bluuebunny/crossref_metadata_2025_split huggingface dataset:
Following Oxygen Consumption in Singlet Oxygen Reactions via Changes in Sensitizer Phosphorescence
Authors: Feng Tingting , Grusenmeyer Tod A. , Lupin Max , Schmehl Russell H. 
Published: November 2014

AbstractThis work reports an examination of singlet oxygen reactions with amino acid substrates by a method involving measurement of the change in phosphorescence intensity of the singlet oxygen sensitizer. The sensitizer, a Ru(II) bipyridyl complex covalently linked to pyrene, has long‐lived phosphorescence in N2 purged aqueous solutions (τ0 ~ 20 μs) that is nearly completely quenched by oxygen in aerated solutions. Irradiation of the complex in water containing sub mM concentrations of histidine, tryptophan and methionine results in a dramatic, easily visible increase in the phosphorescence intensity over a period of 10–100 s. Rate constants for singlet oxygen oxidation of each of the substrates can be obtained by using changes in the phosphorescence intensity in initial rate kinetic analysis. Rate constants obtained in this way compare favorably with those reported in the literature. The method represents a very simple approach for obtaining rate constants for singlet oxygen reactions with various substrates and the kinetics can be extended to nonaqueous solvents.
Budesonide/formoterol maintenance and reliever therapy in asthma control: Acute, dose‐related effects and real‐life effectiveness
Authors: Lin Ching‐Hsiung , Hsu Jeng‐Yuan , Hsiao Yi‐Han , Tseng Ching‐Min , Su Vincent Yi‐Fong , Chen Yu‐Hsuan , Yang Sheau‐Ning , Lee Yu‐Chin , Su Kang‐Cheng , Perng Diahn‐Warng 
Published: November 2014

AbstractBackground and objectiveThe efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real‐life effectiveness are seldom reported.MethodsThis multicenter trial enrolled steroid‐naïve, symptomatic asthmatics with baseline exhaled nitric oxide (eNO) of ≥40 ppb. There were 120 eligible patients who were randomized and received a dose of inhaled budesonide/formoterol 320/9 μg (lower dose budesonide/formoterol), 640/18 μg (higher dose budesonide/formoterol (HDBF)), or terbutaline (TERB) 1 mg. Inflammatory cells and mediators in induced sputum, eNO and lung function were measured at baseline and 6 h (acute phase). Subsequently, all patients used BFMRT as real‐life practice for 24 weeks (maintenance phase).ResultsIn the acute phase, the degree of post‐treatment reduction in total eosinophil counts, interleukin‐8 and matrix metalloproteinase‐9 in induced sputum were significantly greater in group HDBF (vs TERB, P < 0.05). The increase in forced expiratory volume in first second (FEV1) in group HDBF was significantly higher (vs LDBF and TERB, P < 0.05) 3 h after dosing. In the maintenance phase, significant improvement of asthma control (presented by eNO, FEV1 and a five‐item asthma control questionnaire) in real‐life settings was observed at 4 weeks and sustained to the end of study. The rate of patients who followed scheduled visits declined over time (87% at week 4 and 42% at week 24).ConclusionsBudesonide/formoterol as reliever exerts acute, dose‐related anti‐inflammatory effects and FEV1 improvement in symptomatic asthmatics. BFMRT is effective in asthma control. However, the decrease in long‐term follow‐up rate remains an issue to overcome in real‐life settings.
Correlates of Physical Activity in Adults With Rheumatoid Arthritis: A Systematic Review
Authors: Larkin Louise , Kennedy Norelee 
Published: November 2014

Background:Physical activity (PA) is an important component in the management of Rheumatoid Arthritis (RA). To date the correlates of PA have not been thoroughly investigated in the RA population. The aim of this systematic review was to determine the correlates of PA in the adult RA population.Methods:A search of Medline, EMBASE, AMED, CINAHL plus, Pubmed, Web of Science, and the Cochrane Library was conducted. A manual search of reference lists was conducted to compliment the electronic search. Ten studies fulfilled the inclusion criteria and were assessed for methodological quality.Results:Results determined correlates in 4 categories: sociodemographic, physical, psychological and social variables. The variables varied greatly and were inconsistently studied. Changes were noted from a previous review in 2005 in relation to the association between certain variables and PA, including age, gender, disease duration, pain, exercise beliefs and social support.Conclusions:Positive associations with PA were found for motivation, self-efficacy, health perception, and previous PA levels. Negative associations were found for fatigue, a coerced regulation style and certain physiological variables. In addition differences between correlates of PA in the adult RA population and other chronic disease and healthy adult populations have been demonstrated.
Sex Differences in Genetic and Environmental Influences on Percent Body Fatness and Physical Activity
Authors: White Erin , Slane Jennifer D. , Klump Kelly L. , Burt S. Alexandra , Pivarnik Jim 
Published: November 2014

