bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Phase II Single-Center Study of the Safety of a Single Very High Dose of Liposomal Amphotericin B for Antifungal Prophylaxis in Patients with Acute Myeloid Leukemia
Authors: Annino Luciana , Chierichini Anna , Anaclerico Barbara , Finolezzi Erica , Norata Marianna , Cortese Stefania , Cassetta Maria Iris , Fallani Stefania , Novelli Andrea , Girmenia Corrado 
Published: March 2013

ABSTRACT
Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy.
Establishment of anIn Vitrod-Cycloserine-Synthesizing System by UsingO-Ureido-l-Serine Synthase andd-Cycloserine Synthetase Found in the Biosynthetic Pathway
Authors: Uda Narutoshi , Matoba Yasuyuki , Kumagai Takanori , Oda Kosuke , Noda Masafumi , Sugiyama Masanori 
Published: March 2013

ABSTRACTWe have recently cloned a DNA fragment containing a gene cluster that is responsible for the biosynthesis of an antituberculosis antibiotic,d-cycloserine. The gene cluster is composed of 10 open reading frames, designateddcsAtodcsJ. Judging from the sequence similarity between each putative gene product and known proteins, DcsC, which displays high homology to diaminopimelate epimerase, may catalyze the racemization ofO-ureidoserine. DcsD is similar toO-acetylserine sulfhydrylase, which generatesl-cysteine usingO-acetyl-l-serine with sulfide, and therefore, DcsD may be a synthase to generateO-ureido-l-serine usingO-acetyl-l-serine and hydroxyurea. DcsG, which exhibits similarity to a family of enzymes with an ATP-grasp fold, may be an ATP-dependent synthetase convertingO-ureido-d-serine intod-cycloserine. In the present study, to characterize the enzymatic functions of DcsC, DcsD, and DcsG, each protein was overexpressed inEscherichia coliand purified to near homogeneity. The biochemical function of each of the reactions catalyzed by these three proteins was verified by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and, in some cases, mass spectrometry. The results from this study demonstrate that by using a mixture of the three purified enzymes and the two commercially available substratesO-acetyl-l-serine and hydroxyurea, synthesis ofd-cycloserine was successfully attained. Thesein vitrostudies yield the conclusion that DcsD and DcsG are necessary for the syntheses ofO-ureido-l-serine andd-cycloserine, respectively. DcsD was also able to catalyze the synthesis ofl-cysteine when sulfide was added instead of hydroxyurea. Furthermore, the present study shows that DcsG can also form other cyclicd-amino acid analogs, such asd-homocysteine thiolactone.
Characterization of
qnrB
-Like Genes in Citrobacter Species of the American Type Culture Collection
Authors: Saga Tomoo , Sabtcheva Stefana , Mitsutake Kotaro , Ishii Yoshikazu , Tateda Kazuhiro , Yamaguchi Keizo , Kaku Mitsuo 
Published: March 2013

ABSTRACT

Among five American Type Culture Collection (ATCC)
Citrobacter
strains,
qnrB60
in
Citrobacter freundii
ATCC 6879, an isolate from the preantibiotic era, and
qnrB61
in
Citrobacter braakii
ATCC 51113
T
, a type strain belonging to the
C. freundii
complex, were identified. Meanwhile, a truncated
qnrB
-like pseudogene was identified in
C. freundii
ATCC 8090
T
and ATCC 43864. No
qnrB
-like sequence was found in
Citrobacter koseri
ATCC 27028
T
. These findings underscore the close relationship between this species and
qnrB
.
In VitroActivity of Biapenem plus RPX7009, a Carbapenem Combined with a Serine β-Lactamase Inhibitor, against Anaerobic Bacteria
Authors: Goldstein Ellie J. C. , Citron Diane M. , Tyrrell Kerin L. , Merriam C. Vreni 
Published: March 2013

ABSTRACTBiapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine β-lactamases. Biapenem was tested alone and in combination with fixed concentrations of RPX7009 by agar dilution against 377 recent isolates of anaerobes. A separate panel of 27 isolates ofBacteroidesspp. with decreased susceptibility or resistance to imipenem was also tested. Comparator drugs included meropenem, piperacillin-tazobactam, ampicillin-sulbactam, cefoxitin, ceftazidime, metronidazole, clindamycin, and tigecycline plus imipenem, doripenem, and ertapenem for the 27 selected strains. For recent consecutive strains ofBacteroidesspecies, the MIC90for biapenem-RPX7009 was 1 μg/ml, with a MIC90of 4 μg/ml for meropenem. OtherBacteroides fragilisgroup species showed a MIC90of 0.5 μg/ml for both agents. The MIC90s for biapenem-RPX7009 were 0.25 μg/ml forPrevotellaspp., 0.125 μg/ml forFusobacterium nucleatumandFusobacterium necrophorum, 2 μg/ml forFusobacterium mortiferum, 0.5 μg/ml forFusobacterium varium, ≤0.5 μg/ml for Gram-positive cocci and rods, and 0.03 to 8 μg/ml for clostridia. Against 5B. fragilisstrains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those of other carbapenems (≥32 μg/ml). AgainstBacteroidesstrains with an imipenem MIC of 2 μg/ml, biapenem-RPX7009 had MICs of 0.5 to 2 μg/ml, with MICs of 0.5 to 32 μg/ml for meropenem, doripenem, and ertapenem. For strains with an imipenem MIC of 4 μg/ml, the MICs for biapenem-RPX7009 were 4 to 16 μg/ml, with MICs of 8 to >32 μg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and it showed little or no potentiation of biapenem versus anaerobes. Biapenem-RPX7009 showed activity comparable to that of imipenem and was superior to meropenem, doripenem, and ertapenem against imipenem-nonsusceptibleBacteroidesspp.
Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates
Authors: Simitsopoulou Maria , Peshkova Pavla , Tasina Efthymia , Katragkou Aspasia , Kyrpitzi Daniela , Velegraki Aristea , Walsh Thomas J. , Roilides Emmanuel 
Published: March 2013

ABSTRACT

Candida
species other than
Candida albicans
are increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared the
in vitro
activities of all three echinocandins against biofilms formed by different common and infrequently identified
Candida
isolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates of
C. albicans
(15 strains),
Candida parapsilosis
(6 strains),
Candida lusitaniae
(16 strains),
Candida guilliermondii
(5 strains), and
Candida krusei
(12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as ≥50% fungal damage. Planktonic cells of all
Candida
species were susceptible to the three echinocandins, with MICs of ≤1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among the
Candida
species. Thus,
C. lusitaniae
and
C. guilliermondii
biofilms were highly recalcitrant to all echinocandins, with MICs of ≥32 mg/liter. In contrast, the MICs of all three echinocandins for
C. albicans
and
C. krusei
biofilms were relatively low (MICs ≤ 1 mg/liter). While echinocandins exhibited generally high MICs against
C. parapsilosis
biofilms, MFG exhibited the lowest MICs against these isolates (4 mg/liter). A paradoxical growth effect was observed with CAS concentrations ranging from 8 to 64 mg/liter against
C. albicans
and
C. parapsilosis
biofilms but not against
C. krusei
,
C. lusitaniae
, or
C. guilliermondii
. While non-
albicans Candida
planktonic cells were susceptible to all echinocandins, there were drug- and species-specific differences in susceptibility among biofilms of the various
Candida
species, with
C. lusitaniae
and
C. guilliermondii
exhibiting profiles of high MICs of the three echinocandins.
Impact of Primary Elvitegravir Resistance-Associated Mutations in HIV-1 Integrase on Drug Susceptibility and Viral Replication Fitness
Authors: Abram Michael E. , Hluhanich Rebecca M. , Goodman Derrick D. , Andreatta Kristen N. , Margot Nicolas A. , Ye Linda , Niedziela-Majka Anita , Barnes Tiffany L. , Novikov Nikolai , Chen Xiaowu , Svarovskaia Evguenia S. , McColl Damian J. , White Kirsten L. , Miller Michael D. 
Published: March 2013

