bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response‐guided peginterferon‐alpha‐2b plus ribavirin therapy for chronic hepatitis C patients with genotype 2 and high viral loads
Authors: Sato Ken , Hashizume Hiroaki , Yamazaki Yuichi , Horiguchi Norio , Kakizaki Satoru , Takagi Hitoshi , Mori Masatomo ,   the Gunma Liver Study Group
Published: March 2012

Aims:  Optimization of the duration of peginterferon‐α/ribavirin therapy in patients with hepatitis C virus (HCV) genotype 2 and high viral loads remains to be established. We sought to prospectively optimize the treatment duration based on their virological responses.Methods:  Serum HCV RNA levels of less than 50 IU/mL at weeks 2 and 4, and of 50 IU/mL or more at week 4, were defined as a super‐rapid virological response (SRVR), rapid virological response (RVR) and late virological response (LVR), respectively. Treatment for 12, 24 or 48 weeks was assigned to the patients with an SRVR, RVR or LVR, respectively. However, patients with an LVR who expressed a desire to receive the standard therapy duration were given the 24‐week therapy.Results:  The overall sustained virological response (SVR) rate was 78.1% (118/151). The SVR rate in the SRVR group was 93.8% (15/16), which was comparable to the 93.0% (66/71) SVR rate in the RVR group. In the LVR patients, the 48‐week treatment slightly increased the SVR rate to 76.5% (13/17) compared with the 51.1% (24/47) SVR rate in LVR patients who underwent the standard 24‐week treatment. The relapse rate in LVR patients was significantly decreased in patients treated for 48 weeks compared with patients treated for 24 weeks. Multivariate analysis identified the predictive factors for SVR as RVR, prior interferon therapy and total peginterferon‐α‐2b adherence in patients treated for 24 weeks.Conclusion:  Response‐guided therapy may be effective and useful for optimization of the treatment duration.
Accelerated in-vitro release testing methods for extended-release parenteral dosage forms
Authors: Shen Jie , Burgess Diane J 
Published: March 2012

Abstract

Objectives
This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants.

Key findings
Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, ‘real-time’ in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed.

Summary
Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro–in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable.
Computer‐aided diagnosis for dynamic contrast‐enhanced breast MRI of mass‐like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features
Authors: Agliozzo S. , De Luca M. , Bracco C. , Vignati A. , Giannini V. , Martincich L. , Carbonaro L. A. , Bert A. , Sardanelli F. , Regge D. 
Published: March 2012

Purpose: Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer‐aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE‐MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features.Methods: Fifty‐four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass‐like lesions were automatically segmented after image normalization and elastic coregistration of contrast‐enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal‐to‐time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross‐validation and bootstrap method for confidence intervals.Results: SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 0.04 (mean standard deviation), 0.87 0.06, and 0.86 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features.Conclusions: Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.
DNA and Modified Vaccinia Virus Ankara Vaccines Encoding Multiple Cytotoxic and Helper T-Lymphocyte Epitopes of Human Immunodeficiency Virus Type 1 (HIV-1) Are Safe but Weakly Immunogenic in HIV-1-Uninfected, Vaccinia Virus-Naive Adults
Authors: Gorse Geoffrey J. , Newman Mark J. , deCamp Allan , Hay Christine Mhorag , De Rosa Stephen C. , Noonan Elizabeth , Livingston Brian D. , Fuchs Jonathan D. , Kalams Spyros A. , Cassis-Ghavami Farah L. ,   the NIAID HIV Vaccine Trials Network
Published: March 2012

ABSTRACTWe evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.
Humoral Immune Responses in a Human Case of Glanders
Authors: Waag David M. , England Marilyn J. , DeShazer David 
Published: March 2012

ABSTRACTWithin 2 months of acquiring glanders, a patient developed 8-, 16-, and 4-fold increases, respectively, in specific IgA, IgG, and IgM serological titers againstBurkholderia mallei. Within 14 months of infection, the titers decreased to the baseline. Serum from this patient was also highly reactive againstBurkholderia pseudomalleiwhole cells.Burkholderia malleiwhole cells did not react with sera from patients with other diseases. Therefore, an assay using aB. malleicellular diagnostic antigen may be useful for the serodiagnosis of glanders.
Reduced Frequencies and Heightened CD103 Expression among Virus-Induced CD8+T Cells in the Respiratory Tract Airways of Vitamin A-Deficient Mice
Authors: Rudraraju Rajeev , Surman Sherri L. , Jones Bart G. , Sealy Robert , Woodland David L. , Hurwitz Julia L. 
Published: March 2012

