bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of Uropathogenic Escherichia coli Metapopulation Movement during Urinary Tract Infection
Authors: Walters Matthew S. , Lane M. Chelsea , Vigil Patrick D. , Smith Sara N. , Walk Seth T. , Mobley Harry L. T. 
Published: February 2012

ABSTRACT

The urinary tract is one of the most frequent sites of bacterial infection in humans. Uropathogenic
Escherichia coli
(UPEC) strains are the leading cause of urinary tract infections (UTIs) and are responsible for greater than 80% of uncomplicated cases in adults. Infection of the urinary tract occurs in an ascending manner, with colonization of the bladder leading to possible kidney infection and bacteremia. The goal of this study was to examine the population dynamics of UPEC
in vivo
using a murine model of ascending UTI. To track individual UPEC lineages within a host, we constructed 10 isogenic clones of UPEC strain CFT073 by inserting unique signature tag sequences between the
pstS
and
glmS
genes at the attTn7 chromosomal site. Mice were transurethrally inoculated with a mixture containing equal numbers of unique clones. After 4 and 48 h, the tags present in the bladders, kidneys, and spleens of infected mice were enumerated using tag-specific primers and quantitative real-time PCR. The results indicated that kidney infection and bacteremia associated with UTI are most likely the result of multiple rounds of ascension and dissemination from motile UPEC subpopulations, with a distinct bottleneck existing between the kidney and bloodstream. The abundance of tagged lineages became more variable as infection progressed, especially after bacterial ascension to the upper urinary tract. Analysis of the population kinetics of UPEC during UTI revealed metapopulation dynamics, with lineages that constantly increased and decreased in abundance as they migrated from one organ to another.

IMPORTANCE
Urinary tract infections are some of the most common infections affecting humans, and
Escherichia coli
is the primary cause in most uncomplicated cases. These infections occur in an ascending manner, with bacteria traveling from the bladder to the kidneys and potentially the bloodstream. Little is known about the spatiotemporal population dynamics of uropathogenic
E. coli
within a host. Here we describe a novel approach for tracking lineages of isogenic tagged
E. coli
strains within a murine host by the use of quantitative real-time PCR. Understanding the
in vivo
population dynamics and the factors that shape the bacterial population may prove to be of significant value in the development of novel vaccines and drug therapies.
High river temperature reduces survival of sockeye salmon (Oncorhynchus nerka) approaching spawning grounds and exacerbates female mortality
Authors: Martins Eduardo G. , Hinch Scott G. , Patterson David A. , Hague Merran J. , Cooke Steven J. , Miller Kristina M. , Robichaud David , English Karl K. , Farrell Anthony P. 
Published: February 2012

Recent studies have shown that warm temperatures reduce survival of adult migrating sockeye salmon ( Oncorhynchus nerka ), but knowledge gaps exist on where high-temperature-related mortality occurs along the migration and whether females and males are differentially impacted by river temperature. In this study, we monitored 437 radio-tagged Fraser River sockeye salmon and used capture–mark–recapture modelling approaches to investigate whether river thermal conditions differentially influence (i) spatial patterns of survival along a 413-km stretch of migration and (ii) survival of the sexes. Regardless of water temperature, survival decreased in the river section containing the most hydraulically difficult passages of the migration. However, when water temperature was warm (19 °C), survival decreased even further in the final 186 km of the migration prior to reaching the spawning grounds, particularly in females. Female and male survival differed but only when they experienced warm river temperatures. Under such conditions, the overall freshwater migration survival of males was 1.6 times higher (0.79 ± 0.09 standard error, SE) than that of females (0.50 ± 0.11 SE). As maturing female sockeye salmon maintain higher levels of plasma cortisol compared with males, we suspect that females could be immuno-compromised and thus less resistant to pathogens whose rates of development are accelerated by warm temperatures.
Multifractal patterns in the daily catch time series of smooth pink shrimp (Pandalus jordani) from the west coast of Vancouver Island, Canada
Authors: Montes Rodrigo M. , Perry R. Ian , Pakhomov Evgeny A. , Edwards Andrew M. , Boutillier James A. 
Published: February 2012

There is an urgent need for indicators that anticipate changes in populations of exploited marine species. We modelled the complex patterns of variability found in fisheries time series that are not detected using classical models. We applied fractal analyses to detect time-invariant scaling symmetries in daily catch time series from the smooth pink shrimp ( Pandalus jordani ) fishery from the west coast of Vancouver Island, British Columbia, Canada. A universal multifractal model, which accounts for intermittent fluctuations and extreme values in a time series, provided a better fit to daily catches than a monofractal model. Multifractality is an indication of multiple scaling patterns and suggests that more than one process is affecting the variability of catches. Fractal dynamics in catch time series were found for a range of scales between 16 and 120 fishing days. To our knowledge, this is the first time that multifractality has been demonstrated for an invertebrate fishery. The multifractal model has the potential to provide an in-season estimate (up to 120 fishing days) of the variability of shrimp catches based on the variability at time scales less than 1 month. Changes in these fractal patterns may provide an early warning that conditions underlying this fishery are changing.
Temperature variability in the nearshore benthic boundary layer of Lake Opeongo is due to wind-driven upwelling events
Authors: Coman Melissa Anne , Wells Mathew Graeme 
Published: February 2012

