bluuebunny/crossref_metadata_2025_split huggingface dataset:
TU‐D‐BRA‐03: Real‐Time‐Image Guidance in Radiation Therapy: Is There a Role for Ultrasound Imaging?
Authors: Hristov D , Schlosser J , Salisbury K , Oralkan O , Khuri‐Yakub P 
Published: August 2010

The curative potential of External Beam Radiation Therapy (EBRT) is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. Cone‐beam computed tomography, planar x‐ray imaging, radiographic or electromagnetic tracking of implanted fiducials, as well as operator‐performed ultrasound are currently used for EBRT image guidance. However, these technologies are incapable of addressing the challenge of real‐time volumetric (4D) visualization, localization, and tracking of soft‐tissue motion and deformation concurrent with treatment beam delivery. Thus a significant opportunity exists for improving the therapeutic ratio and the safety of EBRT. We will present and discuss two solutions that can realize this opportunity through the integration of spatially localized, remotely controlled operator‐free ultrasound imaging with radiation delivery systems.The first approach relies on a custom designed compact ultrasound probe based on two‐dimensional matrix array of capacitive micro‐machined ultrasonic transducers integrated with radiofrequency electronics. For operator‐free imaging, the probe is to be fixed to a subject by a belt with appropriate acoustical coupling. Dedicated beam forming methodology and image reconstruction is necessary to enable large volume data collection at a volume rate of 3 Hz or higher.The second approach employs a novel, minimally interfering, tele‐robotic ultrasound imaging based on commercial transducers. It uses a customized human‐safe robotic manipulator to control the pressure and pitch of an abdominal probe while avoiding gantry collisions. A haptic device is integrated to remotely control the robotic manipulator motion and image acquisition outside the therapy room.Learning objectives:1. Understand basic relationships between ultrasound imaging system design and performance parameters such as spatial resolution, frame rate, and field of view. Recognize the dependencies between these parameters.2. Identify limitations of current EBRT ultrasound guidance systems and identify physics, design and workflow causes behind them.3. Understand how remote‐operator free imaging and appropriately designed workflow can enable real‐time soft‐tissue image guidance concurrent with radiation delivery and reduce ultrasound localization uncertainties.4. Recognize potential interferences between the radiation delivery system and the operator‐free imaging system and appreciate their magnitude and mutual impact.
WE‐D‐204B‐05: Online Monitoring and Error Detection of Real‐Time Tumor Displacement Prediction Accuracy Using Statistical Process Control
Authors: Malinowski KT , Mc Avoy TJ , George R , Dieterich S , D'Souza WD 
Published: August 2010

Purpose: To investigate two statistical process control (SPC) metrics, the Hotelling (T2) statistic and the input‐variable‐squared‐prediction‐error (Q(x)), for predicting degradation in real‐time tumor displacement accuracy without explicit measurement of tumor displacement. Method and Materials: Independently but concurrently localized tumor and external surrogate positions from a database of Cyberknife Synchrony™ cases (130 treatment fractions from 63 lung tumors, 10 fractions from 5 liver tumors, and 48 fractions from 23 pancreas tumors) were analyzed. Each fraction consisted of 40–112 measurements obtained at an average rate of 0.018 Hz. The first 10 measured internal/external samples in each fraction were used to create fraction‐specific models of tumor displacement using external surrogates. The regression coefficients relating the 3D positions of the 3 skin markers to the 3D tumor positions were calculated using partial‐least‐squares (PLS) regression. The PLS model was applied to all subsequent localizations in the fraction. The T2‐ and Q(x)‐statistics in the training data were used to develop 90th, 95th and 99th percentile ranges of expected T2 and Q(x) values. The sensitivities and specificities of T2, Q(x), T2̆Q(x), and T2̑Q(x) for predicting real‐time tumor displacement errors greater than 3mm and 5mm were determined. Results: The T2, Q(x), T2̆Q(x), and T2̑Q(x) statistics' sensitivities and specificities varied with error threshold and acceptable percentile ranges of values. In general, the Q(x) statistic was associated with high sensitivity and low specificity, while the T2 statistic was associated with moderate sensitivity and moderate specificity. For 90th percentile T2, 99th percentile Q(x) and 3 mm error, the sensitivities of T2, Q(x), T2̆Q(x), and T2̑Q(x) were 69%, 88%, 92%, and 64%, respectively, and the specificities were 62%, 37%, 28%, and 72%, respectively. Conclusion: This study illustrates the feasibility of SPC metrics for detecting breakdowns in tumor displacement prediction accuracy using external sensors.Conflict of Interest: Funded by NIH grant CA 124766
TH‐C‐204C‐02: Advanced MR Spectroscopy Methods for Studying Metabolism and Radiation Treatment Response in Brain Tumors
Authors: Andronesi O , Seco J , Shih H , Sorensen G 
Published: August 2010