ABSTRACTVitamin A deficiency (VAD) has profound effects on immune responses in the gut, but its effect on other mucosal responses is less well understood. Sendai virus (SeV) is a candidate human parainfluenza virus type 1 (hPIV-1) vaccine and a candidate vaccine vector for other respiratory viruses. A single intranasal dose of SeV elicits a protective immune response against hPIV-1 within days after vaccination. To define the effect of VAD on acute responses toward SeV, we monitored both antibodies and CD8+T cells in mice. On day 10 following SeV infection, there was a trend toward lower antibody activities in the nasal washes of VAD mice than in those of controls, while bronchoalveolar lavage (BAL) fluid and serum antibodies were not reduced. In contrast, there was a dramatic reduction of immunodominant CD8+T cell frequencies in the lower respiratory tract (LRT) airways of VAD animals. These T cells also showed unusually high CD103 (the αE subunit of αEβ7) expression patterns. In both VAD and control mice, E-cadherin (the ligand for αEβ7) was better expressed among epithelial cells lining the upper respiratory tract (URT) than in LRT airways. The results support a working hypothesis that the high CD103 expression among T cell populations in VAD mice alters mechanisms of T cell cross talk with URT and LRT epithelial cells, thereby inhibiting T cell migration and egress into the lower airway. Our data emphasize that the consequences of VAD are not limited to gut-resident cells and characterize VAD influences on an immune response to a respiratory virus vaccine.
Rapid Identification of Sporothrix Species by T3B Fingerprinting
Authors: de Oliveira Manoel Marques Evangelista , Sampaio Paula , Almeida-Paes Rodrigo , Pais Célia , Gutierrez-Galhardo Maria Clara , Zancope-Oliveira Rosely Maria 
Published: March 2012

ABSTRACT

This article describes PCR fingerprinting using the universal primer T3B to distinguish among species of the
Sporothrix
complex,
S. brasiliensis
,
S. globosa
,
S. mexicana
, and
S. schenckii
. This methodology generated distinct banding patterns, allowing the correct identification of all 35 clinical isolates at the species level, confirmed by partial calmodulin (CAL) gene sequence analyses. This methodology is simple, reliable, rapid, and cheap, making it an ideal routine identification system for clinical mycology laboratories.
Characterization of Microbiota of Root Canal-Treated Teeth with Posttreatment Disease
Authors: Rôças Isabela N. , Siqueira José F. 
Published: March 2012

ABSTRACT

This study evaluated the microbiota of root canals undergoing retreatment. The most prevalent taxa detected by checkerboard included
Propionibacterium
species,
Fusobacterium nucleatum
, streptococci, and
Pseudoramibacter alactolyticus
. Quantitative real-time PCR detected
Enterococcus faecalis
and streptococci in 38% and 41% of the cases, comprising 9.76% and 65.78% of the total bacterial counts, respectively. The findings call into question the status of
E. faecalis
as the main pathogen and suggest that other species can be candidate pathogens associated with persistent/secondary endodontic infections.
Influenza Virus Sequence Feature Variant Type Analysis: Evidence of a Role for NS1 in Influenza Virus Host Range Restriction
Authors: Noronha Jyothi M. , Liu Mengya , Squires R. Burke , Pickett Brett E. , Hale Benjamin G. , Air Gillian M. , Galloway Summer E. , Takimoto Toru , Schmolke Mirco , Hunt Victoria , Klem Edward , García-Sastre Adolfo , McGee Monnie , Scheuermann Richard H. 
Published: March 2012

ABSTRACTGenetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments. While traditional phylogenetic analysis is useful in tracking the evolutionary heritage of these viruses, the specific genetic determinants that dictate important phenotypic characteristics are often difficult to discern within the complex genetic background arising through evolution. Here we describe a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made available through the public Influenza Research Database resource (www.fludb.org), in which variant types (VTs) identified in defined influenza virus protein sequence features (SFs) are used for genotype-phenotype association studies. Since SFs have been defined for all influenza virus proteins based on known structural, functional, and immune epitope recognition properties, the Flu-SFVT approach allows the rapid identification of the molecular genetic determinants of important influenza virus characteristics and their connection to underlying biological functions. We demonstrate the use of the SFVT approach to obtain statistical evidence for effects of NS1 protein sequence variations in dictating influenza virus host range restriction.
Isolation and Characterization of a Novel Betacoronavirus Subgroup A Coronavirus, Rabbit Coronavirus HKU14, from Domestic Rabbits
Authors: Lau Susanna K. P. , Woo Patrick C. Y. , Yip Cyril C. Y. , Fan Rachel Y. Y. , Huang Yi , Wang Ming , Guo Rongtong , Lam Carol S. F. , Tsang Alan K. L. , Lai Kenneth K. Y. , Chan Kwok-Hung , Che Xiao-Yan , Zheng Bo-Jian , Yuen Kwok-Yung 
Published: March 2012

