bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Characterization of Extraintestinal Escherichia coli Isolates in Japan: Relationship between Sequence Types and Mutation Patterns of Quinolone Resistance-Determining Regions Analyzed by Pyrosequencing
Authors: Aoike Nozomi , Saga Tomoo , Sakata Ryuji , Yoshizumi Ayumi , Kimura Soichiro , Iwata Morihiro , Yoshizawa Sadako , Sugasawa Yasuyuki , Ishii Yoshikazu , Yamaguchi Keizo , Tateda Kazuhiro 
Published: March 2013

ABSTRACT

Infection from fluoroquinolone-resistant
Enterobacteriaceae
is an increasing health problem worldwide. In the present study, we developed a pyrosequencing-based high-throughput method for analyzing the nucleotide sequence of the quinolone resistance-determining regions (QRDRs) of
gyrA
and
parC
. By using this method, we successfully determined the QRDR sequences of 139 out of 140 clinical
Escherichia coli
isolates, 28% of which were nonsusceptible to ciprofloxacin. Sequence results obtained by the pyrosequencing method were in complete agreement with those obtained by the Sanger method. All fluoroquinolone-resistant isolates (
n
= 35; 25%) contained mutations leading to three or four amino acid substitutions in the QRDRs. In contrast, all isolates lacking a mutation in the QRDR (
n
= 81; 57%) were susceptible to ciprofloxacin, levofloxacin, and nalidixic acid. The
qnr
determinants, namely, the
qnrA
,
qnrB
, and
qnrS
genes, were not detected in the isolates, and the
aac(6
′
)-Ib-cr
gene was detected in 2 (1.4%) of the isolates. Multilocus sequence typing of 34 randomly selected isolates revealed that sequence type 131 (ST131) (
n
= 7; 20%) is the most prevalent lineage and is significantly resistant to quinolones (
P
< 0.01). The genetic background of quinolone-susceptible isolates seemed more diverse, and interestingly, neighboring STs of ST131 in the phylogenetic tree were all susceptible to ciprofloxacin. In conclusion, our investigation reveals the relationship between fluoroquinolone resistance caused by mutations of QRDRs and the population structure of clinical extraintestinal
E. coli
isolates. This high-throughput method for analyzing QRDR mutations by pyrosequencing is a powerful tool for epidemiological studies of fluoroquinolone resistance in bacteria.
Broad-Range Direct Detection and Identification of Fungi by Use of the PLEX-ID PCR-Electrospray Ionization Mass Spectrometry (ESI-MS) System
Authors: Simner Patricia J. , Uhl James R. , Hall Leslie , Weber Michelle M. , Walchak Robert C. , Buckwalter Seanne , Wengenack Nancy L. 
Published: March 2013

ABSTRACT
The PLEX-ID system is a novel technology that couples PCR amplification and electrospray ionization-mass spectrometry to identify pathogens directly in clinical specimens. The analytical performance of the PLEX-ID Broad Fungal assay was compared with that of traditional culture identification by using 91 characterized fungal culture isolates (64 manufacturer-claimed and 27 nonclaimed organisms) and directly by using 395 respiratory specimens. Discordant results were resolved by D2 large-subunit ribosomal DNA fungal sequencing. Environmental studies were performed to monitor for potential contamination. The PLEX-ID Broad Fungal assay correctly identified 95.6% (87/91) and 81.3% (74/91) of the culture isolates to the genus and species levels, respectively. Of the manufacturer-claimed organisms, 100% (64/64) and 92.2% (59/64) were correctly identified to the genus and species levels, respectively. Direct analysis of respiratory specimens resulted in 67.6% (267/395) and 66.6% (263/395) agreement with culture results to the genus and species levels, respectively, with 16.2% (64/395) of the results discordant with culture and 16.2% (64/395) not detected by the system. The majority (>95%) of the isolates not detected directly by the PLEX-ID system ultimately grew in low quantities in culture (≤20 colonies). In 20.3% (35/172) of the respiratory specimens where no growth was observed in culture, the PLEX-ID system identified a fungus, suggesting a potential increase in sensitivity over culture in some instances. The PLEX-ID system provides a rapid method for the detection of a broad array of fungi directly in respiratory specimens and has the potential of impacting turnaround times and patient care by reducing the need to wait for the growth of an organism in culture.
Streptococcus anginosusgroup and osteomyelitis: a single centre clinical experience
Authors: Griffin Allen Thomas , Timbrook Tristan , Harting Julie , Christensen Diana 
Published: March 2013

