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  • 1
    In: Magnetic Resonance in Medicine, Wiley, Vol. 91, No. 5 ( 2024-05), p. 1803-1821
    Abstract: has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging–Dynamic Contrast‐Enhanced (OSIPI‐DCE) challenge was designed to benchmark methods to better help the efforts to standardize measurement. Methods A framework was created to evaluate values produced by DCE‐MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' values, the applied software, and a standard operating procedure. These were evaluated using the proposed score defined with accuracy, repeatability, and reproducibility components. Results Across the 10 received submissions, the score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0–1 = lowest–highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. Conclusions This study reports results from the OSIPI‐DCE challenge and highlights the high inter‐software variability within estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real‐world clinical setting, many of these tools may perform differently with different benchmarking methodology.
    Type of Medium: Online Resource
    ISSN: 0740-3194 , 1522-2594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2024
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  • 2
    In: Angewandte Chemie International Edition, Wiley
    Abstract: Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol‐histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O 2 ‐dependent C−S bond formation catalyzed by non‐heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S =1 iron(IV) intermediate supported by a four‐histidine ligand environment (three from the protein residues and one from the substrate) in enabling C−S bond formation in OvoA from Methyloversatilis thermotoleran , which represents the first experimentally observed intermediate spin iron(IV) species in non‐heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C−S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure‐function relationship of high‐valent iron intermediates supported by a histidine rich ligand environment.
    Type of Medium: Online Resource
    ISSN: 1433-7851 , 1521-3773
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 3
    In: Angewandte Chemie, Wiley
    Abstract: Ergothioneine (ESH) and ovothiol A (OSHA) are two natural thiol‐histidine derivatives. ESH has been implicated as a longevity vitamin and OSHA inhibits the proliferation of hepatocarcinoma. The key biosynthetic step of ESH and OSHA in the aerobic pathways is the O 2 ‐dependent C−S bond formation catalyzed by non‐heme iron enzymes (e.g., OvoA in ovothiol biosynthesis), but due to the lack of identification of key reactive intermediate the mechanism of this novel reaction is unresolved. In this study, we report the identification and characterization of a kinetically competent S =1 iron(IV) intermediate supported by a four‐histidine ligand environment (three from the protein residues and one from the substrate) in enabling C−S bond formation in OvoA from Methyloversatilis thermotoleran , which represents the first experimentally observed intermediate spin iron(IV) species in non‐heme iron enzymes. Results reported in this study thus set the stage to further dissect the mechanism of enzymatic oxidative C−S bond formation in the OSHA biosynthesis pathway. They also afford new opportunities to study the structure‐function relationship of high‐valent iron intermediates supported by a histidine rich ligand environment.
    Type of Medium: Online Resource
    ISSN: 0044-8249 , 1521-3757
    RVK:
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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    detail.hit.zdb_id: 506609-8
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    detail.hit.zdb_id: 505872-7
    detail.hit.zdb_id: 1479266-7
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  • 4
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 9 ( 2023-09), p. 3806-3814
    Abstract: Resting‐state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment. METHODS Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one‐time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers. RESULTS Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings. DISCUSSION Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early‐stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present. Highlights Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 5
    In: Bioelectromagnetics, Wiley, Vol. 44, No. 1-2 ( 2023-01), p. 5-16
    Abstract: Previous research has shown that virus infectivity can be dramatically reduced by radio frequency exposure in the gigahertz (GHz) frequency range. Given the worldwide SARS‐CoV‐2 pandemic, which has caused over 1 million deaths and has had a profound global economic impact, there is a need for a noninvasive technology that can reduce the transmission of virus among humans. RF is a potential wide area‐of‐effect viral decontamination technology that could be used in hospital rooms where patients are expelling virus, in grocery and convenience stores where local populations mix, and in first responder settings where rapid medical response spans many potentially infected locations within hours. In this study, we used bovine coronavirus (BCoV) as a surrogate of SARS‐CoV‐2 and exposed it to high peak power microwave (HPPM) pulses at four narrowband frequencies: 2.8, 5.6, 8.5, and 9.3 GHz. Exposures consisted of 2 µs pulses delivered at 500 Hz, with pulse counts varied by decades between 1 and 10,000. The peak field intensities (i.e. the instantaneous power density of each pulse) ranged between 0.6 and 6.5 MW/m 2 , depending on the microwave frequency. The HPPM exposures were delivered to plastic coverslips containing BCoV dried on the surface. Hemagglutination (HA) and cytopathic effect analyses were performed 6 days after inoculation of host cells to assess viral infectivity. No change in viral infectivity was seen with increasing dose (pulse number) across the tested frequencies. Under all conditions tested, exposure did not reduce infectivity more than 1.0 log 10. For the conditions studied, high peak power pulsed RF exposures in the 2–10 GHz range appear ineffective as a virucidal approach for hard surface decontamination. © 2023 Bioelectromagnetics Society.