ABSTRACTElvitegravir (EVG) is an effective HIV-1 integrase (IN) strand transfer inhibitor (INSTI) in advanced clinical development. Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H. In this study, the effect of these primary IN mutations, alone and in combination, on susceptibility to the INSTIs EVG, raltegravir (RAL), and dolutegravir (DTG); IN enzyme activities; and viral replication fitness was characterized. Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for T97A. Less commonly observed primary IN mutations also showed a range of reduced EVG susceptibilities: 40- to 94-fold for T66K and Q148K and 5- to 10-fold for T66A, E92G, and Q148H. Some primary IN mutations exhibited broad cross-resistance between EVG and RAL (T66K, E92Q, Q148R/H/K, and N155H), while others retained susceptibility to RAL (T66I/A, E92G, T97A, and S147G). Dual combinations of primary IN mutations further reduced INSTI susceptibility, replication capacity, and viral fitness relative to either mutation alone. Susceptibility to DTG was retained by single primary IN mutations but reduced by dual mutation combinations with Q148R. Primary EVG RAMs also diminished IN enzymatic activities, concordant with their structural proximity to the active site. Greater reductions in viral fitness of dual mutation combinations may explain why some primary INSTI RAMs do not readily coexist on the same HIV-1 genome but rather establish independent pathways of resistance to EVG.
Phenothiazines Inhibit Hepatitis C Virus Entry, Likely by Increasing the Fluidity of Cholesterol-Rich Membranes
Authors: Chamoun-Emanuelli Ana M. , Pecheur Eve-Isabelle , Simeon Rudo L. , Huang Da , Cremer Paul S. , Chen Zhilei 
Published: March 2013

ABSTRACTDespite recent progress in the development of direct-acting antiviral agents against hepatitis C virus (HCV), more effective therapies are still urgently needed. We and others previously identified three phenothiazine compounds as potent HCV entry inhibitors. In this study, we show that phenothiazines inhibit HCV entry at the step of virus-host cell fusion, by intercalating into cholesterol-rich domains of the target membrane and increasing membrane fluidity. Perturbation of the alignment/packing of cholesterol in lipid membranes likely increases the energy barrier needed for virus-host fusion. A screening assay based on the ability of molecules to selectively increase the fluidity of cholesterol-rich membranes was subsequently developed. One compound that emerged from the library screen, topotecan, is able to very potently inhibit the fusion of liposomes with cell culture-derived HCV (HCVcc). These results yield new insights into HCV infection and provide a platform for the identification of new HCV inhibitors.
Enhanced, Sialoadhesin-Dependent Uptake of Guillain-Barré Syndrome-Associated Campylobacter jejuni Strains by Human Macrophages
Authors: Heikema Astrid P. , Koning Roman I. , Duarte dos Santos Rico Sharon , Rempel Hans , Jacobs Bart C. , Endtz Hubert P. , van Wamel Willem J. B. , Samsom Janneke N. 
Published: March 2013

ABSTRACT

Molecular mimicry between
Campylobacter jejuni
sialylated lipooligosaccharides (LOS) and human nerve gangliosides can trigger the production of cross-reactive antibodies which induce Guillain-Barré syndrome (GBS). To better understand the immune events leading to GBS, it is essential to know how sialylated LOS are recognized by the immune system. Here, we show that GBS-associated
C. jejuni
strains bind to human sialoadhesin (hSn), a conserved, mainly macrophage-restricted I-type lectin. Using hSn-transduced THP-1 cells, we observed that
C. jejuni
strains with α(2,3)-sialylated LOS, including strains expressing GM1a- and GD1a-like epitopes, bind to hSn. This observation is of importance, as these epitopes are frequently the targets of the cross-reactive antibodies detected in GBS patients. Interestingly, the Sn binding domains were not constitutively exposed on the surface of
C. jejuni
. Heat inactivation and the environmental conditions which food-borne
C. jejuni
encounters during its passage through the intestinal tract, such as low pH and contact with bile constituents, exposed LOS and facilitated Sn binding. Sn binding enhanced bacterial uptake and increased the production of interleukin-6 (IL-6) by primary human Sn-expressing monocyte-derived macrophages compared to control conditions, where Sn was blocked using neutralizing antibodies or when nonsialylated
C. jejuni
was used. Sn-mediated uptake has been reported to enhance humoral immune responses. As
C. jejuni
strains expressing ganglioside mimics GD1a and GM1a are closely associated with GBS, Sn binding may be a determining event in the production of cross-reactive antibodies and the development of GBS.
Vascular Endothelial Cell Growth–Activated XBP1 Splicing in Endothelial Cells Is Crucial for Angiogenesis
Authors: Zeng Lingfang , Xiao Qingzhong , Chen Mei , Margariti Andriana , Martin Daniel , Ivetic Aleksandar , Xu Heping , Mason Justin , Wang Wen , Cockerill Gillian , Mori Kazutoshi , Li Julie Yi-shuan , Chien Shu , Hu Yanhua , Xu Qingbo 
Published: March 2013

