bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method
Authors: Mendes Rodrigo E. , Farrell David J. , Sader Helio S. , Flamm Robert K. , Jones Ronald N. 
Published: October 2014

ABSTRACT

Telavancin had MIC
50
and MIC
90
values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible
Staphylococcus aureus
. Telavancin was active against vancomycin-susceptible
Enterococcus faecalis
(MIC
50/90
, 0.12/0.12 μg/ml; 100% susceptible) and
Enterococcus faecium
(MIC
50/90
, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistant
E. faecium
(MIC
50/90
, 1/2 μg/ml) and
E. faecalis
(MIC
50/90
, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤0.015 μg/ml, except against
Streptococcus agalactiae
(i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.
Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells
Authors: Brummelman Jolanda , Veerman Rosanne E. , Hamstra Hendrik Jan , Deuss Anna J. M. , Schuijt Tim J. , Sloots Arjen , Kuipers Betsy , van Els Cécile A. C. M. , van der Ley Peter , Mooi Frits R. , Han Wanda G. H. , Pinelli Elena 
Published: October 2014

ABSTRACT

Bordetella pertussis
is a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to different
B. pertussis
clinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate that
B. pertussis
isolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.
Peroxiredoxin-Glutaredoxin and Catalase Promote Resistance of Nontypeable Haemophilus influenzae 86-028NP to Oxidants and Survival within Neutrophil Extracellular Traps
Authors: Juneau Richard A. , Pang Bing , Armbruster Chelsie E. , Murrah Kyle A. , Perez Antonia C. , Swords W. Edward 
Published: October 2014

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHI) is a common commensal and opportunistic pathogen of the human airways. For example, NTHI is a leading cause of otitis media and is the most common cause of airway infections associated with chronic obstructive pulmonary disease (COPD). These infections are often chronic/recurrent in nature and involve bacterial persistence within biofilm communities that are highly resistant to host clearance. Our previous work has shown that NTHI within biofilms has increased expression of factors associated with oxidative stress responses. The goal of this study was to define the roles of catalase (encoded by
hktE
) and a bifunctional peroxiredoxin-glutaredoxin (encoded by
pdgX
) in resistance of NTHI to oxidants and persistence
in vivo
. Isogenic NTHI strain 86-028NP mutants lacking
hktE
and
pdgX
had increased susceptibility to peroxide. Moreover, these strains had persistence defects in the chinchilla infection model for otitis media, as well as in a murine model for COPD. Additional work showed that
pdgX
and
hktE
were important determinants of NTHI survival within neutrophil extracellular traps (NETs), which we have shown to be an integral part of NTHI biofilms
in vivo
. Based on these data, we conclude that catalase and peroxiredoxin-glutaredoxin are determinants of bacterial persistence during chronic/recurrent NTHI infections that promote bacterial survival within NETs.
Enantioselective Regulation of Lactate Racemization by LarR in Lactobacillus plantarum
Authors: Desguin Benoît , Goffin Philippe , Bakouche Nordine , Diman Aurélie , Viaene Eric , Dandoy Damien , Fontaine Laetitia , Hallet Bernard , Hols Pascal 
Published: October 2014

ABSTRACT

Lactobacillus plantarum
is a lactic acid bacterium that produces a racemic mixture of
l
- and
d
-lactate from sugar fermentation. The interconversion of lactate isomers is performed by a lactate racemase (Lar) that is transcriptionally controlled by the
l
-/
d
-lactate ratio and maximally induced in the presence of
l
-lactate. We previously reported that the Lar activity depends on the expression of two divergently oriented operons: (i) the
larABCDE
operon encodes the nickel-dependent lactate racemase (LarA), its maturases (LarBCE), and a lactic acid channel (LarD), and (ii) the
larR
(
MN
)
QO
operon encodes a transcriptional regulator (LarR) and a four-component ABC-type nickel transporter [Lar(MN), in which the M and N components are fused, LarQ, and LarO]. LarR is a novel regulator of the Crp-Fnr family (PrfA group). Here, the role of LarR was further characterized
in vivo
and
in vitro
. We show that LarR is a positive regulator that is absolutely required for the expression of Lar activity. Using gel retardation experiments, we demonstrate that LarR binds to a 16-bp palindromic sequence (Lar box motif) that is present in the
larR-larA
intergenic region. Mutations in the Lar box strongly affect LarR binding and completely abolish transcription from the
larA
promoter (P

larA

). Two half-Lar boxes located between the Lar box and the −35 box of P

larA

promote LarR multimerization on DNA, and point mutations within one or both half-Lar boxes inhibit P

larA

induction by
l
-lactate. Gel retardation and footprinting experiments indicate that
l
-lactate has a positive effect on the binding and multimerization of LarR, while
d
-lactate antagonizes the positive effect of
l
-lactate. A possible mechanism of LarR regulation by lactate enantiomers is proposed.
Onset of recent exertional dyspnoea in a firefighter with left bundle-branch block
Authors: De Rosa Roberto , Ratti Gennaro , Lamberti Monica 
Published: October 2014

