bluuebunny/crossref_metadata_2025_split huggingface dataset:
A template‐based approach to semi‐quantitative SPECT myocardial perfusion imaging: Independent of normal databases
Authors: Hughes Tyler , Shcherbinin Sergey , Celler Anna 
Published: June 2011

Purpose:Normal patient databases (NPDs) are used to distinguish between normal and abnormal perfusion in SPECT myocardial perfusion imaging (MPI) and have gained wide acceptance in the clinical environment, yet there are limitations to this approach. This study introduces a template‐based method for semi‐quantitative MPI, which attempts to overcome some of the NPD limitations.Methods:Our approach involves the construction of a 3D digital healthy heart template from the delineation of the patient's left ventricle in the SPECT image. This patient‐specific template of the heart, filled with uniform activity, is then analytically projected and reconstructed using the same algorithm as the original image. Subsequent to generating bulls‐eye maps for the patient image (PB) and the template image (TB), a ratio (PB/TB) is calculated, which produces a reconstruction‐artifact corrected image (CB). Finally, a threshold is used to define defects within CB enabling measurements of the perfusion defect extent (EXT). The SPECT‐based template (TS) measurements were compared to those of a CT‐based “ideal” template (TI). Twenty digital phantoms were simulated: male and female, each with one healthy heart and nine hearts with various defects. Four physical phantom studies were performed modeling a healthy heart and three hearts with different defects. The phantom represented a thorax with spine, lung, and left ventricle inserts. Images were acquired on General Electric's (GE) Infinia Hawkeye SPECT/CT camera using standard clinical MPI protocol. Finally, our method was applied to 14 patient MPI rest/stress studies acquired on the GE Infinia Hawkeye SPECT/CT camera and compared to the results obtained from Cedars‐Sinai's QPS software.Results:In the simulation studies, the true EXT correlated well with the TI (slope = 1.08; offset = −0.40%; r = 0.99) and TS (slope = 0.90; offset = 0.27%; r = 0.99) methods with no significant differences between them. Similarly, strong correlations were measured for EXT obtained from QPS and the template method for patient studies (slope = 0.91; offset = 0.45%; r = 0.98). Mean errors in extent for the TS method using simulation, physical phantom, and patient data were 2.7% ± 2.4%, 0.9% ± 0.5%, 2.0% ± 2.7%, respectively.Conclusions:The authors introduced a method for semi‐quantitative SPECT MPI, which offers a patient‐specific approach to define the perfusion defect regions within the heart, as opposed to the patient‐averaged NPD methodology.
Determination of Pentapeptide Repeat Units in Qnr Proteins by the Structure-Based Alignment Approach
Authors: Park Kwang Seung , Lee Jung Hun , Jeong Da Un , Lee Jae Jin , Wu Xing , Jeong Byeong Chul , Kang Choong-Min , Lee Sang Hee 
Published: June 2011

ABSTRACT
The Qnr proteins belong to the pentapeptide repeat protein family. Despite each pentapeptide repeat unit being an important structural determinant, accurately determining pentapeptide repeat units in the Qnr proteins through sequence-based alignments has been challenging. In the present study, the pentapeptide repeat units of the nine representative Qnr proteins have been precisely determined via the structure-based alignment approach using homology modeling and superposition of their best models.
A Small Amount of Fat Does Not Affect Piperaquine Exposure in Patients with Malaria
Authors: Annerberg Anna , Lwin Khin Maung , Lindegardh Niklas , Khrutsawadchai Sakchai , Ashley Elizabeth , Day Nicholas P. J. , Singhasivanon Pratap , Tarning Joel , White Nicholas J. , Nosten François 
Published: June 2011

