bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment and improvement of radiation oncology trainee contouring ability utilizing consensus‐based penalty metrics
Authors: Hallock Abhirami , Bauman Glenn , Read Nancy , D'Souza David , Perera Francisco , Aivas Inge , Best Lara , Cao Jeffrey , Louie Alexander V. , Wiebe Ericka , Sexton Tracy , Gaede Stewart , Battista Jerry , Rodrigues George 
Published: September 2012

AbstractIntroductionThe objective of this study was to develop and assess the feasibility of utilizing consensus‐based penalty metrics for the purpose of critical structure and organ at risk (OAR) contouring quality assurance and improvement.MethodsA Delphi study was conducted to obtain consensus on contouring penalty metrics to assess trainee‐generated OAR contours. Voxel‐based penalty metric equations were used to score regions of discordance between trainee and expert contour sets. The utility of these penalty metric scores for objective feedback on contouring quality was assessed by using cases prepared for weekly radiation oncology radiation oncology trainee treatment planning rounds.ResultsIn two Delphi rounds, six radiation oncology specialists reached agreement on clinical importance/impact and organ radiosensitivity as the two primary criteria for the creation of the Critical Structure Inter‐comparison of Segmentation (CriSIS) penalty functions. Linear/quadratic penalty scoring functions (for over‐ and under‐contouring) with one of four levels of severity (none, low, moderate and high) were assigned for each of 20 OARs in order to generate a CriSIS score when new OAR contours are compared with reference/expert standards. Six cases (central nervous system, head and neck, gastrointestinal, genitourinary, gynaecological and thoracic) then were used to validate 18 OAR metrics through comparison of trainee and expert contour sets using the consensus derived CriSIS functions. For 14 OARs, there was an improvement in CriSIS score post‐educational intervention.ConclusionsThe use of consensus‐based contouring penalty metrics to provide quantitative information for contouring improvement is feasible.
High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin
Authors: Fouhy Fiona , Guinane Caitriona M. , Hussey Seamus , Wall Rebecca , Ryan C. Anthony , Dempsey Eugene M. , Murphy Brendan , Ross R. Paul , Fitzgerald Gerald F. , Stanton Catherine , Cotter Paul D. 
Published: September 2012

ABSTRACT

The infant gut microbiota undergoes dramatic changes during the first 2 years of life. The acquisition and development of this population can be influenced by numerous factors, and antibiotic treatment has been suggested as one of the most significant. Despite this, however, there have been relatively few studies which have investigated the short-term recovery of the infant gut microbiota following antibiotic treatment. The aim of this study was to use high-throughput sequencing (employing both 16S rRNA and
rpoB
-specific primers) and quantitative PCR to compare the gut microbiota of nine infants who underwent parenteral antibiotic treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks after the conclusion of treatment, relative to that of nine matched healthy controls. The investigation revealed that the gut microbiota of the antibiotic-treated infants had significantly higher proportions of
Proteobacteria
(
P
= 0.0049) and significantly lower proportions of
Actinobacteria
(
P
= 0.00001) (and the associated genus
Bifidobacterium
[
P
= 0.0132]) as well as the genus
Lactobacillus
(
P
= 0.0182) than the untreated controls 4 weeks after the cessation of treatment. By week 8, the
Proteobacteria
levels remained significantly higher in the treated infants (
P
= 0.0049), but the
Actinobacteria
,
Bifidobacterium
, and
Lactobacillus
levels had recovered and were similar to those in the control samples. Despite this recovery of total
Bifidobacterium
numbers,
rpoB
-targeted pyrosequencing revealed that the number of different
Bifidobacterium
species present in the antibiotic-treated infants was reduced. It is thus apparent that the combined use of ampicillin and gentamicin in early life can have significant effects on the evolution of the infant gut microbiota, the long-term health implications of which remain unknown.
In VitroActivities of Nine Antifungal Drugs against 81 Phialophora and Cyphellophora Isolates
Authors: Feng Peiying , Najafzadeh M. Javad , Sun Jiufeng , Ahmed Sarah , Xi Liyan , de Hoog G. Sybren , Lai Wei , Lu Chun , Klaassen Corné H. , Meis Jacques F. 
Published: September 2012

