a low, high, or stepwise-increasing TMC380765 concentration(s). HCV replicon RNA from representative samples thus obtained was analyzed using (i) population, (ii) clonal, and (iii) 454 deep sequencing technologies. Depending on the concentration of TMC380765, distinct mutational patterns emerged. In particular, culturing with low concentrations resulted in the selection of low-level resistance mutations (F43S and A156G), whereas high concentrations resulted in the selection of high-level resistance mutations (A156V, D168V, and D168A). Clonal and 454 deep sequencing analysis of the replicon RNA allowed the identification of low-frequency preexisting mutations possibly contributing to the mutational pattern that emerged. Stepwise-increasing TMC380765 concentrations resulted in the emergence and disappearance of multiple replicon variants in response to the changing selection pressure. Moreover, two different codons for the wild-type amino acids were observed at certain NS3 positions within one population of replicons, which may contribute to the emerging mutational patterns. Deep sequencing technologies enabled the study of minority variants present in the HCV quasispecies population present at baseline and during antiviral drug pressure, giving new insights into the dynamics of resistance acquisition by HCV.
Palliation of compression fractures in cancer patients by vertebral augmentation: a retrospective analysis
Authors: Jha Ruchira M , Hirsch Ariel E , Yoo Albert J , Ozonoff Al , Growney Marion , Hirsch Joshua A 
Published: August 2010

AimTo evaluate the efficacy of vertebral augmentation (VA) in cancer patients.Materials and methodsFrom a retrospectively compiled database, 147 cancer cases (236 levels) were treated with VA. Mean age was 71±12 years and 56.5% were female. Variables evaluated include age, sex, procedure type, vertebral level treated, number of levels treated per procedure and technical approach. Outcomes were assessed by a previously described method retrospectively applied from medical records: a binary system of ‘responders’ versus ‘non-responders’ and further subcategorization with a four level pain scale. Two patient groups were analyzed: (1) 147 cancer patients with either osteoporotic or malignant vertebral compression fractures (all compression fractures (ACFs)) and (2) 102 cases with documented metastatic compression fractures (MCFs). Univariate and multivariate analyses determined outcomes.Results93% of MCFs and 88.5% of ACFs showed response to treatment (pain improvement or resolution): 30% of ACFs and 31% of MCFs experienced pain resolution. MCFs showed increasing age to be a predictor of response to treatment in univariate (OR=1.79, p=0.04) and multivariate (OR=2.05, p=0.03) analysis. In ACFs, bipedicular needle approach decreased the odds of pain resolution (OR=0.28, p=0.01). In MCFs, lung cancer (OR=0.06, p=0.03) and multiple myeloma (OR=0.10, p=0.01) decreased the odds of pain resolution.ConclusionsVA provides pain relief for a majority of ACFs and MCFs. Increasing age may be predictive of pain relief outcomes in MCFs. There are special planning, imaging and technical considerations (eg, needle placement) in using VA to treat cancer patients.
RECOGNITION OF HANDWRITTEN DEVANAGARI SCRIPT
Authors: MALIK LATESH , DESHPANDE P. S. 
Published: August 2010

Segmentation of handwritten text into lines, words and characters is one of the important steps in the handwritten text recognition process. In this paper, we propose a float fill algorithm for segmentation of unconstrained Devanagari text into words. Here, a text image is directly segmented into individual words. Rectangular boundaries are drawn around the words and horizontal lines are detected with template matching. A mask is designed for detecting the horizontal line and is applied to each word from left to right and top to bottom of the document. Header lines are removed for character separation. A new segment code features are extracted for each character. In this paper, we present the results of multiple classifier combination for offline handwritten Devanagari characters. The use of regular expressions in handwritten characters is a novel concept and they are defined in a manner so that they can become more robust to noise. We have achieved an accuracy of 94% for word level segmentation, 95% for coarse classification and 85% for fine classification of character recognition. On experimentation with a dataset of 5000 samples of characters, the overall recognition rate observed is 95% as we considered top five choice results. The proposed combined classifier can be applied to handwritten character recognition of any other language like English, Chinese, Arabic, etc. and can recognize the characters with same accuracy.18 For printed characters we have achieved accuracy of 100%, only by applying the regular expression classifier.17
FUZZY-BASED ANALYSIS OF MICROSCOPIC COLOR CERVICAL PAP SMEAR IMAGES: NUCLEI DETECTION
Authors: SOBREVILLA PILAR , MONTSENY EDUARD , VASCHETTO FABIO , LERMA ENRIQUE 
Published: August 2010