ABSTRACT

Dihydroartemisinin-piperaquine is a new, highly effective, and well-tolerated combination treatment for uncomplicated falciparum malaria. The lipophilic characteristic of piperaquine suggests that administration together with fat will increase the oral bioavailability of the drug, and this has been reported for healthy volunteers. This pharmacokinetic study monitored 30 adult patients with uncomplicated falciparum malaria for 4.5 months to evaluate the effects of the concomitant intake of fat on the total piperaquine exposure. The fixed-drug combination of dihydroartemisinin-piperaquine was given with water to fasting patients (
n
= 15) or was coadministered with 200 ml milk containing 6.4 g fat (
n
= 15). The drug combination was generally well tolerated, and there were no severe adverse effects reported for either group during the study. Total piperaquine exposure (area under the concentration-time curve from zero to infinity [AUC
0-∞
]; results are given as medians [ranges]) were not statistically different between fed (29.5 h · μg/ml [20.6 to 58.7 h · μg/ml]) and fasting (23.9 h · μg/ml [11.9 to 72.9 h · μg/ml]) patients, but the interindividual variation was reduced in the fed group. Overall, none of the pharmacokinetic parameters differed statistically between the groups. Total piperaquine exposure correlated well with the day 7 concentrations in the fasted group, but the fed group showed a poor correlation. In conclusion, the coadministration of 6.4 g fat did not have any significant effect on piperaquine pharmacokinetics in the treatment of uncomplicated malaria.
A High-Throughput Screening Assay for Inhibitors of Bacterial Motility Identifies a Novel Inhibitor of the Na+-Driven Flagellar Motor and Virulence Gene Expression in Vibrio cholerae
Authors: Rasmussen Lynn , White E. Lucile , Pathak Ashish , Ayala Julio C. , Wang Hongxia , Wu Jian-He , Benitez Jorge A. , Silva Anisia J. 
Published: June 2011

ABSTRACTNumerous bacterial pathogens, particularly those that colonize fast-flow areas in the bladder and gastrointestinal tract, require motility to establish infection and spread beyond the initially colonized tissue.Vibrio choleraestrains of serogroups O1 and O139, the causative agents of the diarrheal illness cholera, express a single polar flagellum powered by sodium motive force and require motility to colonize and spread along the small intestine. Therefore, motility may be an attractive target for small molecules that can prevent and/or block the infective process. In this study, we describe a high-throughput screening (HTS) assay to identify small molecules that selectively inhibit bacterial motility. The HTS assay was used to screen an ∼8,000-compound structurally diverse chemical library for inhibitors ofV. choleraemotility. The screen identified a group of quinazoline-2,4-diamino analogs that completely suppressed motility without affecting the growth rate in broth. A further study on the effects of one analog, designated Q24DA, showed that it induces a flagellated but nonmotile (Mot−) phenotype and is specific for the Na+-driven flagellar motor of pathogenicVibriospecies. A mutation conferring phenamil-resistant motility did not eliminate inhibition of motility by Q24DA. Q24DA diminished the expression of cholera toxin and toxin-coregulated pilus as well as biofilm formation and fluid secretion in the rabbit ileal loop model. Furthermore, treatment ofV. choleraewith Q24DA impacted additional phenotypes linked to Na+bioenergetics, such as the function of the primary Na+pump, Nqr, and susceptibility to fluoroquinolones. The above results clearly show that the described HTS assay is capable of identifying small molecules that specifically block bacterial motility. New inhibitors such as Q24DA may be instrumental in probing the molecular architecture of the Na+-driven polar flagellar motor and in studying the role of motility in the expression of other virulence factors.
Increasing Chloramphenicol Resistance in Streptococcus pneumoniae Isolates from Papua New Guinean Children with Acute Bacterial Meningitis
Authors: Manning Laurens , Laman Moses , Greenhill Andrew R. , Michael Audrey , Siba Peter , Mueller Ivo , Davis Timothy M. E. 
Published: June 2011

ABSTRACT

In Papua New Guinean (PNG) children with acute bacterial meningitis (ABM), all
Haemophilus influenzae
isolates were resistant to chloramphenicol. Although
Streptococcus pneumoniae
isolates had a median chloramphenicol MIC of 3 μg/ml, it was ≥4 μg/ml in 42.8%, and the likelihood of an area under the 24-hour concentration-time curve/MIC ratio of >100 h at a MIC of ≥4 μg/ml was approximately 50%. All isolates were ceftriaxone sensitive. These data support ceftriaxone rather than conventional chloramphenicol for all PNG children with suspected ABM.
Characterization of Salmonella enterica Serovar Typhimurium Isolates Harboring a Chromosomally Encoded CMY-2 β-Lactamase Gene Located on a Multidrug Resistance Genomic Island
Authors: Shahada Francis , Sekizuka Tsuyoshi , Kuroda Makoto , Kusumoto Masahiro , Ohishi Daiki , Matsumoto Atsuko , Okazaki Hizuru , Tanaka Kiyoshi , Uchida Ikuo , Izumiya Hidemasa , Watanabe Haruo , Tamamura Yukino , Iwata Taketoshi , Akiba Masato 
Published: June 2011

