bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunology of human schistosomiasis
Authors: Colley D. G. , Secor W. E. 
Published: November 2013

SummaryThere is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune‐response‐based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti‐egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections.
The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS‐III): a research program striving to improve blood donor and transfusion recipient outcomes
Authors: Kleinman Steven , Busch Michael P. , Murphy Edward L. , Shan Hua , Ness Paul , Glynn Simone A. ,   The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS‐III)
Published: November 2013

BackgroundThe Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) is a 7‐year multicenter transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute.Study Design and MethodsThe domestic component involves four blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa, which involve US and in‐country investigators.ResultsREDS‐III is using two major methods to address key research priorities in blood banking and transfusion medicine. First, there will be numerous analyses of large “core” databases; the international programs have each constructed a donor and donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Second, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that either are in progress or are scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization, transfusion outcomes, noninfectious transfusion risks, human immunodeficiency virus–related safety issues (particularly in the international programs), emerging infectious agents, blood component quality, donor health and safety, and other donor issues.ConclusionsIt is intended that REDS‐III serve as an impetus for more widespread recipient and linked donor–recipient research in the United States as well as to help assure a safe and available blood supply in the United States and in international locations.
Fitness for Service Assessment on Local Metal Loss Near a
Discontinuity Using Elastic-Plastic Stress Analysis
Authors: Wang Zhanghai (John) , Rodriguez Samuel 
Published: November 2013

Abstract
In fitness for service (FFS) assessments, one issue that people often encounter is a corroded area near a structural discontinuity. In this case, the formula-based sections of the FFS standard are incapable of evaluating the component without resorting to finite element analysis (FEA). In this paper, an FEA-based technical approach for evaluating FFS assessments using an elastic-plastic material model and reformed criteria is proposed.
Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid
Authors: Kato Kelly C. , Morais-Teixeira Eliane , Reis Priscila G. , Silva-Barcellos Neila M. , Salaün Pascal , Campos Paula P. , Dias Corrêa-Junior José , Rabello Ana , Demicheli Cynthia , Frézard Frédéric 
Published: November 2013

ABSTRACT

Pentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected with
Leishmania infantum
were treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy.
Metabolic Engineering of the Regulators in Nitrogen Catabolite Repression To Reduce the Production of Ethyl Carbamate in a Model Rice Wine System
Authors: Zhao Xinrui , Zou Huijun , Fu Jianwei , Zhou Jingwen , Du Guocheng , Chen Jian 
Published: November 2013

ABSTRACTRice wine has been one of the most popular traditional alcoholic drinks in China. However, the presence of potentially carcinogenic ethyl carbamate (EC) in rice wine has raised a series of food safety issues. During rice wine production, the key reason for EC formation is urea accumulation, which occurs because of nitrogen catabolite repression (NCR) inSaccharomyces cerevisiae. NCR represses urea utilization by retaining Gln3p in the cytoplasm when preferred nitrogen sources are present. In order to increase the nuclear localization of Gln3p, some possible phosphorylation sites on the nuclear localization signal were mutated and the nuclear localization regulation signal was truncated, and the disruption ofURE2provided an additional method of reducing urea accumulation. By combining these strategies, the genes involved in urea utilization (DUR1,2andDUR3) could be significantly activated in the presence of glutamine. During shake flask fermentations of the genetically modified strains, very little urea accumulated in the medium. Furthermore, the concentrations of urea and EC were reduced by 63% and 72%, respectively, in a model rice wine system. Examination of the normal nutrients in rice wine indicated that there were few differences in fermentation characteristics between the wild-type strain and the genetically modified strain. These results show that metabolic engineering of the NCR regulators has great potential as a method for eliminating EC during rice wine production.
Cytomegalovirus Survival and Transferability and the Effectiveness of Common Hand-Washing Agents against Cytomegalovirus on Live Human Hands
Authors: Stowell Jennifer D. , Forlin-Passoni Daniela , Radford Kay , Bate Sheri L. , Dollard Sheila C. , Bialek Stephanie R. , Cannon Michael J. , Schmid D. Scott 
Published: November 2013