A major source of temperature variation in nearshore and benthic regions of stratified lakes is due to wind-driven tilting of the thermocline. The maximum displacement of the thermocline depends upon the wind forcing, stratification, and basin morphometry; combined these three-dimensional physical parameters give the dimensionless lake number (LN). We find that the deflection of the thermocline across the length of the basin (Δh*) is correlated to the temporally averaged LN as Δh*/2h1 = 0.37LN–1, where h1 is the depth of the thermocline. We report field observations from Lake Opeongo (Ontario, Canada) showing that during large vertical movements of the thermocline, there are unstable temperature gradients in the benthic layer, as measured by the occurrence of temperature inversions on our thermistor strings. High-frequency waves interacting with the benthic boundary are most likely causing the temperature inversions. Measurements at two shallow slopes of S = 1% and 4%, show that inversions only occur when LN < 5, whereas for S = 8%, the inversions occur only when LN < 2.
Glioblastoma Stem–like Cell Lines with Either Maintenance or Loss of High-Level EGFR Amplification, Generated via Modulation of Ligand Concentration
Authors: Schulte Alexander , Günther Hauke S. , Martens Tobias , Zapf Svenja , Riethdorf Sabine , Wülfing Clemens , Stoupiec Malgorzata , Westphal Manfred , Lamszus Katrin 
Published: February 2012

Abstract
Purpose: Despite the high incidence of epidermal growth factor receptor (EGFR) gene amplification and rearrangement in glioblastomas, no suitable cell line exists that preserves these alterations in vitro and is tumorigenic in immunocompromised mice. On the basis of previous observations that glioblastoma cells cultured with serum lose the EGFR amplification rapidly and that EGF can inhibit the growth of EGFR-amplified tumor cells, we hypothesized that serum-free and EGF-free culture conditions could promote maintenance of the EGFR amplification.
Experimental Design: Cells from EGFR-amplified glioblastomas were taken into culture using neural stem cell conditions with modifications, including varying oxygen concentrations and omission of routine EGF supplementation.
Results: High-level EGFR amplification was rapidly lost in 5 glioblastoma cultures supplemented with EGF, whereas it was preserved in cultures from the same tumors established without EGF. Cultures from 2 glioblastomas developed into pairs of cell lines, with either stable maintenance or irreversible loss of high-level EGFR amplification in the majority of cells. One EGFR-amplified cell line preserved expression of the receptor variant EGFRvIII. Cell lines with high-level EGFR amplification/EGFRvIII expression formed highly aggressive tumors in nude mice, whereas nonamplified cell lines were either nontumorigenic or grew significantly more slowly. In contrast, nonamplified cell lines proliferated faster in vitro. All cell lines responded to erlotinib, with inhibition of receptor activation and proliferation but partly different effects on downstream signaling and migration.
Conclusions: Isogenic glioblastoma cell lines maintaining stable differences in EGFR/EGFRvIII status can be derived by varying exposure to EGF ligand and reflect the intratumoral genetic heterogeneity. Clin Cancer Res; 18(7); 1901–13. ©2012 AACR.
NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies
Authors: Valsasina Barbara , Beria Italo , Alli Cristina , Alzani Rachele , Avanzi Nilla , Ballinari Dario , Cappella Paolo , Caruso Michele , Casolaro Alessia , Ciavolella Antonella , Cucchi Ulisse , De Ponti Anna , Felder Eduard , Fiorentini Francesco , Galvani Arturo , Gianellini Laura M. , Giorgini Maria L. , Isacchi Antonella , Lansen Jaqueline , Pesenti Enrico , Rizzi Simona , Rocchetti Maurizio , Sola Francesco , Moll Jürgen 
Published: February 2012

AbstractPolo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings. Mol Cancer Ther; 11(4); 1006–16. ©2012 AACR.
Body Mass Index and the Risk for Developing Invasive Breast Cancer among High-Risk Women in NSABP P-1 and STAR Breast Cancer Prevention Trials
Authors: Cecchini Reena S. , Costantino Joseph P. , Cauley Jane A. , Cronin Walter M. , Wickerham D. Lawrence , Land Stephanie R. , Weissfeld Joel L. , Wolmark Norman 
Published: February 2012

Abstract
High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women. Cancer Prev Res; 5(4); 583–92. ©2012 AACR.
Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation
Authors: Gallego Pilar , Roldán Vanessa , Torregrosa José Miguel , Gálvez Josefa , Valdés Mariano , Vicente Vicente , Marín Francisco , Lip Gregory Y.H. 
Published: February 2012

Background—
Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF.

