bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonsense and Missense Mutations in
FCY2
and
FCY1
Genes Are Responsible for Flucytosine Resistance and Flucytosine-Fluconazole Cross-Resistance in Clinical Isolates of
Candida lusitaniae
Authors: Florent Martine , Noël Thierry , Ruprich-Robert Gwenaël , Da Silva Bruno , Fitton-Ouhabi Valérie , Chastin Christiane , Papon Nicolas , Chapeland-Leclerc Florence 
Published: May 2009

ABSTRACT

The aim of this work was to elucidate the molecular mechanisms of flucytosine (5FC) resistance and 5FC/fluconazole (FLC) cross-resistance in 11 genetically and epidemiologically unrelated clinical isolates of
Candida lusitaniae
. We first showed that the levels of transcription of the
FCY2
gene encoding purine-cytosine permease (PCP) in the isolates were similar to that in the wild-type strain, 6936. Nucleotide sequencing of the
FCY2
alleles revealed that 5FC and 5FC/FLC resistance could be correlated with a cytosine-to-thymine substitution at nucleotide 505 in the
fcy2
genes of seven clinical isolates, resulting in a nonsense mutation and in a putative nonfunctional truncated PCP of 168 amino acids. Reintroducing a
FCY2
wild-type allele at the
fcy2
locus of a
ura3
auxotrophic strain derived from the clinical isolate CL38
fcy2
(
C505T
) restored levels of susceptibility to antifungals comparable to those of the wild-type strains. In the remaining four isolates, a polymorphic nucleotide was found in
FCY1
where the nucleotide substitution T26C resulted in the amino acid replacement M9T in cytosine deaminase. Introducing this mutated allele into a 5FC- and 5FC/FLC-resistant
fcy1
Δ strain failed to restore antifungal susceptibility, while susceptibility was obtained by introducing a wild-type
FCY1
allele. We thus found a correlation between the
fcy1
T26C mutation and both 5FC and 5FC/FLC resistances. We demonstrated that only two genetic events occurred in 11 unrelated clinical isolates of
C. lusitaniae
to support 5FC and 5FC/FLC resistance: either the nonsense mutation C505T in the
fcy2
gene or the missense mutation T26C in the
fcy1
gene.
Population Pharmacokinetics of Acyclovir in Children and Young People with Malignancy after Administration of Intravenous Acyclovir or Oral Valacyclovir
Authors: Zeng L. , Nath C. E. , Blair E. Y. L. , Shaw P. J. , Stephen K. , Earl J. W. , Coakley J. C. , McLachlan A. J. 
Published: May 2009

ABSTRACT

Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The aim of this study was to characterize the population pharmacokinetics of acyclovir observed following treatment with intravenous acyclovir and oral valacyclovir (valaciclovir) in young people with malignancy. Plasma acyclovir concentration-time data were collected from 43 patients (age range, 9 months to 20 years) who had been given multiple doses of acyclovir (5 mg/kg of body weight) and/or valacyclovir (10 mg/kg). Nonlinear mixed-effect modeling was employed to analyze acyclovir population pharmacokinetics and identify influential covariates. Simulations (
n
= 1,000) were conducted to explore the ability of the current doses to maintain acyclovir concentrations above the recommended 50% inhibitory concentration for HSV or VZV (0.56 mg/liter or 1.125 mg/liter, respectively) for more than 12 h. A one-compartment pharmacokinetic model with first-order elimination best described the acyclovir concentration-time data. The population mean estimates for clearance (CL), volume of distribution (
V
), absorption rate (