    Type of Medium: Online Resource
    ISSN: 0197-8462 , 1521-186X
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 6
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S1 ( 2022-12)
    Abstract: Fluorodeoxyglucose positron emission tomography (FDG‐PET) is an established modality for differential diagnosis of dementia. Deriving phenotypic signatures from FDG‐PET via machine learning is challenging due to the high dimensional nature of brain images relative to the generally small number of labeled examples available for training, the class imbalance among those labels, and the cooccurrence of multiple pathologies. In this study, we developed a multi‐class, multi‐label framework to address these challenges. Method A database of clinically acquired PET/CT images from 3,000 unique patients was used to develop a latent space model using matrix decomposition. This model was then applied to images from a separate cohort of Mayo Clinic Alzheimer’s Disease Research Center participants (n=1,745) labeled as cognitively unimpaired (CU) (n=1,436) or with the following potentially co‐occurring phenotypes: Alzheimer’s disease (AD) (n=165), Lewy body dementia (DLB) (n=92), behavioral variant frontotemporal dementia (bvFTD) (n=43), semantic (svPPA) (n=10) and logopenic (lvPPA) (n=13) variant PPA, and posterior cortical atrophy (PCA) (n=17). A k‐ nearest neighbors classifier that is robust to these imbalanced and overlapping labels was then trained on these examples. The resulting classifier was evaluated by area under receiver‐operator characteristic curve (ROC‐AUC) via leave one out cross validation, using clinical diagnosis as the gold standard. Result ROC curves and AUC scores for each phenotype are illustrated in Fig. 1a. Because the classifier is based on a k‐ nearest neighbors connectivity matrix, it has a convenient graphical representation, where images are nodes and edges are drawn between an image and its set of nearest neighbors in latent space. A self‐organizing force directed graph constructed in this way is illustrated in Fig 1b, highlighting the strong separation of CU and degenerative images, as well as the segregation of each phenotype within the neurodegenerative region of the graph. Conclusion In this study, we developed a machine learning framework for classification of neurodegenerative disease based on k‐ nearest neighbor analysis in a low dimensional latent space projection of FDG‐PET images. By leveraging low‐dimensional representations and k ‐nearest neighbors analysis, this framework is robust in multi‐class, multi‐label tasks with strong class imbalance and provides a highly interpretable graphical representation.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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  • 7
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S5 ( 2022-12)
    Abstract: Fluorodeoxyglucose positron emission tomography (FDG‐PET) is an established modality for differential diagnosis of dementia. Deriving phenotypic signatures from FDG‐PET via machine learning is challenging due to the high dimensional nature of brain images relative to the generally small number of labeled examples available for training, the class imbalance among those labels, and the cooccurrence of multiple pathologies. In this study, we developed a multi‐class, multi‐label framework to address these challenges. Method A database of clinically acquired PET/CT images from 3,000 unique patients was used to develop a latent space model using matrix decomposition. This model was then applied to images from a separate cohort of Mayo Clinic Alzheimer’s Disease Research Center participants (n=1,745) labeled as cognitively unimpaired (CU) (n=1,436) or with the following potentially co‐occurring phenotypes: Alzheimer’s disease (AD) (n=165), Lewy body dementia (DLB) (n=92), behavioral variant frontotemporal dementia (bvFTD) (n=43), semantic (svPPA) (n=10) and logopenic (lvPPA) (n=13) variant PPA, and posterior cortical atrophy (PCA) (n=17). A k‐ nearest neighbors classifier that is robust to these imbalanced and overlapping labels was then trained on these examples. The resulting classifier was evaluated by area under receiver‐operator characteristic curve (ROC‐AUC) via leave one out cross validation, using clinical diagnosis as the gold standard. Result ROC curves and AUC scores for each phenotype are illustrated in Fig. 1a. Because the classifier is based on a k‐ nearest neighbors connectivity matrix, it has a convenient graphical representation, where images are nodes and edges are drawn between an image and its set of nearest neighbors in latent space. A self‐organizing force directed graph constructed in this way is illustrated in Fig 1b, highlighting the strong separation of CU and degenerative images, as well as the segregation of each phenotype within the neurodegenerative region of the graph. Conclusion In this study, we developed a machine learning framework for classification of neurodegenerative disease based on k‐ nearest neighbor analysis in a low dimensional latent space projection of FDG‐PET images. By leveraging low‐dimensional representations and k ‐nearest neighbors analysis, this framework is robust in multi‐class, multi‐label tasks with strong class imbalance and provides a highly interpretable graphical representation.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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  • 8
    In: Restoration Ecology, Wiley, Vol. 30, No. 4 ( 2022-05)
    Abstract: Louisiana contains nearly 40% of estuarine herbaceous wetlands in the contiguous United States, supporting valuable ecosystem services and providing significant economic benefits to the state and the entire United States. However, coastal Louisiana is a hotspot for rapid land loss from factors including hurricanes, land use change, and high subsidence rates contributing to high relative sea‐level rise. The Coastal Protection and Restoration Authority (CPRA) was established after major hurricanes in 2005 to coordinate coastal restoration in Louisiana and develop the Louisiana Coastal Master Plan. The LA Coastal Master Plan uses numerical modeling of multiple scenarios to select a suite of restoration projects based on maximum land area created and flood reduction (as proxies for ecosystem value). Using potential value to aquatic, terrestrial, and social resources, our work compared habitat value of shallow open water areas to emergent wetland. While potential resource benefits varied by emergent wetland salinity type and emergent wetland versus water, they were similar, suggesting that restoration planning based primarily on wetland land area may not achieve the maximum possible ecosystem benefits. After nearly 20 years of integrated restoration planning in coastal Louisiana, a reassessment of restoration planning decision drivers may be beneficial to ensure maximum benefits from coastal restoration. As a result of the Deepwater Horizon oil spill, settlement funds will be a major support to coastal restoration in Louisiana for many years. Assessing potential habitat value to multiple natural and social resources in Louisiana has potential to maximize synergy with large northern Gulf of Mexico restoration programs.
