bluuebunny/crossref_metadata_2025_split huggingface dataset:
A long‐term prospective study to compare the effects of vaginal and abdominal hysterectomy on micturition and defecation
Authors: Lakeman MME , van der Vaart CH , Roovers JPWR 
Published: August 2011

Please cite this paper as: Lakeman M, van der Vaart C, Roovers J. A long‐term prospective study to compare the effects of vaginal and abdominal hysterectomy on micturition and defecation. BJOG 2011;118:1511–1517.Objective  We compared micturition and defecation symptoms with the route of hysterectomy over a period of 10 years.Design  Prospective multicentre observational study.Setting  Thirteen teaching hospitals in the Netherlands.Population  A total of 430 women who underwent vaginal or abdominal hysterectomy for benign conditions (pelvic organ prolapse excluded).Methods  The presence and discomfort experienced as a result of micturition and defecation symptoms were assessed using validated questionnaires before surgery, and at 6 weeks, 6 months, 1 year, 3 years and 10 years after surgery. Statistically significant differences in symptoms between vaginal and abdominal hysterectomy were adjusted for pre‐operative differences in uterine descent, uterine size, parity and indication for hysterectomy.Main outcome measure  Presence of bothersome micturition and defecation symptoms, as assessed by the Urogenital Distress Inventory (UDI) and Defecation Distress Inventory (DDI).Results  Ten years after hysterectomy the response rate was 73%. Preoperatively, no differences were observed in the prevalence of micturition symptoms between patients who underwent vaginal and abdominal hysterectomy. However, 10 years after vaginal hysterectomy, significantly more women had been treated for micturition symptoms (18 versus 8%; P = 0.02; adjusted OR 3.8, 95% CI 1.2–11.6). Defecation symptoms also seemed more common after vaginal hysterectomy (58 versus 46%; P = 0.08). After adjustment, no statistically significant differences in defecation symptoms were found.Conclusions  Despite the same incidence of micturition symptoms before surgery, patients undergoing vaginal hysterectomy are more likely to seek medical help for micturition symptoms. Defecation symptoms were also more common after vaginal hysterectomy; however, this difference was not statistically significant.
Missed opportunities for type 2 diabetes testing following gestational diabetes: a population‐based cohort study
Authors: Shah BR , Lipscombe LL , Feig DS , Lowe JM 
Published: August 2011

Please cite this paper as: Shah B, Lipscombe L, Feig D, Lowe J. Missed opportunities for type 2 diabetes testing following gestational diabetes: a population‐based cohort study. BJOG 2011;118:1484–1490.Objectives  Few women with gestational diabetes (GDM) are tested for type 2 diabetes in the postpartum period. Whether women are having physician visits that could be an opportunity to improve testing rates is unknown. This study sought to evaluate population‐level trends in postpartum diabetes testing after GDM, and to evaluate postpartum physician care for these women.Design  Population‐based cohort study.Setting  Ontario, Canada.Population  Women who delivered between 1994 and 2008.Methods  Using population‐level healthcare databases, we identified 47 691 women with GDM. They were matched to women without GDM.Main outcome measures  An oral glucose tolerance test (OGTT) within 6 months postpartum, the specialty of the physician ordering the test, and ambulatory care visits with physicians from various specialties within 6 months postpartum were recorded.Results  Most women with GDM did not receive an OGTT, although testing rates increased slowly over the 14 years of the study, compared with no change in testing for women who had not had GDM. Virtually all women with GDM had postpartum visits with a family physician or obstetrician, but few OGTTs were ordered by physicians from these specialties.Conclusions  Despite a slow increase in testing over time and high rates of postpartum visits to family physicians and obstetricians, few women with GDM received the recommended diabetes test. This represents a missed opportunity in a high‐risk population. Interventions to change test ordering that target family physicians and obstetricians are most likely to increase the proportion of women with GDM who receive postpartum diabetes testing.
Breaking a paradigm: cosmopolitan and abundant freshwater actinobacteria are low GC
Authors: Ghai Rohit , McMahon Katherine D. , Rodriguez‐Valera Francisco 
Published: August 2011

