Publications by authors named "Kevin M Bradley"

Aim: To evaluate a deep learning-based time-of-flight (DLToF) model trained to enhance the image quality of non-ToF PET images for different tracers, reconstructed using BSREM algorithm, towards ToF images.

Methods: A 3D residual U-NET model was trained using 8 different tracers (FDG: 75% and non-FDG: 25%) from 11 sites from US, Europe and Asia. A total of 309 training and 33 validation datasets scanned on GE Discovery MI (DMI) ToF scanners were used for development of DLToF models of three strengths: low (L), medium (M) and high (H).

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Environmental surveillance and clinical diagnostics heavily rely on the polymerase chain reaction (PCR) for target detection. A growing list of microbial threats warrants new PCR-based detection methods that are highly sensitive, specific, and multiplexable. Here, we introduce a PCR-based icosaplex (20-plex) assay for detecting 18 enteropathogen and two antimicrobial resistance genes.

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By rearranging hydrogen bond donor and acceptor groups within a standard Watson-Crick geometry, DNA can add eight independently replicable nucleotides forming four additional not found in standard Terran DNA. For many applications, the orthogonal pairing of standard and nonstandard pairs offers a key advantage. However, other applications require standard and nonstandard nucleotides to communicate with each other.

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Article Synopsis
  • The study presents a new PCR-based multiplex assay called icosaplex (20-plex) designed to detect 18 enteropathogens and 2 antimicrobial resistance genes with high sensitivity and specificity.
  • It utilizes advanced techniques such as self-avoiding molecular recognition system (SAMRS) and artificially expanded genetic information system (AEGIS) to enhance detection while preventing common issues like primer dimer formation.
  • The assay was tested on a portable sequencing platform, showing strong agreement in results and demonstrating potential for application in wastewater epidemiology, environmental monitoring, and diagnostics for humans and animals.
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We present the draft genome of the bacterium strain AK152, a thermophilic, endospore-spore-forming, anaerobe isolated from a hot spring in Grensdalur, in Southwestern Iceland. This assembled genome will lay the foundation for identifying the carboxylic and amino acid fermentation pathways, suggesting biotechnological applications for this strain.

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Introduction: Higher incidences of interpersonal violence were reported throughout the country during the coronavirus (COVID) time period. We aimed to compare health-care encounters and resource utilization related to interpersonal violence with mental health (MH) disorders before and during the pandemic within a year of the index visit for interpersonal violence.

Methods: A retrospective analysis of the Delaware Healthcare Claims data of all patients aged ≥16 y who suffered interpersonal violence was performed.

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A 79-year-old man found to have a pulmonary nodule and pleural effusion on CT went on to have an 18 F-FDG PET/CT scan. The lung abnormality did not show FDG uptake and appeared benign. However, PET/CT detected moderately increased FDG uptake associated with a left atrial appendage closure device inserted 11 months prior to the PET/CT.

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With just four building blocks, low sequence information density, few functional groups, poor control over folding, and difficulties in forming compact folds, natural DNA and RNA have been disappointing platforms from which to evolve receptors, ligands, and catalysts. Accordingly, synthetic biology has created "artificially expanded genetic information systems" (AEGIS) to add nucleotides, functionality, and information density. With the expected improvements seen in AegisBodies and AegisZymes, the task for synthetic biologists shifts to developing for expanded DNA the same analytical tools available to natural DNA.

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The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the 'molecular tumour board' into 'standard of care' ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting.

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Background: Investigate the potential benefits of sequential deployment of two deep learning (DL) algorithms namely DL-Enhancement (DLE) and DL-based time-of-flight (ToF) (DLT). DLE aims to enhance the rapidly reconstructed ordered-subset-expectation-maximisation algorithm (OSEM) images towards block-sequential-regularised-expectation-maximisation (BSREM) images, whereas DLT aims to improve the quality of BSREM images reconstructed without ToF. As the algorithms differ in their purpose, sequential application may allow benefits from each to be combined.

