bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Vancomycin Trough Concentration and Area under the Concentration-Time Curve in Neonates
Authors: Frymoyer Adam , Hersh Adam L. , El-Komy Mohammed H. , Gaskari Shabnam , Su Felice , Drover David R. , Van Meurs Krisa 
Published: August 2014

ABSTRACT

National treatment guidelines for invasive methicillin-resistant
Staphylococcus aureus
(MRSA) infections recommend targeting a vancomycin 24-h area under the concentration-time curve (AUC
0–24
)-to-MIC ratio of >400. The range of vancomycin trough concentrations that best predicts an AUC
0–24
of >400 in neonates is not known. This understanding would help clarify target trough concentrations in neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine the relationships between trough and AUC
0–24
in the study neonates. Monte Carlo simulations were performed to examine the effect of dose, postmenstrual age (PMA), and serum creatinine level on trough and AUC
0–24
achievement. A total of 1,702 vancomycin concentrations from 249 neonates were available for analysis. The median (interquartile range) PMA was 39 weeks (32 to 42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter, 89% of the study neonates had an AUC
0–24
of >400. Monte Carlo simulations demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of an AUC
0–24
of >400 across a range of PMA, serum creatinine levels, and vancomycin doses. However, a trough of ≥10 mg/liter was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ∼10 mg/liter is likely adequate for most neonates with invasive MRSA infections based on considerations of the AUC
0–24
. Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses is difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization.
Validation of a Model To Predict the Risk of Nephrotoxicity in Patients Receiving Colistin
Authors: Phe Kady , Johnson Michael L. , Palmer Hannah R. , Tam Vincent H. 
Published: August 2014

ABSTRACT
Despite concerns about its nephrotoxicity, colistin often remains the only effective agent for treating multidrug-resistant Gram-negative infections. Published studies have reported a wide range of nephrotoxicity risk factors. To assess the clinical utility of various models, we compared their performances for predicting the risk of nephrotoxicity. We identified a model demonstrating reasonable overall risk assessment, with an observed/expected ratio of 1.29 (95% confidence interval [CI], 0.68 to 1.90) and a positive predictive value of 87.5% for identifying patients at high risk of developing nephrotoxicity.
EUCAST Testing of Isavuconazole Susceptibility in Aspergillus: Comparison of Results for Inoculum Standardization Using Conidium Counting versus Optical Density
Authors: Arendrup Maiken Cavling , Howard Susan , Lass-Flörl Cornelia , Mouton Johan W. , Meletiadis Joseph , Cuenca-Estrella Manuel 
Published: August 2014

ABSTRACT

The EUCAST E.DEF9.1 standard recommends standardization of the inoculum concentration by conidium counting using a hemocytometer rather than a spectrophotometer. In this study, we investigated whether the choice of these methods influenced isavuconazole MICs. A blinded collection of 30 molecularly characterized azole-resistant isolates and 10 wild-type
Aspergillus fumigatus
isolates was shared with four different laboratories. Additionally, each laboratory selected approximately 100
A. fumigatus
isolates and 50 isolates each of
A. flavus
,
A. nidulans
,
A. niger
, and
A. terreus
(1,237 isolates in total). Three laboratories (laboratories 1 to 3) used conidium counting. One laboratory standardized the inoculum using a spectrophotometer (that is, by use of the optical density [OD]) and is referred to as the OD laboratory. Correlation coefficients, intraclass correlation coefficients, and essential agreement were calculated, and 2-log-unit differences were assessed (paired
t
test). The MIC range for the blinded collection was 0.25 to 16 mg/liter, and a 1-dilution-step difference between the MIC
50
and MIC
90
across the four laboratories was detected and a 2-dilution-step difference between the modal MICs was detected. Compared to the results for laboratories 1 and 2, a significant correlation was found for the OD laboratory MIC data (correlation coefficients, 0.85 and 0.93, respectively; intraclass correlation coefficients, 0.88 and 0.96, respectively). The number of mutant isolates whose MICs overlapped those of the wild-type isolates was the lowest for the OD laboratory (14/30 [46.7%] mutant isolates), whereas the numbers were 18/30 (60%) isolates for laboratory 1, 17/30 (56.7%) isolates for laboratory 2, and 21/30 (70%) isolates for laboratory 3. For the
A. flavus
,
A. fumigatus
,
A. nidulans
,
A. niger
, and
A. terreus
isolates, comparative analysis again defined the MIC distributions from the OD laboratory to be in excellent agreement with those from laboratories 1 and 2 across all five
Aspergillus
spp. The findings suggest that EUCAST testing using OD determination is an appropriate alternative for standardization of
Aspergillus
inoculum concentrations.
Silver Resistance Genes Are Overrepresented among Escherichia coli Isolates with CTX-M Production
Authors: Sütterlin Susanne , Edquist Petra , Sandegren Linus , Adler Marlen , Tängdén Thomas , Drobni Mirva , Olsen Björn , Melhus Åsa 
Published: August 2014

