bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioaccumulation of Microcystins in Lettuce
Authors: Hereman Talita Caroline , Bittencourt‐Oliveira Maria do Carmo 
Published: October 2012

The contamination of lettuce (Lactuca sativa L.) by water‐borne crude extracts of the cyanobacterium microcystin‐producing Microcystis aeruginosa (Kützing) Kützing was investigated. The aim of the study was to determine whether bioaccumulation of microcystins occurs in lettuce foliar tissue when sprayed with solutions containing microcystins at concentrations observed in aquatic systems (0.62 to 12.5 μg · L−1). Microcystins were found in lettuce foliar tissues (8.31 to 177.8 μg per Kg of fresh weight) at all concentrations of crude extracts. Spraying with water containing microcystins and cyanobacteria may contaminate lettuce at levels higher than the daily intake of microcystins recommended by the World Health Organization (WHO), underscoring the need to monitor such food exposure pathways by public authorities.
Interferon Regulation Factor‐3 is a Critical Regulator of the Mature of Dendritic Cells from Mice
Authors: Zhang G. , Zhang Z. , Liu Z. 
Published: October 2012

AbstractInterferon regulatory factor‐3 (IRF‐3) plays an important role in virus and double‐stranded RNA‐mediated induction of type I interferon and RANTES (regulated on activation normal T cell expressed and secreted), DNA damage signalling, tumour suppression and virus‐induced apoptosis. IRF‐3 had recently been shown to contribute to T‐cell activation in response to pathogens, which implicated an extensive immunological role for IRF‐3. Dendritic cells (DCs) played critical roles as professional APCs in the development of immune responses. However, it was unclear whether IRF‐3 had any effect on phenotype or function of DCs. In this study, it was shown that IRF‐3 acted as a promoter of DC maturation. The level of IRF‐3 expression was transiently upregulated and accumulated in the nucleus in TNF‐α‐induced immune maturation of mice DC cells. Knockdown of IRF‐3 by small interfering RNA in DC cells resulted in both phenotypic and functional immaturation, even without TNF‐α treatment. Overall, our data demonstrated for the first time that IRF‐3 was a critical regulator of mice DC maturation.
Computer‐aided classification of breast masses using speckle features of automated breast ultrasound images
Authors: Moon Woo Kyung , Lo Chung‐Ming , Chang Jung Min , Huang Chiun‐Sheng , Chen Jeon‐Hor , Chang Ruey‐Feng 
Published: October 2012

Purpose:To develop an ultrasound computer‐aided diagnosis (CAD) system using speckle features of automated breast ultrasound (ABUS) images.Methods:The ABUS images of 147 pathologically proven breast masses (76 benign and 71 malignant cases) were used. For each mass, a volume of interest (VOI) was cropped to define the tumor area, and the average number of speckle pixels within a VOI was calculated. In addition, first‐order and second‐order statistical analyses of the speckle pixels were used to quantify the information of gray‐level distributions and the spatial relations among the pixels. Receiver operating characteristic curve analysis was used to evaluate the performance.Results:The proposed CAD system based on speckle patterns achieved an accuracy of 84.4% (124/147), a sensitivity of 83.1% (59/71), a specificity of 85.5% (65/76), and an Az of 0.91. The performance indices of the speckle features were comparable to the performance indices of the morphological features, which include shape and ellipse‐fitting features (p‐value > 0.05). Furthermore, combining speckle and morphological features yielded an Az that was significantly better than the Az of the morphological features alone (0.96 vs 0.91, p‐value = 0.0154).Conclusions:The results suggest that the proposed speckle features, while combined with morphological features, are promising for the classification of breast masses detected using ABUS.
New Approaches to Sepsis: Molecular Diagnostics and Biomarkers
Authors: Reinhart Konrad , Bauer Michael , Riedemann Niels C. , Hartog Christiane S. 
Published: October 2012

SUMMARY
Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.
West Nile Virus: Biology, Transmission, and Human Infection
Authors: Colpitts Tonya M. , Conway Michael J. , Montgomery Ruth R. , Fikrig Erol 
Published: October 2012

SUMMARY
West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease.
Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions
Authors: Tzouvelekis L. S. , Markogiannakis A. , Psichogiou M. , Tassios P. T. , Daikos G. L. 
Published: October 2012

