bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcranial phase aberration correction using beam simulations and MR‐ARFI
Authors: Vyas Urvi , Kaye Elena , Pauly Kim Butts 
Published: February 2014

Purpose:Transcranial magnetic resonance‐guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation‐MR‐ARFI technique to achieve aberration correction for transcranial MR‐guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR‐ARFI) to correct skull‐caused phase aberrations.Methods:Skull‐based numerical aberrations were obtained from a MR‐guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focused ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR‐ARFI images were used in the hybrid simulation‐MR‐ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16‐aberration and 1024‐aberration) was repeated three times.Results:The corrected MR‐ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation‐MR‐ARFI technique resulted in an average increase in focal MR‐ARFI phase of 44% for the 16‐aberration case and 52% for the 1024‐aberration case, and recovered 83% and 39% of the ideal MR‐ARFI phase for the 16‐aberrations and 1024‐aberration case, respectively.Conclusions:Using one MR‐ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation‐MR‐ARFI technique improved the maximum MR‐ARFI phase of the beamˈs focus.
Model‐based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR‐guided endorectal HIFU ablation array
Authors: Salgaonkar Vasant A. , Prakash Punit , Rieke Viola , Ozhinsky Eugene , Plata Juan , Kurhanewicz John , Hsu I‐C. (Joe) , Diederich Chris J. 
Published: February 2014

Purpose:Feasibility of targeted and volumetric hyperthermia (40–45 °C) delivery to the prostate with a commercial MR‐guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue‐equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy.Methods:The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm2, ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous‐wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W).Results:Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (Tmax < 45 °C) and fail‐safe operation of the ExAblate array (spatial and time averaged acoustic intensity ISATA < 3.4 W/cm2). Tissue volumes with therapeutic temperature levels (T > 41 °C) were estimated. Numerical simulations indicated that T > 41 °C was calculated in 13–23 cm3 volumes for sonications with planar or diverging beam patterns at 0.9–1.2 W/cm2, in 4.5–5.8 cm3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm2, and in ∼6.0 cm3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm2. Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous‐wave sonications (∼0.88 W/cm2, 15 min) were performed in tissue‐mimicking material with real‐time MR‐based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations.Conclusions:The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.
Role of Antibodies in Protection Elicited by Active Vaccination with Genetically Inactivated Alpha Hemolysin in a Mouse Model of Staphylococcus aureus Skin and Soft Tissue Infections
Authors: Mocca Christopher P. , Brady Rebecca A. , Burns Drusilla L. 
Published: February 2014

ABSTRACTDue to the emergence of highly virulent community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) infections,S. aureushas become a major threat to public health. A majority of CA-MRSA skin and soft tissue infections in the United States are caused byS. aureusUSA300 strains that are known to produce high levels of alpha hemolysin (Hla). Therefore, vaccines that contain inactivated forms of this toxin are currently being developed. In this study, we sought to determine the immune mechanisms of protection for this antigen using a vaccine composed of a genetically inactivated form of Hla (HlaH35L). Using a murine model of skin and soft tissue infections (SSTI), we found that BALB/c mice were protected by vaccination with HlaH35L; however, Jh mice, which are deficient in mature B lymphocytes and lack IgM and IgG in their serum, were not protected. Passive immunization with anti-HlaH35L antibodies conferred protection against bacterial colonization. Moreover, we found a positive correlation between the total antibody concentration induced by active vaccination and reduced bacterial levels. Animals that developed detectable neutralizing antibody titers after active vaccination were significantly protected from infection. These data demonstrate that antibodies to Hla represent the major mechanism of protection afforded by active vaccination with inactivated Hla in this murine model of SSTI, and in this disease model, antibody levels correlate with protection. These results provide important information for the future development and evaluation ofS. aureusvaccines.
Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58
Authors: Brown Martha J. , Seitz Hanna , Towne Victoria , Müller Martin , Finnefrock Adam C. 
Published: February 2014

ABSTRACT
Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.
Genetic Diversity and Evolution of Salmonella enterica Serovar Enteritidis Strains with Different Phage Types
Authors: Zheng Jie , Pettengill James , Strain Errol , Allard Marc W. , Ahmed Rafiq , Zhao Shaohua , Brown Eric W. 
Published: February 2014