ABSTRACT

Members of the
Enterobacteriaceae
with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different
Escherichia coli
populations, the presence of three silver resistance genes (
silE
,
silP
, and
silS
) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in
E. coli
isolates of human (
n
= 105) and avian (
n
= 111) origin. The antibiotic profiles were also determined. Isolates harboring CTX-M genes were further characterized, and phenotypic silver resistance was examined. The
silE
gene was present in 13 of the isolates. All of them were of human origin. Eleven of these isolates harbored ESBLs of the CTX-M type (
P
= 0.007), and eight of them were typed as CTX-M-15 and three as CTX-M-14. None of the
silE
-positive isolates was related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58 complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was observed after silver exposure in 12 of them, and a concomitant reduced susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12% of the human
E. coli
isolates but none of the avian isolates harbored silver resistance genes. This indicates another route for or level of silver exposure for humans than that caused by common environmental contamination. Since
silE
-positive isolates were significantly more often found in CTX-M-positive isolates, it is possible that silver may exert a selective pressure on CTX-M-producing
E. coli
isolates.
Surveillance of Viruses in Wild Fish Populations in Areas around the Gulf of Cadiz (South Atlantic Iberian Peninsula)
Authors: Moreno Patricia , Olveira José G. , Labella Alejandro , Cutrín Juan Manuel , Baro Jorge C. , Borrego Juan Jose , Dopazo Carlos P. 
Published: August 2014

ABSTRACT

This report describes a viral epidemiological study of wild fish around the Gulf of Cadiz (southwestern Iberian Peninsula) and is focused on infectious pancreatic necrosis virus (IPNV), viral hemorrhagic septicemia virus (VHSV), and viral nervous necrosis virus (VNNV). One fish species (
Chelon labrosus
) was sampled inside the gulf, at the mouth of the San Pedro River. Another 29 were sampled, in three oceanographic campaigns, at sites around the Bay of Cadiz. The fish were processed individually and subjected to isolation in cell culture and molecular diagnosis. VHSV was not isolated from any species. Thirteen IPNV-type isolates were obtained from barracuda (
Sphyraena sphyraena
), axillary seabream (
Pagellus acarne
), common two-banded seabream (
Diplodus vulgaris
), common pandora (
P. erythrinus
), Senegal seabream (
D. bellottii
), and surmullet (
Mullus surmuletus
). Six VNNV isolates were obtained from axillary seabream, common pandora, black seabream (
Spondyliosoma cantharus
), red mullet (
Mullet barbatus
), Lusitanian toadfish (
Halobatrachus didactylus
), and tub gurnard (
Chelidonichtys lucerna
). In the river mouth, viruses were detected only after reamplification, obtaining prevalence percentages of IPNV and VNNV (44.4 and 63.0%, respectively) much higher than those observed in the oceanographic campaigns (25.7 and 19.6%, respectively). The opposite results were obtained in the case of VHSV after reamplification: 11.1% in the river mouth and 43.6% in the oceanic locations. Analyzing the results with respect to the proximity of the sampling sites to the coast, an anthropogenic influence on wild fish is suggested and discussed. The type of viruses and the presence of natural reassortants are also discussed.
Homeostasis of N-α-Terminal Acetylation of EsxA Correlates with Virulence in Mycobacterium marinum
Authors: Mba Medie Felix , Champion Matthew M. , Williams Emily A. , Champion Patricia A. DiGiuseppe 
Published: August 2014