Magnetic resonance spectroscopy imaging (MRSI) provides completely non‐invasively detailed metabolic information which correlates with physiological or pathological conditions. Hence it is becoming a valuable tool in image guided radio(proton)therapy where it can probe dose conformity (radiation delivered over the tumor volume and surrounding tissues) and could provide in‐vivo new insights about the biology of tumor response to radiation.Traditionally in‐vivo MRSI faces several challenges that may limit its potential such as: 1) inaccuracy in signal localization (chemical shift displacement error and voxel bleeding); 2) low spatial resolution; and 3) long acquisition times for 3D volumetric scans. However recent advances in hardware and pulse sequence design can mitigate many of these problems. Use of adiabatic pulses can provide precise and uniform signal excitation and together with fast acquisition schemes of the k‐space such as spiral trajectories allows fast acquisition of high resolution 3D MRSI scans. In addition real‐time motion correction and shimming strategies can improve the reliability of MRSI scans. Moreover MRSI scans that have multiple frequency dimensions (such as 2D chemical shift correlation spectra) can now be performed in‐vivo to unambiguously identify overlapped metabolite signals.This lecture will begin with an overview of the basic principles of in‐vivo MRS which will be followed by details of advanced MRSI methods such as adiabatic excitation fast spiral acquisition of 3D MRSI data and 2D chemical shift correlation spectra. Examples of in‐vivo MRSI data obtained on brain tumor patients treated with conventional radiotherapy and proton beam therapy will be shown in the end.Learning Objectives:1. Basic principles of MRSI.2. Understand the critical artifacts that might confound MRS and the importance of improved methods for reliable MRSI.3. Clinical applications of MRSI to monitor radiation therapy for brain tumors.
TH‐D‐204B‐03: IMRT and VMAT Inverse Planning with Compressed Sensing Techniques
Authors: Xing L , Zhu L , Meng B , Boyd S 
Published: August 2010

The classical Shannon‐Nyquist sampling theorem specifies that to avoid losing information when capturing a signal one must sample at least two times faster than the signal bandwidth. In many medical applications the Nyquist rate may be either impractical or too expensive to be realized practically. Compressed sensing provides a practically valuable approach for finding optimal solutions with under‐ sampled data. In this talk I will summarize our recent work on using compressed sensing for IMRT and VMAT inverse planning. We show that effective utilization of prior knowledge of the systems through compressed sensing can greatly reduce the required number of measurement samples determined by the Shannon‐Nyquist theorem and leads to significantly improved IMRT/VMAT plans. Compressed sensing has significant interactions and bearings on fields of radiation oncology and medical imaging.Learning Objectives:1. Familiarize with the concept of compressed sensing.2. Understand the fundamental limitations of currently available IMRT and VMAT inverse planning methods.3. Appreciate the need for a compressed sensing based inverse planning.4. Show the impact of the proposed new inverse planning algorithm.5. Provide perspectives on future research topics.
Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci
Authors: Tsubakishita Sae , Kuwahara-Arai Kyoko , Sasaki Takashi , Hiramatsu Keiichi 
Published: August 2010