SUMMARY

The spread of
Enterobacteriaceae
, primarily
Klebsiella pneumoniae
, producing KPC, VIM, IMP, and NDM carbapenemases, is causing an unprecedented public health crisis. Carbapenemase-producing enterobacteria (CPE) infect mainly hospitalized patients but also have been spreading in long-term care facilities. Given their multidrug resistance, therapeutic options are limited and, as discussed here, should be reevaluated and optimized. Based on susceptibility data, colistin and tigecycline are commonly used to treat CPE infections. Nevertheless, a review of the literature revealed high failure rates in cases of monotherapy with these drugs, whilst monotherapy with either a carbapenem or an aminoglycoside appeared to be more effective. Combination therapies not including carbapenems were comparable to aminoglycoside and carbapenem monotherapies. Higher success rates have been achieved with carbapenem-containing combinations. Pharmacodynamic simulations and experimental infections indicate that modification of the current patterns of carbapenem use against CPE warrants further attention. Epidemiological data, though fragmentary in many countries, indicate CPE foci and transmission routes, to some extent, whilst also underlining the lack of international collaborative systems that could react promptly and effectively. Fortunately, there are sound studies showing successful containment of CPE by bundles of measures, among which the most important are active surveillance cultures, separation of carriers, and assignment of dedicated nursing staff.
Occurrence and Evolution of the Paralogous Zinc Metalloproteases IgA1 Protease, ZmpB, ZmpC, and ZmpD in Streptococcus pneumoniae and Related Commensal Species
Authors: Bek-Thomsen Malene , Poulsen Knud , Kilian Mogens 
Published: October 2012

ABSTRACTThe distribution, genome location, and evolution of the four paralogous zinc metalloproteases, IgA1 protease, ZmpB, ZmpC, and ZmpD, inStreptococcus pneumoniaeand related commensal species were studied byin silicoanalysis of whole genomes and by activity screening of 154 representatives of 20 species. ZmpB was ubiquitous in the Mitis and Salivarius groups of the genusStreptococcusand in the generaGemellaandGranulicatella, with the exception of a fragmented gene inStreptococcus thermophilus, the only species with a nonhuman habitat. IgA1 protease activity was observed in all members ofS. pneumoniae,S. pseudopneumoniae,S. oralis,S. sanguinis, andGemella haemolysans, was variably present inS. mitisandS. infantis, and absent inS. gordonii,S. parasanguinis,S. cristatus,S. oligofermentans,S. australis,S. peroris, andS. suis. Phylogenetic analysis of 297zmpsequences and representative housekeeping genes provided evidence for an unprecedented selection for genetic diversification of theiga,zmpB, andzmpDgenes inS. pneumoniaeand evidence of very frequent intraspecies transfer of entire genes and combination of genes. Presumably due to their adaptation to a commensal lifestyle, largely unaffected by adaptive mucosal immune factors, the corresponding genes in commensal streptococci have remained conserved. The widespread distribution and significant sequence diversity indicate an ancient origin of the zinc metalloproteases predating the emergence of the humanoid species.zmpB, which appears to be the ancestral gene, subsequently duplicated and successfully diversified into distinct functions, is likely to serve an important but yet unknown housekeeping function associated with the human host.IMPORTANCEThe paralogous zinc metalloproteases IgA1 protease, ZmpB, ZmpC, and ZmpD have been identified as crucial for virulence of the human pathogenStreptococcus pneumoniae. This study maps the presence of the corresponding genes and enzyme activities inS. pneumoniaeand in related commensal species of the generaStreptococcus,Gemella, andGranulicatella. The distribution, genome location, and sequence diversification indicate thatzmpBis the ancestral gene predating the evolution of today’s humanoid species. The ZmpB protease may play an important but yet unidentified role in the association of streptococci of the Mitis and Salivarius groups with their human host, as it is ubiquitous in these two groups, except for a fragmented gene inStreptococcus thermophilus, the only species not associated with humans. The relative sequence diversification of the IgA1 protease, ZmpB, and ZmpD is striking evidence of differences in selection for diversification of these surface-exposed proteins in the pathogenS. pneumoniaecompared to the closely related commensal streptococci.
An Evolutionary Link between Natural Transformation and CRISPR Adaptive Immunity
Authors: Jorth Peter , Whiteley Marvin 
Published: October 2012

ABSTRACT

Natural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history of
Aggregatibacter actinomycetemcomitans
, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.