Background—
Vascular endothelial cell growth factor plays a pivotal role in angiogenesis via regulating endothelial cell proliferation. The X-box binding protein 1 (XBP1) is believed to be a signal transducer in the endoplasmic reticulum stress response. It is unknown whether there is crosstalk between vascular endothelial cell growth factor signaling and XBP1 pathway.

Methods and Results—

We found that vascular endothelial cell growth factor induced the kinase insert domain receptor internalization and interaction through C-terminal domain with the unspliced XBP1 and the inositol requiring enzyme 1 α in the endoplasmic reticulum, leading to inositol requiring enzyme 1 α phosphorylation and XBP1 mRNA splicing, which was abolished by siRNA-mediated knockdown of kinase insert domain receptor. Spliced XBP1 regulated endothelial cell proliferation in a PI3K/Akt/GSK3β/β-catenin/E2F2–dependent manner and modulated the cell size increase in a PI3K/Akt/GSK3β/β-catenin/E2F2–independent manner. Knockdown of XBP1 or inositol requiring enzyme 1 α decreased endothelial cell proliferation via suppression of Akt/GSK3β phosphorylation, β-catenin nuclear translocation, and E2F2 expression. Endothelial cell–specific knockout of XBP1 (
XBP1ecko
) in mice retarded the retinal vasculogenesis in the first 2 postnatal weeks and impaired the angiogenesis triggered by ischemia. Reconstitution of XBP1 by Ad-XBP1s gene transfer significantly improved angiogenesis in ischemic tissue in
XBP1ecko
mice. Transplantation of bone marrow from wild-type o
XBP1ecko
mice could also slightly improve the foot blood reperfusion in ischemic
XBP1ecko
mice.

Conclusions—
These results suggest that XBP1 can function via growth factor signaling pathways to regulate endothelial proliferation and angiogenesis.
A Retinotopic Attentional Trace after Saccadic Eye Movements: Evidence from Event-related Potentials
Authors: Talsma Durk , White Brian J. , Mathôt Sebastiaan , Munoz Douglas P. , Theeuwes Jan 
Published: March 2013

AbstractSaccadic eye movements are a major source of disruption to visual stability, yet we experience little of this disruption. We can keep track of the same object across multiple saccades. It is generally assumed that visual stability is due to the process of remapping, in which retinotopically organized maps are updated to compensate for the retinal shifts caused by eye movements. Recent behavioral and ERP evidence suggests that visual attention is also remapped, but that it may still leave a residual retinotopic trace immediately after a saccade. The current study was designed to further examine electrophysiological evidence for such a retinotopic trace by recording ERPs elicited by stimuli that were presented immediately after a saccade (80 msec SOA). Participants were required to maintain attention at a specific location (and to memorize this location) while making a saccadic eye movement. Immediately after the saccade, a visual stimulus was briefly presented at either the attended location (the same spatiotopic location), a location that matched the attended location retinotopically (the same retinotopic location), or one of two control locations. ERP data revealed an enhanced P1 amplitude for the stimulus presented at the retinotopically matched location, but a significant attenuation for probes presented at the original attended location. These results are consistent with the hypothesis that visuospatial attention lingers in retinotopic coordinates immediately following gaze shifts.
Affective and Executive Network Processing Associated with Persuasive Antidrug Messages
Authors: Ramsay Ian S. , Yzer Marco C. , Luciana Monica , Vohs Kathleen D. , MacDonald Angus W. 
Published: March 2013