SummaryFree‐living Actinobacteria are universally recognized as high‐GC organisms. Freshwater Actinobacteria have been identified as abundant and prevalent members of freshwater microbial communities, but the two most common lineages (acI and acIV) have remained impossible to culture to date. We have analysed metagenomic data from lakes and estuaries, and show that members of acI and acIV are indeed abundant. We then show that the majority of actinobacterial reads from metagenomic datasets (both lakes and estuaries) are consistently low GC. Analysis of assembled scaffolds from these datasets also confirms that actinobacterial scaffolds are primarily low GC, although high‐GC scaffolds were also observed, indicating both types of Actinobacteria coinhabit. Phylogenetic analysis of 16S rRNA gene sequences, both from PCR‐based clone libraries and metagenomic reads, and the discovery of a low‐GC scaffold containing a partial 16S rRNA gene, points to the abundance of the well‐known acI and acIV lineages of freshwater in these habitats, both of which appear to be low GC.
Correlative microscopy for phylogenetic and ultrastructural characterization of microbial communities
Authors: Knierim Bernhard , Luef Birgit , Wilmes Paul , Webb Richard I. , Auer Manfred , Comolli Luis R. , Banfield Jillian F. 
Published: August 2011

SummaryTransmission electron microscopy (TEM) can provide ultrastructural information for cells in microbial community samples and phylogenetic information can be recovered via molecular surveys. Here we report an approach to link these data sets by coupling fluorescence in situ hybridization (FISH) with either conventional biological or cryogenic TEM. The method could fundamentally improve our understanding of the organization and functioning of microbial communities in natural systems.
Surgical management of recurrent laryngeal neuropathy
Authors: Cramp P. , Barakzai S. Z. 
Published: August 2011

SummaryRecurrent laryngeal neuropathy (RLN, laryngeal hemiplegia, laryngeal paralysis, ‘roaring’) is common in the equine industry with a prevalence ranging from 2.6–11% in light breeds (Raphel 1982;Lane 1987;Morris and Seeherman 1990) up to 38% in draught breeds (Brakenhoffet al. 2006;Perkinset al. 2009). There are a number of different surgical treatments currently available and more being developed. This article aims to discuss factors affecting choice of treatment and then provide an evidence‐based approach to describe surgical approaches, success rates and morbidity. Specific details of surgical methods are not given as they are readily available in surgical textbooks (Stick 2006;McGorumet al. 2007).
Poincaré inequalities, embeddings, and wild groups
Authors: Naor Assaf , Silberman Lior 
Published: August 2011

AbstractWe present geometric conditions on a metric space (Y,dY) ensuring that, almost surely, any isometric action onYby Gromov’s expander-based random group has a common fixed point. These geometric conditions involve uniform convexity and the validity of nonlinear Poincaré inequalities, and they are stable under natural operations such as scaling, Gromov–Hausdorff limits, and Cartesian products. We use methods from metric embedding theory to establish the validity of these conditions for a variety of classes of metric spaces, thus establishing new fixed point results for actions of Gromov’s ‘wild groups’.
Dosimetric intercomparison for multicenter clinical trials using a patient‐based anatomic pelvic phantom
Authors: Ebert M. A. , Harrison K. M. , Howlett S. J. , Cornes D. , Bulsara M. , Hamilton C. S. , Kron T. , Joseph D. J. , Denham J. W. 
Published: August 2011

Purpose:To assess dose delivery accuracy to clinically significant points in a realistic patient geometry for two separate pelvic radiotherapy scenarios.Methods:An inhomogeneous pelvic phantom was transported to 36 radiotherapy centers in Australia and New Zealand. The phantom was treated according to Phase III rectal and prostate trial protocols. Point dose measurements were made with thermoluminescent dosimeters (TLDs) and an ionisation chamber. Comprehensive site‐demographic, treatment planning, and physical data were collected for correlation with measurement outcomes.Results:Dose delivery to the prescription point for the rectal treatment was consistent with planned dose (mean difference between planned and measured dose − 0.1 ± 0.3% std err). Dose delivery in the region of the sacral hollow was consistently higher than planned (+1.2 ± 0.2%). For the prostate treatment, dose delivery to the prostate volume was consistent with planned doses (−0.49 ± 0.2%) and planned dose uniformity, though with a tendency to underdose the PTV at the prostate‐rectal border. Measured out‐of‐field doses were significantly higher than planned.Conclusions:A phantom based on realistic anatomy and heterogeneity can be used to comprehensively assess the influence of multiple aspects of the radiotherapy treatment process on dose delivery. The ability to verify dose delivery for two trials with a single phantom was advantageous.
Investigating the limit of detectability of a positron emission mammography device: A phantom study
Authors: Shkumat Nicholas A. , Springer Adam , Walker Christopher M. , Rohren Eric M. , Yang Wei T. , Adrada Beatriz E. , Arribas Elsa , Carkaci Selin , Chuang Hubert H. , Santiago Lumarie , Mawlawi Osama R. 
Published: August 2011