IMPORTANCE
The human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogen
Aggregatibacter actinomycetemcomitans
, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competent
A. actinomycetemcomitans
strains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.
DECREASING SIZE OF RADIOSENSITIVE CAPSULES FROM MICRO TO NANO, AND ITS INCREASED ANTITUMOR EFFECT AND DECREASING ADVERSE EFFECT
Authors: HARADA S. , EHARA S. , ISHII K. , YAMAZAKI H. , MATSUYAMA S. , SATO T. , KAMIYA T. , SERA K. , SAITO Y. 
Published: October 2012

We have been developing microcapsules that release anticancer drug with response to radiation. We attempted to decrease the diameter of capsules. Then, two categories were tested in VIVO in C3He mice: (1) the antitumor effect in combination with radiation and subcutaneously injected nanocapsules, (2) the kidnetics of nanocapsules when they were injected intravenously. Microcapsules were produced by spraying a mixture of 3.0 % hyaluronic acid, 2.0 % alginate, 3.0 % H2O2, and 0.3 mmol carboplatin (Pt containing anticancer drug) onto a mixture of vibrated 0.3 mol FeCl 2 and 0.15 mol CaCl 2. The antitumor effect was measured by measuring tumor diameter every day. The kinetics of microcapsules were expressed as the numbers of capsules in 5 views (25 × 25 μm) of micro PIXE camera and Pt concentration of quantiative PIXE. The generated microcapsules 752 ± 64 nm, which were significantly downsized relative to previous capsules. The accumulations of capsules in lungs, liver, and kidneys were decreased by downsizing, whereas those of tumors were increased. By adjusting Pt concentration in tumor, there were no significant differences in antitumor effect between not downsized and downsized microcapsules with combination with radiation. Decreased trapping of downsized microcapsules to lungs, liver, and kidneys, also increased trapping in tumors will lead to new targeted chemoradiotherapy via intravenous injection of microcapsules.
Specific Lymphocyte Subsets Predict Response to Adoptive Cell Therapy Using Expanded Autologous Tumor-Infiltrating Lymphocytes in Metastatic Melanoma Patients
Authors: Radvanyi Laszlo G. , Bernatchez Chantale , Zhang Minying , Fox Patricia S. , Miller Priscilla , Chacon Jessica , Wu Richard , Lizee Gregory , Mahoney Sandy , Alvarado Gladys , Glass Michelle , Johnson Valen E. , McMannis John D. , Shpall Elizabeth , Prieto Victor , Papadopoulos Nicholas , Kim Kevin , Homsi Jade , Bedikian Agop , Hwu Wen-Jen , Patel Sapna , Ross Merrick I. , Lee Jeffrey E. , Gershenwald Jeffrey E. , Lucci Anthony , Royal Richard , Cormier Janice N. , Davies Michael A. , Mansaray Rahmatu , Fulbright Orenthial J. , Toth Christopher , Ramachandran Renjith , Wardell Seth , Gonzalez Audrey , Hwu Patrick 
Published: October 2012

Abstract
Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response.
Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined.
Results: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T cells in the infusion product, a more differentiated effector phenotype of the CD8+ population, and a higher frequency of CD8+ T cells coexpressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified.
Conclusion: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8+ T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. Clin Cancer Res; 18(24); 6758–70. ©2012 AACR.
Limited Induction of Tumor Cross-Reactive T Cells without a Measurable Clinical Benefit in Early Melanoma Patients Vaccinated with Human Leukocyte Antigen Class I–Modified Peptides
Authors: Filipazzi Paola , Pilla Lorenzo , Mariani Luigi , Patuzzo Roberto , Castelli Chiara , Camisaschi Chiara , Maurichi Andrea , Cova Agata , Rigamonti Gianluigi , Giardino Felicetta , Di Florio Annabella , Asioli Marco , Frati Paola , Sovena Gloria , Squarcina Paola , Maio Michele , Danielli Riccardo , Chiarion-Sileni Vanna , Villa Antonello , Lombardo Claudia , Tragni Gabrina , Santinami Mario , Parmiani Giorgio , Rivoltini Licia 
Published: October 2012

