Purpose
Magnetic resonance‐guided focused ultrasound (MRgFUS) is emerging as a treatment alternative for osteoid osteoma and painful bone metastases. This study describes a new simulation platform ...that predicts the distribution of heat generated by MRgFUS when applied to bone tissue.
Methods
Calculation of the temperature distribution was performed using two mathematical models. The first determined the propagation and absorption of acoustic energy through each medium, and this was performed using a multilayered approximation of the Rayleigh integral method. The ultrasound energy distribution derived from these equations could then be converted to heat energy, and the second mathematical model would then use the heat generated to determine the final temperature distribution using a finite‐difference time‐domain application of Pennes’ bio‐heat transfer equation. Anatomical surface geometry was generated using a modified version of a mesh‐based semiautomatic segmentation algorithm, and both the acoustic and thermodynamic models were calculated using a parallelized algorithm running on a graphics processing unit (GPU) to greatly accelerate computation time. A series of seven porcine experiments were performed to validate the model, comparing simulated temperatures to MR thermometry and assessing spatial, temporal, and maximum temperature accuracy in the soft tissue.
Results
The parallelized algorithm performed acoustic and thermodynamic calculations on grids of over 108 voxels in under 30 s for a simulated 20 s of heating and 40 s of cooling, with a maximum time per calculated voxel of less than 0.3 μs. Accuracy was assessed by comparing the soft tissue thermometry to the simulation in the soft tissue adjacent to bone using four metrics. The maximum temperature difference between the simulation and thermometry in a region of interest around the bone was measured to be 5.43 ± 3.51°C average absolute difference and a percentage difference of 16.7%. The difference in heating location resulted in a total root‐mean‐square error of 4.21 ± 1.43 mm. The total size of the ablated tissue calculated from the thermal dose approximation in the simulation was, on average, 67.6% smaller than measured from the thermometry. The cooldown was much faster in the simulation, where it decreased by 14.22 ± 4.10°C more than the thermometry in 40 s after sonication ended.
Conclusions
The use of a Rayleigh‐based acoustic model combined with a discretized bio‐heat transfer model provided a rapid three‐dimensional calculation of the temperature distribution through bone and soft tissue during MRgFUS application, and the parallelized GPU algorithm provided the computational speed that would be necessary for an intraoperative treatment planning software platform.
The accumulation of damaged proteins can perturb cellular homeostasis and provoke aging and cellular damage. Quality control systems, such as the unfolded protein response (UPR), inflammatory ...signaling and protein degradation, mitigate the residence time of damaged proteins. In the present study, we have examined the UPR and inflammatory signaling in the liver of young (~6 months) and old (~28 months) mice (n=8/group), and the ability of trehalose, a compound linked to increased protein stability and autophagy, to counteract age-induced effects on these systems. When used, trehalose was provided for 4 weeks in the drinking water immediately prior to sacrifice (n=7/group). Livers from old mice were characterized by activation of the UPR, increased inflammatory signaling and indices of liver injury. Trehalose treatment reduced the activation of the UPR and inflammatory signaling, and reduced liver injury. Reductions in proteins involved in autophagy and proteasome activity observed in old mice were restored following trehalose treatment. The autophagy marker, LC3B-II, was increased in old mice treated with trehalose. Metabolomics analyses demonstrated that reductions in hexosamine biosynthetic pathway metabolites and nicotinamide in old mice were restored following trehalose treatment. Trehalose appears to be an effective intervention to reduce age-associated liver injury and mitigate the need for activation of quality control systems that respond to disruption of proteostasis.
The primary objective of this study was to use high-resolution micro-CT images to create accurate three-dimensional (3D) models of several intratemporal structures, and to compare several surgically ...important dimensions within the temporal bone. The secondary objective was to create a statistical shape model (SSM) of a dominant and non-dominant sigmoid sinus (SS) to provide a template for automated segmentation algorithms.
A free image processing software, 3D Slicer, was utilized to create three-dimensional reconstructions of the SS, jugular bulb (JB), facial nerve (FN), and external auditory canal (EAC) from micro-CT scans. The models were used to compare several clinically important dimensions between the dominant and non-dominant SS. Anatomic variability of the SS was also analyzed using SSMs generated using the Statismo software framework.