ABSTRACT

Congenital cytomegalovirus (CMV) transmission can occur when women acquire CMV while pregnant. Infection control guidelines may reduce risk for transmission. We studied the duration of CMV survival after application of bacteria to the hands and after transfer from the hands to surfaces and the effectiveness of cleansing with water, regular and antibacterial soaps, sanitizer, and diaper wipes. Experiments used CMV AD169 in saliva at initial titers of 1 × 10
5
infectious particles/ml. Samples from hands or surfaces (points between 0 and 15 min) were placed in culture and observed for at least 2 weeks. Samples were also tested using CMV real-time PCR. After application of bacteria to the hands, viable CMV was recovered from 17/20 swabs at 0 min, 18/20 swabs at 1 min, 5/20 swabs at 5 min, and 4/20 swabs at 15 min. After transfer, duration of survival was at least 15 min on plastic (1/2 swabs), 5 min on crackers and glass (3/4 swabs), and 1 min or less on metal and cloth (3/4 swabs); no viable virus was collected from wood, rubber, or hands. After cleansing, no viable virus was recovered using water (0/22), plain soap (0/20), antibacterial soap (0/20), or sanitizer (0/22). Viable CMV was recovered from 4/20 hands 10 min after diaper wipe cleansing. CMV remains viable on hands for sufficient times to allow transmission. CMV may be transferred to surfaces with reduced viability. Hand-cleansing methods were effective at eliminating viable CMV from hands.
CT-diagnosed emphysema and prognosis of chronic airflow obstruction: a retrospective study
Authors: Kurashima Kazuyoshi , Fukuda Chiaki , Nakamoto Keitaro , Takaku Yotaro , Hijikata Naoya , Hoshi Toshiko , Kanauchi Tetsu , Ueda Miyuki , Takayanagi Noboru , Sugita Yutaka , Araki Ryuichiro 
Published: November 2013

ObjectiveCT-diagnosed emphysema is associated with poor prognosis in chronic obstructive pulmonary disease (COPD). Its clinical impacts on prognoses of asthma with chronic airflow obstruction (CAO) are not well known. We sought to compare mortalities and prognostic factors in COPD and asthma with CAO by the presence or absence of CT-diagnosed emphysema.DesignRetrospective cohort study.SettingReferral centre hospital for respiratory disease.Participants1272 patients aged over 40 years with CAO (January 2000 to December 2011). CAO was defined as a forced expiratory volume in 1 s/forced vital capacity <0.7 after bronchodilator use throughout the observation period.Primary and secondary outcome measurementsOverall mortality served as the primary endpoint. We compared mortalities and prognostic factors of COPD and asthma subgroups with or without emphysema. Secondary endpoints were the prevalence of COPD and asthma in patients with CAO.ResultsOverall, diagnoses included COPD with emphysema in 517 (40.6%) patients, COPD without emphysema in 104 (8.2%) patients, asthma with emphysema in 178 (13.9%) patients, asthma without emphysema in 169 (13.3%) patients, other respiratory diseases (RD) with emphysema in 128 (10.1%) patients, and other RD without emphysema in 176 (13.8%) patients. Patients with asthma without emphysema had the best prognosis followed by those with asthma with emphysema, COPD without emphysema and COPD with emphysema. Each subgroup had distinct prognostic factors. Presence of emphysema was an independent risk factor for de novo lung cancer among patients with CAO.ConclusionsPatients with asthma with CAO have a better prognosis than patients with COPD. The presence of CT-diagnosed emphysema predicts poor prognosis in COPD and asthma with CAO.
Microbiological findings of vulvovaginitis in prepubertal girls
Authors: Bumbulienė Žana , Venclavičiūtė Karolina , Ramašauskaitė Diana , Arlauskienė Audronė , Bumbul Elžbieta , Drąsutienė Gražina 
Published: November 2013

Abstract

Objective
To compare vaginal culture results between prepubertal girls with and without vulvovaginitis, and obtain an overview of the most commonly encountered microbes.