Background:Knowing the extent to which genetic and environmental factors influence percent body fatness (%Fat) and physical activity (PA) would be beneficial, since both are tightly correlated with future health outcomes. Thus, the purpose was to evaluate sex differences in genetic and environmental influences on %Fat and physical activity behavior in male and female adolescent twins.Methods:Subjects were adolescent (age range 8.3 to 16.6 yr) twins. %Fat (n = 518 twins) was assessed by bioelectrical impedance analysis (BIA) and PA (n = 296 twins) was measured using 3-Day PA Recall. Each activity was converted to total MET-minutes. Univariate twin models were used to examine sex differences in genetic and environmental factors influencing %Fat and PA.Results:%Fat was influenced by genetic effects in both boys and girls (88% and 90%, respectively), with slightly higher heritability estimates for girls. PA was influenced solely by environmental effects for both sexes with higher shared environmental influences in boys (66%) and higher nonshared effects in girls (67%).Conclusions:When developing interventions to increase PA in adolescents, it is important to consider the environment in which it takes place as it is the primary contributor to PA levels.
Patterns and Determinants of Physical Activity Among Saudi Adolescents
Authors: Al-Hazzaa Hazzaa M. , Alahmadi Mohammad A. , Al-Sobayel Hana I. , Abahussain Nada A. , Qahwaji Dina M. , Musaiger Abdulrahman O. 
Published: November 2014

Background:Few studies have reported comprehensive and valid physical activity (PA) data for Saudi youth. Therefore, the purpose of this study was to examine patterns and determinants of PA among Saudi adolescents.Methods:A cross-sectional study was conducted in Saudi secondary schools (15–19 years) during 2009/2010 and used multistage stratified cluster sample (N = 2866, 51.7% females). Weight, height, sedentary behaviors, PA, and dietary habits were assessed.Results:Roughly 44% of males and 20% of females were active (≥ 1 hour/day). Males in public schools were more active than in private schools, whereas the opposite was true for females. Females exercise mostly at home, whereas males exercise at public places. The majority of females exercise alone or with relatives, whereas males largely exercise with friends. Males were active for health and recreation whereas females were active for weight loss and recreation. Lack of time was the primary reason for inactivity in both sexes. The predictors of total PA time were gender, intakes of fruit, milk, energy drinks and vegetables and waist/height ratio (R2 = 0.145).Conclusions:The high inactivity levels, especially among females, are of great concern. Promotion of active living among youth should be a national public health priority.
First Report of a Clinical, Multidrug-Resistant Enterobacteriaceae Isolate Coharboring Fosfomycin Resistance Gene
fosA3
and Carbapenemase Gene
bla
KPC-2
on the Same Transposon, Tn
1721
Authors: Li Gang , Zhang Ying , Bi Dexi , Shen Pinghua , Ai Fuqi , Liu Hong , Tian Yueru , Ma Yiming , Wang Bei , Rajakumar Kumar , Ou Hong-Yu , Jiang Xiaofei 
Published: November 2014