Three-dimensional models from 38 temporal bones were generated and analyzed. Right dominance was observed in 74% of the paired SSs. All distances were significantly shorter on the dominant side (p < 0.05), including: EAC - SS (dominant: 13.7 ± 3.4 mm; non-dominant: 15.3 ± 2.7 mm), FN - SS (dominant: 7.2 ± 1.8 mm; non-dominant: 8.1 ± 2.3 mm), 2nd genu FN - superior tip of JB (dominant: 8.7 ± 2.2 mm; non-dominant: 11.2 ± 2.6 mm), horizontal distance between the superior tip of JB - descending FN (dominant: 9.5 ± 2.3 mm; non-dominant: 13.2 ± 3.5 mm), and horizontal distance between the FN at the stylomastoid foramen - JB (dominant: 5.4 ± 2.2 mm; non-dominant: 7.7 ± 2.1). Analysis of the SSMs indicated that SS morphology is most variable at its junction with the transverse sinus, and least variable at the JB.
This is the first known study to investigate the anatomical variation and relationships of the SS using high resolution scans, 3D models and statistical shape analysis. This analysis seeks to guide neurotological surgical approaches and provide a template for automated segmentation and surgical simulation.
Abstract
The International Cancer Genome Consortium (ICGC) was established to bring together researchers from around the globe to comprehensively analyze the genomic, transcriptomic, and epigenomic ...changes in 50 different tumour types or subtypes that are of clinical and societal importance across the globe (International network of cancer genome projects. Nature 464, 993-998 (15 April 2010)). As of November 2015, the ICGC has received commitments from researchers and funding organizations in Asia, Australia, Europe, North America and South America for 89 project teams in 17 jurisdictions to study more than 25,000 tumour genomes. Processed data is available via the Data Coordination Centre (http://dcc.icgc.org) based at the Ontario Institute for Cancer Research and is updated semi-annually. The November 2015 release (Version 20) includes datasets from 66 ICGC projects. In total, ICGC data release 20 comprises data from 14,767 cancer genomes. The Pan-Cancer Analysis of Whole Genomes (PCAWG) project of the ICGC and The Cancer Genome Atlas (TCGA) is coordinating analysis of more than 2,800 cancer genomes, with the extensive use of cloud computing. Because of the very large size of the pan-cancer dataset, with 5,000 whole genome sequences, PCAWG is using a distributed compute cloud environment (generated by computing centres in the USA, Europe and Asia) that meets the project's technical requirements and the bioethical framework of ICGC and its member projects. Each genome is being characterized through a suite of standardized algorithms, including alignment to the reference genome, uniform quality assessment, and the calling of multiple classes of somatic mutations. Scientists participating in the research projects of PCAWG are addressing a series of fundamental questions about cancer biology and evolution based on these data. The first phase of ICGC, which is slated for completion in 2018, has focused on developing extensive catalogs of tumour genomic information. The proposed second phase, ICGCmed, will link genomics to clinical information and health, including lifestyle, patient history, response to therapies, and underlying causes of disease, for a broad spectrum of cancers, including preneoplastic lesions, early cancers and metastases. The goal will be to accelerate the movement of genomic information into the clinic to guide prevention, early detection, diagnosis, and prognosis, and provide the information needed to match a patient's disease to the most effective combinations of therapy. The ICGC develops policies and quality control criteria to help harmonize the work of member projects located in different jurisdictions. Data produced by ICGC projects are made rapidly and freely available to qualified researchers around the world via the data cloud and through the ICGC Data Coordination Center at (http://dcc.icgc.org). More information can be found on www.icgc.org.
Citation Format: Jennifer L. Jennings, Thomas J. Hudson. International Cancer Genome Consortium (ICGC). abstract. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 130.
Genomic testing has enhanced pre-surgical decision making for cytologically indeterminate thyroid nodules, but there remains uncertainty regarding RAS mutations. The addition of extra genetic ...alterations to previous driver mutation panels has been shown to improve predictive value. This study aims to evaluate the relationship between the mutant allele frequency (AF) and likelihood of malignancy in thyroid nodules with RAS mutations.
A retrospective cohort review was performed evaluating patients with indeterminate cytology (Bethesda categories III, IV and V) and ThyroSeq® v3 testing demonstrating a RAS mutation, who underwent surgery. Univariate and multivariate regression analyses were used to evaluate relationships between AF, other genetic alterations, and malignancy.