k
a

), and bioavailability (
F
) were 3.55 liters/h, 7.36 liters, 0.63 h
−1
, and 0.60, respectively. Inclusion of body weight and estimated creatinine CL (CL
CR
) in the final model reduced the interindividual variabilities in CL and
V
from 61% to 24% and from 75% to 36%, respectively. Simulations revealed that with the use of the current doses, maximal efficacy can be achieved in over 45% of patients weighing 25 to 50 kg and with CL
CR
levels of 2.0 to 4.0 liters/h/m
2
, but only in a much smaller proportion of patients, with low weights (10 kg) and high CL
CR
s (5.5 liters/h/m
2
), suggesting that higher doses are required for this subgroup. This validated population pharmacokinetic model for acyclovir may be used to develop dosing guidelines for safe and effective antiviral therapy in young people with malignancy.
Multicenter, Randomized Study of the Efficacy and Safety of Intravenous Iclaprim in Complicated Skin and Skin Structure Infections
Authors: Krievins D. , Brandt R. , Hawser S. , Hadvary P. , Islam K. 
Published: May 2009

ABSTRACTIclaprim is a novel antibacterial agent that is currently in development for the treatment of complicated skin and skin structure infections (cSSSI). Iclaprim specifically and selectively inhibits bacterial dihydrofolate reductase, a critical enzyme in the bacterial folate pathway, and exhibits an extended spectrum of activity against various resistant pathogens, including methicillin (meticillin)-resistantStaphylococcus aureus(MRSA). The objective of this randomized, double-blind phase II study was to compare the efficacy and safety of iclaprim to those of vancomycin in patients with cSSSI. Patients were randomized to receive 0.8 mg iclaprim/kg of body weight, 1.6 mg/kg iclaprim, or 1 g vancomycin twice a day for 10 days. Clinical cure rates for the 0.8- and 1.6-mg/kg-iclaprim treatment groups were comparable to that for the vancomycin treatment group (26/28 patients [92.9%], 28/31 patients [90.3%], and 26/28 patients [92.9%], respectively). Iclaprim also showed high microbiological eradication rates. Iclaprim exhibited an eradication rate of 80% and 72% versus 59% observed with vancomycin forS. aureus, the pathogen most frequently isolated at baseline. Five MRSA cases were observed, four in the 0.8-mg/kg-iclaprim arm and one in the vancomycin arm, and all were both clinically and microbiologically cured. Iclaprim exhibited a safety profile similar to that of vancomycin, an established drug for the treatment of cSSSI. Results from this study indicate that iclaprim is a promising new therapy for the treatment of cSSSI, in particular those caused byS. aureus, including MRSA.
Noncanonical Vancomycin Resistance Cluster from
Desulfitobacterium hafniense
Y51
Authors: Kalan Lindsay , Ebert Sara , Kelly Tom , Wright Gerard D. 
Published: May 2009

ABSTRACT

The glycopeptide vancomycin is a drug of last resort for infection with gram-positive organisms, and three genes are vital to resistance:
vanH
,
vanA
, and
vanX
. These genes are found in a
vanHAX
cluster, which is conserved across pathogenic bacteria, glycopeptide antibiotic producers, and other environmental bacteria. The genome sequence of the anaerobic, gram-positive, dehalogenating bacterium
Desulfitobacterium hafniense
Y51 revealed a predicted
vanA
homolog; however, it exists in a
vanAWK-murFX
cluster, unlike those of other vancomycin-resistant organisms. Using purified recombinant VanA from
D. hafniense
Y51, we determined its substrate specificity and found it to have a 42-fold preference for
d
-lactate over
d
-alanine, confirming its activity as a
d
-Ala-
d
-Lac ligase and its annotation as VanA. Furthermore, we showed that
D. hafniense
Y51 is highly resistant to vancomycin, with a MIC for growth of 64 μg/ml. Finally,

vanA
Dh

is expressed during growth in vancomycin, as demonstrated by reverse transcription-PCR. This finding represents a new glycopeptide antibiotic resistance gene cluster and expands the genetic diversity of resistance to this important class of antibiotic.
AmpDIIs Involved in Expression of the Chromosomal L1 and L2 β-Lactamases ofStenotrophomonas maltophilia
Authors: Yang Tsuey-Ching , Huang Yi-Wei , Hu Rouh-Mei , Huang Shao-Cheng , Lin Yu-Tzu 
Published: May 2009