ABSTRACTCyphellophora guyanensis(n= 15), otherCyphellophoraspecies (n= 11),Phialophora europaea(n= 43), and otherPhialophoraspecies (n= 12) were testedin vitroagainst nine antifungal drugs. The MIC90s across all of the strains (n= 81) were, in increasing order, as follows: posaconazole, 0.063 μg/ml; itraconazole, 0.5 μg/ml; voriconazole, 1 μg/ml; micafungin, 1 μg/ml; terbinafine, 2 μg/ml; isavuconazole, 4 μg/ml; caspofungin, 4 μg/ml; fluconazole, 8 μg/ml; amphotericin B, 16 μg/ml.
Prevention and Treatment of Virulent Bacterial Biofilms with an Enzymatic Nitric Oxide-Releasing Dressing
Authors: Sulemankhil Imran , Ganopolsky Jorge Gabriel , Dieni Christopher Anthony , Dan Andrei Florin , Jones Mitchell Lawrence , Prakash Satya 
Published: September 2012

ABSTRACT

The use of percutaneous medical devices often results in nosocomial infections. Attachment of microorganisms to the surfaces of these medical devices triggers biofilm formation, which presents significant complications to the health of a patient and may lead to septicemia, thromboembolism, or endocarditis if not correctly treated. Although several antimicrobials are commonly used for prevention of biofilm formation, they have limited efficacy against formed biofilms. In this study, we report the use of an enzymatic, gaseous nitric oxide (gNO)-releasing dressing for the prevention and treatment of
Acinetobacter baumannii
, methicillin-resistant
Staphylococcus aureus
, and
Pseudomonas aeruginosa
biofilms. Results show that the bactericidal activity against biofilms of the test strains was dependent on time and rate of gNO release from the dressing. Following 6 h of treatment, gNO-releasing dressings significantly inhibited the growth of test strains relative to vehicle control dressings, demonstrating eradication of bacterial concentrations of up to 10
5
CFU/cm
2
. Complete cell death was observed for both prevention of biofilm formation and treatment of 24-h-grown biofilms after 6 h of treatment with the gNO-releasing dressings. Further, gNO-releasing dressings were more efficient against formed biofilms than other antimicrobial agents currently used. These results demonstrate that the gNO-releasing dressing can produce sufficient levels of gNO over a therapeutically relevant duration for maximal bactericidal effects against virulent bacterial strains known to cause nosocomial infections.
Red Man Syndrome Adverse Reaction following Intravenous Infusion of Cefepime
Authors: Panos George , Watson Dionysios C. , Sargianou Maria , Kampiotis Dionysios , Chra Paraskevi 
Published: September 2012

ABSTRACT
We report the first case of cefepime-induced “red-man syndrome,” which appeared 30 min following drug infusion and was confirmed with a rechallenge test. This syndrome is classically associated with vancomycin infusion and is the result of non-IgE mediated mast cell degranulation. While this adverse effect can be easily managed with drug withdrawal and antihistamine administration, it is unknown whether it can be prevented with slower cefepime infusion and preinfusion antihistamines, as is the case with vancomycin.
Structure-Activity Relationships among the Kanamycin Aminoglycosides: Role of Ring I Hydroxyl and Amino Groups
Authors: Salian Sumantha , Matt Tanja , Akbergenov Rashid , Harish Shinde , Meyer Martin , Duscha Stefan , Shcherbakov Dmitri , Bernet Bruno B. , Vasella Andrea , Westhof Eric , Böttger Erik C. 
Published: September 2012