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Arthropod-borne viruses are major causes of human and animal disease, especially in endemic low- and middle-income countries. Mosquito-borne pathogen surveillance is essential for risk assessment and vector control responses. Sentinel chicken serosurveillance (antibody testing) and mosquito pool screening (by RT-qPCR or virus isolation) are currently used to monitor arbovirus transmission, however substantial time lags of seroconversion and/or laborious mosquito identification and RNA extraction steps sacrifice their early warning value.

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Many efforts have sought to apply laboratory evolution (LIVE) to natural nucleic acid (NA) scaffolds to directly evolve functional molecules. However, synthetic biology can move beyond natural NA scaffolds to create molecular systems whose libraries are far richer reservoirs of functionality than natural NAs. For example, "artificially expanded genetic information systems" (AEGIS) add up to eight nucleotides to the four found in standard NA.

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Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain.

Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m)/capecitabine (625 mg/m days 1-21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUV) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m) for a further induction cycle, then concurrently with radiotherapy over 25 fractions.

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Recently reported "displaceable probe" loop amplification (DP-LAMP) architecture has shown to amplify viral RNA from SARS-CoV-2 with little sample processing. The architecture allows signals indicating the presence of target nucleic acids to be spatially separated, and independent in sequence, from the complicated concatemer that LAMP processes create as part of their amplification process. This makes DP-LAMP an attractive molecular strategy to integrate with trap and sampling innovations to detect RNA from arboviruses carried by mosquitoes in the field.

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Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson's disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson's disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals.

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The ability of nucleic acids to catalyze reactions (as well as store and transmit information) is important for both basic and applied science, the first in the context of molecular evolution and the origin of life and the second for biomedical applications. However, the catalytic power of standard nucleic acids (NAs) assembled from just four nucleotide building blocks is limited when compared with that of proteins. Here, we assess the evolutionary potential of libraries of nucleic acids with six nucleotide building blocks as reservoirs for catalysis.

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Objective: CT and staging laparoscopy are routinely used to stage patients with gastric cancer, however the role of F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with CT (PET-CT) is uncertain. This systematic review synthesised the evidence regarding the impact of baseline PET-CT staging on treatment decisions and patient outcomes.

Methods: Systematic database searches were performed without date restriction.

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Purpose: To improve the quantitative accuracy and diagnostic confidence of PET images reconstructed without time-of-flight (ToF) using deep learning models trained for ToF image enhancement (DL-ToF).

Methods: A total of 273 [F]-FDG PET scans were used, including data from 6 centres equipped with GE Discovery MI ToF scanners. PET data were reconstructed using the block-sequential-regularised-expectation-maximisation (BSREM) algorithm with and without ToF.

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We present a case of sporadic Creutzfeldt-Jakob disease with profoundly abnormal 18fluoro-deoxy-glucose positron emission tomography with computed tomography (FDG PET-CT) at an early stage, and correlate this with the clear findings at magnetic resonance imaging and also postmortem histology. Prion diseases are rare but important causes of cognitive impairment. The role of FDG PET-CT is discussed, along with other investigations such as electroencephalography and cerebro-spinal fluid analyses.

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Purpose: To enhance the image quality of oncology [F]-FDG PET scans acquired in shorter times and reconstructed by faster algorithms using deep neural networks.

Methods: List-mode data from 277 [F]-FDG PET/CT scans, from six centres using GE Discovery PET/CT scanners, were split into ¾-, ½- and ¼-duration scans. Full-duration datasets were reconstructed using the convergent block sequential regularised expectation maximisation (BSREM) algorithm.

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18F-fluorodeoxyglucose PET-CT may guide treatment decisions in patients with oesophageal adenocarcinoma (OAC). This study evaluated the added value of maximum standardised uptake value (SUVmax) to a novel DNA-damage immune response (DDIR) assay to improve pathological response prediction. The diagnostic accuracy of PET response and the prognostic significance of PET metrics for recurrence-free survival (RFS) and overall survival (OS) were assessed.

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