bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance
Authors: Fernández Lucía , Hancock Robert E. W. 
Published: October 2012

SUMMARY
The substantial use of antibiotics in the clinic, combined with a dearth of new antibiotic classes, has led to a gradual increase in the resistance of bacterial pathogens to these compounds. Among the various mechanisms by which bacteria endure the action of antibiotics, those affecting influx and efflux are of particular importance, as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. This review evaluates the impact of porins and efflux pumps on two major types of resistance, namely, mutational and adaptive types of resistance, both of which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms. In particular, we explain how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics. The identification of porins and pumps as major resistance markers has opened new possibilities for the development of novel therapeutic strategies directed specifically against these mechanisms.
Helminth Infections and Host Immune Regulation
Authors: McSorley Henry J. , Maizels Rick M. 
Published: October 2012

SUMMARYHelminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.
Thermal Control of Microbial Development and Virulence: Molecular Mechanisms of Microbial Temperature Sensing
Authors: Shapiro Rebecca S. , Cowen Leah E. 
Published: October 2012

ABSTRACT
Temperature is a critical and ubiquitous environmental signal that governs the development and virulence of diverse microbial species, including viruses, archaea, bacteria, fungi, and parasites. Microbial survival is contingent upon initiating appropriate responses to the cellular stress induced by severe environmental temperature change. In the case of microbial pathogens, development and virulence are often coupled to sensing host physiological temperatures. As such, microbes have developed diverse molecular strategies to sense fluctuations in temperature, and nearly all cellular molecules, including proteins, lipids, RNA, and DNA, can act as thermosensors that detect changes in environmental temperature and initiate relevant cellular responses. The myriad of molecular mechanisms by which microbes sense and respond to temperature reveals an elegant repertoire of strategies to orchestrate cellular signaling, developmental programs, and virulence with spatial and temporal environmental cues.
Toward a Semisynthetic Stress Response System To Engineer Microbial Solvent Tolerance
Authors: Zingaro Kyle A. , Papoutsakis Eleftherios Terry 
Published: October 2012

ABSTRACTStrain tolerance to toxic metabolites is an important trait for many biotechnological applications, such as the production of solvents as biofuels or commodity chemicals. Engineering a complex cellular phenotype, such as solvent tolerance, requires the coordinated and tuned expression of several genes. Using combinations of heat shock proteins (HSPs), we engineered a semisynthetic stress response system inEscherichia colicapable of tolerating high levels of toxic solvents. Simultaneous overexpression of the HSPs GrpE and GroESL resulted in a 2-fold increase in viable cells (CFU) after exposure to 5% (vol/vol) ethanol for 24 h. Co-overexpression of GroESL and ClpB on coexisting plasmids resulted in 1,130%, 78%, and 25% increases in CFU after 24 h in 5% ethanol, 1%n-butanol, and 1%i-butanol, respectively. Co-overexpression of GrpE, GroESL, and ClpB on a single plasmid produced 200%, 390%, and 78% increases in CFU after 24 h in 7% ethanol, 1%n-butanol, or 25% 1,2,4-butanetriol, respectively. Overexpression of other autologous HSPs (DnaK, DnaJ, IbpA, and IbpB) alone or in combinations failed to improve tolerance. Expression levels of HSP genes, tuned through inducible promoters and the plasmid copy number, affected the effectiveness of the engineered stress response system. Taken together, these data demonstrate that tuned co-overexpression of GroES, GroEL, ClpB, and GrpE can be engaged to engineer a semisynthetic stress response system capable of greatly increasing the tolerance ofE. colito solvents and provides a starting platform for engineering customized tolerance to a wide variety of toxic chemicals.IMPORTANCEMicrobial production of useful chemicals is often limited by the toxicity of desired products, feedstock impurities, and undesired side products. Improving tolerance is an essential step in the development of practical platform organisms for production of a wide range of chemicals. By overexpressing autologous heat shock proteins inEscherichia coli, we have developed a modular semisynthetic stress response system capable of improving tolerance to ethanol,n-butanol, and potentially other toxic solvents. Using this system, we demonstrate that a practical stress response system requires both tuning of individual gene components and a reliable framework for gene expression. This system can be used to seek out new interacting partners to improve the tolerance phenotype and can be used in the development of more robust solvent production strains.
Survey of UK and New Zealand gastroenterologists’ practice regarding dietary advice and food exclusion in irritable bowel syndrome and inflammatory bowel disease
Authors: Inns Stephen James , Emmanuel Anton V 
Published: October 2012