ABSTRACT
The kanamycins form an important subgroup of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside antibiotics, comprising kanamycin A, kanamycin B, tobramycin, and dibekacin. These compounds interfere with protein synthesis by targeting the ribosomal decoding A site, and they differ in the numbers and locations of amino and hydroxy groups of the glucopyranosyl moiety (ring I). We synthesized kanamycin analogues characterized by subtle variations of the 2′ and 6′ substituents of ring I. The functional activities of the kanamycins and the synthesized analogues were investigated (i) in cell-free translation assays on wild-type and mutant bacterial ribosomes to study drug-target interaction, (ii) in MIC assays to assess antibacterial activity, and (iii) in rabbit reticulocyte translation assays to determine activity on eukaryotic ribosomes. Position 2′ forms an intramolecular H bond with O5 of ring II, helping the relative orientations of the two rings with respect to each other. This bond becomes critical for drug activity when a 6′-OH substituent is present.
T-2307 Causes Collapse of Mitochondrial Membrane Potential in Yeast
Authors: Shibata Tatsuya , Takahashi Toshinari , Yamada Eio , Kimura Akiko , Nishikawa Hiroshi , Hayakawa Hiroyoshi , Nomura Nobuhiko , Mitsuyama Junichi 
Published: September 2012

ABSTRACT

T-2307, an arylamidine compound, has been previously reported to have broad-spectrum
in vitro
and
in vivo
antifungal activities against clinically significant pathogens, including
Candida
species,
Cryptococcus neoformans
, and
Aspergillus
species, and is now undergoing clinical trials. Here we investigated the mechanism of action of T-2307 using yeast cells and mitochondria isolated from yeast and rat liver. Nonfermentative growth of
Candida albicans
and
Saccharomyces cerevisiae
in glycerol medium, in which yeasts relied on mitochondrial respiratory function, was inhibited at 0.001 to 0.002 μg/ml (0.002 to 0.004 μM) of T-2307. However, fermentative growth in dextrose medium was not inhibited by T-2307. Microscopic examination using Mitotracker fluorescent dye, a cell-permeant mitochondrion-specific probe, demonstrated that T-2307 impaired the mitochondrial function of
C. albicans
and
S. cerevisiae
at concentrations near the MIC in glycerol medium. T-2307 collapsed the mitochondrial membrane potential in mitochondria isolated from
S. cerevisiae
at 20 μM. On the other hand, in isolated rat liver mitochondria, T-2307 did not have any effect on the mitochondrial membrane potential at 10 mM. Moreover, T-2307 had little inhibitory and stimulatory effect on mitochondrial respiration in rat liver mitochondria. In conclusion, T-2307 selectively disrupted yeast mitochondrial function, and it was also demonstrated that the fungal mitochondrion is an attractive antifungal target.
Construction and Evaluation of a Novel Recombinant T Cell Epitope-Based Vaccine against Coccidioidomycosis
Authors: Hurtgen Brady J. , Hung Chiung-Yu , Ostroff Gary R. , Levitz Stuart M. , Cole Garry T. 
Published: September 2012

ABSTRACTClinical and animal studies of coccidioidomycosis have demonstrated that activated CD4+T lymphocytes are essential for protection against this fungal respiratory disease. We previously reported a vaccine againstCoccidioidesinfection which contained three recombinant CD4+T cell-reactive proteins and induced a robust, protective immune response in mice. Due to the anticipated high cost of production and clinical assessment of this multivalent vaccine, we generated a single protein which contained immunodominant T cell epitopes of the three polypeptides. Epitopes were initially identified by computational prediction of their ability to bind promiscuously to human major histocompatibility complex class II (MHC II) molecules. Cellular immunoassays confirmed the immunogenicity of the synthesized epitope peptides, whilein vitrobinding assays revealed a range of peptide affinity for MHC II. A DNA construct was synthesized for bacterial expression of a recombinant protein vaccine which contained five epitopes with the highest affinity for human MHC II, each fused with leader and spacer peptides proposed to optimize epitope processing and presentation to T cell receptors. Recall assays of immune T lymphocytes obtained from human MHC II-expressing HLA-DR4 transgenic mice confirmed that 4 of the 5 epitope peptides were processed. Mice immunized with the epitope-based vaccine admixed with a synthetic oligodeoxynucleotide adjuvant or loaded into yeast glucan particles and then challenged intranasally withCoccidioidesshowed early lung infiltration of activated T helper-1 (Th1), Th2, and Th17 cells, elevated gamma interferon (IFN-γ) and interleukin (IL)-17 production, significant reduction of fungal burden, and prolongation of survival compared to nonvaccinated mice. This is the first report of an epitope-based vaccine against coccidioidomycosis.
CsrRS and Environmental pH Regulate Group B Streptococcus Adherence to Human Epithelial Cells and Extracellular Matrix
Authors: Park Su Eun , Jiang Shengmei , Wessels Michael R. 
Published: September 2012