AbstractPurposeThe Streptococcus anginosus group comprises three species of bacteria classified within the viridans streptococci. This group is known for abscess formation and endocarditis. While a variety of sites in the body claim anginosus streptococci as an agent of infection, osteomyelitis is unusual. The objective of this study was to describe a series of patients with osteomyelitis due to S anginosus group pathogens in terms of demographics, comorbidities, presentation and outcomes.Study designWe reviewed our database for cases of osteomyelitis caused by S anginosus organisms. Data described included demographics, comorbidities, site of infection, route of infection (haematogenous versus contiguous), laboratory data and course.Results11 patients with S anginosus group osteomyelitis were identified. All cases arose from a contiguous anatomical site, with the exception of one haematogenous case. Five instances were related to foot osteomyelitis while three, two and one case, respectively, were related to mandibular, cranial and vertebral osteomyelitis. Seventy-five per cent of patients had associated abscesses. The mean length of antibiotic treatment was 10.9 weeks. One patient failed therapy while four others relapsed.ConclusionsOsteomyelitis due to the S anginosus group is uncommonly reported. Our case series illustrates the virulence of these organisms in the context of osteomyelitis and the importance of aggressive management.
Evidence of Eocene high-temperature/high-pressure metamorphism of ophiolitic rocks and granitoid intrusion related to Neotethyan subduction processes (Doğanşehir area, SE Anatolia)
Authors: Karaoğlan Fatİh , Parlak Osman , Robertson Alastair , Thöni Martin , Klötzli Urs , Koller Friedrich , Okay Aral İ. 
Published: March 2013

Abstract
New data for regionally important granulite facies metaophiolitic rocks and cross-cutting granitoids rocks are presented and discussed. The high-temperature/high-pressure Berit metaophiolite is cut by unmetamorphosed Eocene (51–45 Ma) granitoid rocks. The highest metamorphic grade occurs in blocks of mafic granulites. Enveloping amphibolite facies rocks reflect retrograde metamorphism related to exhumation. Sm–Nd (pyroxene–garnet–amphibole–whole rock) isochron ages of 52–50 Ma for the granulite facies rocks are interpreted to represent the time of cooling of the granulite facies rocks. The over-riding Malatya metamorphic unit to the north is also intruded by Eocene granitoid rocks. The granulite facies metamorphism of the meta-ophiolitic rocks is inferred to have formed in the roots of an Eocene magmatic arc, with accentuated heat flow being provided by subduction of a spreading ridge, or rupture of the subducting slab. The high-temperature/high-pressure metamorphism was followed by exhumation, as indicated by field structural relations and the evidence of retrograde metamorphism. The Eocene arc magmatism can best be explained by northward subduction of the Southern Neotethys, which persisted after the time of latest Cretaceous regional ophiolite emplacement until the collision of the Eurasian (Anatolian) and Arabian continents during the Early–Mid Miocene. Subsequent Plio-Quaternary left-lateral strike-slip strongly affected the area.

Supplementary-material:

Four supplementary tables giving the whole rock geochemistry of the granitoids, mineral geochemistry of the granulite facies rocks, LA-MC-ICP-MS zircon U–Pb data belonging to granitoids and Sm–Nd data belonging to granulite facies rocks and two documents giving the detailed analytical procedures and detailed petrography of the granitoids are available at
www.geolsoc.org.uk/SUP18588
The Proteasome Inhibitor Carfilzomib Functions Independently of p53 to Induce Cytotoxicity and an Atypical NF-κB Response in Chronic Lymphocytic Leukemia Cells
Authors: Gupta Sneha V. , Hertlein Erin , Lu Yanhui , Sass Ellen J. , Lapalombella Rosa , Chen Timothy L. , Davis Melanie E. , Woyach Jennifer A. , Lehman Amy , Jarjoura David , Byrd John C. , Lucas David M. 
Published: March 2013

