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  • 1
    In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Informa UK Limited, Vol. 21, No. sup1 ( 2020-11-02), p. 74-81
    Type of Medium: Online Resource
    ISSN: 2167-8421 , 2167-9223
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2705061-0
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  • 2
    In: Advances in Radiation Oncology, Elsevier BV, Vol. 6, No. 4 ( 2021-07), p. 100708-
    Type of Medium: Online Resource
    ISSN: 2452-1094
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2847724-8
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Gastrointestinal and Liver Physiology Vol. 294, No. 6 ( 2008-06), p. G1344-G1353
    In: American Journal of Physiology-Gastrointestinal and Liver Physiology, American Physiological Society, Vol. 294, No. 6 ( 2008-06), p. G1344-G1353
    Abstract: Isoforms of protein kinase C (PKC) have been shown to modulate some cellular responses such as pathological secretion and generation of inflammatory mediators during acute pancreatitis (AP). We propose that PKC also participates in premature zymogen activation within the pancreatic acinar cell, a key event in the initiation of AP. This hypothesis was examined in in vivo and cellular models of caerulein-induced AP using PKC activators and inhibitors. Phorbol ester, 12- O-tetradecanoylphorbol-13-acetate (TPA, 200 nM), a known activator of PKC, enhanced zymogen activation at both 0.1 nM and 100 nM caerulein, concentrations which mimic physiological and supraphysiological effects of the hormone cholecystokinin, respectively, in preparations of pancreatic acinar cells. Isoform-specific PKC inhibitors for PKC-δ and PKC-ε reduced supraphysiological caerulein-induced zymogen activation. Using a cell-free reconstitution system, we showed that inhibition of PKC-δ and -ε, reduced zymogen activation in both zymogen granule-enriched and microsomal fractions. In dispersed acinar cells, 100 nM caerulein stimulation caused PKC-δ and -ε isoform translocation to microsomal membranes using cell fractionation and immunoblot analysis. PKC translocation was confirmed with in vivo studies and immunofluorescence microscopy in pancreatic tissues from rats treated with or without 100 nM caerulein. PKC-ε redistributed from an apical to a supranuclear region following caerulein administration. The signal for PKC-ε overlapped with granule membrane protein, GRAMP-92, an endosomal/lysosomal marker, in a supranuclear region where zymogen activation takes place. These results indicate that PKC-δ and -ε isoforms translocate to specific acinar cell compartments and modulate zymogen activation.
    Type of Medium: Online Resource
    ISSN: 0193-1857 , 1522-1547
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477329-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 564-564
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 564-564
    Abstract: Introduction: Superparamagnetic relaxometry (SPMR) is an emerging technology that holds potential for use as a second-line screening modality to improve early cancer detection. During SPMR scanning, targeted superparamagnetic iron oxide nanoparticles (SPIONs) specifically bind to cancer cells and their spatial distribution can be characterized by measurement of the magnetic field relaxation following a brief excitation pulse. Highly sensitive superconducting quantum interference devices (SQUIDs) detect relaxation of clusters of SPIONs bound to small tumors. Challenges inherent to the SPMR technology include measurement noise, as well as the competing influence of SPION uptake by healthy organs (namely the liver), which also contributes to the overall SPMR signal. Hence, manual and stand-alone classification of the SPMR data into positive (i.e., the subject has cancer) or negative (i.e., the subject does not have cancer) screen results can be erroneous. Methods: We employed a data-driven approach based on Gaussian process (GP) formulation tailored to SPMR datasets to systematically quantify the probability of cancer. In silico, we simulated the SPION uptake process and generated SPMR signals that closely resembled experimental data collected in mouse models of cancer. We investigated the classification accuracy for different amounts of SPION accumulation within the tumor, as well as different levels of measurement noise (coefficient of variation (CV)). In a phantom study, a mouse liver was simulated by clustering together nine cotton swabs containing a total of 150 μg of immobilized SPIONs, while a mouse tumor was simulated by a single cotton swab containing either 9.4 μg or 14.4 μg of immobilized SPIONs. An additional nine cotton swabs containing 