ABSTRACT

The mycobacterial Esx-1 (ESAT-6 system 1) exporter translocates virulence factors across the cytoplasmic membrane to the cell wall, cell surface, and the bacteriological medium
in vitro
. The mechanisms underlying substrate targeting to distinct locations are unknown. Several Esx-1 substrates are N-α-terminally acetylated. The role of this rare modification in bacteria is unclear. We sought to identify genes required for Esx-1 substrate modification, transport, and localization. Pathogenic mycobacteria lyse
Acanthamoeba castellanii
in an Esx-1-dependent manner. We conducted a genetic screen to identify
Mycobacterium marinum
strains which failed to lyse amoebae. We identified a noncytotoxic
M. marinum
strain with a transposon insertion in a predicted N-α-terminal acetyltransferase not previously linked to mycobacterial pathogenesis. Disruption of this gene led to attenuation of virulence, failure to induce a type I interferon response during macrophage infection, and loss of hemolytic activity. The major Esx-1 substrates, EsxA and EsxB, were exported to the cell surface, but only low levels were released into the bacteriological medium. The balance of EsxA N-α-terminal acetylation was disrupted, resulting in a mycobacterial strain in which surface-associated EsxA was hyperacetylated. Genetic complementation completely restored Esx-1 function and the levels of N-α-terminally acetylated EsxA on the surface but restored only low levels of Esx-1 substrates in the bacteriological medium. Our results reveal a novel gene required for mycobacterial Esx-1 export. Our findings indicate that maintaining the homeostasis of Esx-1 substrate N-α-terminal acetylation is essential for Esx-1-mediated virulence. We propose an inverse correlation between EsxA acetylation and virulence.
Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection
Authors: Pettigrew Melinda M. , Marks Laura R. , Kong Yong , Gent Janneane F. , Roche-Hakansson Hazeline , Hakansson Anders P. 
Published: August 2014

ABSTRACT

Streptococcus pneumoniae
is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms
in vitro
and
in vivo
. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the
S. pneumoniae
transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed
S. pneumoniae
, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of
S. pneumoniae
pathogenesis.
Mid- and long-term outcomes of carotid-cavernous fistula endovascular management with Onyx and n-BCA: experience of a single tertiary center
Authors: Barber Sean M , Rangel-Castilla Leonardo , Zhang Y Jonathan , Klucznik Richard , Diaz Orlando 
Published: August 2014

IntroductionEndovascular therapy is the preferred treatment for most carotid-cavernous fistulas (CCFs). Early reports have documented excellent initial clinical and radiographic outcomes after embolization of CCFs with Onyx or n-butyl cyanoacrylate (n-BCA), but little evidence is available about the long-term durability of this technique.ObjectiveTo characterize the long-term durability of CCF liquid embolization.MethodsThe authors retrospectively reviewed a database of 24 CCFs in 21 consecutive patients who underwent Onyx or n-BCA embolization of a CCF from 2006 to 2013 at our institution.ResultsA total of 25 Onyx or n-BCA embolization procedures were attempted and 24 successfully completed during the study, resulting in complete or near-complete occlusion by the end of the study in all 24 CCFs (obliteration success, 100%). Attempted embolization in a single CCF failed initially, but was performed successfully at a later date by a different approach. None of the 24 CCFs recanalized, regrew, or required any further treatment subsequent to Onyx or n-BCA embolization throughout a mean 12.4 months of angiographic follow-up (range 1–36 months). Clinically significant complications were seen in three embolization procedures, including cranial nerve palsies (n=1), embolic infarct (n=1), and intraperitoneal hemorrhage (n=1).ConclusionsEarly evidence has indicated that endovascular embolization with Onyx is relatively safe and effective at achieving an initial angiographic cure for CCFs. Results of our series suggest that angiographic and clinical outcomes of Onyx and n-BCA embolization remain stable at mid- and long-term follow-up.
Global Heritage Stone: Estremoz Marbles, Portugal
Authors: Lopes Luís , Martins Ruben 
Published: August 2014