Abstract
Purpose: The proteasome consists of chymotrypsin-like (CT-L), trypsin-like, and caspase-like subunits that cleave substrates preferentially by amino acid sequence. Proteasomes mediate degradation of regulatory proteins of the p53, Bcl-2, and nuclear factor-κB (NF-κB) families that are aberrantly active in chronic lymphocytic leukemia (CLL). CLL remains an incurable disease, and new treatments are especially needed in the relapsed/refractory setting. We therefore investigated the effects of the proteasome inhibitor carfilzomib (CFZ) in CLL cells.
Experimental Design: Tumor cells from CLL patients were assayed in vitro using immunoblotting, real-time polymerase chain reaction, and electrophoretic mobility shift assays. In addition, a p53 dominant-negative construct was generated in a human B-cell line.
Results: Unlike bortezomib, CFZ potently induces apoptosis in CLL patient cells in the presence of human serum. CLL cells have significantly lower basal CT-L activity compared to normal B and T cells, although activity is inhibited similarly in T cells versus CLL. Co-culture of CLL cells on stroma protected from CFZ-mediated cytotoxicity; however, PI3K inhibition significantly diminished this stromal protection. CFZ-mediated cytotoxicity in leukemic B cells is caspase-dependent and occurs irrespective of p53 status. In CLL cells, CFZ promotes atypical activation of NF-κB evidenced by loss of cytoplasmic IκBα, phosphorylation of IκBα, and increased p50/p65 DNA binding, without subsequent increases in canonical NF-κB target gene transcription.
Conclusions: Together, these data provide new mechanistic insights into the activity of CFZ in CLL and support phase I investigation of CFZ in this disease. Clin Cancer Res; 19(9); 2406–19. ©2013 AACR.
Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy
Authors: Ma Chao , Cheung Ann F. , Chodon Thinle , Koya Richard C. , Wu Zhongqi , Ng Charles , Avramis Earl , Cochran Alistair J. , Witte Owen N. , Baltimore David , Chmielowski Bartosz , Economou James S. , Comin-Anduix Begonya , Ribas Antoni , Heath James R. 
Published: March 2013

AbstractAdoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.Significance: A longitudinal functional study of adoptively transferred TCR–engineered lymphocytes yielded revealing snapshots for understanding the changes of antitumor responses over time in ACT immunotherapy of patients with advanced melanoma. Cancer Discov; 3(4); 418–29. ©2013 AACR.See related commentary by Speiser, p. 379This article is highlighted in the In This Issue feature, p. 363
Sox18 Genetically Interacts With VegfC to Regulate Lymphangiogenesis in Zebrafish
Authors: Cermenati Solei , Moleri Silvia , Neyt Christine , Bresciani Erica , Carra Silvia , Grassini Daniela R. , Omini Alice , Goi Michela , Cotelli Franco , François Mathias , Hogan Benjamin M. , Beltrame Monica 
Published: March 2013

Objective—
Lymphangiogenesis is regulated by transcription factors and by growth factor pathways, but their interplay has not been extensively studied so far. We addressed this issue in zebrafish.

Approach and Results—

Mutations in the transcription factor–coding gene
SOX18
and in
VEGFR3
cause lymphedema, and the VEGFR3/Flt4 ligand VEGFC plays an evolutionarily conserved role in lymphangiogenesis. Here, we report a strong genetic interaction between Sox18 and VegfC in the early phases of lymphatic development in zebrafish. Knockdown of
sox18
selectively impaired lymphatic sprouting from the cardinal vein and resulted in defective lymphatic thoracic duct formation. Sox18 and the related protein Sox7 play redundant roles in arteriovenous differentiation. We used a novel transgenic line that enables inducible expression of a dominant-negative mutant form of mouse Sox18 protein. Our data led us to conclude that Sox18 is crucially involved in lymphangiogenesis after arteriovenous differentiation. Combined partial knockdown of
sox18
and
vegfc
, using subcritical doses of specific morpholinos, revealed a synergistic interaction in both venous and lymphatic sprouting from the cardinal vein and greatly impaired thoracic duct formation.