32.3 μg of immobilized SPIONs ( & lt;5 μg per phantom) were evenly distributed within the scan plane to represent background SPIONs not bound to the tumor or liver. For each of the tumor phantoms, 18 datasets were collected using a magnetic relaxometry device (Senior Scientific LLC) by moving the phantom to 18 different locations. Moreover, 10 datasets were collected without using the tumor phantom to represent the expected signal from healthy mice. In each iteration, the background SPION phantoms were randomly relocated within the scan plane. Results: Our in silico analysis for tumor accumulations of 3% and 5% of the injected SPION dose achieved 87% and 97% classification accuracies, respectively, when CV=0 and 75% and 93% when CV=0.015. Similarly, in our phantom study, classification accuracies of 87.5% and 96.4%, respectively, were reported for the 9.4 μg and 14.4 μg tumor phantoms. Conclusion: Using a data-driven GP model, tumor-status classification accuracies of up to 96.4% were achieved in SPMR phantom datasets. In the future, we plan to evaluate the accuracy of our classifier in preclinical settings using animal datasets. Citation Format: Javad Sovizi, Sara L. Thrower, David Fuentes, Wolfgang Stefan, John D. Hazle, Kelsey Mathieu. Binary classification of superparamagnetic relaxometry data for cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 564. doi:10.1158/1538-7445.AM2017-564
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 5, No. Supplement_3 ( 2023-08-04), p. iii12-iii12
    Abstract: Radiotherapy (RT) targets are commonly defined on post-operative (post-op) MRI registered to CT simulation images. However, changes can occur between surgery and simulation due to tumor progression and post-operative healing. In this work, we evaluate the impact of treatment planning using MR images taken at the time of CT simulation (MR-sim) versus post-op MRI. METHODS We evaluated 30 patients with primary HGG who received post-op MRI followed by RT planned using an MR-sim. We retrospectively delineated the gross tumor volume (GTV), clinical target volume (CTV), and normal structures on the post-op MRI and generated an experimental RT plan for these volumes. The RT plans based on post-op and MR-sim images were compared to determine the volume of tumor tissue that would have been undertreated, and the amount of normal brain tissue that would have been exposed to radiation (overtreated) had the plan been based on the post-op imaging. RESULTS The mean length between post-op imaging and MR-sim was 26 days (range: 12-42). A mean of 7.3cc (range 0.36cc–25.23cc) and 32.4cc (0.35–140.14cc) of the GTV and CTV, respectively, were undertreated on the post-op MRI plan compared to the MR-sim plan. The plan based on post-op target volumes resulted in a mean decrease in prescription dose coverage of the MR-sim-based GTV and CTV of 15.8% (max 72%) and 11.7% (max 57%), respectively. A mean of 14.5cc (0.04cc–53.9cc) and 47.5cc (range 2.4–179.2) of non-target brain tissue as identified on the MR-sim were included in the post-op MRI-based GTV and CTV, respectively. On average, the optic chiasm and brainstem would have received 191cGy and 117cGy more dose than intended, respectively. CONCLUSIONS Our findings confirm the valuable impact of RT planning using MR-sim in HGG to optimize treatment targets and reduce the exposure of normal tissue to unnecessary toxicity.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 6
    Online Resource
    Online Resource
    Elsevier BV ; 2024
    In:  Practical Radiation Oncology ( 2024-3)
    In: Practical Radiation Oncology, Elsevier BV, ( 2024-3)
    Type of Medium: Online Resource
    ISSN: 1879-8500
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e14013-e14013
    Abstract: e14013 Background: Ipilimumab/Nivolumab (Ipi/Nivo) significantly transformed outcomes for patients with melanoma brain metastases (MBM), however inter- and intra-patient responses can vary widely. The purpose of this study is to develop and calibrate an imaging-based mathematical model to predict lesion-specific immune response to Ipi/Nivo in patients with MBM to guide early local treatments such as radiotherapy and evaluate the prognostic value of identifying treatment resistant lesions. Methods: Baseline and follow-up 3D T1-W contrast MRIs of patients who solely received Ipi/Nivo after diagnosis with MBM were used to segment individual brain metastases and track serial volumetric data for each lesion to develop a mechanistic model (eq 1). After applying appropriate assumptions to our model, tumor burden ( ρ), intrinsic lesion growth rate ( α 0 ), Ipi/Nivo-induced kill rate ( μ) and immune response strength ( Λ) were quantified for each lesion. Growth rate shortly after the start of treatment ( α 1 ) was calculated using the short-term model solution (eq 2). dρ/dt= (α 0 - μ+μ.