Monoallelic deletion of the short arm of chromosome 17 (del17p) is a recurrent abnormality in cancers with poor outcomes. Best studied in relation to haematological malignancies, associated functional outcomes are attributed mainly to loss and/or dysfunction of TP53, which is located at 17p13.1, but the wider impact of deletion of other genes located on 17p is poorly understood.
View Article and Find Full Text PDFIntroduction: Around the world, rates of induction of labour (IOL) among nulliparous mothers have increased in the last 10 years. In Australia, rates have increased over the last decade by 43%, from 32% to 46%. There is growing concern about the rapid rise in IOL before 41 weeks for nulliparous women without medical complications because of the associated increased rates of caesarean section, reduced satisfaction with birth, and birth trauma.
View Article and Find Full Text PDFChronic lymphocytic leukaemia (CLL) is the most common form of leukaemia among adults, particularly in Western nations. The introduction of Bruton's tyrosine kinase (BTK) inhibitors as a treatment of CLL, namely, ibrutinib, which is a first-generation BTK inhibitor, has significantly improved the treatment landscape for CLL. However, ibrutinib has been associated with an increased risk of atrial fibrillation (AF) and hypertension.
View Article and Find Full Text PDFIntrinsically disordered proteins (IDPs) often contain proline residues that undergo cis/trans isomerization. While molecular dynamics (MD) simulations have the potential to fully characterize the proline cis and trans subensembles, they are limited by the slow timescales of isomerization and force field inaccuracies. NMR spectroscopy can report on ensemble-averaged observables for both the cis-proline and trans-proline states, but a full atomistic characterization of these conformers is challenging.
View Article and Find Full Text PDFBackground: Patients from socioeconomically disadvantaged backgrounds are underserved in randomised controlled trials, yet they experience a much greater burden of disease compared with patients from socioeconomically advantaged areas. It is crucial to make trials more inclusive to ensure that treatments and interventions are safe and effective in real-world contexts. Improving how information about trials is verbally communicated is an unexplored strategy to make trials more inclusive.
View Article and Find Full Text PDFImmune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4 T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively.
View Article and Find Full Text PDFPurpose: This study examined treatment outcomes (depression and anxiety symptoms) up to 24 months after completion of a therapist-supported digital mental health intervention (DMHI).
Methods: The sample consisted of 380 participants who participated in an eight-week DMHI from February 6, 2017 to May 20, 2019. Participants reported depression and anxiety symptoms at eight timepoints from baseline to 24 months.
Background: Although pet hamsters are widely available, the literature on their husbandry and health is limited, and guidelines for the care of hamsters are variable. This study investigated housing in different dwarf hamster species, focusing on factors affecting co-housing failure.
Methods: An online cross-sectional survey shared on social media investigated potential factors influencing co-housing failure of dwarf hamsters in captivity, such as sex, species and resources provided.
Previous research on fielding in cricket and baseball has focused on the technique and speed-accuracy trade-off of the throw in isolation from a typical sequence of fielding actions; approach, gather and throw. The present study aimed to determine whether a speed-accuracy trade-off existed in fielding and where within the above sequence the trade-off occurs. Participants, who were elite cricketers, were required to run to a stationary ball and throw to the centre of a target in order to run-out a virtual batter.
View Article and Find Full Text PDFMantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma that is incurable with existing therapies, and therefore presents a significant unmet clinical need. The ability of this disease to overcome therapy, including those that target the B cell receptor pathway which has a pathogenic role in MCL, highlights the need to develop new treatment strategies. Herein, we demonstrate that a distinguishing feature of lymph node resident MCL cells is the expression of phosphatidylinositol 3-kinase γ (PI3Kγ), a PI3K isoform that is not highly expressed in other B cells or B-cell malignancies.
View Article and Find Full Text PDFThe value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity.
View Article and Find Full Text PDFUp-to-date information on coronavirus disease 2019 (COVID-19) outcomes and risk factors in haematopoietic cell transplantation (HCT) recipients is required to inform on decisions about cancer treatment and COVID-19 mitigation strategies. We performed a meta-analysis to address this knowledge gap. All studies with at least five patients who reported COVID-19-related deaths in HCT recipients were included.