ABSTRACTWe describe the isolation and characterization of a novelBetacoronavirussubgroup A coronavirus, rabbit coronavirus HKU14 (RbCoV HKU14), from domestic rabbits. The virus was detected in 11 (8.1%) of 136 rabbit fecal samples by reverse transcriptase PCR (RT-PCR), with a viral load of up to 108copies/ml. RbCoV HKU14 was able to replicate in HRT-18G and RK13 cells with cytopathic effects. Northern blotting confirmed the production of subgenomic mRNAs coding for the HE, S, NS5a, E, M, and N proteins. Subgenomic mRNA analysis revealed a transcription regulatory sequence, 5′-UCUAAAC-3′. Phylogenetic analysis showed that RbCoV HKU14 formed a distinct branch amongBetacoronavirussubgroup A coronaviruses, being most closely related to but separate from the speciesBetacoronavirus 1. A comparison of the conserved replicase domains showed that RbCoV HKU14 possessed <90% amino acid identities to most members ofBetacoronavirus 1in ADP-ribose 1″-phosphatase (ADRP) and nidoviral uridylate-specific endoribonuclease (NendoU), indicating that RbCoV HKU14 should represent a separate species. RbCoV HKU14 also possessed genomic features distinct from those of otherBetacoronavirussubgroup A coronaviruses, including a unique NS2a region with a variable number of small open reading frames (ORFs). Recombination analysis revealed possible recombination events during the evolution of RbCoV HKU14 and members ofBetacoronavirus 1, which may have occurred during cross-species transmission. Molecular clock analysis using RNA-dependent RNA polymerase (RdRp) genes dated the most recent common ancestor of RbCoV HKU14 to around 2002, suggesting that this virus has emerged relatively recently. Antibody against RbCoV was detected in 20 (67%) of 30 rabbit sera tested by an N-protein-based Western blot assay, whereas neutralizing antibody was detected in 1 of these 20 rabbits.
Barriers and bridges to infection prevention and control: results of a qualitative case study of a Netherlands' surgical unit
Authors: Backman Chantal , Marck Patricia B , Krogman Naomi , Taylor Geoff , Sales Anne , Bonten Marc J M , Gigengack-Baars Ada C M 
Published: March 2012

ObjectivesThe objectives of the study are to observe the overall work environment including infection prevention and control (IP&C) practices on the target surgical unit; to analyse the policies and procedures in the hospital and unit environments; to analyse the barriers and bridges to IP&C that practitioners identify in visual narratives of their unit environment and to collect monthly specific IP&C-related anonymised data.DesignIn this qualitative case study analysis, a socio-ecological approach on health systems informed the research design and provided a framework to better understand the complexity of implementing effective IP&C.SettingThe study was conducted on a surgical unit at a Netherlands' hospital that reported successful reductions in the prevalence of targeted multidrug-resistant organisms.MethodsResearch methods included unit observations (n=3), review of relevant policies and procedures, five practitioner-led photo walkabouts of the unit (n=7), three photo elicitation focus groups with practitioners (n=13) and the review of related IP&C data.ResultsThe findings indicate some conditions and processes present that may influence the low prevalence of multidrug-resistant organisms, including the ‘search and destroy’ active surveillance strategy, low occupancy rates, a centralised bed cleaning system and the presence of an active grass roots Hygiene in Practice group, which engages practitioners in several ongoing activities to promote IP&C on the units.ConclusionsFurther research on the benefits of practitioner-led community of practices on IP&C practices such as the Hygiene in Practice group is also recommended. Additional case studies to compare theses practices with other acute care hospital around the world would be a valuable way to better understand what IP&C programmes are most effective in which contexts and for what reasons. Further data are available by contacting the primary author directly.
Foreign field hospitals after the 2010 Haiti earthquake: how good were we?
Authors: Gerdin Martin , Wladis Andreas , von Schreeb Johan 
Published: March 2012

ObjectiveTo assess the timing and activities of foreign field hospitals (FFH) deployed during the first month after the Haiti earthquake and to evaluate adherence to WHO/Pan American Health Organization (PAHO) guidelines. Results were compared with data from past sudden-onset disasters.MethodsA systematic attempt was made to contact all relief actors within the health care sector involved in the 12 January through 12 February 2010 FFH deployment. This was done using an email-based questionnaire and a web survey. In addition, the authors undertook a literature review using PubMed and the Google search engine between March 2010 and May 2011. The authors contacted key informants and agencies identified by direct observations in the field by email or phone.ResultsA total of 44 FFH were identified. The first FFH was operational on day two post-earthquake. The number of FFH beds peaked at about 3300 on day 17 post-earthquake. During the first month, the authors estimate that FFH conducted no more than 12 000 major surgical operations. While 25% of the FFH adhered to either WHO/PAHO first essential deployment requirements, none followed both requirements of WHO/PAHO. Compared with the 2005 earthquake in Pakistan, twice as many FFH provided medical care, resulting in three times more FFH beds.ConclusionsThe present study suggests that more FFH were sent to Haiti than to any previous sudden-onset disasters, but due to lack of data and transparency it remains impossible to determine to what extent did the first wave of FFH do any good in Haiti.
Survey of trainee attitudes to preparation for and participation in the FCEM examination
Authors: Cooper Jamie G , Rutherford Elaine , Hamer Wayne 
Published: March 2012

