bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genetic System for Clostridium ljungdahlii: a Chassis for Autotrophic Production of Biocommodities and a Model Homoacetogen
Authors: Leang Ching , Ueki Toshiyuki , Nevin Kelly P. , Lovley Derek R. 
Published: December 2012

ABSTRACT

Methods for genetic manipulation of
Clostridium ljungdahlii
are of interest because of the potential for production of fuels and other biocommodities from carbon dioxide via microbial electrosynthesis or more traditional modes of autotrophy with hydrogen or carbon monoxide as the electron donor. Furthermore, acetogenesis plays an important role in the global carbon cycle. Gene deletion strategies required for physiological studies of
C. ljungdahlii
have not previously been demonstrated. An electroporation procedure for introducing plasmids was optimized, and four different replicative origins for plasmid propagation in
C. ljungdahlii
were identified. Chromosomal gene deletion via double-crossover homologous recombination with a suicide vector was demonstrated initially with deletion of the gene for FliA, a putative sigma factor involved in flagellar biogenesis and motility in
C. ljungdahlii
. Deletion of
fliA
yielded a strain that lacked flagella and was not motile. To evaluate the potential utility of gene deletions for functional genomic studies and to redirect carbon and electron flow, the genes for the putative bifunctional aldehyde/alcohol dehydrogenases,
adhE1
and
adhE2
, were deleted individually or together. Deletion of
adhE1
, but not
adhE2
, diminished ethanol production with a corresponding carbon recovery in acetate. The double deletion mutant had a phenotype similar to that of the
adhE1
-deficient strain. Expression of
adhE1
in
trans
partially restored the capacity for ethanol production. These results demonstrate the feasibility of genetic investigations of acetogen physiology and the potential for genetic manipulation of
C. ljungdahlii
to optimize autotrophic biocommodity production.
Autofluorescence as a Tool for Structural Analysis of Biofilms Formed by Nonpigmented Rapidly Growing Mycobacteria
Authors: Muñoz-Egea María-Carmen , García-Pedrazuela María , Mahillo Ignacio , García María Jesús , Esteban Jaime 
Published: December 2012

ABSTRACT
The structure of biofilms formed by seven nonpigmented rapidly growing mycobacteria, including saprophytes and opportunistic species, was analyzed. Analysis included amount of covered surface, thickness, cell viability, and presence of intrinsic autofluorescence at different times using confocal laser scanning microscopy and image analysis. Autofluorescence was detected inside and outside cells of all mycobacteria.
Escherichia coli and Klebsiella pneumoniae Producing CTX-M Cephalosporinase from Swine Finishing Barns and Their Association with Antimicrobial Use
Authors: Mollenkopf Dixie F. , Mirecki Jennifer M. , Daniels Joshua B. , Funk Julie A. , Henry Steven C. , Hansen Glenn E. , Davies Peter R. , Donovan Tara S. , Wittum Thomas E. 
Published: December 2012

ABSTRACT

We report the recovery of
Escherichia coli
or
Klebsiella pneumoniae
containing the extended-spectrum β-lactamase gene
bla
CTX-M
from 24 of 1,495 (1.6%) swine fecal samples in 8 of 50 (16%) finishing barns located in 5 U.S. states. We did not detect an association between antimicrobial use and recovery of
bla
CTX-M
.
Aeromonas and Pseudomonas Species Carriers of
ampC
FOX Genes in Aquatic Environments
Authors: Voolaid Veiko , Tenson Tanel , Kisand Veljo 
Published: December 2012

ABSTRACT

Resistance to beta-lactam antibiotics is evolutionarily ancient, and resistance to new drugs develops and quickly spreads. Most studies on beta-lactam resistance concentrate on pathogens in medical and veterinary settings. We show that
ampC
FOX genes can be found in natural environmental isolates.
The Type III Secretion System of Bradyrhizobium japonicum USDA122 Mediates Symbiotic Incompatibility with
Rj2
Soybean Plants
Authors: Tsukui Takahiro , Eda Shima , Kaneko Takakazu , Sato Shusei , Okazaki Shin , Kakizaki-Chiba Kaori , Itakura Manabu , Mitsui Hisayuki , Yamashita Akifumi , Terasawa Kimihiro , Minamisawa Kiwamu 
Published: December 2012