BackgroundThis study aimed to assess the dietary advice practice of UK and New Zealand (NZ) adult gastroenterologists in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).MethodsA questionnaire regarding dietary advice practice was emailed or mailed to all members of the British Society of Gastroenterology (n=983) and the NZ Society of Gastroenterology (n=54).Results363 questionnaires were returned in the UK (response rate 37%) and 51 in NZ (94%). More respondents gave specific dietary advice to more than 25% of their patients on IBS than IBD (84% vs 27% UK, 90% vs 55% NZ; p=0.001 for both) and gave advice about dietary exclusions to more than 25% of patients on IBS than IBD (61% vs 13% UK, 77% vs 14% NZ; p<0.001 for both). They were most likely to provide dietary advice to patients with small bowel Crohn's disease, difficult to control IBD, diarrhoea predominant IBS and difficult to control IBS. The majority of respondents agreed strongly or a little that dietary exclusion was effective in the treatment of IBS, compared to the minority in IBD (71% vs 39% UK, 84% vs 43% p<0.05 for both).ConclusionsUK and NZ gastroenterologists give dietary advice more commonly to IBS than IBD patients. The majority of gastroenterologists have some confidence in the use of dietary exclusion in IBS, the converse is true in IBD. However, the advice given is largely empiric and mostly comprises the exclusion of fibre, dairy and wheat.
Biomarker Discovery in Non–Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
Authors: Botling Johan , Edlund Karolina , Lohr Miriam , Hellwig Birte , Holmberg Lars , Lambe Mats , Berglund Anders , Ekman Simon , Bergqvist Michael , Pontén Fredrik , König André , Fernandes Oswaldo , Karlsson Mats , Helenius Gisela , Karlsson Christina , Rahnenführer Jörg , Hengstler Jan G , Micke Patrick 
Published: October 2012

AbstractPurpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non–small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P &lt; 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P &lt; 0.001) with a false discovery rate &lt;1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194–204. ©2012 AACR.
Redirecting Gene-Modified T Cells toward Various Cancer Types Using Tagged Antibodies
Authors: Tamada Koji , Geng Degui , Sakoda Yukimi , Bansal Navneeta , Srivastava Ratika , Li Zhaoyang , Davila Eduardo 
Published: October 2012

Abstract
Purpose: To develop an adaptable gene-based vector that will confer immune cell specificity to various cancer types.
Experimental Design: Human and mouse T cells were genetically engineered to express a chimeric antigen receptor (CAR) that binds a fluorescein isothiocyanate (FITC) molecule, termed anti-FITC CAR T cells. Various antibodies (Ab) currently in clinical use including cetuximab (Ctx), trastuzumab (Her2), and rituximab (Rtx) were conjugated with FITC and tested for their ability to bind tumor cells, activate T cells, and induce antitumor effects in vitro and in vivo.
Results: Anti-FITC CAR T cells recognize various cancer types when bound with FITC-labeled Abs resulting in efficient target lysis, T-cell proliferation, and cytokine/chemokine production. The treatment of immunocompromised mice with human anti-FITC CAR T cells plus FITC-labeled cetuximab (FITC-Ctx) delayed the growth of colon cancer but unexpectedly led to the outgrowth of EGF receptor (EGFR)-negative tumor cells. On the other hand, in a human pancreatic cancer cell line with uniform EGFR expression, anti-FITC CAR T cells plus FITC-Ctx eradicated preestablished late-stage tumors. In immunocompetent mice, anti-FITC CAR T cells exhibited potent antitumor activity against syngeneic mouse breast cancer expressing Her2 and B-cell lymphoma expressing CD20 by combining with FITC-Her2 and FITC-Rtx, respectively. In addition, the activity of anti-FITC CAR T cells could be attenuated by subsequent injections of nonspecific FITC-IgG.
Conclusion: These studies highlight an applicability of anti-tag CAR technology to treat patients with different types of cancers and a possibility to regulate CAR T-cell functions with competing FITC molecules. Clin Cancer Res; 18(23); 6436–45. ©2012 AACR.
N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure
Authors: Choi Eui-Young , Bahrami Hossein , Wu Colin O. , Greenland Philip , Cushman Mary , Daniels Lori B. , Almeida Andre L.C. , Yoneyama Kihei , Opdahl Anders , Jain Aditya , Criqui Michael H. , Siscovick David , Darwin Christine , Maisel Alan , Bluemke David A. , Lima Joao A.C. 
Published: October 2012