Methods and Results—

We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0–3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0–6; 29% with a score ≥3 [ie, high risk]). Median follow-up was 861 days (range, 718–1016 days). Independent predictors for major bleeding were age ≥75 years (hazard ratio [HR], 1.74; 95% CI, 1.05–2.87;
P
=0.030), male sex (HR, 1.70; 95% CI, 1.03–2.80;
P
=0.036), renal impairment (HR, 2.12; 95% CI, 1.20–3.73;
P
=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73–9.67;
P
<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03–5.06;
P
=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13–4.18;
P
=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40–3.46;
P
=0.001), heart failure (HR, 1.78; 95% CI, 1.20–2.86;
P
=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20–2.86;
P
<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68–2.49;
P
<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27–1.81;
P
<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all-cause mortality (HR, 1.68; 95% CI, 1.40–2.01;
P
<0.001).

Conclusions—
The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events.
Is There a Clinically Significant Interaction Between Calcium Channel Antagonists and Clopidogrel?
Authors: Good Christopher W. , Steinhubl Steven R. , Brennan Danielle M. , Lincoff A. Michael , Topol Eric J. , Berger Peter B. 
Published: February 2012

Background—
Clopidogrel is an inactive prodrug; it is converted to its active metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel blockers (CCBs). Several studies have reported that CCBs reduce the ability of clopidogrel to inhibit platelet aggregability; one suggested that CCBs reduce the efficacy of clopidogrel.

Methods and Results—
We performed a post hoc analysis of the Clopidogrel for the Reduction of Events During Observation (CREDO) study to compare the treatment effect of clopidogrel in patients on CCBs versus not on CCBs. In CREDO, 2116 patients were randomly assigned to pretreatment with 300 mg clopidogrel 3–24 hours before a planned percutaneous coronary intervention followed by 1 year of 75 mg/d clopidogrel, versus 75 mg clopidogrel at the time of the procedure and continued for 28 days only. The primary end points were a combined end point of death, myocardial infarction, and stroke at 28 days and 1 year. Among the 580 patients (27%) on CCBs at enrollment, at 28 days, the combined end point was reached in 17 patients (6%) on clopidogrel versus 28 (9%) on placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.39–1.29). At 1 year, the combined end point was reached in 27 patients (10%) on clopidogrel versus 46 (15%) on placebo (HR, 0.68; 95% CI, 0.42–1.09). The treatment effect of clopidogrel was similar in patients not on CCBs at 1 year (HR, 0.78; 95% CI, 0.56–1.09). After adjustment for differences between patients on and not on CCB, there was still no evidence of an interaction between clopidogrel treatment and CCB (HR for patients not on CCBs, 0.87; 95% CI, 0.62–1.23; HR for patients on CCBs, 0.74; 95% CI, 0.45–1.21).

Conclusions—
In CREDO, there was no evidence that CCBs decrease the efficacy of clopidogrel.
When Collateral Supply is Accounted For Epicardial Stenosis Does Not Increase Microvascular Resistance
Authors: Layland Jamie , MacIsaac Andrew I. , Burns Andrew T. , Somaratne Jithendra B. , Leitl George , Whitbourn Robert J. , Wilson Andrew M. 
Published: February 2012

Background—
The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis.

Methods and Results—

Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89,
P
=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06,
P
<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89,
P
=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78,
P
=0.42).

Conclusions—
When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.
Vascular Tissue Reaction to Acute Malapposition in Human Coronary Arteries
Authors: Gutiérrez-Chico Juan Luis , Wykrzykowska Joanna , Nüesch Eveline , van Geuns Robert Jan , Koch Karel T. , Koolen Jacques J. , di Mario Carlo , Windecker Stephan , van Es Gerrit-Anne , Gobbens Pierre , Jüni Peter , Regar Evelyn , Serruys Patrick W. 
Published: February 2012

Background—
The vascular tissue reaction to acute incomplete stent apposition (ISA) is not well known. The aim of this study was to characterize the vascular response to acute ISA in vivo and to look for predictors of incomplete healing.

Methods and Results—
Optical coherence tomography studies of 66 stents of different designs, implanted in 43 patients enrolled in 3 randomized trials, were analyzed sequentially after implantation and at 6 to 13 months. Seventy-eight segments with acute ISA were identified in 36 of the patients and matched with the follow-up study by use of fiduciary landmarks. The morphological pattern of healing in the ISA segments was categorized as homogeneous, layered, crenellated, bridged, partially bridged, or bare, depending on the persistence of ISA and on the coverage. After 6 months, acute ISA volume decreased significantly, and 71.5% of the ISA segments were completely integrated into the vessel wall. Segments with acute ISA had higher risk of delayed coverage than well-apposed segments (relative risk 2.37, 95% confidence interval 2.01–2.78). Acute ISA size (estimated as ISA volume or maximum ISA distance per strut) was an independent predictor of ISA persistence and of delayed healing at follow-up.

Conclusions—
Neointimal healing tends to reduce ISA, with the malapposed stent struts often integrated completely into the vessel wall, resulting in characteristic morphological patterns. Coverage of ISA segments is delayed with respect to well-apposed segments. The larger the acute ISA, the greater the likelihood of persistent malapposition at follow-up and delayed healing.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00617084 and NCT00934752.