Conclusions—
This interaction suggests a previously unappreciated crosstalk between the growth factor and transcription factor pathways that regulate lymphangiogenesis in development and disease.
Nitroglycerine-Induced Vasodilation for Assessment of Vascular Function
Authors: Maruhashi Tatsuya , Soga Junko , Fujimura Noritaka , Idei Naomi , Mikami Shinsuke , Iwamoto Yumiko , Kajikawa Masato , Matsumoto Takeshi , Hidaka Takayuki , Kihara Yasuki , Chayama Kazuaki , Noma Kensuke , Nakashima Ayumu , Goto Chikara , Higashi Yukihito 
Published: March 2013

Objective—
Nitroglycerine-induced vasodilation has been used as a control test for flow-mediated vasodilation (FMD) to differentiate endothelium-dependent from endothelium-independent response when evaluating endothelial function in humans. Recently, nitroglycerine-induced vasodilation has also been reported to be impaired in patients with atherosclerosis. The purpose of this study was to determine the relationships between nitroglycerine-induced vasodilation and cardiovascular risk factors.

Approach and Results—

We measured nitroglycerine-induced vasodilation and FMD in 436 subjects who underwent health examinations (mean age, 53±19 years; age range, 19–86 years), including patients with cardiovascular diseases. There was a significant relationship between nitroglycerine-induced vasodilation and FMD (
r
=0.42;
P
<0.001). Univariate regression analysis revealed that nitroglycerine-induced vasodilation correlated with age (
r
=−0.34;
P
<0.001), systolic blood pressure (
r
=−0.32;
P
<0.001), diastolic blood pressure (
r
=−0.24;
P
<0.001), heart rate (
r
=−0.21;
P
<0.001), glucose (
r
=−0.23;
P
<0.001), and smoking pack-year (
r
=−0.12;
P
=0.01), as well as Framingham risk score (
r
=−0.30;
P
<0.001). Nitroglycerine-induced vasodilation was significantly smaller in patients with cardiovascular disease than in both subjects with and without cardiovascular risk factors (10.5±5.6% versus 13.7±5.4% and 15.3±4.3%;
P
<0.001, respectively), whereas there was no significant difference in nitroglycerine-induced vasodilation between subjects with and without cardiovascular risk factors. Multivariate analysis revealed that male sex, body mass index, hypertension, diabetes mellitus, baseline brachial artery diameter, and FMD were independent predictors of nitroglycerine-induced vasodilation.

Conclusions—
These findings suggest that nitroglycerine-induced vasodilation may be a marker of the grade of atherosclerosis. FMD should be interpreted as an index of vascular function reflecting both endothelium-dependent vasodilation and endothelium-independent vasodilation in subjects with impaired nitroglycerine-induced vasodilation.
Influence of Crossover on Mortality in a Randomized Study of Revascularization in Patients With Systolic Heart Failure and Coronary Artery Disease
Authors: Doenst Torsten , Cleland John G.F. , Rouleau Jean L. , She Lilin , Wos Stanislaw , Ohman E. Magnus , Krzeminska-Pakula Maria , Airan Balram , Jones Robert H. , Siepe Matthias , Sopko George , Velazquez Eric J. , Racine Normand , Gullestad Lars , Filgueira Jose Luis , Lee Kerry L. 
Published: March 2013

Background—
To assess the influence of therapy crossovers on treatment comparisons and mortality at 5 years in patients with ischemic heart disease and heart failure randomly assigned to medical therapy alone (MED) or to MED and coronary artery bypass graft (CABG) surgery in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.

Methods and Results—

The influence of early crossover (within the first year after randomization) on 5-year mortality was assessed using time-dependent multivariable Cox models. CABG was performed in 65/602 patients (10.8%) assigned to MED, and 55/610 patients (9.0%) assigned to CABG received MED only. Common reasons for crossover from MED to CABG were progressive symptoms or acute decompensation. MED-assigned patients who underwent CABG had lower 5-year mortality than those who received MED only (25% vs 42%; hazard ratio, 0.50; 95% confidence interval, 0.30–0.85;
P
=0.008).The main reason for crossover from CABG to MED was patient/family decision. Five patients did not undergo their assigned CABG within a year but died before receiving surgery without status change. They were deemed crossover to MED. The CABG-to-MED crossover population had higher 5-year mortality compared with those treated with CABG per-protocol (59% vs 33%; hazard ratio, 2.01; 95% confidence interval, 1.36–2.96;
P
<0.001). CABG was associated with lower mortality compared with MED in per-protocol and several time-dependent analyses (all
P
<0.05).