ABSTRACT

Since 2004, extended-spectrum cephalosporin (ESC)-resistant
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) isolates have been detected from cattle in the northern major island of Japan, Hokkaido. Resistance to ESCs was found to be mediated by CMY-2 type β-lactamase among 22 epidemiologically unrelated isolates showing indistinguishable pulsed-field gel electrophoresis patterns. Southern blot analysis using I-CeuI-digested genomic DNA demonstrated that the CMY-2 β-lactamase gene (
bla
CMY-2
) was integrated in a 2.5-Mb chromosomal fragment. Genetic analysis of
S
. Typhimurium isolate L-3553 indicated that
bla
CMY-2
was located on a unique 125-kb genomic island, GI-VII-6, which consists of 140 open reading frames. Pairwise alignment of GI-VII-6 and
Escherichia coli
plasmid pAR060302 (size, 167 kb) revealed that a large proportion of GI-VII-6 (99%) shows a high sequence similarity (>99%) with pAR060302. GI-VII-6 contains 11 antimicrobial resistance genes including
sul1
,
qacE
Δ
1
,
aadA2
, and
dfrA12
in the
aadA2
region;
sugE1
and
bla
CMY-2
in the
bla
CMY-2
region; and
sul2
,
strA
,
strB
,
tet
(A), and
floR
in the
floR
region. Two directly repeated IS
26
copies were present at both ends of GI-VII-6. Junction regions of GI-VII-6 were flanked by an 8-bp direct repeat, indicating that GI-VII-6 was acquired by transposition involving IS
26
transposase. PCR scanning revealed that the overall structure of GI-VII-6 was almost identical in the 22 isolates. Phylogenetic analysis suggested that
S
. Typhimurium isolates harboring GI-VII-6 belong to a different genomic lineage than other whole-genome-sequenced
S
. Typhimurium strains. These data indicate that a particular clone of
S
. Typhimurium harboring GI-VII-6 has spread among the cattle population in Hokkaido, Japan.
Lack of an Effect of Standard and Supratherapeutic Doses of Linezolid on QTc Interval Prolongation
Authors: Damle Bharat , LaBadie Robert R. , Cuozzo Cheryl , Alvey Christine , Choo Heng Wee , Riley Steve , Kirby Deborah 
Published: June 2011

ABSTRACT

A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were <10 ms, which indicates an absence of clinically significant QTc prolongation. At 2 and 4 h after the moxifloxacin dose, corresponding to the population
T
max
, the lower bound of the two-sided 90% CI for QTcF when comparing moxifloxacin to placebo was >5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted.
Infection of Polarized Airway Epithelial Cells by Normal and Small-Colony Variant Strains of Staphylococcus aureus Is Increased in Cells with Abnormal Cystic Fibrosis Transmembrane Conductance Regulator Function and Is Influenced by NF-κB
Authors: Mitchell Gabriel , Grondin Gilles , Bilodeau Ginette , Cantin André M. , Malouin François 
Published: June 2011