Background—
Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population.

Methods and Results—

A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54–2.46,
P
<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046,
P
<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3–10%, >10% =0.175,
P
=0.019; category-less net reclassification index=0.561,
P
<0.001).

Conclusions—
Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00005487.
Moderate Aortic Enlargement and Bicuspid Aortic Valve Are Associated With Aortic Dissection in Turner Syndrome
Authors: Carlson Misty , Airhart Nathan , Lopez Leo , Silberbach Michael 
Published: October 2012

Background—
Girls and women with Turner syndrome are at risk for aortic dissection and rupture. However, the size of the aorta and the clinical characteristics among those with Turner syndrome and dissection have received little attention.

Methods and Results—

We obtained medical records from 20 individuals who voluntarily participated in the International Turner Syndrome Aortic Dissection Registry. Type A dissections occurred in 17 of 20 (85%) cases, and type B occurred in 3 cases of which 1 occurred after coarctation stent placement. Of those with spontaneous aortic dissections, 18 of 19 (95%) had an associated cardiac malformation that included a bicuspid aortic valve. In 1 individual there was no predisposing finding other than the presence of Turner syndrome. Associated pregnancy was documented in 1 of 19 (5%). More than half (13/19, 68%) came to medical attention >24 hours after the onset of symptoms. For those with type A dissections, the mean ascending aortic size index was 2.7±0.6 cm/m
2
(n=9).

Conclusions—

Aortic dissection in Turner syndrome occurs in young individuals at smaller aortic diameters than in the general population or other forms of genetically triggered aortopathy. The absence of aortic valve or other cardiac malformations appears to markedly reduce the risk of aortic dissection However, aortic dissection can occur in Turner syndrome without cardiac malformations or hypertension. Individuals with Turner syndrome who are >18 years of age with an ascending aortic size index >2.5 cm/m
2
should be considered for an aortic operation to prevent aortic dissection.
Trends in the Incidence of Atrial Fibrillation in Older Patients Initiating Dialysis in the United States
Authors: Goldstein Benjamin A. , Arce Cristina M. , Hlatky Mark A. , Turakhia Mintu , Setoguchi Soko , Winkelmayer Wolfgang C. 
Published: October 2012

Background—
One sixth of US dialysis patients 65 years of age have been diagnosed with atrial fibrillation/flutter (AF). Little is known, however, about the incidence of AF in this population.

Methods and Results—
We identified 258 605 older patients (≥67 years of age) with fee-for-service Medicare initiating dialysis in 1995 to 2007, who had not been diagnosed with AF within the previous 2 years. Patients were followed for newly diagnosed AF. Multivariable proportional hazard regression was used to examine temporal trends and associations of race and ethnicity with incident AF. We also studied temporal trends in the mortality and risk of ischemic stroke after new AF. Over 514 395 person-years of follow-up, 76 252 patients experienced incident AF for a crude AF incidence rate of 148/1000 person-years. Incidence of AF increased by 11% (95% confidence interval, 5–16) from 1995 to 2007. Compared with non-Hispanic whites, blacks (−30%), Asians (−19%), Native Americans (−42%), and Hispanics (−29%) all had lower rates of incident AF. Mortality after incident AF decreased by 22% from 1995 to 2008. Even more pronounced reductions were seen for incident ischemic stroke during these years.