Λ).ρ - μ.Λ.ρ 2 (eq 1) ρ(t)≈e α 1.t (eq 2) Change in BM volume between baseline and last follow-up was used to classify each lesion as either ‘responder’ or ‘non-responder’; these were compared with the Wilcoxon-rank-sum test. The highest α 1 value for any one BM within a patient tumor was evaluated for its potential to sort patient overall survival (OS). Because the median survival was not reached for this cohort, we determined the α 1 threshold of 0.005 to sort patients using an optimization routine that generates the maximum AUC to separate the cohort into 2 groups on an ROC curve. Kaplan-Meier (KM) curves were compared between these 2 groups. Results: In 23 patients, we evaluated 61 lesions. At the lesion level, model parameters representing μ and Λ were significantly different between responder and non-responder lesions (p-values 〈 0.0001 and 0.0004, respectively). The highest α 1 value for any one BM within a patient tumor was used to sort patient overall survival (OS) into prognostically ‘favorable’ or ‘unfavorable’ groups based on patient survival to ±1,200 days. In this limited cohort, OS KM curves by most aggressive lesion for favorable (α 1 〈 0.005) vs. unfavorable (α 1 〉 0.005) were not significant by log-rank test (p = 0.3263). Conclusions: In this limited cohort, we demonstrate feasibility to leverage serial conventional imaging and tumor volumetric data to calibrate a mechanistic model to predict per-lesion treatment response of MBM to Ipi/Nivo. Although the p-value between groups was found to be insignificant when predicting survival using α 1 , this is likely because of the small number of patients included in this study (n=23). Furthermore, when taken together with the notable AUC (=0.7917) observed in the ROC curve, this promising result supports further investigation in a larger cohort.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2016
    In:  International Journal of Radiation Oncology*Biology*Physics Vol. 95, No. 5 ( 2016-08), p. 1520-1526
    In: International Journal of Radiation Oncology*Biology*Physics, Elsevier BV, Vol. 95, No. 5 ( 2016-08), p. 1520-1526
    Type of Medium: Online Resource
    ISSN: 0360-3016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 9
    In: Nature Computational Science, Springer Science and Business Media LLC, Vol. 2, No. 9 ( 2022-09-08), p. 605-616
    Abstract: The clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought to determine whether there were common patterns of disease progression that could aid in the design and analysis of clinical trials. We developed an approach based on a mixture of Gaussian processes to identify clusters of patients sharing similar disease progression patterns, modeling their average trajectories and the variability in each cluster. We show that ALS progression is frequently nonlinear, with periods of stable disease preceded or followed by rapid decline. We also show that our approach can be extended to Alzheimer’s and Parkinson’s diseases. Our results advance the characterization of disease progression of ALS and provide a flexible modeling approach that can be applied to other progressive diseases.
    Type of Medium: Online Resource
    ISSN: 2662-8457
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 3029424-1
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  • 10
    In: Sensors, MDPI AG, Vol. 22, No. 18 ( 2022-09-08), p. 6785-
    Abstract: (1) Background: The Exradin W2 is a commercially available scintillator detector designed for reference and relative dosimetry in small fields. In this work, we investigated the performance of the W2 scintillator in a 10 MV flattening-filter-free photon beam and compared it to the performance of ion chambers designed for small field measurements. (2) Methods: We measured beam profiles and percent depth dose curves with each detector and investigated the linearity of each system based on dose per pulse (DPP) and pulse repetition frequency. (3) Results: We found excellent agreement between the W2 scintillator and the ion chambers for beam profiles and percent depth dose curves. Our results also showed that the two-voltage method of calculating the ion recombination correction factor was sufficient to correct for the ion recombination effect of ion chambers, even at the highest DPP. (4) Conclusions: These findings show that the W2 scintillator shows excellent agreement with ion chambers in high DPP conditions.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2052857-7
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