ABSTRACT

In order to understand the genetic background and dissemination mechanism of carbapenem resistance and fosfomycin resistance in
Enterobacteriaceae
isolates, we studied a clinical
Escherichia coli
strain HS102707 isolate and an
Enterobacter aerogenes
strain HS112625 isolate, both of which were resistant to carbapenem and fosfomycin and positive for the
bla
KPC-2
and
fosA3
genes. In addition, a clinical
Klebsiella pneumoniae
strain HS092839 isolate which was resistant to carbapenem was also studied. A 70-kb plasmid was successfully transferred to recipient
E. coli
J53 by a conjugation test. PCR and Southern blot analysis showed that
bla
KPC-2
was located on this plasmid. The complete sequence of pHS102707 showed that this plasmid belongs to the P11 subfamily (IncP1) and has a replication gene, several plasmid-stable genes, an intact type IV secretion system gene cluster, and a composite transposon Tn
1721
-Tn
3
that harbored
bla
KPC-2
. Interestingly, a composite IS
26
transposon carrying
fosA3
was inserted in the Tn
1721-tnpA
gene in pHS102707 and pHS112625, leading to the disruption of Tn
1721-tnpA
and the deletion of Tn
1721-tnpR
. However, only IS
26
with a truncated Tn
21-tnpR
was inserted in pHS092839 at the same position. To our knowledge, this is the first report of
fosA3
and
bla
KPC-2
colocated in the same Tn
1721
-Tn
3
–like composite transposon on a novel IncP group plasmid.
Optimization of a Nucleic Acid-Based Reporter System To Detect Mycobacterium tuberculosis Antibiotic Sensitivity
Authors: Mulvey Matthew C. , Lemmon Margaret , Rotter Stephanie , Lees Jonathan , Einck Leo , Nacy Carol A. 
Published: November 2014

ABSTRACT

We previously reported the development of a prototype antibiotic sensitivity assay to detect drug-resistant
Mycobacterium tuberculosis
using infection by mycobacteriophage to create a novel nucleic acid transcript, a surrogate marker of mycobacterial viability, detected by reverse transcriptase PCR (M. C. Mulvey et al., mBio
3:
e00312-11, 2012). This assay detects antibiotic resistance to all drugs, even drugs for which the resistance mechanism is unknown or complex: it is a phenotypic readout using nucleic acid detection. In this report, we describe development and characteristics of an optimized reporter system that directed expression of the RNA cyclase ribozyme, which generated circular RNA through an intramolecular splicing reaction and led to accumulation of a new nucleic acid sequence in phage-infected bacteria. These modifications simplified the assay, increased the limit of detection from 10
4
to <10
2
M. tuberculosis
cells, and correctly identified the susceptibility profile of
M. tuberculosis
strains exposed for 16 h to either first-line or second-line antitubercular drugs. In addition to phenotypic drug resistance or susceptibility, the assay reported streptomycin MICs and clearly detected 10% drug-resistant cells in an otherwise drug-susceptible population.
Evaluation of Pyrosequencing for Detecting Extensively Drug-Resistant Mycobacterium tuberculosis among Clinical Isolates from Four High-Burden Countries
Authors: Ajbani Kanchan , Lin Shou-Yean Grace , Rodrigues Camilla , Nguyen Duylinh , Arroyo Francine , Kaping Janice , Jackson Lynn , Garfein Richard S. , Catanzaro Donald , Eisenach Kathleen , Victor Thomas C. , Crudu Valeru , Gler Maria Tarcela , Ismail Nazir , Desmond Edward , Catanzaro Antonino , Rodwell Timothy C. 
Published: November 2014

ABSTRACT

Reliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance in
Mycobacterium tuberculosis
isolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identify
M. tuberculosis
(via the IS
6110
marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets included
katG
, the
inhA
promoter and the
ahpC-oxyR
intergenic region for isoniazid (INH) resistance; the
rpoB
core region for rifampin (RIF) resistance;
gyrA
for fluoroquinolone (FQ) resistance; and
rrs
for amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.
Overproduction of the MtrCDE Efflux Pump in Neisseria gonorrhoeae Produces Unexpected Changes in Cellular Transcription Patterns
Authors: Ohneck Elizabeth A. , Goytia Maira , Rouquette-Loughlin Corinne E. , Joseph Sandeep J. , Read Timothy D. , Jerse Ann E. , Shafer William M. 
Published: November 2014

ABSTRACT

The global consequence of drug efflux gene overexpression in bacteria has not been specifically analyzed because strains showing high-level expression typically have mutations in genes encoding regulatory proteins that control other genes. Results from a transcriptional profiling study performed with a strain of
Neisseria gonorrhoeae
that is capable of high-level transcription of the
mtrCDE
efflux pump operon independently of control by cognate regulatory proteins revealed that its overexpression has ramifications for systems other than drug efflux.
Novel Rate-Area-Shape Modeling Approach To Quantify Bacterial Killing and Regrowth for
In Vitro
Static Time-Kill Studies
Authors: Cheah Soon-Ee , Li Jian , Nation Roger L. , Bulitta Jürgen B. 
Published: November 2014