AbstractPurpose: The progressive immune dysfunctions that occur in patients with advanced melanoma make them unlikely to efficiently respond to cancer vaccines. A multicenter randomized phase II trial was conducted to test whether immunization with modified HLA class I tumor peptides in the context of adjuvant therapy results in better immunologic responses and improved clinical outcomes in patients with early melanoma (stages IIB/C-III).Experimental Design: Forty-three patients were enrolled to undergo vaccination (n = 22) or observation (n = 21). The vaccine included four HLA-A*0201–restricted modified peptides (Melan-A/MART-1[27L], gp100[210M], NY-ESO-1[165V], and Survivin[97M]) emulsified in Montanide ISA51 and injected subcutaneously in combination with cyclophosphamide (300 mg/m2) and low-dose IL-2 (3 × 106 IU). The immune responses were monitored using ex vivo IFN-γ–ELISpot, HLA/multimer staining, and in vitro short-term peptide sensitization assays.Results: Vaccination induced a rapid and persistent increase in specific effector memory CD8+ T cells in 75% of the patients. However, this immunization was not associated with any significant increase in disease-free or overall survival as compared with the observation group. An extensive immunologic analysis revealed a significantly reduced cross-recognition of the corresponding native peptides and, most importantly, a limited ability to react to melanoma cells.Conclusions: Adjuvant setting is an appealing approach for testing cancer vaccines because specific CD8+ T cells can be efficiently induced in most vaccinated patients. However, the marginal antitumor activity of the T cells induced by modified peptides in this study largely accounts for the observed lack of benefit of vaccination. These findings suggest reconsidering this immunization strategy, particularly in early disease. Clin Cancer Res; 18(23); 6485–96. ©2012 AACR.
A Phase II, Randomized, Placebo-Controlled Study of Vismodegib as Maintenance Therapy in Patients with Ovarian Cancer in Second or Third Complete Remission
Authors: Kaye Stanley B. , Fehrenbacher Louis , Holloway Robert , Amit Amnon , Karlan Beth , Slomovitz Brian , Sabbatini Paul , Fu Ling , Yauch Robert L. , Chang Ilsung , Reddy Josina C. 
Published: October 2012

Abstract
Purpose: Hedgehog pathway inhibition has been suggested as a potential maintenance treatment approach in ovarian cancer through disruption of tumor–stromal interactions. Vismodegib is an orally available Hedgehog pathway inhibitor with clinical activity in advanced basal cell carcinoma and medulloblastoma. This phase II, randomized, double-blind, placebo-controlled trial was designed to provide a preliminary estimate of efficacy in patients with ovarian cancer in second or third complete remission (CR).
Experimental Design: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third CR were randomized 1:1 to vismodegib (GDC-0449; 150 mg daily) or placebo three to 14 weeks after completing chemotherapy. Treatment continued until radiographic progression or toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS).
Results: One hundred four patients were randomized to vismodegib (n = 52) or placebo (n = 52); median PFS was 7.5 months and 5.8 months, respectively [HR 0.79; 95% confidence interval (CI), 0.46–1.35]. The HR was 0.66 (95% CI, 0.36–1.20) for second CR patients (n = 84) and 1.79 (95% CI, 0.50–6.48) for third CR patients (n = 20). The most common adverse events in the vismodegib arm were dysgeusia/ageusia, muscle spasms, and alopecia. Grade 3/4 adverse events occurred in 12 patients (23.1%) with vismodegib and six (11.5%) with placebo. Hedgehog expression was detected in 13.5% of archival tissues.
Conclusions: In this study, the sought magnitude of increase in PFS was not achieved for vismodegib maintenance versus placebo in patients with ovarian cancer in second or third CR. The frequency of Hedgehog ligand expression was lower than expected. Clin Cancer Res; 18(23); 6509–18. ©2012 AACR.
Impact of an Electronic Medical Record-Based Clinical Decision Support Tool for Dysphagia Screening on Care Quality
Authors: Lakshminarayan Kamakshi , Rostambeigi Nassir , Fuller Candace C. , Peacock James M. , Tsai Albert W. 
Published: October 2012

Background and Purpose—
Dysphagia screening (DS) before oral intake in patients with acute stroke is a hospital-level performance measure. We report outcomes of an initiative to improve compliance to this quality measure.

Methods—
The design was a pre- versus postintervention comparison study. The Intervention was an electronic medical record-based clinical DS system embedded within stroke admission orders. The clinical DS was designed to facilitate DS in patients with stroke. The primary outcome was compliance to a process measure in patients with ischemic stroke: performance of a swallow screen before oral intake.

Results—

DS measure compliance increased from 36% to 74% (
P
=0.001). Chart audits found screened patients were more likely to have clinical DS-embedded admission orders initiated or stroke unit admission.

Conclusion—
The electronic medical record offers a ready platform for clinical DS implementation. DS is a difficult performance measure to improve. The described clinical DS has the potential for improving performance on this challenging care quality measure.