Thirty-nine patients met criteria, 77% of the thyroid nodules (30/39) were found to be malignant. None demonstrated aggressive pathology. On univariate regression, there was no relationship between AF and likelihood of malignancy. There was, however, a significant correlation between AF and the rate of an additional genetic alteration. Multivariate analysis found a trend between RAS, a second genetic alteration and malignancy, but it did not reach statistical significance.
There was no direct relationship between the level of allelic frequency in thyroid nodules expressing RAS mutations and the likelihood of malignancy. There was a statistically significant relationship between increasing AF and the presence of a second genetic abnormality, suggesting a possible progression from initial driver mutation and then a second genetic alteration prior to malignant transformation.
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage ...1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 × 10−8) and 1.14 (trend; P = 1.32 × 10−5), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 × 10−4). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 × 10−11). This locus has also been implicated in prostate cancer.
In the first half of 2003, the number of
C. difficile
infections (22.5 per 1000 admissions) increased in Quebec, Canada. This outbreak was associated with fluoroquinolone and cephalosporin use as ...well as an increase in
C. difficile
–associated mortality (to 6.9 percent) and colectomy (to 1.9 percent). The outbreak strain was found to have enhanced virulence, as suggested by the presence of binary toxin genes and the partial deletion of a toxin-repressor gene.
In the first half of 2003, the number of
C. difficile
infections (22.5 per 1000 admissions) increased in Quebec, Canada. This outbreak was associated with fluoroquinolone and cephalosporin use as well as an increase in
C. difficile
–associated mortality and colectomy.
Clostridium difficile
is the leading cause of nosocomial infectious diarrhea.
1
The most important risk factor for
C. difficile
–associated diarrhea is prior antibiotic use.
2
Some patients remain asymptomatic after exposure to
C. difficile,
whereas illness ranging from mild diarrhea to fulminant colitis develops in others.
2
Only 1 to 5 percent of affected patients have severe disease, leading to colectomy, intensive care, or death.
3
,
4
The best-described
C. difficile
virulence factors are toxins A and B, encoded by the genes
tcdA
and
tcdB,
respectively.
5
Together with two regulatory genes (
tcdC
and
tcdD
) and a porin gene (
tcdE
), . . .
A clinical perspective Hudson, Thomas J
Nature (London),
10/2013, Letnik:
502, Številka:
7471
Journal Article
Recenzirano
In future, it will be useful to correlate genes identified as being relevant to multiple cancer types with drug responses, although this information will require greater integra- tion of genomic ...profiles in clinical trials and cancer registries13, and new models of data sharing among research institutions14.
Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions,
and
, that have been described as ...oncogenic events in thyroid neoplasms.
We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either
or
gene fusion.
This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the
fusion and seven had the
fusion. Of the five nodules in the
group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven
nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the
fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions.
nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas
nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment.
Crown gall (CG) is a globally distributed and economically important disease of grapevine and other important crop plants. The causal agent of CG is
or
strains that harbor a tumor-inducing plasmid ...(pTi). The microbial community within the CG tumor has not been widely elucidated and it is not known if certain members of this microbial community promote or inhibit CG. This study investigated the microbiotas of grapevine CG tumor tissues from seven infected vineyards located in Hungary, Japan, Tunisia, and the United States. Heavy co-amplification of grapevine chloroplast and mitochondrial ribosomal RNA genes was observed with the widely used Illumina V3-V4 16S rRNA gene primers, requiring the design of a new reverse primer to enrich for bacterial 16S rRNA from CG tumors. The operational taxonomic unit (OTU) clustering approach is not suitable for CG microbiota analysis as it collapsed several ecologically distinct
species into a single OTU due to low interspecies genetic divergence. The CG microbial community assemblages were significantly different across sampling sites (ANOSIM global
= 0.63,
value = 0.001) with evidence of site-specific differentially abundant ASVs. The presence of
in the CG microbiota is almost always accompanied by
and
, the latter may promote the spread of pTi plasmid by way of acyl-homoserine lactone signal production, whereas the former may take advantage of the presence of substrates associated with plant cell wall growth and repair. The technical and biological insights gained from this study will contribute to the understanding of complex interaction between the grapevine and its microbial community and may facilitate better management of CG disease in the future.
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