AbstractPrevious research has highlighted brain regions associated with socioemotional processes in persuasive message encoding, whereas cognitive models of persuasion suggest that executive brain areas may also be important. The current study aimed to identify lateral prefrontal brain areas associated with persuasive message viewing and understand how activity in these executive regions might interact with activity in the amygdala and medial pFC. Seventy adolescents were scanned using fMRI while they watched 10 strongly convincing antidrug public service announcements (PSAs), 10 weakly convincing antidrug PSAs, and 10 advertisements (ads) unrelated to drugs. Antidrug PSAs compared with nondrug ads more strongly elicited arousal-related activity in the amygdala and medial pFC. Within antidrug PSAs, those that were prerated as strongly persuasive versus weakly persuasive showed significant differences in arousal-related activity in executive processing areas of the lateral pFC. In support of the notion that persuasiveness involves both affective and executive processes, functional connectivity analyses showed greater coactivation between the lateral pFC and amygdala during PSAs known to be strongly (vs. weakly) convincing. These findings demonstrate that persuasive messages elicit activation in brain regions responsible for both emotional arousal and executive control and represent a crucial step toward a better understanding of the neural processes responsible for persuasion and subsequent behavior change.
Attention-modulated Alpha-band Oscillations Protect against Intrusion of Irrelevant Information
Authors: Payne Lisa , Guillory Sylvia , Sekuler Robert 
Published: March 2013

Abstract
Combining high-density scalp EEG recordings with a sensitive analog measure of STM's fidelity, we characterized the temporal dynamics of intentional ignoring and related those dynamics to the intrusion of task-irrelevant information. On each trial of the task, two study Gabors were briefly presented in succession. A green or red disc preceding each Gabor signified whether that Gabor should be remembered or ignored, respectively. With cue–stimulus intervals of 300, 600, or 900 msec presented in separate sessions, we found that the onset of posterior, prestimulus alpha oscillations varied with the length of the interval. Although stimulus onset time was entirely predictable, the longer the cue–stimulus interval, the earlier the increase in prestimulus alpha power. However, the alpha-band modulation was not simply locked to the cue offset. The temporal envelopes of posterior alpha-band modulation were strikingly similar for both cued attending and cued ignoring and differed only in magnitude. This similarity suggests that cued attending includes suppression of task-irrelevant, spatial processing. Supporting the view that alpha-band oscillations represent inhibition, our graded measure of recall revealed that, when the stimulus to be ignored appears second in the sequence, peristimulus alpha power predicted the degree to which that irrelevant stimulus distorted subsequent recall of the stimulus that was to be remembered. These results demonstrate that timely deployment of attention-related alpha-band oscillations can aid STM by filtering out task-irrelevant information.
Aortopexy for Innominate Artery Tracheal Compression in Children
Authors: Wine Todd M. , Colman Kathryn L. , Mehta Deepak K. , Maguire Raymond C. , Morell Victor O. , Simons Jeffrey P. 
Published: March 2013

Objectives(1) Evaluate the presentation, diagnostic workup, and outcomes of contemporary surgical intervention for airway obstruction from innominate artery tracheal compression in children. (2) Assess the significance of synchronous airway lesions in the treatment of innominate artery tracheal compression.Study DesignCase series with chart review.SettingTertiary care children's hospital.MethodsThis study is a retrospective medical record review of 26 consecutive children who underwent aortopexy for innominate artery tracheal compression at a tertiary care children's hospital. Presenting symptoms, diagnostic workup, presence of synchronous airway lesions, length of hospitalization, and treatment outcomes were examined.ResultsTwenty‐six patients (17 male, 65%) were included in the study. All were diagnosed with bronchoscopy and confirmed with radiographic imaging. Median age at diagnosis and surgery was 9.7 and 10.0 months, respectively. Presenting symptoms included noisy breathing (93%), cough (78%), dyspnea (44%), apnea (44%), cyanosis (19%), and recurrent respiratory infections (15%). Average degree of tracheal compression was 71% (SD, 12%). Fifteen of 26 (58%) patients had synchronous airway lesions, including mild laryngomalacia and subglottic stenosis. Median length of stay was 2 days. Median follow‐up was 10 months. Subjective improvement occurred in all 21 patients for whom follow‐up information was available.ConclusionAnterior tracheal vascular compression can cause a variety of airway symptoms. Mild synchronous airway lesions are common and do not prevent successful aortopexy. Aortopexy is a viable treatment option for symptomatic anterior tracheal vascular compression from the innominate artery.