ABSTRACT

The infection of nonphagocytic host cells by
Staphylococcus aureus
and more particularly by small-colony variants (SCVs) may contribute to the persistence of this pathogen in the lungs of cystic fibrosis (CF) patients. The development of chronic infections is also thought to be facilitated by the proinflammatory status of CF airways induced by an activation of NF-κB. The aim of this study was to compare the infection of non-CF and CF-like airway epithelial cells by
S. aureus
strains (normal and SCVs) and to determine the impact of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and NF-κB on the infection level of these cells by
S. aureus
. We developed an
S. aureus
infection model using polarized airway epithelial cells grown at the air-liquid interface and expressing short hairpin RNAs directed against CFTR to mimic the CF condition. A pair of genetically related CF coisolates with the normal and SCV phenotypes was characterized and used. Infection of both cell lines (non-CF and CF-like) was more productive with the SCV strain than with its normal counterpart. However, both normal and SCV strains infected more CF-like than non-CF cells. Accordingly, inhibition of CFTR function by CFTR
inh
-172 increased the
S. aureus
infection level. Experimental activation of NF-κB also increased the level of infection of polarized pulmonary epithelial cells by
S. aureus
, an event that could be associated with that observed when CFTR function is inhibited or impaired. This study supports the hypothesis that the proinflammatory status of CF tissues facilitates the infection of pulmonary epithelial cells by
S. aureus
.
Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells
Authors: Benoit Vivian M. , Fischer Joshua R. , Lin Yi-Pin , Parveen Nikhat , Leong John M. 
Published: June 2011

ABSTRACT

After transmission by an infected tick, the Lyme disease spirochete,
Borrelia burgdorferi
sensu lato, colonizes the mammalian skin and may disseminate systemically. The three major species of Lyme disease spirochete—
B. burgdorferi
sensu stricto,
B. garinii
, and
B. afzelii
—are associated with different chronic disease manifestations. Colonization is likely promoted by the ability to bind to target tissues, and Lyme disease spirochetes utilize multiple adhesive molecules to interact with diverse mammalian components. The allelic variable surface lipoprotein decorin binding protein A (DbpA) promotes bacterial binding to the proteoglycan decorin and to the glycosaminoglycan (GAG) dermatan sulfate. To assess allelic variation of DbpA in GAG-, decorin-, and cell-binding activities, we expressed
dbpA
alleles derived from diverse Lyme disease spirochetes in
B. burgdorferi
strain B314, a noninfectious and nonadherent strain that lacks
dbpA
. Each DbpA allele conferred upon
B. burgdorferi
strain B314 the ability to bind to cultured kidney epithelial (but not glial or endothelial) cells, as well as to purified decorin and dermatan sulfate. Nevertheless, allelic variation of DbpA was associated with dramatic differences in substrate binding activity. In most cases, decorin and dermatan sulfate binding correlated well, but DbpA of
B. afzelii
strain VS461 promoted differential binding to decorin and dermatan sulfate, indicating that the two activities are separable. DbpA from a clone of
B. burgdorferi
strain N40 that can cause disseminated infection in mice displayed relatively low adhesive activity, indicating that robust DbpA-mediated adhesive activity is not required for spread in the mammalian host.
Discrepancy between participants' understanding and desire to know in informed consent: are they informed about what they really want to know?
Authors: Koh Jiwon , Goh Eurah , Yu Kyung-Sang , Cho Belong , Yang Jeong Hee 
Published: June 2011

BackgroundParticipants' understanding of clinical trials is important in informed consent. However, little is known about what information participants really want to know.AimsTo demonstrate the existence of a discrepancy between participants' understanding and their desire to know.MethodsThe participants in clinical trials at Seoul National University Hospital were surveyed. The survey consisted of 11 statements based on the essential elements of informed consent. The participants gave two responses to each statement on a five-point Likert scale to rate their subjective understanding and desire to know, respectively. Information discrepancy was defined as the difference between these two ratings: if understanding exceeded desire to know for a particular item, it was defined as ‘over-informed’; if desire to know exceeded understanding for a particular item, it was defined as ‘under-informed’.ResultsParticipants reported good understanding of ‘voluntariness’, ‘duration’, ‘study involves research’ and poor understanding of ‘confidentiality’, ‘compensation’, ‘benefits’, ‘procedures’ and ‘risks or discomforts’. For ‘risks or discomforts’, ‘who to contact’, ‘voluntariness’, ‘duration’ and ‘procedures’, participants reported high desire to know compared with ‘confidentiality’, ‘purpose’, ‘study involves research’ and ‘benefits’. The elements ‘study involves research’, ‘voluntariness’, ‘duration’, ‘purpose’ and ‘who to contact’ were over-informed, while ‘compensation’, ‘risks or discomforts’, ‘procedures’, ‘confidentiality’ and ‘benefits’ were under-informed. Participants over 50 years of age, those without a college education and those whose participation was less voluntary were relatively less informed about the clinical trials.ConclusionsAn information discrepancy was observed between the participants' understanding and their desire to know. By putting more emphasis on under-informed elements, the quality of informed consent could be improved.
Characteristics of epileptic episodes in UK dog breeds: an epidemiological approach
Authors: Short A. D. , Dunne A. , Lohi H. , Boulton S. , Carter S. D. , Timofte D. , Ollier W. E. R. 
Published: June 2011