The Pap Smear test, or cervico-vaginal cytology, is globally the most used and suitable method for screening cervical cancer precursor lesions, with a significant impact in reducing the incidence and mortality rates. However, Pap test suffers from subjective variability and no specificity, being the most controversial point the persistence of false negatives; i.e., normal cytological report for a woman with existing dysplasia, pre-malignant, or malignant lesions of the cervix. This is due in large part to the vast number of cells that must be reviewed by a technician for determining the possible existence of a small number of malignant or pre-malignant cells. Automated systems that include technician knowledge and interpretation could not only reduce sample examination time but also avoid misclassification of samples because of human errors. Here we present part of our ongoing work toward automation of cervical screening process. Specifically, since in cytological studies nuclei are considered the most informative regions, and an accurate segmentation is needed for extracting meaningful cell features, we propose an automated nuclei detection algorithm that integrates color information, cytopathologists knowledge, and fuzzy systems. Results have shown that besides a high performance and efficiency, the speed of the algorithm is very high.
Novel Nonmajor Histocompatibility Complex–Linked Loci From Mouse Chromosome 17 Confer Susceptibility to Viral-Mediated Chronic Autoimmune Myocarditis
Authors: Poffenberger Maya C. , Shanina Iryna , Aw Connie , El Wharry Nahida , Straka Nadine , Fang Dianne , Baskin-Hill Annie E. , Spiezio Sabrina H. , Nadeau Joseph H. , Horwitz Marc S. 
Published: August 2010

Background—
Development of viral-induced chronic myocarditis is thought to involve both environmental and genetic factors. However, to date, no susceptibility genes have been identified.

Methods and Results—
We sought to identify loci that confer susceptibility to viral-induced chronic myocarditis with the use of chromosome substitution strain mice that are composed of 1 chromosome from the disease susceptible A/J strain on an otherwise resistant C57BL/6 background. By this method, we identified chromosome 17 to confer susceptibility. To further isolate the region of susceptibility, 8 strains of mice congenic for different portions of chromosome 17 were generated. Characterization of these strains identified at least 4 susceptibility loci on the chromosome. Three of these loci are located in the proximal 22.8 cM, whereas the fourth locus is located in the portion of the chromosome distal to 34.3 cM.

Conclusions—
We have identified 4 loci that confer susceptibility of viral-induced chronic myocarditis. Of these loci, 3 were distinct from the major histocompatibility complex locus and thus represent novel susceptibility loci. The close proximately of the 2 novel loci with susceptibility loci for other autoimmune diseases such as type 1 diabetes and chronic experimental autoimmune thyroiditis suggests the presence of global autoimmune susceptibility genes.
Improved Prediction of Cardiovascular Disease Based on a Panel of Single Nucleotide Polymorphisms Identified Through Genome-Wide Association Studies
Authors: Davies Robert W. , Dandona Sonny , Stewart Alexandre F.R. , Chen Li , Ellis Stephan G. , Wilson Tang W.H. , Hazen Stanley L. , Roberts Robert , McPherson Ruth , Wells George A. 
Published: August 2010

Background—
Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) at multiple loci that are significantly associated with coronary artery disease (CAD) risk. In this study, we sought to determine and compare the predictive capabilities of 9p21.3 alone and a panel of SNPs identified and replicated through GWAS for CAD.

Methods and Results—

We used the Ottawa Heart Genomics Study (OHGS) (3323 cases, 2319 control subjects) and the Wellcome Trust Case Control Consortium (WTCCC) (1926 cases, 2938 control subjects) data sets. We compared the ability of allele counting, logistic regression, and support vector machines. Two sets of SNPs, 9p21.3 alone and a set of 12 SNPs identified by GWAS and through a model-fitting procedure, were considered. Performance was assessed by measuring area under the curve (AUC) for OHGS using 10-fold cross-validation and WTCCC as a replication set. AUC for logistic regression using OHGS increased significantly from 0.555 to 0.608 (
P
=3.59×10
−14
) for 9p21.3 versus the 12 SNPs, respectively. This difference remained when traditional risk factors were considered in a subgroup of OHGS (1388 cases, 2038 control subjects), with AUC increasing from 0.804 to 0.809 (
P
=0.037). The added predictive value over and above the traditional risk factors was not significant for 9p21.3 (AUC 0.801 versus 0.804,
P
=0.097) but was for the 12 SNPs (AUC 0.801 versus 0.809,
P
=0.0073). Performance was similar between OHGS and WTCCC. Logistic regression outperformed both support vector machines and allele counting.

Conclusions—
Using the collective of 12 SNPs confers significantly greater predictive capabilities for CAD than 9p21.3, whether traditional risks are or are not considered. More accurate models probably will evolve as additional CAD-associated SNPs are identified.
Acquired von Willebrand Syndrome in Patients With an Axial Flow Left Ventricular Assist Device
Authors: Meyer Anna L. , Malehsa Doris , Bara Christoph , Budde Ulrich , Slaughter Mark S. , Haverich Axel , Strueber Martin 
Published: August 2010

Background—
Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy.

Methods and Results—
Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified.

Conclusions—
A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device.