ABSTRACTTwoampDhomologues,ampDIandampDII, ofStenotrophomonas maltophiliahave been cloned and analyzed. Comparative genomic analysis revealed that the genomic context of theampDIIgenes is quite different, whereas that of theampDIgenes is more conserved inS. maltophiliastrains. TheampDsystem ofS. maltophiliais distinct from that of theEnterobacteriaceaeandPseudomonas aeruginosain three respects. (i) AmpDIofS. maltophiliais not encoded in anampDEoperon, in contrast to what happens in theEnterobacteriaceaeandP. aeruginosa. (ii) The AmpD systems of theEnterobacteriaceaeandP. aeruginosaare generally involved in the regulation ofampR-linkedampCgene expression, while AmpDIofS. maltophiliais responsible for the regulation of two intrinsic β-lactamase genes, of which the L2 gene, but not the L1 gene, is linked toampR. (iii)S. maltophiliaexhibits a one-step L1 and L2 gene derepression model involvingampDI, distinct from the two- or three-step derepression of theEnterobacteriaceaeandP. aeruginosa. Moreover, theampDIandampDIIgenes are constitutively expressed and not regulated by the inducer and AmpR protein, and the expression ofampDIIis weaker than that ofampDI. Finally, AmpDIIis not associated with the derepression of β-lactamases, and its role inS. maltophiliaremains unclear.
Selective Upregulation of Endothelial E-Selectin in Response toHelicobacter pylori-Induced Gastritis
Authors: Svensson Helena , Hansson Malin , Kilhamn Jan , Backert Steffen , Quiding-Järbrink Marianne 
Published: May 2009

ABSTRACTHelicobacter pyloriis one of the most common bacterial pathogens, infecting up to 50% of the world's population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect ofH. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, inH. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, theH. pyloritype IV secretion system encoded by thecagpathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to α5β1 integrins. Thus, endothelial E-selectin expression induced byH. pyloriprobably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected withcagPAI-positiveH. pyloristrains and may thereby contribute to tissue damage in these individuals.
Advances in the diagnosis of acute pancreatitis
Authors: Rickes S , Uhle C 
Published: May 2009

Abstract
Early and accurate assessment of both the aetiology and the severity of acute pancreatitis enables clinicians to follow therapeutic algorithms and can result in better outcomes. Technological advances over the past decade, in particular the development of imaging modalities, have revolutionised the management of patients with acute pancreatitis. This article reviews approaches to determining the diagnosis, aetiology and severity of acute pancreatitis, with particular emphasis on new imaging techniques.
Neuroendocrine tumours of the gallbladder: three cases and a review of the literature
Authors: Iype S , Mirza T A , Propper D J , Bhattacharya S , Feakins R M , Kocher H M 
Published: May 2009

Abstract
Primary neuroendocrine tumours (NETs) of the gallbladder are rare. In the absence of any randomised controlled trials or prospective case series, we sought trends for clinical presentation and management based on 60 patients from published literature over the last 15 years, as well as three patients from our experience, and categorised them into various subgroups according to the WHO classification for NETs. Well-differentiated NETs have an indolent course and better prognosis. Poorly differentiated neuroendocrine carcinomas, which may be of large-cell or small-cell type and may coexist with other types of carcinoma, have a poor outcome. A variety of surgical and chemotherapeutic approaches have been adopted. Surgical excision appears to prolong life, with chemotherapy perhaps adding a marginal advantage.
Evaluation of the thyroid nodule
Authors: Ghassi D , Donato A 
Published: May 2009