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) is one of the most important multidrug-resistant pathogens around the world. MRSA is generated when methicillin-susceptible
S. aureus
(MSSA) exogenously acquires a methicillin resistance gene,
mecA
, carried by a mobile genetic element, staphylococcal cassette chromosome
mec
(SCC
mec
), which is speculated to be transmissible across staphylococcal species. However, the origin/reservoir of the
mecA
gene has remained unclear. Finding the origin/reservoir of the
mecA
gene is important for understanding the evolution of MRSA. Moreover, it may contribute to more effective control measures for MRSA. Here we report on one of the animal-related
Staphylococcus
species,
S. fleurettii
, as the highly probable origin of the
mecA
gene. The
mecA
gene of
S. fleurettii
was found on the chromosome linked with the essential genes for the growth of staphylococci and was not associated with SCC
mec
. The
mecA
locus of the
S. fleurettii
chromosome has a sequence practically identical to that of the
mecA
-containing region (∼12 kbp long) of SCC
mec
. Furthermore, by analyzing the corresponding gene loci (over 20 kbp in size) of
S. sciuri
and
S. vitulinus
, which evolved from a common ancestor with that of
S. fleurettii
, the speciation-related
mecA
gene homologues were identified, indicating that
mecA
of
S. fleurettii
descended from its ancestor and was not recently acquired. It is speculated that SCC
mec
came into form by adopting the
S. fleurettii mecA
gene and its surrounding chromosomal region. Our finding suggests that SCC
mec
was generated in
Staphylococcus
cells living in animals by acquiring the intrinsic
mecA
region of
S. fleurettii
, which is a commensal bacterium of animals.
Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of
Klebsiella pneumoniae
in a
Caenorhabditis elegans
Model
Authors: Bialek Suzanne , Lavigne Jean-Philippe , Chevalier Jacqueline , Marcon Estelle , Leflon-Guibout Véronique , Davin Anne , Moreau Richard , Pagès Jean-Marie , Nicolas-Chanoine Marie-Hélène 
Published: August 2010

ABSTRACT

Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for
Klebsiella pneumoniae
. The potential impact of this multidrug resistance (MDR) on the virulence of
K. pneumoniae
was evaluated in the
Caenorhabditis elegans
model. For 2 of the 3 MDR clinical isolates studied, a significant increase in
acrB
transcription was found in comparison with their antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative strains with altered porin expression were studied. Strains proved or suspected to overexpress an efflux system were significantly more virulent than the ATCC and revertant strains (time to kill 50% of nematodes [LT
50
] in days: 3.4 to 3.8 ± 0.2 versus 4.1 to 4.4 ± 0.3,
P
< 0.001). Inversely, strains with altered porin expression were significantly less virulent, independently of the expression level of efflux system (LT
50
= 5.4 to 5.6 ± 0.2,
P
< 0.001). Altered porin expression did not change MICs of CMP and NAL but did those of FOX (4 to 16× MIC) and ertapenem (16 to 64× MIC). The strains with a normally or an overexpressed efflux system that received the β-lactamase CTX-M-15 became more widely resistant without modification of their virulence potential, suggesting that balance between resistance and virulence is dependent on the type of resistance mechanisms. In conclusion, this study shows that the expression of both efflux systems and porins is a key factor not only for antibiotic resistance but also virulence potential in
K. pneumoniae
.
Tyrosine Phosphatase Inhibitor-3 Sensitizes Melanoma and Colon Cancer to Biotherapeutics and Chemotherapeutics
Authors: Kundu Suman , Fan Keke , Cao Mingli , Lindner Daniel J. , Tuthill Ralph , Liu Lili , Gerson Stanton , Borden Ernest , Yi Taolin 
Published: August 2010