Purpose:A new positron emission mammography (PEM) device (PEM Flex Solo II, Naviscan Inc., San Diego, CA) has recently been introduced and its performance characteristics have been documented. However, no systematic assessment of its limit of detectability has been evaluated. The aim of this work is to investigate the limit of detectability of this new PEM system using a novel, customized breast phantom.Methods:Two sets of F‐18 infused gelatin breast phantoms of varying thicknesses (2, 4, 6, and 8 cm) were constructed with and without (blank) small, shell‐less contrast objects (2 mm thick disks) of varying diameters (3–14.5 mm) [volumes: 0.15–3.3 cc] and activity concentration to background ratio (ACR) (2.7–58). For the phantom set with contrast objects, the disks were placed centrally inside the phantoms and both phantom sets were imaged for a period of 10 min on the PEM device. In addition, scans for the 2 and 6 cm phantoms were repeated at different times (0, 90, and 150 min) post phantom construction to evaluate the impact of total activity concentration (count density) on lesion detectability. Each object from each phantom scan was then segmented and placed randomly in a corresponding blank phantom image. The resulting individual images were presented blindly to seven physician observers (two nuclear medicine and five breast imaging radiologists) and scored in a binary fashion (1—correctly identified object, 0—incorrect). The sensitivity, specificity, and accuracy of lesion detectability were calculated and plots of sensitivity versus ACR and lesion diameters for different phantom thicknesses and count density were generated.Results:The overall (mean) detection sensitivity across all variables was 0.68 (95% CI: [0.64, 0.72]) with a corresponding specificity of 0.93 [0.87, 0.98], and diagnostic accuracy of 0.72 [0.70, 0.75]. The smallest detectable object varied strongly as a function of ACR, as sensitivity ranged from 0.36 [0.29, 0.44] for the smallest lesion size (3 mm) to 0.80 [0.75, 0.84] for the largest (14.5 mm).Conclusions:The detectability performance of this PEM system demonstrated its ability to resolve small objects with low activity concentration ratios which may assist in the identification of early stage breast cancer. The results of this investigation can be used to correlate lesion detectability with tumor size, ACR, count rate, and breast thickness.
Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages
Authors: Beare Paul A. , Gilk Stacey D. , Larson Charles L. , Hill Joshua , Stead Christopher M. , Omsland Anders , Cockrell Diane C. , Howe Dale , Voth Daniel E. , Heinzen Robert A. 
Published: August 2011

ABSTRACT

Central to Q fever pathogenesis is replication of the causative agent,
Coxiella burnetii
, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes.
C. burnetii
modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a
C. burnetii
strain carrying IcmD inactivated by the
Himar1
transposon to investigate the requirements for Dot/Icm function in
C. burnetii
parasitism of human THP-1 macrophage-like cells. The
icmD
::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the
icmD
::Tn mutant required complementation with
icmD
,
-J
, and
-B
, indicating a polar effect of the transposon insertion on downstream
dot
/
icm
genes. Induction of
icmDJB
expression at 1 day postinfection resulted in
C. burnetii
replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by
C. burnetii
. However, illustrating the metabolic flexibility of
C
.
burnetti
, the
icmD
::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in
trans
, and within a phenotypically similar PV generated by the protozoan parasite
Leishmania amazonensis
, where host cells are devoid of Dot/Icm T4BSS effector proteins.