ABSTRACT

The
rhcJ
and
ttsI
mutants of
Bradyrhizobium japonicum
USDA122 for the type III protein secretion system (T3SS) failed to secrete typical effector proteins and gained the ability to nodulate
Rj2
soybean plants (Hardee), which are symbiotically incompatible with wild-type USDA122. This suggests that effectors secreted via the T3SS trigger incompatibility between these two partners.
Activation of an Essential Calcium Signaling Pathway in Saccharomyces cerevisiae by Kch1 and Kch2, Putative Low-Affinity Potassium Transporters
Authors: Stefan Christopher P. , Zhang Nannan , Sokabe Takaaki , Rivetta Alberto , Slayman Clifford L. , Montell Craig , Cunningham Kyle W. 
Published: December 2012

ABSTRACT

In the budding yeast
Saccharomyces cerevisiae
, mating pheromones activate a high-affinity Ca
2+
influx system (HACS) that activates calcineurin and is essential for cell survival. Here we identify extracellular K
+
and a homologous pair of transmembrane proteins, Kch1 and Kch2 (Prm6), as necessary components of the HACS activation mechanism. Expression of Kch1 and especially Kch2 was strongly induced during the response to mating pheromones. When forcibly overexpressed, Kch1 and Kch2 localized to the plasma membrane and activated HACS in a fashion that depended on extracellular K
+
but not pheromones. They also promoted growth of
trk1 trk2
mutant cells in low K
+
environments, suggesting they promote K
+
uptake. Voltage-clamp recordings of protoplasts revealed diminished inward K
+
currents in
kch1 kch2
double-mutant cells relative to the wild type. Conversely, heterologous expression of Kch1 in HEK293T cells caused the appearance of inwardly rectifying K
+
currents. Collectively, these findings suggest that Kch1 and Kch2 directly promote K
+
influx and that HACS may electrochemically respond to K
+
influx in much the same way as the homologous voltage-gated Ca
2+
channels in most animal cell types.
Why do clinicians not refer patients to online decision support tools? Interviews with front line clinics in the NHS
Authors: Elwyn Glyn , Rix Andrew , Holt Tom , Jones Deborah 
Published: December 2012

ObjectiveTo assess whether clinical teams would direct patients to use web-based patient decision support interventions (DESIs) and whether patients would use them.DesignRetrospective semistructured interviews and web server log analysis.Participants and settings57 NHS professionals (nurses, doctors and others) in orthopaedic, antenatal, breast, urology clinics and in primary care practices across 22 NHS sites given access to DESIs hosted on the NHS Direct website.ResultsFewer than expected patients were directed to use the web tools. The most significant obstacles to referral to the tools were the attitudes of clinicians and clinical teams. Technical problems contributed to the problems but the low uptake was mainly explained by clinicians’ limited understanding of how patient DESIs could be helpful in clinical pathways, their perception that ‘shared decision-making’ was already commonplace and that, in their view, some patients are resistant to being involved in treatment decisions. External factors, such as efficiency targets and ‘best practice’ recommendations were also cited being significant barriers. Clinicians did not feel the need to refer patients to use decision support tools, web-based or not, and, as a result, felt no requirement to change existing practice routines. Uptake is highest when clinicians set expectations that these tools are integral to practice and embed their use into clinical pathways.ConclusionsExisting evidence of patient benefit and the free availability of patient DESIs via the web are not sufficient drivers to achieve routine use. Health professionals were not motivated to refer patients to these interventions. Clinicians will not use these interventions simply because they are made available, despite good evidence of benefit to patients. These attitudes are deep seated and will not be modified by solely developing web-based interventions: a broader strategy will be required to embed DESIs into routine practice.
Clinical features of myocardial infarction and myocarditis in young adults: a retrospective study
Authors: Pellaton Cyril , Monney Pierre , Ludman Andrew James , Schwitter Juerg , Eeckhout Eric , Hugli Olivier , Muller Olivier 
Published: December 2012