ABSTRACT

Phage typing has been used for the epidemiological surveillance of
Salmonella enterica
serovar Enteritidis for over 2 decades. However, knowledge of the genetic and evolutionary relationships between phage types is very limited, making differences difficult to interpret. Here, single nucleotide polymorphisms (SNPs) identified from whole-genome comparisons were used to determine the relationships between some
S
. Enteritidis phage types (PTs) commonly associated with food-borne outbreaks in the United States. Emphasis was placed on the predominant phage types PT8, PT13a, and PT13 in North America. With >89,400 bp surveyed across 98
S
. Enteritidis isolates representing 14 distinct phage types, 55 informative SNPs were discovered within 23 chromosomally anchored loci. To maximize the discriminatory and evolutionary partitioning of these highly homogeneous strains, sequences comprising informative SNPs were concatenated into a single combined data matrix and subjected to phylogenetic analysis. The resultant phylogeny allocated most
S
. Enteritidis isolates into two distinct clades (clades I and II) and four subclades. Synapomorphic (shared and derived) sets of SNPs capable of distinguishing individual clades/subclades were identified. However, individual phage types appeared to be evolutionarily disjunct when mapped to this phylogeny, suggesting that phage typing may not be valid for making phylogenetic inferences. Furthermore, the set of SNPs identified here represents useful genetic markers for strain differentiation of more clonal
S
. Enteritidis strains and provides core genotypic markers for future development of a SNP typing scheme with
S
. Enteritidis.
Rolling Circle Amplification for Direct Detection of
rpoB
Gene Mutations in Mycobacterium tuberculosis Isolates from Clinical Specimens
Authors: Chen Xiaoyou , Wang Bin , Yang Wen , Kong Fanrong , Li Chuanyou , Sun Zhaogang , Jelfs Peter , Gilbert Gwendolyn L. 
Published: February 2014

ABSTRACT

Rapid and accurate detection of multidrug resistance (MDR) in
Mycobacterium tuberculosis
is essential to improve treatment outcomes and reduce global transmission but remains a challenge. Rifampin (RIF) resistance is a reliable marker of MDR tuberculosis (TB) since by far the majority of RIF-resistant strains are also isoniazid (INH) resistant. We have developed a rapid, sensitive, and specific method for detecting the most common mutations associated with RIF resistance, in the RIF resistance determining region (RRDR) of
rpoB
, using a cocktail of six padlock probes and rolling circle amplification (RCA). We used this method to test 46 stored
M. tuberculosis
clinical isolates with known RIF susceptibility profiles (18 RIF resistant, 28 susceptible), a standard susceptible strain (H37Rv, ATCC 27294) and 78
M. tuberculosis
culture-positive clinical (sputum) samples, 59 of which grew RIF-resistant strains. All stored clinical isolates were correctly categorized, by the padlock probe/RCA method, as RIF susceptible or resistant; the sensitivity and specificity of the method, for direct detection of phenotypically RIF-resistant
M. tuberculosis
in clinical specimens, were 96.6 and 89.5%, respectively. This method is rapid, simple, and inexpensive and has the potential for high-throughput routine screening of clinical specimens for MDR
M. tuberculosis
, particularly in high prevalence settings with limited resources.
Performance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory
Authors: Buitrago M. J. , Bernal-Martinez L. , Castelli M. V. , Rodriguez-Tudela J. L. , Cuenca-Estrella M. 
Published: February 2014

ABSTRACT
A retrospective analysis of real-time PCR (RT-PCR) results for 151 biopsy samples obtained from 132 patients with proven invasive fungal diseases was performed. PCR-based techniques proved to be fast and sensitive and enabled definitive diagnosis in all cases studied, with detection of a total of 28 fungal species.
Modified CLSI Extended-Spectrum β-Lactamase (ESBL) Confirmatory Test for Phenotypic Detection of ESBLs among Enterobacteriaceae Producing Various β-Lactamases
Authors: Poulou Aggeliki , Grivakou Evgenia , Vrioni Georgia , Koumaki Vassiliki , Pittaras Theodoros , Pournaras Spyros , Tsakris Athanassios 
Published: February 2014