Introduction and aimsIn the UK, specialist trainees in emergency medicine are required to pass the Fellowship of the College of Emergency Medicine (FCEM). This examination assesses clinical knowledge, attitudes and skills, management principles, critical appraisal, and the ability to search medical literature and synthesise information. The aims of this study were to ascertain what resources trainees felt were most valuable in preparation for the FCEM and to obtain trainee feedback on the running of the FCEM.MethodsA questionnaire was developed in conjunction with the TSC into nine parts covering all aspects of preparation for and experience of sitting the FCEM. Email addresses of those trainees who had sat the FCEM examination in 2006 and 2007 were provided by the CEM and questionnaires were sent electronically to recipients. Responses were collated and analysed using Microsoft Excel.ResultsThere was a response rate of 42% (86/203), of whom about three-quarters felt well prepared for the FCEM. The most highly valued resources for exam preparation were practice questions, private study and small group work. A yearly mock FCEM examination was felt to be important by those who had such access and local trainer involvement in exam preparation was perceived significant for success.ConclusionsTraining programmes should make sure that facilities and expertise are available at a local level to allow trainees to have access to everything that is considered important in order to pass the FCEM.
COMMUTATIVE AUTOMORPHIC LOOPS OF ORDER p3
Authors: DE BARROS DYLENE AGDA SOUZA , GRISHKOV ALEXANDER , VOJTĚCHOVSKÝ PETR 
Published: March 2012

A loop is said to be automorphic if its inner mappings are automorphisms. For a prime p, denote by [Formula: see text] the class of all 2-generated commutative automorphic loops Q possessing a central subloop Z ≅ ℤp such that Q/Z ≅ ℤp × ℤp. Upon describing the free 2-generated nilpotent class two commutative automorphic loop and the free 2-generated nilpotent class two commutative automorphic p-loop Fp in the variety of loops whose elements have order dividing p2 and whose associators have order dividing p, we show that every loop of [Formula: see text] is a quotient of Fp by a central subloop of order p3. The automorphism group of Fp induces an action of GL 2(p) on the three-dimensional subspaces of Z(Fp) ≅ (ℤp)4. The orbits of this action are in one-to-one correspondence with the isomorphism classes of loops from [Formula: see text]. We describe the orbits, and hence we classify the loops of [Formula: see text] up to isomorphism. It is known that every commutative automorphic p-loop is nilpotent when p is odd, and that there is a unique commutative automorphic loop of order 8 with trivial center. Knowing [Formula: see text] up to isomorphism, we easily obtain a classification of commutative automorphic loops of order p3. There are precisely seven commutative automorphic loops of order p3 for every prime p, including the three abelian groups of order p3.
Translation Initiation Factor eIF4E Is a Target for Tumor Cell Radiosensitization
Authors: Hayman Thomas J. , Williams Eli S. , Jamal Muhammad , Shankavaram Uma T. , Camphausen Kevin , Tofilon Philip J. 
Published: March 2012

Abstract
A core component in the cellular response to radiation occurs at the level of translational control of gene expression. Because a critical element in translation control is the availability of the initiation factor eIF4E, which selectively enhances the cap-dependent translation of mRNAs, we investigated a regulatory role for eIF4E in cellular radiosensitivity. eIF4E silencing enhanced the radiosensitivity of tumor cell lines but not normal cells. Similarly, pharmacologic inhibition of eIF4E with ribavirin also enhanced tumor cell radiosensitivity. eIF4E attenuation did not affect cell-cycle phase distribution or radiation-induced apoptosis, but it delayed the dispersion of radiation-induced γH2AX foci and increased the frequency of radiation-induced mitotic catastrophe. Radiation did not affect 4E-BP1 phosphorylation or cap-complex formation but it increased eIF4E binding to more than 1,000 unique transcripts including many implicated in DNA replication, recombination, and repair. Taken together, our findings suggest that eIF4E represents a logical therapeutic target to increase tumor cell radiosensitivity. Cancer Res; 72(9); 2362–72. ©2012 AACR.