Design
Prospective descriptive study.

Setting
Outpatient clinic of Vilnius University Hospital Santariskiu Klinikos during September 2011–December 2012.

Patients
115 prepubertal girls with vulvovaginitis symptoms and additionally 20 age-matched asymptomatic girls.

Methods
Each girl had a vaginal smear carried out using a sterile swab from the introitus or lower third of the vagina. All samples were referred to the microbiology laboratory where standard microbiological diagnostic procedures were performed.

Results
Positive microbiological findings were seen in all 115 (100%) symptomatic girls and in 12 (60%) control group girls (p&lt;0.001). Pathogenic bacteria were found only in symptomatic girls. Statistically significant differences in bacteria culture results (pure or mixed) and growth of isolated bacteria colonies between patients versus healthy girls were found (p&lt;0.05). The dominant bacteria in the target group, accounting for 66% of all isolated microbes, were Escherichia coli, Enterococcus faecalis, Staphylococcus coagulase negative, Streptococcus α haemolyticus and A group Streptococcus β haemolyticus. The bacteria of faecal origin were isolated from 61 (53%) girls with vulvovaginitis and from 5 (25%) girls without vaginal inflammation (p&lt;0.05). Instances of Candida species were extremely rare (2.6%).

Conclusions
Positive microbiological findings, mixed bacteria cultures and a high growth of bacteria colonies are found significantly more often in girls with vulvovaginitis. The main causative premenarchal vulvovaginitis agents are faecal in origin.
Tumor-Infiltrating Lymphocytes Expressing the Tissue Resident Memory Marker CD103 Are Associated with Increased Survival in High-Grade Serous Ovarian Cancer
Authors: Webb John R. , Milne Katy , Watson Peter , deLeeuw Ronald J. , Nelson Brad H. 
Published: November 2013

AbstractBackground: The presence of CD8+ tumor-infiltrating lymphocytes (TIL) is associated with prolonged survival in high-grade serous ovarian cancer (HGSC) and other epithelial cancers. Survival is most strongly associated with intraepithelial versus intrastromal CD8+ TILs; however, the mechanisms that promote the intraepithelial localization of TILs remain poorly understood. We hypothesized that intraepithelial CD8+ TILs, like normal mucosal intraepithelial lymphocytes, might express CD103, a subunit of αE/β7 integrin, which binds E-cadherin on epithelial cells.Methods: A large collection of primary ovarian tumors (HGSC, endometrioid, mucinous, and clear cell) was analyzed by immunohistochemistry for the presence of TIL-expressing CD103. The activation and differentiation status of CD103+ TILs were assessed by flow cytometry. The prognostic significance of TIL subsets was evaluated by Kaplan–Meier analysis.Results: CD103+ TILs were present in all major ovarian cancer subtypes and were most abundant in HGSC. CD103+ TILs were preferentially localized to epithelial regions of tumors and were comprised predominantly of CD8+ T cells expressing activation (HLA-DR, Ki-67, PD-1) and cytolytic (TIA-1) markers, as well as CD56+ NK cells. Tumor infiltration by CD103+ TILs was strongly associated with patient survival in HGSC. Tumors containing CD8+ TILs that were CD103− showed poor prognosis equivalent to tumors lacking CD8+ TILs altogether.Conclusions: CD103+ TILs comprise intraepithelial, activated CD8+ T cells, and NK cells and are strongly associated with patient survival in HGSC. CD103 may serve as a useful marker for enriching the most beneficial subsets of TILs for immunotherapy. Clin Cancer Res; 20(2); 434–44. ©2013 AACR.
Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation
Authors: Simon Manuel , Stefan Nikolas , Borsig Lubor , Plückthun Andreas , Zangemeister-Wittke Uwe 
Published: November 2013