In this study, previously unreported cohort characteristics and seizure patterns for canine epilepsy were identified from a series of UK‐based epileptic dogs containing 1260 cases from 79 known pedigree breeds and a group of crossbreed dogs.
Palaeozoic–Mesozoic history of SE Asia
Authors: Metcalfe Ian 
Published: June 2011

Abstract
SE Asia comprises a collage of Gondwana-derived continental blocks assembled by the closure of multiple Tethyan and back-arc ocean basins now represented by suture zones. Two major biogeographical boundaries, the Late Palaeozoic Gondwana–Cathaysia divide and the Cenozoic-Recent Australia–Asia divide (Wallace Line) are present. Palaeozoic and Mesozoic evolution involved the rifting and separation of three collages of continental terranes from eastern Gondwana and the opening and closure of three successive ocean basins, the Palaeo-Tethys (Devonian–Triassic), Meso-Tethys (Permian–Cretaceous) and Ceno-Tethys (Late Triassic–Cenozoic). This led to the opening and closing of ocean gateways and provision of shallow-marine and terrestrial land bridges and stepping-stones for biotic migration. The SE Asia core (Sundaland) comprises a western Sibumasu block, an eastern Indochina–East Malaya block, and the Sukhothai Island Arc terrane between. The Jinghong, Nan-Uttaradit and Sra Kaeo sutures represent the Sukhothai closed back-arc basin. The Palaeo-Tethys is represented by the Changning-Menglian, Chiang Mai/Inthanon and Bentong-Raub suture zones. The West Sumatra and West Burma blocks were accreted to the Sundaland core in the Late Permian–Early Triassic. SW Borneo and/or East Java–West Sulawesi are now identified as the missing ‘Argoland’ that separated from NW Australia in the Jurassic and accreted to SE Sundaland in the Cretaceous.
The ICOS/ICOSL Pathway Is Required for Optimal Antitumor Responses Mediated by Anti–CTLA-4 Therapy
Authors: Fu Tihui , He Qiuming , Sharma Padmanee 
Published: June 2011

Abstract
The anti–CTL-associated antigen 4 (anti–CTLA-4) antibody ipilimumab is the first agent to show improved survival in a randomized phase III trial that enrolled patients with metastatic melanoma. Studies are ongoing to identify mechanisms that elicit clinical benefit in the setting of anti–CTLA-4 therapy. We previously reported that treated patients had an increase in the frequency of T cells expressing the inducible costimulator (ICOS) molecule, a T-cell–specific molecule that belongs to the CD28/CTLA-4/B7 immunoglobulin superfamily. ICOS and its ligand (ICOSL) have been shown to play diverse roles in T-cell responses such as mediating autoimmunity as well as enhancing the development/activity of regulatory T cells. These seemingly opposing roles have made it difficult to determine whether the ICOS/ICOSL pathway is necessary for antitumor responses. To determine whether the ICOS/ICOSL pathway might play a causal role in the antitumor effects mediated by anti–CTLA-4, we conducted studies in ICOS-sufficient and ICOS-deficient mice bearing B16/BL6 melanoma. We show that ICOS+ T cells comprised a population of Th1 cytokine producing and tumor antigen-specific effector cells. Furthermore, in the absence of ICOS, antitumor T-cell responses elicited by anti–CTLA-4 are significantly diminished, thereby impairing tumor rejection. Our findings establish that the ICOS/ICOSL pathway is necessary for the optimal therapeutic effect of anti–CTLA-4, thus implicating this pathway as a target for future combinatorial strategies to improve the efficacy of anti–CTLA-4 therapy. Cancer Res; 71(16); 5445–54. ©2011 AACR.