BackgroundThe presence of a left bundle-branch block (LBBB) among firefighters raises questions about stratifying risk of subsequent cardiovascular events as this conduction disorder may mask underlying coronary artery disease. This report describes the case of a firefighter with a history LBBB with exertional dyspnoea of recent onset after work activity.Case reportA 39-year-old male firefighter with LBBB developed exertional dyspnoea after a prolonged session of work. ECG and treadmill test only showed a permanent LBBB; echocardiography and myocardial scintigraphy did not add to this. However, multislice CT (MSCT) showed a significant stenosis in the mid-left anterior descending artery (LAD). Coronary angiography confirmed the stenosis with subsequent placement of a coronary stent.ConclusionsAn occupational physician should take into account that factors such as age and low cardiovascular risk do not always exclude heart disease, especially when there are conduction system abnormalities that can mask possible coronary artery disease.
Continued high rates of antibiotic prescribing to adults with respiratory tract infection: survey of 568 UK general practices
Authors: Gulliford Martin C , Dregan Alex , Moore Michael V , Ashworth Mark , Staa Tjeerd van , McCann Gerard , Charlton Judith , Yardley Lucy , Little Paul , McDermott Lisa 
Published: October 2014

ObjectivesOverutilisation of antibiotics may contribute to the emergence of antimicrobial drug resistance, a growing international concern. This study aimed to analyse the performance of UK general practices with respect to antibiotic prescribing for respiratory tract infections (RTIs) among young and middle-aged adults.SettingData are reported for 568 UK general practices contributing to the Clinical Practice Research Datalink.ParticipantsParticipants were adults aged 18–59 years. Consultations were identified for acute upper RTIs including colds, cough, otitis-media, rhino-sinusitis and sore throat.Primary and secondary outcome measuresFor each consultation, we identified whether an antibiotic was prescribed. The proportion of RTI consultations with antibiotics prescribed was estimated.ResultsThere were 568 general practices analysed. The median general practice prescribed antibiotics at 54% of RTI consultations. At the highest prescribing 10% of practices, antibiotics were prescribed at 69% of RTI consultations. At the lowest prescribing 10% of practices, antibiotics were prescribed at 39% RTI consultations. The median practice prescribed antibiotics at 38% of consultations for ‘colds and upper RTIs’, 48% for ‘cough and bronchitis’, 60% for ‘sore throat’, 60% for ‘otitis-media’ and 91% for ‘rhino-sinusitis’. The highest prescribing 10% of practices issued antibiotic prescriptions at 72% of consultations for ‘colds’, 67% for ‘cough’, 78% for ‘sore throat’, 90% for ‘otitis-media’ and 100% for ‘rhino-sinusitis’.ConclusionsMost UK general practices prescribe antibiotics to young and middle-aged adults with respiratory infections at rates that are considerably in excess of what is clinically justified. This will fuel antibiotic resistance.
Hormonal contraception and regulation of menstruation: a study of young women's attitudes towards ‘having a period’
Authors: Newton Victoria Louise , Hoggart Lesley 
Published: October 2014

BackgroundIrregular bleeding is one of the most common side effects of hormonal contraception and a key reason for the discontinuation of hormonal methods.Study designA qualitative study in which 12 young women volunteered to be interviewed in depth, along with six focus group discussions (23 participants). The study had two main research objectives: to document and investigate what young women think and feel about menstruation and contraception, and to explore young women's preferences regarding the intersection of contraceptives and bleeding patterns.ResultsAlthough participants held a broad view that menstruation can be an inconvenience, they did ascribe positive values to having a regular bleed. Bleeding was seen as a signifier of non-pregnancy and also an innate part of being a woman. A preference for a ‘natural’ menstruating body was a strong theme, and the idea of selecting a hormonal contraceptive that might stop the bleeding was not overly popular, unless the young woman suffered with painful natural menstruation. Contraceptives that mimicked the menstrual cycle were acceptable to most, suggesting that cyclic bleeding still holds a symbolic function for women.ConclusionsWhen counselling young women about the effect of different contraceptive modalities on their bleeding, practitioners should explore how the women feel about their bleeding, including how they might feel if their bleeding stopped or if they experienced erratic bleeding patterns. Practitioners also need to recognise the subjective understanding of the ‘natural body’ as held by some women, and in these cases to support them in their seeking out of non-hormonal methods of contraception.
Weighted Congestion Games
Authors: Bhawalkar Kshipra , Gairing Martin , Roughgarden Tim 
Published: October 2014