ObjectivesTo evaluate the prevalence and clinical presentation of myocardial infarction (MI) and myocarditis in young adults presenting with chest pain (CP) and an elevated serum troponin I (TnI) to the emergency department (ED).DesignRetrospective, observational, single-centre study.ParticipantsAll consecutive patients 18–40 years old admitted to the ED for CP with an elevated TnI concentration.Primary outcome measuresPrevalence of MI, myocarditis and the characterisation of clinical presentation.Results1588 patients between 18 and 40 years old were admitted to the ED with CP during 30 consecutive months. 49 (3.1%) patients with an elevated TnI (>0.09 μg/l) were included. 32.7% (16/49) were diagnosed with MI (11 ST-elevation myocardial infarction (STEMI) and 5 non-ST-elevation myocardial infarction (NSTEMI)) and 59.2% (29/49) with myocarditis. Compared with patients with myocarditis, MI patients were older (34.1±3.8 vs 26.9±6.4, p=0.0002) with more cardiovascular risk factors (mean 2.06 vs 0.69). Diabetes (18.8% vs 0%, p=0.0039), dyslipidaemia (56.2% vs 3.4%, p<0.0001) and family history of coronary artery disease (CAD) (37.5% vs 10.3% p=0.050) were associated with MI. Fever or recent viral illness were present in 75.9% (22/29) of patients with myocarditis, and in 0% of MI patients (p<0.0001). During follow-up, two patients with myocarditis were re-admitted for CP.ConclusionsIn this study, 32.7% of patients <40-year-old admitted to an ED with CP and elevated TnI had a diagnosis of MI. Key distinctive clinical factors include diabetes, dyslipidaemia, family history of CAD and fever or recent viral illness.
Predictors of cardiovascular events in a contemporary population with impaired glucose tolerance: an observational analysis of the Nateglinide and Valsartan in impaired glucose tolerance outcomes research (NAVIGATOR) trial
Authors: Preiss David , Thomas Laine E , Sun Jie-Lena , Haffner Steven M , Holman Rury R , Standl Eberhard , Leiter Lawrence A , Mazzone Theodore , Rutten Guy E , Tognoni Gianni , Martinez Felipe A , Chiang Fu-Tien , Califf Robert M , McMurray John J 
Published: December 2012

ObjectivesRisk factors for cardiovascular events are well established in general populations and those with diabetes but have been sparsely studied in impaired glucose tolerance (IGT). We sought to identify predictors of (1) a composite cardiovascular outcome (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and (2) cardiovascular death, among patients with IGT.DesignWe studied participants enrolled in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Predictors of cardiovascular events were identified in observational analyses.SettingClinical trial participants in 40 countries.Participants9306 participants with biochemically confirmed IGT at high risk of cardiovascular events participated in NAVIGATOR.Primary and secondary outcome measuresCox proportional hazard regression models were constructed using variables (demographic data, medical history, clinical features, biochemical results and ECG findings) recorded at baseline to identify variables associated with and predictive of cardiovascular events.ResultsOver 6.4 years, 639 (6.9%) participants experienced a cardiovascular event, and 244 (2.6%) cardiovascular death. While predictors of both outcomes included established risk factors such as existing cardiovascular disease, male gender, older age, current smoking status and higher low-density lipoprotein cholesterol, other variables such as reduced estimated glomerular filtration rate, previous thromboembolic disease, atrial fibrillation, higher urinary albumin/creatinine ratio and chronic obstructive pulmonary disease were also important predictors. Glycaemic measures were not predictive of cardiovascular events. c-Statistics for predicting cardiovascular events and cardiovascular death were 0.74 and 0.82, respectively. This compares with c-statistics for cardiovascular events and cardiovascular death of 0.65 and 0.71, respectively, using the classical Framingham risk factors of age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension and smoking status.ConclusionsThe most powerful independent predictors of cardiovascular events in IGT included both established risk factors and other variables excluding measures of glycaemia, allowing effective identification of high-risk individuals.
Instruments used to measure the effectiveness of palliative care education initiatives at the undergraduate level: a critical literature review
Authors: Frey Rosemary Ann , Gott Merryn , Neil Hayley 
Published: December 2012