Conclusions—
CABG reduced mortality in both the per-protocol and crossover STICH patient populations. Crossover from assigned therapy, therefore, diminished the impact of CABG on survival in STICH when analyzed by intention to treat.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00023595.
Metabolite Profiling Identifies a Branched Chain Amino Acid Signature in Acute Cardioembolic Stroke
Authors: Kimberly W. Taylor , Wang Yu , Pham Ly , Furie Karen L. , Gerszten Robert E. 
Published: March 2013

Background and Purpose—
There is limited information about changes in metabolism during acute ischemic stroke. The identification of changes in circulating plasma metabolites during cerebral infarction may provide insight into disease pathogenesis and identify novel biomarkers.

Methods—
We performed filament occlusion of the middle cerebral artery of Wistar rats and collected plasma and cerebrospinal fluid 2 hours after the onset of ischemia. Plasma samples from control and patients with acute stroke were also analyzed. All samples were examined using liquid chromatography followed by tandem mass spectrometry. Positively charged metabolites, including amino acids, nucleotides, and neurotransmitters, were quantified using electrospray ionization followed by scheduled multiple reaction monitoring.

Results—

The concentrations of several metabolites were altered in the setting of cerebral ischemia. We detected a reduction in the branched chain amino acids (valine, leucine, isoleucine) in rat plasma, rat cerebrospinal fluid, and human plasma compared with respective controls (16%, 23%, and 17%, respectively;
P
<0.01 for each). In patients, lower branched chain amino acids levels also correlated with poor neurological outcome (modified Rankin Scale, 0–2 versus 3–6;
P
=0.002).

Conclusions—
Branched chain amino acids are reduced in ischemic stroke, and the degree of reduction correlates with worse neurological outcome. Whether branched chain amino acids are in a causal pathway or are an epiphenomenon of ischemic stroke remains to be determined.
Method for Enhancing Real-World Use of a More Affected Arm in Chronic Stroke
Authors: Taub Edward , Uswatte Gitendra , Mark Victor W. , Morris David M. , Barman Joydip , Bowman Mary H. , Bryson Camille , Delgado Adriana , Bishop-McKay Staci 
Published: March 2013

Background and Purpose—
Constraint-induced movement therapy is a set of treatments for rehabilitating motor function after central nervous system damage. We assessed the roles of its 2 main components.

Methods—
A 2×2 factorial components analysis with random assignment was conducted. The 2 factors were type of training and presence/absence of a set of techniques to facilitate transfer of therapeutic gains from the laboratory to the life situation (Transfer Package; TP). Participants (N=40) were outpatients ≥1-year after stroke with hemiparesis. The different treatments, which in each case targeted the more affected arm, lasted 3.5 hours/d for 10 weekdays. Spontaneous use of the more affected arm in daily life and maximum motor capacity of that arm in the laboratory were assessed with the Motor Activity Log and the Wolf Motor Function Test, respectively.

Results—

Use of the TP, regardless of the type of training received, resulted in Motor Activity Log gains that were 2.4 times as large as the gains in its absence (
P
<0.01). These clinical results parallel previously reported effects of the TP on neuroplastic change. Both the TP and training by shaping enhanced gains on the Wolf Motor Function Test (
P
<0.05). The Motor Activity Log gains were retained without loss 1 year after treatment. An additional substudy (N=10) showed that a single component of the TP, weekly telephone contact with participants for 1 month after treatment, doubled Motor Activity Log scores at 6-month follow-up.

Conclusions—
The TP is a method for enhancing both spontaneous use of a more affected arm after chronic stroke and its maximum motor capacity. Shaping enhances the latter.
Cross-border Patients and Informed Choices on Treatment in English and French Law and the Patients’ Rights Directive
Authors: Taylor Simon 
Published: March 2013

Abstract
Developments in European Union law have created rules favourable to cross-border patient movement. However, where national laws on patient rights differ, this may limit movement by creating confusion for patients and by reducing their confidence in seeking treatment abroad. This article examines the extent to which English and French law recognize a patient right to information regarding treatment. In light of the differences between the two systems concerning both the form and the content of the law, highlighted by recent developments in French law, the article then considers whether the Patients’ Rights Directive can provide a framework for coordination of national rules.