We characterize the Price of Anarchy (POA) in weighted congestion games, as a function of the allowable resource cost functions. Our results provide as thorough an understanding of this quantity as is already known for nonatomic and unweighted congestion games, and take the form of universal (cost function-independent) worst-case examples. One noteworthy by-product of our proofs is the fact that weighted congestion games are “tight,” which implies that the worst-case price of anarchy with respect to pure Nash equilibria, mixed Nash equilibria, correlated equilibria, and coarse correlated equilibria are always equal (under mild conditions on the allowable cost functions). Another is the fact that, like nonatomic but unlike atomic (unweighted) congestion games, weighted congestion games with trivial structure already realize the worst-case POA, at least for polynomial cost functions.
We also prove a new result about unweighted congestion games: the worst-case price of anarchy in symmetric games is as large as in their more general asymmetric counterparts.
Multiprogram Throughput Metrics
Authors: Eyerman Stijn , Michaud Pierre , Rogiest Wouter 
Published: October 2014

Running multiple programs on a processor aims at increasing the throughput of that processor. However, defining meaningful throughput metrics in a simulation environment is not as straightforward as reporting execution time. This has led to an ongoing debate on what forms a meaningful throughput metric for multiprogram workloads. We present a method to construct throughput metrics in a systematic way: we start by expressing assumptions on job size, job distribution, scheduling, and so forth that together define a theoretical throughput experiment. The throughput metric is then the average throughput of this experiment. Different assumptions lead to different metrics, so one should be aware of these assumptions when making conclusions based on results using a specific metric.
Throughput metrics should always be defined from explicit assumptions, because this leads to a better understanding of the implications and limits of the results obtained with that metric. We elaborate multiple metrics based on different assumptions. In particular, we identify the assumptions that lead to the commonly used weighted speedup and harmonic mean of speedups. Our study clarifies that they are actual throughput metrics, which was recently questioned. We also propose some new throughput metrics, which cannot always be expressed as a closed formula. We use real experimental data to characterize metrics and show how they relate to each other.
Disaggregated Data and Beyond: Future Queries in Cancer Control Research
Authors: Nguyen Anh Bao , Chawla Neetu , Noone Anne-Michelle , Srinivasan Shobha 
Published: November 2014

Abstract
The goal of health equity requires the collection and reporting of disaggregated data in underrepresented populations such as Asian American (AA) and Native Hawaiian and Other Pacific Islander (NHOPI) communities. A recent Department of Health and Human Services report outlines the necessity for disaggregated data, which would offer communities, providers, and planners better tools to address health problems. In a recent collaboration, the National Cancer Institute (NCI) and several registries published a series of articles tracking cancer incidence data on AA and NHOPI communities using data from the NCI's Surveillance, Epidemiology, and End Results (SEER) program. The findings indicate a need for concentrated focus and planning for the next stages of cancer prevention and control for AA and NHOPI subpopulations. In this article, we provide (i) the context for the perpetuation of the model minority myth as well as historical and sociocultural factors that have shaped health and disease for AA and NHOPI subgroups; (ii) potential strategies for research and public health policy for AA and NHOPI groups using subpopulation-based approaches while addressing challenges and limitations; and (iii) a portfolio analysis of currently funded projects within the NCI/DCCPS to identify gaps and areas of potential research.
See all the articles in this CEBP Focus section, “Cancer in Asian and Pacific Islander Populations.”
Cancer Epidemiol Biomarkers Prev; 23(11); 2266–72. ©2014 AACR.
Cancer In Silico Drug Discovery: A Systems Biology Tool for Identifying Candidate Drugs to Target Specific Molecular Tumor Subtypes
Authors: San Lucas F. Anthony , Fowler Jerry , Chang Kyle , Kopetz Scott , Vilar Eduardo , Scheet Paul 
Published: October 2014

Abstract
Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. Mol Cancer Ther; 13(12); 3230–40. ©2014 AACR.
HIF1α Regulates mTOR Signaling and Viability of Prostate Cancer Stem Cells
Authors: Marhold Maximilian , Tomasich Erwin , El-Gazzar Ahmed , Heller Gerwin , Spittler Andreas , Horvat Reinhard , Krainer Michael , Horak Peter 
Published: October 2014