Conclusions—
The incidence of AF is high in older patients initiating dialysis in the United States and has been increasing over the 13 years of study. Mortality declined during that time but remained >50% during the first year after newly diagnosed AF. Because data on warfarin use were not available, we were unable to study whether trends toward better outcomes could be explained by higher rates of oral anticoagulation.
Antihypertensive Treatment Prolongs Tissue Plasminogen Activator Door-to-Treatment Time
Authors: Skolarus Lesli E. , Scott Phillip A. , Burke James F. , Adelman Eric E. , Frederiksen Shirley M. , Kade Allison M. , Kalbfleisch Jack D. , Ford Andria L. , Meurer William J. 
Published: October 2012

Background and Purpose—
Identifying modifiable tissue plasminogen activator treatment delays may improve stroke outcomes. We hypothesized that prethrombolytic antihypertensive treatment (AHT) may prolong door-to-treatment time (DTT).

Methods—

We performed an analysis of consecutive tissue plasminogen activator–treated patients at 24 randomly selected community hospitals in the Increasing Stroke Treatment through Interventional Behavior Change Tactics (INSTINCT) trial between 2007 and 2010. DTT among stroke patients who received prethrombolytic AHT were compared with those who did not receive prethrombolytic AHT. We then calculated a propensity score for the probability of receiving prethrombolytic AHT using logistic regression with demographics, stroke risk factors, home medications, stroke severity (National Institutes of Health Stroke Scale), onset-to-door time, admission glucose, pretreatment blood pressure, emergency medical service transport, and location at time of stroke as independent variables. A paired
t
test was performed to compare the DTT between the propensity-matched groups.

Results—
Of 534 tissue plasminogen activator–treated stroke patients analyzed, 95 received prethrombolytic AHT. In the unmatched cohort, patients who received prethrombolytic AHT had a longer DTT (mean increase, 9 minutes; 95% confidence interval, 2–16 minutes) than patients who did not. After propensity matching, patients who received prethrombolytic AHT had a longer DTT (mean increase, 10.4 minutes; 95% confidence interval, 1.9–18.8) than patients who did not receive prethrombolytic AHT.

Conclusion—
Prethrombolytic AHT is associated with modest delays in DTT. This represents a potential target for quality-improvement initiatives. Further research evaluating optimum prethrombolytic hypertension management is warranted.
Atmosphere–Land Surface Interactions over the Southern Great Plains: Characterization from Pentad Analysis of DOE ARM Field Observations and NARR
Authors: Ruiz-Barradas Alfredo , Nigam Sumant 
Published: October 2012

Abstract
The Department of Energy Atmospheric Radiation Measurement Program (ARM) Southern Great Plains (SGP) site data are analyzed to provide insight into atmosphere–land surface interactions generating summertime precipitation variability. Pentad-averaged (5 days) data are analyzed; the average is long enough to suppress synoptic variability but sufficiently short to resolve atmosphere–land surface interactions. Intercomparison with the precipitation-assimilating North American Regional Reanalysis (NARR) helps with in-depth investigation of the processes. The analysis seeks to ascertain the process sequence, especially the role of evapotranspiration and soil-moisture–radiation feedbacks in the generation of regional precipitation variability at this temporal scale.
Transported moisture dominates over evapotranspiration in precipitation variability over the region, from both magnitude of the contribution to regional water balance and its apparent temporal lead at pentad resolution. Antecedent and contemporaneous evapotranspiration are found to be negatively correlated with precipitation, albeit statistically insignificant; only lagging correlations are positive, peaking at 2-pentad lag following precipitation, substantiating the authors’ characterization of the water balance over SGP, and extending the authors’ previous findings on the dominance of moisture flux convergence in generating precipitation variability at monthly scales.
Precipitation episodes are linked with net negative surface radiation anomalies (i.e., with an energy-deprived land surface state that cannot fuel evapotranspiration), ruling out radiatively driven positive feedback on precipitation. Although the net longwave signal is positive because of a colder land surface (less upward terrestrial radiation), it is more than offset by the cloudiness-related reduction in downward shortwave radiation. Thus, ARM (NARR) data do not support the soil-moisture–precipitation feedback hypothesis over the SGP at pentad time scales; however, it may work at subpentad resolution and over other regions.