ABSTRACT

Streptococcus agalactiae
(group B
Streptococcus
or GBS) is a common colonizer of the gastrointestinal and genital tracts and an important cause of invasive infections in newborn infants and in adults with predisposing chronic conditions or advanced age. Attachment to epithelial surfaces at mucosal sites is a critical step in the successful colonization of a human host, and regulation of this process is likely to play an important role in both commensalism and dissemination to cause invasive disease. We found that inactivation of the CsrRS (or CovRS) two-component system increased GBS adherence to epithelial cells derived from human vaginal, cervical, and respiratory epithelium, as well as increasing adherence to extracellular matrix proteins and increasing biofilm formation on polystyrene. Neutral (as opposed to acidic) pH enhanced GBS binding to vaginal epithelial cells and to fibrinogen and fibronectin, effects that were partially dependent on CsrRS. The regulatory effects of CsrRS and environmental pH on bacterial adherence correlated with their effects on the expression of multiple surface adhesins, as assessed by quantitative reverse transcription-PCR. We conclude that GBS adherence to epithelial and abiotic surfaces is regulated by the CsrRS two-component system and by environmental pH through their regulatory effects on the expression of bacterial surface adhesins. Dynamic regulation of GBS adherence enhances the organism's adaptability to survival in multiple niches in the human host.
First reported detection of a low pathogenicity avian influenza virus subtype H9 infection in domestic fowl in England
Authors: Parker C. D. , Reid S. M. , Ball A. , Cox W. J. , Essen S. C. , Hanna A. , Mahmood S. , Slomka M. J. , Irvine R. M. , Brown I. H. 
Published: September 2012

In December 2010, infection with a H9N1 low pathogenicity avian influenza (LPAI) virus was detected in a broiler breeder flock in East Anglia. Disease suspicion was based on acute drops in egg production in two of four sheds on the premises, poor egg shell quality and evidence of diarrhoea. H9N1 LPAI virus infection was confirmed by real‐time reverse transcription PCR. Sequencing revealed high nucleotide identity of 93.6 per cent and 97.9 per cent with contemporary North American H9 and Eurasian N1 genes, respectively. Attempted virus isolation in embryonated specific pathogen free (SPF) fowls' eggs was unsuccessful. Epidemiological investigations were conducted to identify the source of infection and any onward spread. These concluded that infection was restricted to the affected premises, and no contacts or movements of poultry, people or fomites could be attributed as the source of infection. However, the infection followed a period of extremely cold weather and snow which impacted on the biosecurity protocols on site, and also led to increased wild bird activity locally, including waterfowl and game birds around the farm buildings. Analysis of the N1 gene sequence suggested direct introduction from wild birds. Although H9 infection in poultry is not notifiable, H9N2 LPAI viruses have been associated with production and mortality episodes in poultry in many parts of Asia and the Middle East. In the present H9N1 outbreak, clinical signs were relatively mild in the poultry with no mortality, transient impact on egg production and no indication of zoonotic spread. However, this first reported detection of H9 LPAI virus in chickens in England was also the first H9 UK poultry case for 40 years, and vindicates the need for continued vigilance and surveillance of avian influenza viruses in poultry populations.
Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors
Authors: Manzoor Ashley A. , Lindner Lars H. , Landon Chelsea D. , Park Ji-Young , Simnick Andrew J. , Dreher Matthew R. , Das Shiva , Hanna Gabi , Park Won , Chilkoti Ashutosh , Koning Gerben A. , ten Hagen Timo L.M. , Needham David , Dewhirst Mark W. 
Published: September 2012

