Publications by authors named "Paul Kennedy"

Purpose: To evaluate the value of pre-treatment MRI-based radiomics in patients with hepatocellular carcinoma (HCC) for the prediction of response to Yttrium 90 radiation segmentectomy.

Methods: This retrospective study included 154 patients (38 female; mean age 66.8 years) who underwent contrast-enhanced MRI prior to radiation segmentectomy.

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Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms.

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Unlabelled: Squamous cell carcinomas, which arise from the cells that line the mucosal surfaces of the head and neck, represent the most common type of head and neck cancers (HNSCC). Human papillomavirus (HPV) infection has been strongly associated with the development of oropharyngeal cancers, which are cancers that occur in the back of the throat, including the tonsils and base of the tongue. HNSCCs with and without HPV infection have distinct pathology, with HPV-positive patients having higher levels of immune infiltration, activation in the tumor microenvironment and better response to radiation and chemotherapy.

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Background: Visualising patient genomic data in a cohort with embedding data analytics models can provide relevant and sensible patient comparisons to assist a clinician with treatment decisions. As immersive technology is actively used around the medical world, there is a rising demand for an efficient environment that can effectively display genomic data visualisations on immersive devices such as a Virtual Reality (VR) environment. The VR technology will allow clinicians, biologists, and computer scientists to explore a cohort of individual patients within the 3D environment.

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CTLA-4 is a crucial immune checkpoint receptor involved in the maintenance of immune homeostasis, tolerance, and tumor control. Antibodies targeting CTLA-4 have been promising treatments for numerous cancers, but the mechanistic basis of their anti-tumoral immune-boosting effects is poorly understood. Although the ctla4 gene also encodes an alternatively spliced soluble variant (sCTLA-4), preclinical/clinical evaluation of anti-CTLA-4-based immunotherapies have not considered the contribution of this isoform.

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Objective: Treatment pathways are step-by-step plans outlining the recommended medical care for specific diseases; they get revised when different treatments are found to improve patient outcomes. Examining health records is an important part of this revision process, but inferring patients' actual treatments from health data is challenging due to complex event-coding schemes and the absence of pathway-related annotations. The objective of this study is to develop a method for inferring actual treatment steps for a particular patient group from administrative health records - a common form of tabular healthcare data - and address several technique- and methodology-based gaps in treatment pathway-inference research.

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Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies is challenging due to its immunosuppressive microenvironment. Efforts to date have focused on using immunotherapy to increase tumour immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; immune checkpoint inhibitors; drugs which enhance macrophage and natural killer T (NKT) cell function; modulation of the cyclic GMP-AMP synthase-stimulator of interferon genes pathway; and engineering neuroblastoma-targeting chimeric-antigen receptor-T cells. Some of these strategies have strong preclinical foundation and are being tested clinically, although none have demonstrated notable success in treating paediatric neuroblastoma to date.

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Tunicamycins (TUNs) are -derived natural products, widely used to block protein -glycosylation in eukaryotes or cell wall biosynthesis in bacteria. Modified or synthetic TUN analogues that uncouple these activities have considerable potential as novel mode-of-action antibacterial agents. Chemically modified TUNs reported previously with attenuated activity on yeast have pinpointed eukaryotic-specific chemophores in the uridyl group and the -acyl chain length and terminal branching pattern.

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Machine learning provides many powerful and effective techniques for analysing heterogeneous electronic health records (EHR). Administrative Health Records (AHR) are a subset of EHR collected for administrative purposes, and the use of machine learning on AHRs is a growing subfield of EHR analytics. Existing reviews of EHR analytics emphasise that the data-modality of the EHR limits the breadth of suitable machine learning techniques, and pursuable healthcare applications.

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Purpose: (1) Assess the diagnostic performance of liver 3D magnetic resonance elastography (MRE) parameters (including stiffness, storage/loss modulus and damping ratio) compared to liver stiffness measured with 2D MRE for noninvasive detection of advanced liver fibrosis (F3-F4) and cirrhosis (F4) in patients with chronic liver disease. (2) Assess the value of serum markers (FIB-4) in detecting advanced liver fibrosis and cirrhosis in the same patients.

Methods: This was a single center, prospective IRB-approved cross-sectional study that included 49 patients (M/F: 23/26, mean age 50.

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The increasing rates of breast cancer, particularly in emerging economies, have led to interest in scalable deep learning-based solutions that improve the accuracy and cost-effectiveness of mammographic screening. However, such tools require large volumes of high-quality training data, which can be challenging to obtain. This paper combines the experience of an AI startup with an analysis of the FAIR principles of the eight available datasets.