Abstract
Paleozoic calcitic marbles are found in the Estremoz Anticline, Ossa-Morena Zone (Southern Branch of the European Variscides in Portugal). This 40 km NW–SE structure presents outcrop continuity and intense mining activity since the Roman Period. The structure has a Precambrian core and the younger rocks are from the Devonian Period. The marbles occupy an intermediate stratigraphic position in the Cambrian age Volcano Sedimentary Sequence. The Variscan Orogeny had two pulses with different intensities under ductile and brittle tension fields. The Alpine Cycle also caused more fracturing of the marbles. The geological features imprinted in the marbles are beautiful aesthetic patterns highlighted when used as dimension stone.
Since the Roman period, pieces of art made with Estremoz Marble were exported abroad and can be found in museums and archaeological sites throughout Europe and North Africa countries. Present day, Estremoz Marble objects can be found all over the world.
The very rich marble based heritage is omnipresent in cities, and the countryside is marked by intense mining activity side by side with rural industries; therefore the region has unique characteristics allowing the development of integrated industrial tourism routes, promoting sustainable development of industrial, scientific and technological cultural opportunities.
The historical and widespread application of these marbles in national and international monuments, some of them already part of the UNESCO World Heritage Sites, is a condition to propose them as Global Heritage Stone Resource for their international recognition.
QSPR Models for Octane Number Prediction
Authors: Al-Fahemi Jabir H. , Albis Nahla A. , Gad Elshafie A. M. 
Published: August 2014

Quantitative structure-property relationship (QSPR) is performed as a means to predict octane number of hydrocarbons via correlating properties to parameters calculated from molecular structure; such parameters are molecular mass M, hydration energy EH, boiling point BP, octanol/water distribution coefficient logP, molar refractivity MR, critical pressure CP, critical volume CV, and critical temperature CT. Principal component analysis (PCA) and multiple linear regression technique (MLR) were performed to examine the relationship between multiple variables of the above parameters and the octane number of hydrocarbons. The results of PCA explain the interrelationships between octane number and different variables. Correlation coefficients were calculated using M.S. Excel to examine the relationship between multiple variables of the above parameters and the octane number of hydrocarbons. The data set was split into training of 40 hydrocarbons and validation set of 25 hydrocarbons. The linear relationship between the selected descriptors and the octane number has coefficient of determination (R2=0.932), statistical significance (F=53.21), and standard errors (s =7.7). The obtained QSPR model was applied on the validation set of octane number for hydrocarbons giving RCV2=0.942 and s=6.328.
Mapping the Articular Contact Area of the Long Head of the Biceps Tendon on the Humeral Head
Authors: Morris Brent J. , Byram Ian R. , Lathrop Ray A. , Dunn Warren R. , Kuhn John E. 
Published: August 2014

The purpose of this investigation was to calculate the contact surface area of the long head of the biceps (LHB) in neutral position and abduction. We sought to determine whether the LHB articulates with the humeral head in a consistent pattern comparing articular contact area in neutral position and abduction. Eleven fresh frozen matched cadaveric shoulders were analyzed. The path of the biceps tendon on the articular surface of the humeral head and the total articular surface were digitized using a MicronTracker 2 H3-60 three-dimensional optical tracker. Contact surface area was significantly less in abduction than in neutral position (P=0.002) with a median ratio of 41% (36%, 47.5%). Ratios of contact area in neutral position to full articular surface area were consistent between left and right shoulders (rho=1, P=0.017) as were ratios of abduction area to full articular surface area (rho= 0.97, P=0.005). The articular contact surface area is significantly greater in neutral position than abduction. The ratios of articular contact surface areas to total humeral articular surface areas have a narrow range and are consistent between left and right shoulders of the same cadaver.
AXL Mediates Resistance to Cetuximab Therapy
Authors: Brand Toni M. , Iida Mari , Stein Andrew P. , Corrigan Kelsey L. , Braverman Cara M. , Luthar Neha , Toulany Mahmoud , Gill Parkash S. , Salgia Ravi , Kimple Randall J. , Wheeler Deric L. 
Published: August 2014

Abstract
The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non–small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated, and tightly associated with EGFR expression in cells resistant to cetuximab (CtxR cells). Using RNAi methods and novel AXL-targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation, and MAPK signaling in CtxR cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in CtxR cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft models, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab-resistant cancers. Cancer Res; 74(18); 5152–64. ©2014 AACR.