Abstract
Fusion toxins used for cancer-related therapy have demonstrated short circulation half-lives, which impairs tumor localization and, hence, efficacy. Here, we demonstrate that the pharmacokinetics of a fusion toxin composed of a designed ankyrin repeat protein (DARPin) and domain I–truncated Pseudomonas Exotoxin A (PE40/ETA″) can be significantly improved by facile bioorthogonal conjugation with a polyethylene glycol (PEG) polymer at a unique position. Fusion of the anti-EpCAM DARPin Ec1 to ETA″ and expression in methionine-auxotrophic E. coli enabled introduction of the nonnatural amino acid azidohomoalanine (Aha) at position 1 for strain-promoted click PEGylation. PEGylated Ec1-ETA″ was characterized by detailed biochemical analysis, and its potential for tumor targeting was assessed using carcinoma cell lines of various histotypes in vitro, and subcutaneous and orthotopic tumor xenografts in vivo. The mild click reaction resulted in a well-defined mono-PEGylated product, which could be readily purified to homogeneity. Despite an increased hydrodynamic radius resulting from the polymer, the fusion toxin demonstrated high EpCAM-binding activity and retained cytotoxicity in the femtomolar range. Pharmacologic analysis in mice unveiled an almost 6-fold increase in the elimination half-life (14 vs. 82 minutes) and a more than 7-fold increase in the area under the curve (AUC) compared with non-PEGylated Ec1-ETA″, which directly translated in increased and longer-lasting effects on established tumor xenografts. Our data underline the great potential of combining the inherent advantages of the DARPin format with bioorthogonal click chemistry to overcome the limitations of engineering fusion toxins with enhanced efficacy for cancer-related therapy. Mol Cancer Ther; 13(2); 375–85. ©2013 AACR.
Using Benefit-Based Tailored Treatment to Improve the Use of Antihypertensive Medications
Authors: Sussman Jeremy , Vijan Sandeep , Hayward Rod 
Published: November 2013

Background—
Current guidelines for prescribing antihypertensive medications focus on reaching specific blood pressure targets. We sought to determine whether antihypertensive medications could be used more effectively by a treatment strategy based on tailored estimates of cardiovascular disease events prevented.

Methods and Results—
We developed a nationally representative sample of American adults aged 30 to 85 years with no history of myocardial infarction, stroke, or severe congestive heart failure using the National Health and Nutrition Examination Survey III. We then created a simulation model to estimate the effects of 5 years of treatment with treat-to-target (treatment to specific blood pressure goals) and benefit-based tailored treatment (treatment based on estimated cardiovascular disease event reduction) approaches to antihypertensive medication management. All effect size estimates were derived directly from meta-analyses of randomized trials. We found that 55% of the overall population of 176 million Americans would be treated identically under the 2 treatment approaches. Benefit-based tailored treatment would prevent 900 000 more cardiovascular disease events and save 2.8 million more quality-adjusted life-years, despite using 6% fewer medications over 5 years. In the 45% of the population treated differently by the strategies, benefit-based tailored treatment would save 159 quality-adjusted life-years per 1000 treated versus 74 quality-adjusted life-years per 1000 treated by the treat-to-target approach. The findings were robust to sensitivity analyses.