Abstract
Tumor-initiating subpopulations of cancer cells, also known as cancer stem cells (CSC), were recently identified and characterized in prostate cancer. A well-characterized murine model of prostate cancer was used to investigate the regulation of hypoxia-inducible factor 1α (HIF1A/HIF1α) in CSCs and a basal stem cell subpopulation (Lin−/Sca-1+/CD49f+) was identified, in primary prostate tumors of mice, with elevated HIF1α expression. To further analyze the consequences of hypoxic upregulation on stem cell proliferation and HIF1α signaling, CSC subpopulations from murine TRAMP-C1 cells (Sca-1+/CD49f+) as well as from a human prostate cancer cell line (CD44+/CD49f+) were isolated and characterized. HIF1α levels and HIF target gene expression were elevated in hypoxic CSC-like cells, and upregulation of AKT occurred through a mechanism involving an mTOR/S6K/IRS-1 feedback loop. Interestingly, resistance of prostate CSCs to selective mTOR inhibitors was observed because of HIF1α upregulation. Thus, prostate CSCs show a hypoxic deactivation of a feedback inhibition of AKT signaling through IRS-1. In light of these results, we propose that deregulation of the PI3K/AKT/mTOR pathway through HIF1α is critical for CSC quiescence and maintenance by attenuating CSC metabolism and growth via mTOR and promoting survival by AKT signaling. We also propose that prostate CSCs can exhibit primary drug resistance to selective mTOR inhibitors.
Implications: This work contributes to a deeper understanding of hypoxic regulatory mechanisms in CSCs and will help devise novel therapies against prostate cancer. Mol Cancer Res; 13(3); 556–64. ©2014 AACR.
A Novel Preclinical Method to Quantitatively Evaluate Early-Stage Metastatic Events at the Murine Blood–Brain Barrier
Authors: Adkins Chris E. , Nounou Mohamed I. , Mittapalli Rajendar K. , Terrell-Hall Tori B. , Mohammad Afroz S. , Jagannathan Rajaganapathi , Lockman Paul R. 
Published: October 2014

Abstract
The observation that approximately 15% of women with disseminated breast cancer will develop symptomatic brain metastases combined with treatment guidelines discouraging single-agent chemotherapeutic strategies facilitates the desire for novel strategies aimed at outright brain metastasis prevention. Effective and robust preclinical methods to evaluate early-stage metastatic processes, brain metastases burden, and overall mean survival are lacking. Here, we develop a novel method to quantitate early metastatic events (arresting and extravasation) in addition to traditional end time-point parameters such as tumor burden and survival in an experimental mouse model of brain metastases of breast cancer. Using this method, a reduced number of viable brain-seeking metastatic cells (from 3,331 ± 263 cells/brain to 1,079 ± 495 cells/brain) were arrested in brain one week postinjection after TGFβ knockdown. Treatment with a TGFβ receptor inhibitor, galunisertib, reduced the number of arrested cells in brain to 808 ± 82 cells/brain. Furthermore, we observed a reduction in the percentage of extravasated cells (from 63% to 30%) compared with cells remaining intralumenal when TGFβ is knocked down or inhibited with galunisertib (40%). The observed reduction of extravasated metastatic cells in brain translated to smaller and fewer brain metastases and resulted in prolonged mean survival (from 36 days to 62 days). This method opens up potentially new avenues of metastases prevention research by providing critical data important to early brain metastasis of breast cancer events. Cancer Prev Res; 8(1); 68–76. ©2014 AACR.
Impact of Identification Method on the Inferred Characteristics and Variability of Australian East Coast Lows
Authors: Pepler Acacia S. , Di Luca Alejandro , Ji Fei , Alexander Lisa V. , Evans Jason P. , Sherwood Steven C. 
Published: October 2014

Abstract
The Australian east coast low (ECL) is both a major cause of damaging severe weather and an important contributor to rainfall and dam inflow along the east coast, and is of interest to a wide range of groups including catchment managers and emergency services. For this reason, several studies in recent years have developed and interrogated databases of east coast lows using a variety of automated cyclone detection methods and identification criteria. This paper retunes each method so that all yield a similar event frequency within the ECL region, to enable a detailed intercomparison of the similarities, differences, and relative advantages of each method. All methods are shown to have substantial skill at identifying ECL events leading to major impacts or explosive development, but the choice of method significantly affects both the seasonal and interannual variation of detected ECL numbers. This must be taken into consideration in studies on trends or variability in ECLs, with a subcategorization of ECL events by synoptic situation of key importance.