    Type of Medium: Online Resource
    ISSN: 1061-2971 , 1526-100X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    detail.hit.zdb_id: 914746-9
    SSG: 12
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  • 9
    In: British Journal of Haematology, Wiley, Vol. 197, No. 3 ( 2022-05), p. 326-338
    Abstract: It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI)  〉  30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post‐transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013–2017) ( N  = 16 182) using MUD ( n  = 11 801), haplo ( n  = 2894) and CBU ( n  = 1487) were included. The primary outcome was non‐relapse mortality (NRM). The analysis demonstrated a significant, non‐linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25–30 [hazard ratio (HR) 1.66–1.71, p   〈  0.05] and MUD transplants at a BMI of 25–45 (HR, 1.61–3.47, p   〈  0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1475751-5
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  • 10
    In: Alzheimer's & Dementia, Wiley, Vol. 18, No. S5 ( 2022-12)
    Abstract: In vivo tau‐positron emission tomography (PET) is an attractive biomarker for Alzheimer’s disease (AD) diagnosis and treatment. However, tau‐PET is less widely available than other modalities. In this study, we tested cross‐modality synthesis of tau‐PET brain images from fluorodeoxyglucose F‐18 (FDG)‐PET using a deep convolutional neural network (CNN). Method Participants (n=1,192) who had brain FDG‐PET with 18 F‐FDG and tau‐PET with Flortaucipir (F‐18‐AV‐1451) were included for training and testing. This cohort spanned normal aging (ages 26‐98), pre‐clinical, and clinical AD and related disorders including the FTD and DLB spectrum. External validation was done using ADNI (n=288). The PET scans were co‐registered to the corresponding MRI and subsequently warped to Mayo Clinic Adult Lifespan Template (MCALT) space. Tau‐PET images were SUVR‐normalized to the cerebellar crus, and FDG to the pons. A 3D dense‐U‐net model was utilized as an architecture. Cross‐validation experiments were conducted using 5‐fold validations (60% training set, 20% validation set, and 20% test set) with mean squared error as the loss function. Result Our dense‐U‐net model successfully synthesized tau‐PET from metabolic images with good correlation and low prediction error for regional SUVRs (Figure 1A‐C). The model showed a robust prediction ability, performing accurately in an independent, external ADNI cohort (Figure 1D‐F). The model‐imputed tau‐PET significantly improved performance in classifying tau positivity (mean AUROC(±SD)=0.78±0.04 and 0.85±0.03 for FDG‐PET and synthesized tau‐PET, respectively) and diagnostic groups (cognitively unimpaired with abnormal amyloid‐PET vs. cognitively impaired with abnormal amyloid‐PET) compared to the original input FDG data (mean AUROC(±SD)=0.89±0.04, 0.85±0.05 0.91±0.04 for actual tau‐PET, FDG‐PET and synthesized tau‐PET, respectively) (Figure 2), suggesting enhanced clinical utility for metabolic images. The ADNI cohort also showed similar results (for tau positivity: AUROC=0.66 and 0.78 for FDG‐PET and synthesized tau‐PET, respectively; for CU A+ vs. CI A+: AUROC=0.86, 0.62, and 0.73 for actual tau‐PET, FDG‐PET, and synthesized tau‐PET; Figure 3). Conclusion We showed that using a CNN model to predict tau‐PET from FDG‐PET is feasible. The synthesized tau‐PET can augment the value of FDG‐PET, facilitating the multi‐modal diagnosis of AD.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2201940-6
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