Abstract
Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566–75. ©2012 AACR.
Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients
Authors: Brown Janet E. , Cook Richard J. , Lipton Allan , Coleman Robert E. 
Published: September 2012

AbstractPurpose: Survival is highly variable in women with bone metastases from breast cancer and prognostic factors are needed. We analyzed data from a phase III trial comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer and bone metastases to identify variables prognostic for overall survival.Experimental Design: Patients who received ZOL (n = 435) with bone marker assessments and complete baseline data were included. Relative risks (RR) of death over 24 months were assessed using a stratified Cox regression analysis. A reduced model was generated using stepwise backward elimination until only significant (P &lt; 0.05) variables remained.Results: Only 5 of 19 variables analyzed remained significantly prognostic for survival in the reduced multivariate model. These included age more than 50 years (RR 1.78–2.53, P ≤ 0.01 for each decade &gt;50 versus ≤50); Functional Assessment of Cancer Therapy-General (FACT-G) score less than 65 units (P &lt; 0.05 vs. ≥75 units); impaired (PS ≥ 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG) performance status (RR 1.74, P &lt; 0.01); prior versus no prior chemotherapy (RR 1.97; P &lt; 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase ≥ upper limit of normal (ULN) but &lt; 2 × ULN correlated with a two-fold increased risk of death, and LDH &gt; 2 × ULN correlated with a six-fold increased risk of death versus LDH &lt; ULN (P &lt; 0.0001 for both). Baseline bone marker levels were not significantly correlated with survival after adjustment for other significant covariates.Conclusions: This retrospective analysis shows that LDH levels correlate strongly with survival in patients with bone metastases from breast cancer and confirms the relevance of previously described prognostic factors. Clin Cancer Res; 18(22); 6348–55. ©2012 AACR.
TLE1 Is an Anoikis Regulator and Is Downregulated by Bit1 in Breast Cancer Cells
Authors: Brunquell Chris , Biliran Hector , Jennings Scott , Ireland Shubha Kale , Chen Renwei , Ruoslahti Erkki 
Published: September 2012

Abstract
TLE1 is a Groucho-related transcriptional repressor protein that exerts survival and antiapoptotic function in several cellular systems and has been implicated in the pathogenesis of cancer. In the present study, we found that TLE1 is a regulator of anoikis in normal mammary epithelial and breast carcinoma cells. The induction of apoptosis following loss of cell attachment to the extracellular matrix (anoikis) in untransformed mammary epithelial MCF10A cells was associated with significant downregulation of TLE1 expression. Forced expression of exogenous TLE1 in these cells promoted resistance to anoikis. In breast cancer cells, TLE1 expression was significantly upregulated following detachment from the extracellular matrix. Genetic manipulation of TLE1 expression via overexpression and downregulation approaches indicated that TLE1 promotes the anoikis resistance and anchorage-independent growth of breast carcinoma cells. Mechanistically, we show that TLE1 inhibits the Bit1 anoikis pathway by reducing the formation of the proapoptotic Bit1-AES complex in part through sequestration of AES in the nucleus. The mitochondrial release of Bit1 during anoikis as well as exogenous expression of the cytoplasmic localized Bit1 or its cell death domain induced cytoplasmic translocation and degradation of nuclear TLE1 protein. These findings indicate a novel role for TLE1 in the maintenance of anoikis resistance in breast cancer cells. This conclusion is supported by an immunohistochemical analysis of a breast cancer tissue array illustrating that TLE1 is selectively upregulated in invasive breast tumors relative to noninvasive ductal carcinoma in situ and normal mammary epithelial tissues. Mol Cancer Res; 10(11); 1482–95. ©2012 AACR.