Abstract
The annual incidence of thyroid cancer worldwide is 1 case per 100 000 men and 2.6 cases per 100 000 women. Most thyroid nodules are asymptomatic and are discovered incidentally on physical examination, self-palpation or incidentally on imaging studies performed for unrelated reasons. Although the majority of both palpable and non-palpable thyroid nodules are benign, ∼5% may represent thyroid cancer. Thyroid-stimulating hormone, thyroid ultrasound and fine-needle aspiration biopsy are key tests to guide management. Physicians caring for patients with thyroid nodules need to develop a rational, cost-effective approach to ordering and interpreting imaging and diagnostic tests in the evaluation of the thyroid nodule.
Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients
Authors: Sherlock M , O’Sullivan E , Agha A , Behan L A , Owens D , Finucane F , Rawluk D , Tormey W , Thompson C J 
Published: May 2009

Abstract

Background
Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented.

Objective
To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions.

Methods
All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium &lt;130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis.

Results
Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p&lt;0.001), intracranial neoplasm (56/355, 15.8%; p&lt;0.001) and subarachnoid haemorrhage (62/316, 19.6%; p&lt;0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p&lt;0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12–28)) than normonatraemic patients (median 12 days (IQR 10.5–15)) (p&lt;0.001).

Conclusions
Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.
Nicotine: does it have a role in the treatment of skin disease?
Authors: Ingram J R 
Published: May 2009

AbstractEpidemiological evidence suggests that, although smoking is detrimental in some skin diseases, it is of benefit in others such as pemphigus and Behcet disease. Evidence that nicotine is of therapeutic value in selected skin diseases is limited to case reports. There has been renewed interest in nicotinic acetylcholine receptor agonists, such as nicotine, after the discovery of a “nicotinic anti-inflammatory pathway”. Nicotinic acetylcholine receptors exist in abundance in human skin, but it is unknown whether they exert an anti-inflammatory effect. Randomised controlled trials of nicotine preparations in those skin conditions that occur less often in smokers are necessary to establish the value of nicotine, if any, in the treatment of skin disease.
Respecting autonomy in young people
Authors: Beach R , Proops R 
Published: May 2009

Abstract
Paediatricians have a duty to protect the life and health of their patients and to respect their autonomy. Usually, there will be no conflict between these duties. Both children and parents want effective care and agree to the medical interventions that that are most likely to provide it. However, when children refuse or resist such interventions, it may be unclear when the duty to protect trumps the duty to respect. This is because children may have differing levels of autonomy, sometimes making them competent to make medical decisions for themselves and at other times not. Further, there may be conflict between the children and their parents in such circumstances. Children may refuse treatments that parents desire or vice versa. Sometimes paediatricians may agree with the child in the face of legal powers of parental guardianship. At other times they may agree with the parents, facing the prospect of forcing treatment on an unwilling child with potentially devastating psychological consequences. This paper will explore this potential ethical and legal minefield by evaluating some practical clinical cases based on the experiences of the primary author. It provides a range of examples of these different types of conflicts, including especially problematic “hard cases” that concern the withdrawal of life-sustaining treatment and child protection. The goal of the article is not simply to morally and legally outline the boundaries of such tensions in paediatric care. It also provides concrete advice about how they should best be resolved in everyday clinical practice.
TENSOR CORRELATION IN He AND Li ISOTOPES BASED ON TENSOR OPTIMIZED SHELL MODEL WITH UNITARY CORRELATION OPERATOR
Authors: MYO TAKAYUKI , KATŌ KIYOSHI , KIKUCHI YUMA , TOKI HIROSHI , IKEDA KIYOMI 
Published: May 2009

We show the importance of the tensor correlation on the structures of He and Li isotopes. We develop the tensor optimized shell model (TOSM) to describe the strong tensor correlation of the nuclear force in nuclei. We investigate the exotic structures of 9,10,11 Li based on the 9 Li +n+n model where TOSM is used for 9 Li . The coupling between the tensor correlation in 9 Li and the extra two neutrons emerges Pauli-blocking, which increases the s2 component and develops the halo structure in 11 Li . We further treat the short range repulsion of the nuclear force by the unitary correlation operator method (UCOM), while the tensor correlation is described by TOSM. We propose a new approach of TOSM+UCOM to describe nuclei from the nuclear force.
Teaching skills and concepts for embedded systems design
Authors: Bertels Peter , D'Haene Michiel , Degryse Tom , Stroobandt Dirk 
Published: May 2009