Abstract
Drug resistance is a major obstacle in cancer treatments and diminishes the clinical efficacy of biological, cytotoxic, or targeted therapeutics. Being an antiapoptotic mediator of chemoresistance in breast and lung cancer cells, MKP1 phosphatase might be targeted for overcoming chemoresistance and improving therapeutic efficacy. In this work, tyrosine phosphatase inhibitor-3 (TPI-3) was identified as a novel small molecule inhibitor of MKP1 and was capable of sensitizing tumors to bio- and chemotherapeutics in mice as a tolerated oral agent. Effective against recombinant MKP1, TPI-3 selectively increased MKP1 phosphosubstrates in Jurkat cells and induced cell death via apoptosis at nanomolar concentrations. TPI-3 also increased MKP1 phosphosubstrates in WM9 human melanoma cells and synergized with biotherapeutic IFNα2b in the growth inhibition of melanoma cells in vitro (combination index, &lt;1). WM9 xenografts unresponsive to individual agents were significantly inhibited (62%, P = 0.001) in mice by a tolerated combination of oral TPI-3 (10 mg/kg, 5 d/wk) and IFNα2b. MKP1 expression was detected in human melanoma cell lines and tissue samples at levels up to six times higher than those in normal or nonmalignant melanocytes. TPI-3 also interacted positively with chemotherapeutics, 5-fluorouracil/leucovorin, against MC-26 colon cancer cells in vitro and in mice. Altogether, our data show the preclinical activities of TPI-3 in overcoming cancer resistance to bio- and chemotherapeutics, implicate MKP1 as a drug-resistant molecule in melanoma, and support the targeting of MKP1 for improving cancer therapeutic efficacy. Mol Cancer Ther; 9(8); 2287–96. ©2010 AACR.
Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues
Authors: Saito Yasuyuki , Iwamura Hiroko , Kaneko Tetsuya , Ohnishi Hiroshi , Murata Yoji , Okazawa Hideki , Kanazawa Yoshitake , Sato-Hashimoto Miho , Kobayashi Hisae , Oldenborg Per-Arne , Naito Makoto , Kaneko Yoriaki , Nojima Yoshihisa , Matozaki Takashi 
Published: August 2010

AbstractThe molecular basis for regulation of dendritic cell (DC) development and homeostasis remains unclear. Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is predominantly expressed in DCs, mediates cell-cell signaling by interacting with CD47, another immunoglobulin superfamily protein. We now show that the number of CD11chigh DCs (conventional DCs, or cDCs), in particular, that of CD8−CD4+ (CD4+) cDCs, is selectively reduced in secondary lymphoid tissues of mice expressing a mutant form of SIRPα that lacks the cytoplasmic region. We also found that SIRPα is required intrinsically within cDCs or DC precursors for the homeostasis of splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPα mutant mice into DCs induced by either macrophage-granulocyte colony-stimulating factor or Flt3 ligand in vitro was not impaired. Although the accumulation of the immediate precursors of cDCs in the spleen was also not impaired, the half-life of newly generated splenic CD4+ cDCs was markedly reduced in SIRPα mutant mice. Both hematopoietic and nonhematopoietic CD47 was found to be required for the homeostasis of CD4+ cDCs and CD8−CD4−(double negative) cDCs in the spleen. SIRPα as well as its ligand, CD47, are thus important for the homeostasis of CD4+ cDCs or double negative cDCs in lymphoid tissues.
A SNP associated with alternative splicing of RPT5b causes unequal redundancy between RPT5a and RPT5b among Arabidopsis thaliananatural variation
Authors: Guyon-Debast Anouchka , Lécureuil Alain , Bonhomme Sandrine , Guerche Philippe , Gallois Jean-Luc 
Published: August 2010

Abstract

Background
The proteasome subunit RPT5, which is essential for gametophyte development, is encoded by two genes in Arabidopsis thaliana; RPT5a and RPT5b. We showed previously that RPT5a and RPT5b are fully redundant in the Columbia (Col-0) accession, whereas in the Wassilewskia accession (Ws-4), RPT5b does not complement the effect of a strong rpt5a mutation in the male gametophyte, and only partially complements rpt5a mutation in the sporophyte. RPT5b

Col-0
and RPT5b

Ws-4
differ by only two SNPs, one located in the promoter and the other in the seventh intron of the gene.

Results
By exploiting natural variation at RPT5b we determined that the SNP located in RPT5b intron seven, rather than the promoter SNP, is the sole basis of this lack of redundancy. In Ws-4 this SNP is predicted to create a new splicing branchpoint sequence that induces a partial mis-splicing of the pre-mRNA, leading to the introduction of a Premature Termination Codon. We characterized 5 accessions carrying this A-to-T substitution in intron seven and observed a complete correlation between this SNP and both a 10 to 20% level of the RPT5b pre-mRNA mis-splicing and the lack of ability to complement an rpt5a mutant phenotype.