BackgroundThe increase in the numbers of patients with palliative care needs has resulted in growing pressures on the small number of specialist palliative care providers within the New Zealand context. These pressures can potentially be eased by ensuring an adequately trained workforce, beginning with undergraduate training in the healthcare field. The goal of the present review is to ascertain what tools exist to measure the effectiveness of undergraduate palliative care education initiatives.MethodA systematic review of qualitative and quantitative literature was undertaken. Searches within ERIC, CINAHL Plus, Medline and Medline in Progress, and Google Scholar databases were conducted for the period 1990–2011. A checklist adapted from Hawkeret alwas used to select and assess data.Results14 of the 112 articles met the inclusion criteria. Overall inconsistencies in the amount of validation information provided and a narrow focus on aspects of palliative care competence was apparent. No universally applicable validated questionnaire to assess the effectiveness of undergraduate palliative care education could be identified.ConclusionsThe increased focus by educational institutions on instilling palliative care skills in healthcare students necessitates the development of comprehensive and validated tools to evaluate the effectiveness of education initiatives.
The lived experience of physicians dealing with patient death
Authors: Whitehead Paul Richard 
Published: December 2012

BackgroundA growing body of research indicates that physicians suffer high levels of stress, depression and burnout. Related literature has found that physician stress can negatively impact patient care. This study builds upon previous research that found some dying patients experienced ‘iatrogenic suffering’ caused by the way physicians communicated with them regarding terminal diagnoses and palliative treatment. The goal of this research was to explore physicians’ experiences of dealing with patient death in order to understand how such experiences affect them and their communication with patients.MethodsThis study used qualitative methods to conduct and analyse 10 individual, semistructured interviews with senior physicians from several specialty areas at a large, tertiary care hospital. The resulting themes were validated using member checks and expert review.ResultsThis article presents five essential themes that provide a concise description of the lived experience of patient death for these physicians. Interpretation: These themes indicate that physicians can experience very strong and lasting emotional reactions to some patient deaths, and also that patient death can elicit intense experiences related to professional responsibility and competence. A key finding is the description of a complex process of managing the balance between personal and professional reactions in the face of patient death. The implication is that difficulties negotiating this balance may lead to unintended lapses in compassion and suboptimal outcomes in patient care.
Whole slide images for primary diagnostics of paediatric pathology specimens: a feasibility study
Authors: Al-Janabi Shaimaa , Huisman André , Nikkels Peter G J , ten Kate Fiebo J W , van Diest Paul J 
Published: December 2012

IntroductionWhole slide images (WSI) have been used in many pathology applications such as teleconsultation, teaching and research, but not in primary diagnostics. The aim of this study was to test the feasibility of using WSI in primary diagnostics of paediatric pathology specimens and placental tissue.Materials and methodsEighty consecutive tissues biopsies and resections from patients under 18 years old were selected, as well as 20 placentas. These cases had been diagnosed in the year 2009 by a single pathologist. The same pathologist who had performed the original diagnosis based on light microscopy was asked to rediagnose these 100 cases on WSI scanned at 20× magnification as well as by light microscopy having the original clinical information available, but blinded to the original light microscopic diagnoses. The original diagnoses were compared with WSI based diagnoses and rediagnoses by light microscopy and classified as concordant, mildly discordant (without clinical consequences) and discordant (with clinical consequences).ResultsThe original diagnoses were concordant with WSI and light microscopic diagnoses in 90% and 93% of cases respectively, which was not significantly different. Digital reassessment yielded eight mild discrepancies and two discrepant cases (2%) where the difference in diagnoses could have clinical implications for the patient. Light microscopic reassessment showed seven mild discrepancies. It turned out to be difficult to identify nucleated red blood cells on WSI, even when scanned at 40×.ConclusionsPrimary diagnostics of paediatric tissue biopsies and resections can generally well be done on WSI. However, some difficulties were encountered in examining placenta tissue where the identification of nucleated red blood cells may need higher resolution or even scanning at multiple focus depths, which is well possible on most current slide scanners.
CXCR2 Expression in Tumor Cells Is a Poor Prognostic Factor and Promotes Invasion and Metastasis in Lung Adenocarcinoma
Authors: Saintigny Pierre , Massarelli Erminia , Lin Steven , Ahn Young-Ho , Chen Yulong , Goswami Sangeeta , Erez Baruch , O'Reilly Michael S. , Liu Diane , Lee J. Jack , Zhang Li , Ping Yuan , Behrens Carmen , Solis Soto Luisa M. , Heymach John V. , Kim Edward S. , Herbst Roy S. , Lippman Scott M. , Wistuba Ignacio I. , Hong Waun Ki , Kurie Jonathan M. , Koo Ja Seok 
Published: December 2012