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Article Synopsis
  • Finding vaccines for certain parasites is really tricky, and there are not many approved vaccines for the diseases they cause.
  • Some types of vaccines work better, but they can also be more dangerous.
  • Scientists are trying a new method using computer programs to find good vaccine ideas based on a parasite's proteins, and they’ve even ranked proteins from Toxoplasma gondii to see which ones might help the immune system the most!
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Objective: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants in the dystrophin gene (). Hypermethylated CGG expansions within 5' UTR are associated with an intellectual development disorder. Here, we demonstrate the diagnostic utility of genomic short-read sequencing (SRS) and transcriptome sequencing to identify a novel structural variant (SV) and a CGG expansion in a patient with DMD for whom conventional diagnostic testing failed to yield a genetic diagnosis.

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Reverse vaccinology (RV) was described at its inception in 2000 as an in silico process that starts from the genomic sequence of the pathogen and ends with a list of potential protein and/or peptide candidates to be experimentally validated for vaccine development. Twenty-two years later, this process has evolved from a few steps entailing a handful of bioinformatics tools to a multitude of steps with a plethora of tools. Other in silico related processes with overlapping workflow steps have also emerged with terms such as subtractive proteomics, computational vaccinology, and immunoinformatics.

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Volumetric phase-contrast magnetic resonance imaging with three-dimensional velocity encoding (4D flow MRI) has shown utility as a non-invasive tool to examine altered blood flow in chronic liver disease. Novel 4D flow MRI pulse sequences with spatio-temporal acceleration can mitigate the long acquisition times of standard 4D flow MRI, which are an impediment to clinical adoption. The purpose of our study was to demonstrate feasibility of a free-breathing, spatio-temporal (k-t) accelerated 4D flow MRI acquisition for flow quantification in abdominal vessels and to compare its image quality, flow quantification and inter-observer reproducibility with a standard respiratory navigator-gated 4D flow MRI acquisition.

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Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT receptor family. 5-HTRs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular.

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Article Synopsis
  • The study looked at new ways to diagnose a liver condition called clinically significant portal hypertension by measuring different factors in patients' livers and spleens.
  • They used various medical imaging techniques and compared the results to traditional methods.
  • The results showed that some measurements, like liver T-HBP and ΔT, were good indicators for diagnosing this condition.
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  • This narrative review covers advancements in care and prevention of fragility fractures in New Zealand from 2012 to 2022, focusing on clinical standards and public awareness for bone health.
  • It outlines a strategic approach initiated by Osteoporosis New Zealand, promoting a national alliance to enhance care for those at risk of fractures.
  • The establishment of the Live Stronger for Longer program has led to improved clinical guidelines and a bi-national registry for monitoring and enhancing fracture care across all 22 New Zealand hospitals treating hip fracture patients.
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The significant advancement of inexpensive and portable virtual reality (VR) and augmented reality devices has re-energised the research in the immersive analytics field. The immersive environment is different from a traditional 2D display used to analyse 3D data as it provides a unified environment that supports immersion in a 3D scene, gestural interaction, haptic feedback and spatial audio. Genomic data analysis has been used in oncology to understand better the relationship between genetic profile, cancer type, and treatment option.

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Objectives: Portal hypertension (PH) is associated with complications such as ascites and esophageal varices and is typically diagnosed through invasive hepatic venous pressure gradient (HVPG) measurement, which is not widely available. In this study, we aim to assess the diagnostic performance of 2D/3D MR elastography (MRE) and shear wave elastography (SWE) measures of liver and spleen stiffness (LS and SS) and spleen volume, to noninvasively diagnose clinically significant portal hypertension (CSPH) using HVPG measurement as the reference.

Methods: In this prospective study, patients with liver disease underwent 2D/3D MRE and SWE of the liver and spleen, as well as HVPG measurement.

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The World Health Organisation reported in 2020 that six of the top 10 sources of death in low-income countries are parasites. Parasites are microorganisms in a relationship with a larger organism, the host. They acquire all benefits at the host's expense.

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Unlabelled: Magnetic Resonance Elastography (MRE) is a developing imaging technique that enables non-invasive estimation of tissue mechanical properties through the combination of induced mechanical displacements in the tissue and Magnetic Resonance Imaging (MRI). The mechanical drivers necessary to produce shear waves in the tissue have been a focus of engineering effort in the development and refinement of MRE. The potential targeting of smaller and stiffer tissues calls for increases in actuation frequency and refinement of mechanical driver positioning.

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Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of action for CD8 T cell (CTL)-mediated tumor killing. Mechanistically, IFNγ stimulates ACSL4 and alters tumor cell lipid pattern, thereby increasing incorporations of AA into C16 and C18 acyl chain-containing phospholipids.

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Background: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma.

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There is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer.

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