Publications by authors named "Giles R"

There is increasing recognition in the field of health and social care research that community-engaged methods should include patients and the public throughout the research process. Therefore, individuals from all backgrounds should be involved in the research. We explored the public and patient engagement experience in research and how researchers and community groups can work together to make the research process more inclusive and sustainable.

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Article Synopsis
  • Immune-oncology strategies are improving treatment for renal cell carcinoma (RCC), especially with the introduction of immunotherapy in the perioperative setting.
  • Adjuvant therapy with pembrolizumab has shown benefits in disease-free survival post-surgery but there's limited support for neoadjuvant therapies outside trials; both strategies have their risks and challenges.
  • While adjuvant immunotherapy is now a standard treatment, understanding the optimal use of neoadjuvant approaches is still unclear and requires further research in biomarker development and clinical trials.
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While the centrality of posttranscriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one of the most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (mU54). Here, we uncover contributions of mU54 to both tRNA maturation and protein synthesis.

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After moderate to severe traumatic brain injury (TBI), sleep disturbance commonly emerges during the confused post-traumatic amnesia (PTA) recovery stage. However, the evaluation of early sleep disturbance during PTA, its recovery trajectory, and influencing factors is limited. This study aimed to evaluate sleep outcomes in patients experiencing PTA using ambulatory gold-standard polysomnography (PSG) overnight and salivary endogenous melatonin (a hormone that influences the sleep-wake cycle) assessment at two time-points.

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The endothelial linings of capillaries, such as those in the kidney and small intestines, possess fenestrae that facilitate fluid and exchange of small molecules. Alterations in the size and number of endothelial fenestrae have been implicated in the pathogenesis of various diseases. The re-creation of fenestrated endothelium using human induced pluripotent stem cells (hiPSCs) provides a promising avenue to investigate the involvement of fenestrae in disease mechanisms and pharmacodynamics.

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Vascular smooth muscle cells (VSMCs) play a pivotal role in vascular homeostasis, with dysregulation leading to vascular complications. Human-induced pluripotent stem-cell (hiPSC)-derived VSMCs offer prospects for personalized disease modeling and regenerative strategies. Current research lacks comparative studies on the impact of three-dimensional (3D) substrate properties under cyclic strain on phenotypic adaptation in hiPSC-derived VSMCs.

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ESA's Jupiter Icy Moons Explorer (JUICE) will provide a detailed investigation of the Jovian system in the 2030s, combining a suite of state-of-the-art instruments with an orbital tour tailored to maximise observing opportunities. We review the Jupiter science enabled by the JUICE mission, building on the legacy of discoveries from the Galileo, Cassini, and Juno missions, alongside ground- and space-based observatories. We focus on remote sensing of the climate, meteorology, and chemistry of the atmosphere and auroras from the cloud-forming weather layer, through the upper troposphere, into the stratosphere and ionosphere.

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Background Away rotations allow emergency medicine (EM)-bound fourth-year medical students to experience a residency program's educational culture and influence the ranking of residency programs. The financial cost and geographic distance have limited student participation in away electives. In recent years, COVID-19 pandemic-related restrictions on away rotations resulted in the creation of multiple virtual courses.

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Background: There is inconsistency in outcomes collected in renal cell cancer (RCC) intervention effectiveness studies and variability in their definitions. This makes critical summaries of the evidence base difficult and sub-optimally informative for clinical practice guidelines and decision-making by patients and healthcare professionals. A solution is to develop a core outcome set (COS), an agreed minimum set of outcomes to be reported in all trials in a clinical area.

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RNAs are central to protein synthesis, with ribosomal RNA, transfer RNAs and messenger RNAs comprising the core components of the translation machinery. In addition to the four canonical bases (uracil, cytosine, adenine, and guanine) these RNAs contain an array of enzymatically incorporated chemical modifications. Transfer RNAs (tRNAs) are responsible for ferrying amino acids to the ribosome, and are among the most abundant and highly modified RNAs in the cell across all domains of life.

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Background: Refractory ventricular dysrhythmia, or electrical storm, is a cardiac condition consisting of three or more episodes of ventricular dysrhythmia resistant to treatment within a 24-hour period. These dysrhythmias carry high morbidity and mortality if not diagnosed and abated promptly. When traditional resuscitative algorithms fail to return a patient to a perfusing rhythm, providers need to consider other, more novel techniques to terminate these dangerous dysrhythmias.

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Expression of concern for 'Direct observation of the THz Kerr effect (TKE) in deionized, distilled and buffered (PBS) water' by Andrzej Dobek , , 2017, , 26749-26757, https://doi.org/10.1039/c7cp04061j.

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Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making.

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In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER).

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The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective.

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Article Synopsis
  • - CIViC is a public, crowd-sourced database that compiles peer-reviewed research on the clinical significance of cancer variants to aid in cancer management.
  • - It offers structured data in real-time to facilitate global access and is designed to keep up with evolving variant interpretation guidelines and enhance collaboration with other resources.
  • - The platform has successfully expanded to include new Evidence Types related to cancer variants and now features contributions from over 300 experts, covering more than 3200 variants across 470 genes from over 3100 published studies.
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Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements.

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The effect of LC mobile phase composition and flow rate (2-50 µL/min) on mobility behavior in vacuum differential mobility spectrometry (vDMS) was investigated for electrosprayed isobaric antidepressant drugs (AD); amitriptyline, maprotiline, venlafaxine; and structurally related antidepressants nortriptyline, imipramine, and desipramine. While at 2 µL/min, no difference in compensation voltage was observed with methanol and acetonitrile, at 50 µL/min, acetonitrile used for LC elution of analytes enabled the selectivity of the mobility separation to be improved. An accurate and sensitive method could be developed for the quantification of six AD drugs in human plasma using trap/elute micro-LC setup hyphenated to vDMS with mass spectrometric detection in the selected ion monitoring mode.

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Study Objectives: Sleep disturbance often emerges in the early recovery phase following a moderate to severe traumatic brain injury, known as posttraumatic amnesia. Actigraphy is commonly employed to assess sleep, as it is assumed that patients in posttraumatic amnesia (who display confusion, restlessness, and agitation) would better tolerate this measure over gold-standard polysomnography (PSG). This study evaluated the agreement between PSG and actigraphy for determining (sleep/wake time, sleep efficiency, sleep latency, and awakenings) in patients experiencing posttraumatic amnesia.

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Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery.

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As guidelines, therapies, and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public domain, crowd-sourced, and adaptable knowledgebase of evidence for the Clinical Interpretation of Variants in Cancer, designed to reduce barriers to knowledge sharing and alleviate the variant interpretation bottleneck.

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Background: Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel-Lindau (VHL) disease.

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