Smart devices are omnipresent today and the design of these embedded systems requires a multidisciplinary approach. It is important that students in electrical engineering and computer science learn these different aspects of embedded systems design. Our course on Complex Systems Design Methodology presents an overview of embedded systems design with a strong focus on the main concepts, preparing the students for more detailed follow-up courses on specific topics.
Imparting the theoretical concepts to the students is not sufficient, however. Hands-on sessions are indispensable for the students to acquire the necessary skills. In this article we present our approach for these hands-on sessions, which is to pose relatively small problems in separate sessions, each focusing on a single design aspect. Five years after the introduction of this new course at Ghent University, we can conclude that students not only like this course, but that their design skills have also improved by our new, aspect-focused, approach.
Multi-processor programming in the embedded system curriculum
Authors: Hansson Andreas , Akesson Benny , van Meerbergen Jef 
Published: May 2009

Teaching embedded system design is challenging, as the subject covers a wide range of aspects, and also involves skills that students do not learn from a text book. As a result, hands-on projects, with varying degree of complexity, are the most common approach in existing courses. Traditionally, the projects are limited to uni-processor systems, and do not address the complications involved in parallelising applications and mapping them to multi-processor systems.
In this paper, we describe a two-year-old embedded systems design course given at Eindhoven University of Technology. In the course, groups of four students are faced with the problem of putting an embedded JPEG decoder on the market within one semester. The starting point is a decoder written in sequential C and an embedded multiprocessor system, running on an FPGA. We describe the ideas and organisation of the course, and give examples of what challenges the students, as well as the instructors, are faced with. We exemplify results and give suggestions to those wishing to teach embedded multi-processor programming elsewhere.
Common Fixed Point Theorems for Weakly Compatible Pairs on Cone Metric Spaces
Authors: Jungck G. , Radenovic S. , Radojevic S. , Rakocevic V. 
Published: May 2009

AbstractWe prove several fixed point theorems on cone metric spaces in which the cone does not need to be normal. These theorems generalize the recent results of Huang and Zhang (2007), Abbas and Jungck (2008), and Vetro (2007). Furthermore as corollaries, we obtain recent results of Rezapour and Hamlborani (2008).
Wave-Driven Inner-Shelf Motions on the Oregon Coast*
Authors: Kirincich Anthony R. , Lentz Steven J. , Barth John A. 
Published: May 2009

Abstract
Recent work by S. Lentz et al. documents offshore transport in the inner shelf due to a wave-driven return flow associated with the Hasselmann wave stress (the Stokes–Coriolis force). This analysis is extended using observations from the central Oregon coast to identify the wave-driven return flow present and quantify the potential bias of wind-driven across-shelf exchange by unresolved wave-driven circulation. Using acoustic Doppler current profiler (ADCP) measurements at six stations, each in water depths of 13–15 m, observed depth-averaged, across-shelf velocities were generally correlated with theoretical estimates of the proposed return flow. During times of minimal wind forcing, across-shelf velocity profiles were vertically sheared, with stronger velocities near the top of the measured portion of the water column, and increased in magnitude with increasing significant wave height, consistent with circulation due to the Hasselmann wave stress. Yet velocity magnitudes and vertical shears were stronger than that predicted by linear wave theory, and more similar to the stratified “summer” velocity profiles described by S. Lentz et al. Additionally, substantial temporal and spatial variability of the wave-driven return flow was found, potentially due to changing wind and wave conditions as well as local bathymetric variability. Despite the wave-driven circulation found, subtracting estimates of the return flow from the observed across-shelf velocity had no significant effect on estimates of the across-shelf exchange due to along-shelf wind forcing at these water depths along the Oregon coast during summer.