ABSTRACT

In vitro
static concentration time-kill (SCTK) studies are a cornerstone for antibiotic development and designing dosage regimens. However, mathematical approaches to efficiently model SCTK curves are scarce. The currently used model-free, descriptive metrics include the log
10
change in CFU from 0 h to a defined time and the area under the viable count versus time curve. These metrics have significant limitations, as they do not characterize the rates of bacterial killing and regrowth and lack sensitivity. Our aims were to develop a novel rate-area-shape modeling approach and to compare, against model-free metrics, its relative ability to characterize the rate, extent, and timing of bacterial killing and regrowth from SCTK studies. The rate-area-shape model and the model-free metrics were applied to data for colistin and doripenem against six
Acinetobacter baumannii
strains. Both approaches identified exposure-response relationships from 0.5- to 64-fold the MIC. The model-based approach estimated an at least 10-fold faster killing by colistin than by doripenem at all multiples of the MIC. However, bacterial regrowth was more extensive (by 2 log
10
) and occurred approximately 3 h earlier for colistin than for doripenem. The model-free metrics could not consistently differentiate the rate and extent of killing between colistin and doripenem. The time to 2 log
10
killing was substantially faster for colistin. The rate-area-shape model was successfully implemented in Excel. This new model provides an improved framework to distinguish between antibiotics with different rates of bacterial killing and regrowth and will enable researchers to better characterize SCTK experiments and design subsequent dynamic studies.
Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus
Authors: Arinuma Yoshiyuki , Kikuchi Hirotoshi , Wada Tatsuhiko , Nagai Tatsuo , Tanaka Sumiaki , Oba Hiroshi , Hirohata Shunsei 
Published: November 2014

BackgroundManifestations in neuropsychiatric systemic lupus erythematosus (NPSLE), especially active diffuse NPSLE syndromes, are some of the most difficult complications of the disease. For the evaluation and the diagnosis of central nervous system manifestations, including NPSLE, MRI is a very useful tool to detect the various abnormalities. However, the relationship between brain MRI findings and clinical variables has not yet been clarified in patients with diffuse NPSLE.ObjectivesThe aim of this study is to investigate the pathogenesis of diffuse NPSLE, by comparing various parameters such as serum autoantibodies and cytokines in cerebrospinal fluid (CSF) with abnormal findings revealed on brain MRIs in patients with diffuse NPSLE.MethodsFifty-three patients with diffuse NPSLE admitted to our University Hospital from 1992 to 2012 were exhaustively enrolled in this study. Their medical charts and brain MRI scans were reviewed. The relationship of MRI abnormalities with various parameters was analysed.ResultsAs many as 25 of 53 patients (47.2%) had abnormal MRI findings. MRI findings improved after treatment in 10 of 17 patients for whom follow-up studies were available. MRI abnormalities were not correlated with age at the onset of diffuse NPSLE. However, the disease duration of SLE was significantly longer in patients with abnormal MRI findings (p=0.0009). MRI abnormalities were not significantly associated with serum autoantibodies. However, there were significant elevations of the CSF protein level (p=0.0106) and the CSF interleukin 6 level (p=0.0225) in patients with abnormal MRI findings. Patients with MRI abnormalities showed significantly higher overall mortality (p=0.0348).ConclusionsThe results revealed that MRI abnormalities in diffuse NPSLE might be heterogeneous with regard to their reversibility. These data also indicate that patients with diffuse NPSLE and MRI abnormalities have more severe inflammation in the central nervous system related to the activity of diffuse NPSLE, as evidenced by poorer prognosis.
Twist1 Is a Key Regulator of Cancer-Associated Fibroblasts
Authors: Lee Keun-Woo , Yeo So-Young , Sung Chang Ohk , Kim Seok-Hyung 
Published: November 2014