IMPORTANCE
Coxiella burnetii
, the cause of human Q fever, is the only bacterial pathogen known to replicate in a vacuole resembling a phagolysosome. The organism manipulates host macrophages to promote the biogenesis of a vacuolar compartment permissive for growth. By analogy to the well-established cellular microbiology of
Legionella pneumophila
, the Dot/Icm type IVB secretion system of
C. burnetii
is implicated as a critical virulence factor in host cell modification that delivers proteins with effector functions directly into the host cell cytosol. Using new genetic tools, we verify that Dot/Icm function is essential for productive infection of human macrophages by
C. burnetii
. Interestingly, despite the production of homologous secretion systems,
L. pneumophila
and
C. burnetii
have strikingly different temporal requirements for Dot/Icm function during their respective infectious cycles.
TGF-β/SMAD/GLI2 Signaling Axis in Cancer Progression and Metastasis
Authors: Javelaud Delphine , Alexaki Vasileia I. , Dennler Sylviane , Mohammad Khalid S. , Guise Theresa A. , Mauviel Alain 
Published: August 2011

Abstract
The Hedgehog (HH) and TGF-β signaling pathways represent essential regulators of cell proliferation and differentiation during embryogenesis. Pathway deregulation is a characteristic of various cancers. Recently, evidence for a convergence of these pathways at the level of the GLI2 transcription factor in the context of tumor initiation and progression to metastasis has emerged. This short review summarizes recent knowledge about GLI2 function and mechanisms of action downstream of TGF-β in cancer. Cancer Res; 71(17); 5606–10. ©2011 AACR.
p38γ Promotes Breast Cancer Cell Motility and Metastasis through Regulation of RhoC GTPase, Cytoskeletal Architecture, and a Novel Leading Edge Behavior
Authors: Rosenthal Devin T. , Iyer Harish , Escudero Silvia , Bao Liwei , Wu Zhifen , Ventura Alejandra C. , Kleer Celina G. , Arruda Ellen M. , Garikipati Krishna , Merajver Sofia D. 
Published: August 2011

Abstract
Understanding the molecular alterations that confer cancer cells with motile, metastatic properties is needed to improve patient survival. Here, we report that p38γ motogen-activated protein kinase regulates breast cancer cell motility and metastasis, in part, by controlling expression of the metastasis-associated small GTPase RhoC. This p38γ–RhoC regulatory connection was mediated by a novel mechanism of modulating RhoC ubiquitination. This relationship persisted across multiple cell lines and in clinical breast cancer specimens. Using a computational mechanical model based on the finite element method, we showed that p38γ-mediated cytoskeletal changes are sufficient to control cell motility. This model predicted novel dynamics of leading edge actin protrusions, which were experimentally verified and established to be closely related to cell shape and cytoskeletal morphology. Clinical relevance was supported by evidence that elevated expression of p38γ is associated with lower overall survival of patients with breast cancer. Taken together, our results offer a detailed characterization of how p38γ contributes to breast cancer progression. Herein we present a new mechanics-based analysis of cell motility, and report on the discovery of a leading edge behavior in motile cells to accommodate modified cytoskeletal architecture. In summary, these findings not only identify a novel mechanism for regulating RhoC expression but also advance p38γ as a candidate therapeutic target. Cancer Res; 71(20); 6338–49. ©2011 AACR.
Novel Cryo-Imaging of the Glioma Tumor Microenvironment Reveals Migration and Dispersal Pathways in Vivid Three-Dimensional Detail
Authors: Burden-Gulley Susan M. , Qutaish Mohammed Q. , Sullivant Kristin E. , Lu Hong , Wang Jing , Craig Sonya E.L. , Basilion James P. , Wilson David L. , Brady-Kalnay Susann M. 
Published: August 2011

AbstractTraditional methods of imaging cell migration in the tumor microenvironment include serial sections of xenografts and standard histologic stains. Current molecular imaging techniques suffer from low resolution and difficulty in imaging through the skull. Here we show how computer algorithms can be used to reconstruct images from tissue sections obtained from mouse xenograft models of human glioma and can be rendered into three-dimensional images offering exquisite anatomic detail of tumor cell dispersal. Our findings identify human LN-229 and rodent CNS-1 glioma cells as valid systems to study the highly dispersive nature of glioma tumor cells along blood vessels and white matter tracts in vivo. This novel cryo-imaging technique provides a valuable tool to evaluate therapeutic interventions targeted at limiting tumor cell invasion and dispersal. Cancer Res; 71(17); 5932–40. ©2011 AACR.
Estrogen-Dependent Gene Transcription in Human Breast Cancer Cells Relies upon Proteasome-Dependent Monoubiquitination of Histone H2B
Authors: Prenzel Tanja , Begus-Nahrmann Yvonne , Kramer Frank , Hennion Magali , Hsu Chieh , Gorsler Theresa , Hintermair Corinna , Eick Dirk , Kremmer Elisabeth , Simons Mikael , Beissbarth Tim , Johnsen Steven A. 
Published: August 2011