Conclusions—
We found that benefit-based tailored treatment was both more effective and required less antihypertensive medication than current guidelines based on treating to specific blood pressure goals.
Enhanced Expression of β3-Adrenoceptors in Cardiac Myocytes Attenuates Neurohormone-Induced Hypertrophic Remodeling Through Nitric Oxide Synthase
Authors: Belge Catharina , Hammond Joanna , Dubois-Deruy Emilie , Manoury Boris , Hamelet Julien , Beauloye Christophe , Markl Andreas , Pouleur Anne-Catherine , Bertrand Luc , Esfahani Hrag , Jnaoui Karima , Götz Konrad R. , Nikolaev Viacheslav O. , Vanderper Annelies , Herijgers Paul , Lobysheva Irina , Iaccarino Guido , Hilfiker-Kleiner Denise , Tavernier Geneviève , Langin Dominique , Dessy Chantal , Balligand Jean-Luc 
Published: November 2013

Background—
β1-2-adrenergic receptors (AR) are key regulators of cardiac contractility and remodeling in response to catecholamines. β3-AR expression is enhanced in diseased human myocardium, but its impact on remodeling is unknown.

Methods and Results—
Mice with cardiac myocyte-specific expression of human β3-AR (β3-TG) and wild-type (WT) littermates were used to compare myocardial remodeling in response to isoproterenol (Iso) or Angiotensin II (Ang II). β3-TG and WT had similar morphometric and hemodynamic parameters at baseline. β3-AR colocalized with caveolin-3, endothelial nitric oxide synthase (NOS) and neuronal NOS in adult transgenic myocytes, which constitutively produced more cyclic GMP, detected with a new transgenic FRET sensor. Iso and Ang II produced hypertrophy and fibrosis in WT mice, but not in β3-TG mice, which also had less re-expression of fetal genes and transforming growth factor β1. Protection from Iso-induced hypertrophy was reversed by nonspecific NOS inhibition at low dose Iso, and by preferential neuronal NOS inhibition at high-dose Iso. Adenoviral overexpression of β3-AR in isolated cardiac myocytes also increased NO production and attenuated hypertrophy to Iso and phenylephrine. Hypertrophy was restored on NOS or protein kinase G inhibition. Mechanistically, β3-AR overexpression inhibited phenylephrine-induced nuclear factor of activated T-cell activation.

Conclusions—
Cardiac-specific overexpression of β3-AR does not affect cardiac morphology at baseline but inhibits the hypertrophic response to neurohormonal stimulation in vivo and in vitro, through a NOS-mediated mechanism. Activation of the cardiac β3-AR pathway may provide future therapeutic avenues for the modulation of hypertrophic remodeling.
Validation of a Pattern Scaling Approach for Determining the Maximum Available Renewable Freshwater Resource
Authors: Ishizaki Yasuhiro , Yokohata Tokuta , Emori Seita , Shiogama Hideo , Takahashi Kiyoshi , Hanasaki Naota , Nozawa Toru , Ogura Tomoo , Nakaegawa Toshiyuki , Yoshimori Masakazu , Yoshida Ai , Watanabe Shigeru 
Published: November 2013

Abstract
A pattern scaling approach allows projection of regional climate changes under a wide range of emission scenarios. A basic assumption of this approach is that the spatial response pattern to global warming (scaling pattern) is the same for all emission scenarios. Precipitation minus evapotranspiration (PME) over land can be considered to be a measure of the maximum available renewable freshwater resource, and estimation of PME is fundamentally important for the assessment of water resources. The authors assessed the basic assumption of pattern scaling for PME by the use of five global climate models. A significant scenario dependency (SD) of the scaling pattern of PME was found over some regions. This SD of the scaling pattern of PME was mainly due to the SD and the nonlinear response of large-scale atmospheric and oceanic changes. When the SD of the scaling pattern of PME is significant in a target area, projections of the impact of climate change need to carefully take into consideration the SD. Although the SD of the anthropogenic aerosol scaling patterns tended to induce SDs of precipitation and evapotranspiration scaling patterns, the SDs of precipitation and evapotranspiration tended to cancel each other out. As a result, the SD of the PME scaling pattern tended to be insignificant over most regions where the SD of anthropogenic aerosol scaling patterns were significant. The authors could not find large impacts of land use change on PME scaling pattern, but the former may influence the latter on different time scales or spatial scales.