Abstract
Cancer-associated fibroblasts (CAF) are key contributors to malignant progression, but their critical regulators remain largely unknown. In this study, we examined the role of Twist1, a central regulator of epithelial–mesenchymal transition in carcinoma cells, in the transdifferentiation of normal quiescent fibroblasts to CAF and we defined its upstream controls and downstream effectors. Primary human gastric fibroblast and CAF cultures were established from gastrectomy specimens and validated as nontumor cells by somatic mutation analyses. In these cultures, exposure to the proinflammatory cytokine IL6 commonly expressed in tumors was sufficient to induce Twist1 expression in normal fibroblasts and transdifferentiate them into CAFs via STAT3 phosphorylation. In xenograft models, tumor infiltration of Twist1-expressing CAFs was enhanced strongly by ectopic IL6 expression in gastric or breast cancer cells. We found that Twist1 expression was necessary and sufficient for CAF transdifferentiation. Enforced expression of Twist1 in normal fibroblasts was also sufficient to drive CAF marker expression and malignant character in gastric cancer cells both in vitro and in vivo. Conversely, silencing the expression of Twist1 in CAFs abrogated their tumor-promoting properties. Downstream of Twist1, we defined the chemokine CXCL12 as a transcriptional target. Clinically, CXCL12 and Twist1 expression were correlated in CAFs present in gastric tumor specimens. Finally, ectopic expression of Twist1 in normal fibroblasts suppressed premature senescence, whereas Twist1 attenuation accelerated senescence in CAFs. Our findings define Twist1 as a compelling target to deprogram the tumor-supporting features of the cancer microenvironment. Cancer Res; 75(1); 73–85. ©2014 AACR.
Targeting of miR34a–NOTCH1 Axis Reduced Breast Cancer Stemness and Chemoresistance
Authors: Park Eun Young , Chang EunSun , Lee Eun Ji , Lee Hyun-Woo , Kang Hyeok-Gu , Chun Kyung-Hee , Woo Yu Mi , Kong Hyun Kyung , Ko Je Yeong , Suzuki Hiromu , Song Erwei , Park Jong Hoon 
Published: November 2014

Abstract
Human breast cancers include cancer stem cell populations as well as nontumorigenic cancer cells. Breast cancer stem cells have self-renewal capability and are resistant to conventional chemotherapy. miRNAs regulate the expression of many target genes; therefore, dysregulation of miRNAs has been associated with the pathogenesis of human diseases, including cancer. However, a role for miRNA dysregulation in stemness and drug resistance has yet to be identified. Members of the miR34 family are reportedly tumor-suppressor miRNAs and are associated with various human cancers. Our results confirm that miR34a expression was downregulated in MCF7/ADR cells compared with MCF7 cells. We hypothesized that this reduction was due to the p53 (TP53) mutation in MCF7/ADR cells. In this study, we found that primary and mature miR34a were suppressed by treatment with p53 RNAi or the dominant-negative p53 mutant in MCF7 cells. Ectopic miR34a expression reduced cancer stem cell properties and increased sensitivity to doxorubicin treatment by directly targeting NOTCH1. Furthermore, tumors from nude mice treated with miR34a were significantly smaller compared with those of mice treated with control lentivirus. Our research suggests that the ectopic expression of miR34a represents a novel therapeutic approach in chemoresistant breast cancer treatment. Cancer Res; 74(24); 7573–82. ©2014 AACR.
The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer
Authors: Luo Leo Y. , Kim Eejung , Cheung Hiu Wing , Weir Barbara A. , Dunn Gavin P. , Shen Rhine R. , Hahn William C. 
Published: November 2014

Abstract
High-grade serous ovarian cancers (HGSOC) are characterized by widespread recurrent regions of copy-number gain and loss. Here, we interrogated 50 genes that are recurrently amplified in HGSOC and essential for cancer proliferation and survival in ovarian cancer cell lines. FRS2 is one of the 50 genes located on chromosomal region 12q15 that is focally amplified in 12.5% of HGSOC. We found that FRS2-amplified cancer cell lines are dependent on FRS2 expression, and that FRS2 overexpression in immortalized human cell lines conferred the ability to grow in an anchorage-independent manner and as tumors in immunodeficient mice. FRS2, an adaptor protein in the FGFR pathway, induces downstream activation of the Ras–MAPK pathway. These observations identify FRS2 as an oncogene in a subset of HGSOC that harbor FRS2 amplifications.
Implications: These studies identify FRS2 as an amplified oncogene in a subset of HGSOC. FRS2 expression is essential to ovarian cancer cells that harbor 12q15 amplification. Mol Cancer Res; 13(3); 502–9. ©2014 AACR.