ABSTRACT

The worldwide dissemination of
Enterobacteriaceae
producing AmpC β-lactamases and carbapenemases makes difficult the phenotypic detection of extended-spectrum β-lactamases (ESBLs), as they may be masked by these additional enzymes. A modification of the CLSI ESBL confirmatory test was developed and evaluated in a comparative study for its ability to successfully detect ESBLs among
Enterobacteriaceae
producing various carbapenemases (
Klebsiella pneumoniae
carbapenemase [KPC], VIM, NDM, and OXA-48) and plasmidic or derepressed AmpCs. The modified CLSI ESBL confirmatory test was performed with cefotaxime and ceftazidime disks with and without clavulanate, on which both boronic acid (BA) and EDTA were dispensed. A total of 162 genotypically confirmed ESBL-positive
Enterobacteriaceae
isolates (83 carbapenemase/ESBL producers, 25 AmpC/ESBL producers, and 54 ESBL-only producers) were examined. For comparison, 139 genotypically confirmed ESBL-negative
Enterobacteriaceae
isolates (94 of them possessed carbapenemases and 20 possessed AmpCs) were also tested. The standard CLSI ESBL confirmatory test was positive for 106 of the 162 ESBL producers (sensitivity, 65.4%) and showed false-positive results for 4 of the 139 non-ESBL producers (specificity, 97.1%). The modified CLSI ESBL confirmatory test detected 158 of 162 ESBL producers (sensitivity, 97.5%) and showed no false-positive results for non-ESBL producers (specificity, 100%). The findings of the study demonstrate that the modified CLSI ESBL confirmatory test using antibiotic disks containing both BA and EDTA accurately detects ESBLs in
Enterobacteriaceae
regardless of the coexistence of additional β-lactam resistance mechanisms.
Molecular Characterizations of PCR-Positive Mycoplasma pneumoniae Specimens Collected from Australia and China
Authors: Xue Guanhua , Wang Qinning , Yan Chao , Jeoffreys Neisha , Wang Liqiong , Li Shaoli , Gilbert Gwendolyn L. , Sun Hongmei 
Published: February 2014

ABSTRACT

Mycoplasma pneumoniae
is an important cause of community-acquired pneumonia (CAP). In this study,
M. pneumoniae
strains in PCR-positive specimens collected from patients in Sydney, Australia (30 samples), and Beijing, China (83 samples), were characterized using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA), P1-restriction fragment length polymorphism (RFLP) analysis, and sequencing of domain V of the 23S rRNA gene to compare genotype distribution and macrolide resistance rates between locations. Eighteen distinct MLVA types were identified in specimens from Sydney, of which 10 were known (types E, G, J, M, N, P, U, V, S, and X) and 8 previously unknown. Strains were equally distributed between P1-RFLP type 1 and type 2 variants. Among samples from Beijing, MLVA types E, G, J, P, U, X, and Z and four new types were identified. Most specimens belonged to P1-RFLP type 1. A nomenclature based on five VNTR loci is proposed to designate MLVA patterns. Macrolide resistance-associated mutations were identified in only 1 of 30 specimens (3.3%) from Sydney and 71 of 83 (85.5%) from Beijing (
P
< 0.05). This study demonstrated that although multiple individual
M. pneumoniae
strains were circulating in Beijing, the genotypes were less diverse than those in Sydney. However, the greatest regional difference was in the incidence of macrolide resistance, which may reflect differences in antibiotic use and/or measures in resistance control.
Development of a Two-Step Multiplex PCR Assay for Typing of Capsular Polysaccharide Synthesis Gene Clusters of Streptococcus suis
Authors: Okura Masatoshi , Lachance Claude , Osaki Makoto , Sekizaki Tsutomu , Maruyama Fumito , Nozawa Takashi , Nakagawa Ichiro , Hamada Shigeyuki , Rossignol Céline , Gottschalk Marcelo , Takamatsu Daisuke 
Published: February 2014

ABSTRACT

We developed a practical and easy two-step multiplex PCR assay to aid in serotyping of
Streptococcus suis
. The assay accurately typed almost all of the serotype reference strains and field isolates of various serotypes and also identified the genotypes of capsular polysaccharide synthesis gene clusters of some serologically nontypeable strains.
Real-Time Whole-Genome Sequencing for Routine Typing, Surveillance, and Outbreak Detection of Verotoxigenic Escherichia coli
Authors: Joensen Katrine Grimstrup , Scheutz Flemming , Lund Ole , Hasman Henrik , Kaas Rolf S. , Nielsen Eva M. , Aarestrup Frank M. 
Published: February 2014