Conclusion
The accession-dependent unequal redundancy between RPT5a and RPT5b genes illustrates an example of evolutionary drifting between duplicated genes through alternative splicing.
Extramammary Paget's disease with the appearance of a nodule: a case report
Authors: Wang Xia , Yang Wenlin , Yang Jian 
Published: August 2010

Abstract

Background
Extramammary Paget's disease (EMPD) remains a rare condition with only a limited number of cases reported in the literature. EMPD is mainly composed of intraepidermal Paget cells, and possesses variable clinical behaviors and histological appearances, leading to difficulty in the diagnosis of this disease.

Case presentation
We here report a case of primary EMPD with the appearance of a nodule on the background of erythema. Histological assessment showed Paget cell infiltration throughout the epidermis with dermal spread. Using immunohistochemistry, the expressions of CK7, CK19, CK20, GCDFP-15, CEA, S-100 protein and bcl-2 were examined to elucidate the cellular differentiation of the carcinoma.

Conclusion
According to the histological assessment, this case was diagnosed as primary EMPD with carcinoma cells invading into the dermis, but without lymph node infiltration.
The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats
Authors: Liu Que , Adams Lisa , Broyde Anatoly , Fernandez Rayne , Baron Alain D , Parkes David G 
Published: August 2010

Abstract

Background
Activation of glucagon-like peptide-1 (GLP-1) receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS) rats.

Methods
DSS rats were fed low salt (LS, 0.3% NaCl) or high salt (HS, 8% NaCl) diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min), or GLP-1 (25 pmol/kg/min) for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day) or AC3174 plus captopril.

Results
HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP) was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p < 0.05). AC3174 plus captopril attenuated the deleterious effects of high salt on posterior wall thickness, LV mass, and the ratio of LV mass to body weight (P ≤ 0.05). In contrast, GLP-1 had no effect on these cardiovascular parameters. All treatments reduced LV wall stress. GLP-1, AC3174, captopril, or AC3174 plus captopril normalized fasting insulin and HOMA-IR (P ≤ 0.05). AC3174, captopril, or AC3174 plus captopril improved renal function (P ≤ 0.05). Renal morphology in HS rats was associated with extensive sclerosis. Monotherapy with AC3174, captopril, or GLP-1 attenuated renal damage. However, AC3174 plus captopril produced the most effective improvement.

Conclusions
Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.
ΔNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation
Authors: Craig Ashley L , Holcakova Jitka , Finlan Lee E , Nekulova Marta , Hrstka Roman , Gueven Nuri , DiRenzo James , Smith Graeme , Hupp Ted R , Vojtesek Borivoj 
Published: August 2010

AbstractBackgroundΔNp63α is an epithelial progenitor cell marker that maintains epidermal stem cell self-renewal capacity. Previous studies revealed that UV-damage induced p53 phosphorylation is confined to ΔNp63α-positive cells in the basal layer of human epithelium.ResultsWe now report that phosphorylation of the p53 tumour suppressor is positively regulated by ΔNp63α in immortalised human keratinocytes. ΔNp63α depletion by RNAi reduces steady-state ATM mRNA and protein levels, and attenuates p53 Serine-15 phosphorylation. Conversely, ectopic expression of ΔNp63α in p63-null tumour cells stimulates ATM transcription and p53 Serine-15 phosphorylation. We show that ATM is a direct ΔNp63α transcriptional target and that the ΔNp63α response element localizes to the ATM promoter CCAAT sequence. Structure-function analysis revealed that the ΔNp63-specific TA2 transactivation domain mediates ATM transcription in coordination with the DNA binding and SAM domains.ConclusionsGermline p63 point mutations are associated with a range of ectodermal developmental disorders, and targeted p63 deletion in the skin causes premature ageing. The ΔNp63α-ATM-p53 damage-response pathway may therefore function in epithelial development, carcinogenesis and the ageing processes.