Abstract
The estrogen receptor-α (ERα) determines the phenotype of breast cancers where it serves as a positive prognostic indicator. ERα is a well-established target for breast cancer therapy, but strategies to target its function remain of interest to address therapeutic resistance and further improve treatment. Recent findings indicate that proteasome inhibition can regulate estrogen-induced transcription, but how ERα function might be regulated was uncertain. In this study, we investigated the transcriptome-wide effects of the proteasome inhibitor bortezomib on estrogen-regulated transcription in MCF7 human breast cancer cells and showed that bortezomib caused a specific global decrease in estrogen-induced gene expression. This effect was specific because gene expression induced by the glucocorticoid receptor was unaffected by bortezomib. Surprisingly, we observed no changes in ERα recruitment or assembly of its transcriptional activation complex on ERα target genes. Instead, we found that proteasome inhibition caused a global decrease in histone H2B monoubiquitination (H2Bub1), leading to transcriptional elongation defects on estrogen target genes and to decreased chromatin dynamics overall. In confirming the functional significance of this link, we showed that RNA interference–mediated knockdown of the H2B ubiquitin ligase RNF40 decreased ERα-induced gene transcription. Surprisingly, RNF40 knockdown also supported estrogen-independent cell proliferation and activation of cell survival signaling pathways. Most importantly, we found that H2Bub1 levels decrease during tumor progression. H2Bub1 was abundant in normal mammary epithelium and benign breast tumors but absent in most malignant and metastatic breast cancers. Taken together, our findings show how ERα activity is blunted by bortezomib treatment as a result of reducing the downstream ubiquitin-dependent function of H2Bub1. In supporting a tumor suppressor role for H2Bub1 in breast cancer, our findings offer a rational basis to pursue H2Bub1-based therapies for future management of breast cancer. Cancer Res; 71(17); 5739–53. ©2011 AACR.
Age- and Sex-Specific Trends in the Incidence of Hospitalized Acute Coronary Syndromes in Western Australia
Authors: Nedkoff Lee J. , Briffa Tom G. , Preen David B. , Sanfilippo Frank M. , Hung Joseph , Ridout Stephen C. , Knuiman Matthew , Hobbs Michael 
Published: August 2011

Background—
The incidence of myocardial infarction has declined during the past 4 decades in many populations. However, there are limited population data measuring trends in acute coronary syndromes (ACS). We therefore examined temporal trends in the incidence of hospitalized ACS by age and sex in a population-based cohort.

Methods and Results—
The Western Australian Data Linkage System, a repository of linked administrative health data, was used to identify 29 421 incident ACS hospitalizations between 1996 and 2007. Poisson log-linear regression models were used to calculate incidence rate changes. Age-standardized incidence rates of ACS declined annually in men by 1.7% (95% confidence interval [CI], −2.1 to −1.3) and in women by 1.6% (95% CI, −2.1 to −1.0). These declining rates were underpinned by annual reductions in the incidence of unstable angina (men, −3.0%; 95% CI, −3.7 to −2.4; women, −2.5; 95% CI, −3.3 to −1.7), whereas annual changes in myocardial infarction incidence were less (men, −1.0%; 95% CI, −1.5 to −0.5; women, −0.8%; 95% CI, −1.6 to 0). However, the overall trends masked age group differences, with ACS incidence increasing annually in 35- to 54-year-old women (2.3%; 95% CI, 1.0 to 3.8), predominantly driven by increasing incidence of myocardial infarction.

Conclusions—
The age-standardized incidence of ACS decreased significantly in Western Australia from 1996 to 2007. However, an increase in ACS incidence in women ages 35 to 54 years is troubling and warrants further investigation.