ABSTRACT

Fast and accurate identification and typing of pathogens are essential for effective surveillance and outbreak detection. The current routine procedure is based on a variety of techniques, making the procedure laborious, time-consuming, and expensive. With whole-genome sequencing (WGS) becoming cheaper, it has huge potential in both diagnostics and routine surveillance. The aim of this study was to perform a real-time evaluation of WGS for routine typing and surveillance of verocytotoxin-producing
Escherichia coli
(VTEC). In Denmark, the Statens Serum Institut (SSI) routinely receives all suspected VTEC isolates. During a 7-week period in the fall of 2012, all incoming isolates were concurrently subjected to WGS using IonTorrent PGM. Real-time bioinformatics analysis was performed using web-tools (
www.genomicepidemiology.org
) for species determination, multilocus sequence type (MLST) typing, and determination of phylogenetic relationship, and a specific VirulenceFinder for detection of
E. coli
virulence genes was developed as part of this study. In total, 46 suspected VTEC isolates were characterized in parallel during the study. VirulenceFinder proved successful in detecting virulence genes included in routine typing, explicitly verocytotoxin 1 (
vtx1
), verocytotoxin 2 (
vtx2
), and intimin (
eae
), and also detected additional virulence genes. VirulenceFinder is also a robust method for assigning verocytotoxin (
vtx
) subtypes. A real-time clustering of isolates in agreement with the epidemiology was established from WGS, enabling discrimination between sporadic and outbreak isolates. Overall, WGS typing produced results faster and at a lower cost than the current routine. Therefore, WGS typing is a superior alternative to conventional typing strategies. This approach may also be applied to typing and surveillance of other pathogens.
Genome Scale Patterns of Recombination between Coinfecting Vaccinia Viruses
Authors: Qin Li , Evans David H. 
Published: February 2014

ABSTRACTRecombination plays a critical role in virus evolution. It helps avoid genetic decline and creates novel phenotypes. This promotes survival, and genome sequencing suggests that recombination has facilitated the evolution of human pathogens, including orthopoxviruses such as variola virus. Recombination can also be used to map genes, but although recombinant poxviruses are easily produced in culture, classical attempts to map the vaccinia virus (VACV) genome this way met with little success. We have sequenced recombinants formed when VACV strains TianTan and Dryvax are crossed under different conditions. These were a single round of growth in coinfected cells, five rounds of sequential passage, or recombinants obtained using leporipoxvirus-mediated DNA reactivation. Our studies showed that recombinants contain a patchwork of DNA, with the number of exchanges increasing with passage. Further passage also selected for TianTan DNA and correlated with increased plaque size. The recombinants produced through a single round of coinfection contain a disproportionate number of short conversion tracks (<1 kbp) and exhibited 1 exchange per 12 kbp, close to the ∼1 per 8 kbp in the literature. One by-product of this study was that rare mutations were also detected; VACV replication produces ∼1 × 10−8mutation per nucleotide copied per cycle of replication and ∼1 large (21 kbp) deletion per 70 rounds of passage. Viruses produced using DNA reactivation appeared no different from recombinants produced using ordinary methods. An attractive feature of this approach is that when it is combined with selection for a particular phenotype, it provides a way of mapping and dissecting more complex virus traits.IMPORTANCEWhen two closely related viruses coinfect the same cell, they can swap genetic information through a process called recombination. Recombination produces new viruses bearing different combinations of genes, and it plays an important role in virus evolution. Poxviruses are a family of viruses that includes variola (or smallpox) virus, and although poxviruses are known to recombine, no one has previously mapped the patterns of DNAs exchanged between viruses. We coinfected cells with two different vaccinia poxviruses, isolated the progeny, and sequenced them. We show that poxvirus recombination is a very accurate process that assembles viruses containing DNA copied from both parents. In a single round of infection, DNA is swapped back and forth ∼18 times per genome to make recombinant viruses that are a mosaic of the two parental DNAs. This mixes many different genes in complex combinations and illustrates how recombination can produce viruses with greatly altered disease potential.