View Article and Find Full Text PDFBackground: Understanding patient and health practitioner perspectives on clinical trials can inform opportunities to enhance trial conduct and design, and therefore patient experience. Patients with haematological cancers have faced additional risk and uncertainty during the pandemic but it is unclear how they and practitioners have experienced cancer trials during this period. In the context of a haemato-oncology trial (PETReA), we compared patient and practitioner views and experiences of PETReA before and during COVID-19.
View Article and Find Full Text PDFBMC Med Res Methodol
January 2022
Background: We consider cluster size data of SARS-CoV-2 transmissions for a number of different settings from recently published data. The statistical characteristics of superspreading events are commonly described by fitting a negative binomial distribution to secondary infection and cluster size data as an alternative to the Poisson distribution as it is a longer tailed distribution, with emphasis given to the value of the extra parameter which allows the variance to be greater than the mean. Here we investigate whether other long tailed distributions from more general extended Poisson process modelling can better describe the distribution of cluster sizes for SARS-CoV-2 transmissions.
View Article and Find Full Text PDFPurpose: B-cell receptor (BCR) signaling is critical for the pathogenesis of chronic lymphocytic leukemia (CLL), promoting both malignant cell survival and disease progression. Although vital, understanding of the wider signaling network associated with malignant BCR stimulation is poor. This is relevant with respect to potential changes in response to therapy, particularly involving kinase inhibitors.
View Article and Find Full Text PDF18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is now established as the gold-standard imaging modality for both staging and response assessment in follicular lymphoma (FL). In this Perspective, we propose where PET can, and cannot, guide clinicians in their therapeutic approach. PET at diagnosis and pretreatment is important for staging, with greater sensitivity compared with standard CT, and consequent improved outcomes in truly limited-stage FL.
View Article and Find Full Text PDFChronic lymphocytic leukaemia (CLL) exhibits variable clinical course and response to therapy, but the molecular basis of this variability remains incompletely understood. Data independent acquisition (DIA)-MS technologies, such as SWATH (Sequential Windowed Acquisition of all THeoretical fragments), provide an opportunity to study the pathophysiology of CLL at the proteome level. Here, a CLL-specific spectral library (7736 proteins) is described alongside an analysis of sample replication and data handling requirements for quantitative SWATH-MS analysis of clinical samples.
View Article and Find Full Text PDFPrognostication in patients with chronic lymphocytic leukemia (CLL) is challenging due to heterogeneity in clinical course. We hypothesize that constitutional genetic variation affects disease progression and could aid prognostication. Pooling data from seven studies incorporating 842 cases identifies two genomic locations associated with time from diagnosis to treatment, including 10q26.
View Article and Find Full Text PDFThe COVID-19 pandemic has been a disruptive event for cancer patients, especially those with haematological malignancies (HM). They may experience a more severe clinical course due to impaired immune responses. This multi-center retrospective UK audit identified cancer patients who had SARS-CoV-2 infection between 1 March and 10 June 2020 and collected data pertaining to cancer history, COVID-19 presentation and outcomes.
View Article and Find Full Text PDFAn increasing number of genome-wide association studies (GWAS) summary statistics is made available to the scientific community. Exploiting these results from multiple phenotypes would permit identification of novel pleiotropic associations. In addition, incorporating prior biological information in GWAS such as group structure information (gene or pathway) has shown some success in classical GWAS approaches.
View Article and Find Full Text PDFCOVID-19 emerged in November 2019 leading to a global pandemic that has not only resulted in widespread medical complications and loss of life, but has also impacted global economies and transformed daily life. The current rapid response study in a convenience online sample quickly recruited 2,065 participants across the United States, Canada, and Europe in late March and early April 2020. Cross-sectional findings indicated elevated anxiety and depressive symptoms compared to historical norms, which were positively associated with COVID-19 concern more strongly than epidemiological data signifying risk (e.
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