AbstractCXCR2 in non–small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53–mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small-molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was determined in 70 human NSCLC cell lines. Invasion and metastasis were decreased in CXCR2 knockdown clones in vitro and in vivo. SB225002 decreased invasion in vitro. In lung adenocarcinomas, CXCR2 expression in tumor cells was associated with smoking and poor prognosis. CXCR2 axis gene expression profiles in human NSCLC cell lines and lung adenocarcinomas defined a cluster driven by CXCL5 and associated with smoking, poor prognosis, and RAS pathway activation. Expression of CXCL5 was regulated by promoter methylation. The CXCR2 axis may be an important target in smoking-related lung adenocarcinoma. Cancer Res; 73(2); 571–82. ©2012 AACR.
High-Avidity T Cells Are Preferentially Tolerized in the Tumor Microenvironment
Authors: Zhu Ziqiang , Singh Vinod , Watkins Stephanie K. , Bronte Vincenzo , Shoe Jennifer L. , Feigenbaum Lionel , Hurwitz Arthur A. 
Published: December 2012

AbstractOne obstacle in eliciting potent antitumor immune responses is the induction of tolerance to tumor antigens. TCRlo mice bearing a TCR transgene specific for the melanoma antigen tyrosinase-related protein-2 (TRP-2, Dct) harbor T cells that maintain tumor antigen responsiveness but lack the ability to control melanoma outgrowth. We used this model to determine whether higher avidity T cells could control tumor growth without becoming tolerized. As a part of the current study, we developed a second TRP-2–specific TCR transgenic mouse line (TCRhi) that bears higher avidity T cells and spontaneously developed autoimmune depigmentation. In contrast to TCRlo T cells, which were ignorant of tumor-derived antigen, TCRhi T cells initially delayed subcutaneous B16 melanoma tumor growth. However, persistence in the tumor microenvironment resulted in reduced IFN-γ production and CD107a (Lamp1) mobilization, hallmarks of T-cell tolerization. IFN-γ expression by TCRhi T cells was critical for upregulation of MHC-I on tumor cells and control of tumor growth. Blockade of PD-1 signals prevented T-cell tolerization and restored tumor immunity. Depletion of tumor-associated dendritic cells (TADC) reduced tolerization of TCRhi T cells and enhanced their antitumor activity. In addition, TADCs tolerized TCRhi T cells but not TCRlo T cells in vitro. Our findings show that T-cell avidity is a critical determinant of not only tumor control but also susceptibility to tolerization in the tumor microenvironment. For this reason, care should be exercised when considering T-cell avidity in designing cancer immunotherapeutics. Cancer Res; 73(2); 595–604. ©2012 AACR.
Clonal Progression of Prostate Cancers from Gleason Grade 3 to Grade 4
Authors: Sowalsky Adam G. , Ye Huihui , Bubley Glenn J. , Balk Steven P. 
Published: December 2012

Abstract
Low-grade prostate cancers (Gleason pattern 3, G3) detected on needle biopsies are generally viewed as indolent and suitable for conservative management with only interval repeat biopsies to monitor by watchful waiting. Higher grade tumors eventually emerge in 20% to 30% of these cases, but this process may only reflect incomplete sampling on the initial biopsy, such that it remains unknown whether G3 tumors generally progress to higher grades. In this study, we examined a series of adjacent G3 and Gleason pattern 4 (G4) tumors in radical prostatectomy specimens and found that all were concordant for the TMPRSS2:ERG gene fusion. Using hybrid-capture and deep sequencing in four fusion-positive cases, we found that adjacent laser-capture microdissected G3 and G4 tumors had identical TMPRSS2:ERG fusion breakpoints, confirming their clonal origin. Two of these G3 tumors had deletion of a single PTEN gene that was also deleted in the adjacent G4, while the G4 tumors in two cases had additional PTEN losses. These findings establish that a subset of G3 tumors progress to G4 or emerge from a common precursor. Further, they show that G3 tumors that progress to G4 may have molecular features distinguishing them from G3 tumors that do not progress. Thus, determining the spectrum of these genetic or epigenetic features may allow for the identification of G3 tumors on needle biopsies that are truly indolent versus those that have the potential to progress or that may already be associated with a G4 tumor that was not sampled at the initial biopsy, therefore, requiring more aggressive surveillance or intervention. Cancer Res; 73(3); 1050–5. ©2012 AACR.