The actin regulatory protein fascin (FSCN1) and epithelial mesenchymal transition (EMT) transcription factor (TF) SLUG/SNAI2 have been shown to be expressed in PDAC and its precursor lesions (pancreatic intraepithelial neoplasia (PanIN), graded 1-3) in in vitro and murine in vivo studies. Our aim was to investigate the expression of FSCN1 and EMT-TFs and their association with survival in human PanIN and PDAC.
Health care professionals with positive attitudes towards the functional abilities of patients with low back pain are more likely to encourage activity and avoidance of rest as per recommended guidelines. This study investigated whether medical student training fosters positive attitudes towards patients with back pain and their ability to function.First (n = 202) and final (n = 146) year medical students at the University of Glasgow completed the Health Care Professionals' Pain and Impairment Relationship Scale (HC-PAIRS) questionnaire. This measures attitudes of clinicians towards the functional ability of patients with back pain. A group of first (n = 62) and final year (n = 61) business students acted as non-health care controls. Attitudes were compared using two-way ANOVA with year of study and discipline of degree as independent variables.Both year of study [F(1,465) = 39.5, p < 0.01] and discipline of degree [F(1,465) = 43.6, p < 0.01] had significant effects on total HC-PAIRS scores and there was a significant interaction effect [F(1,465) = 9.5, p < 0.01]. Medical students commenced their course with more positive attitudes than non-health care students (65.7 vs. 69.2 respectively; p < 0.01)--lower scores translating into more positive attitudes. In their final year, the difference between the two student groups had widened (56.4 vs. 65.3; p < 0.01).Undergraduate medical training promotes positive attitudes towards the functional ability of patients with back pain, suggesting that students may be more likely to develop an evidence-based approach to this patient group after qualification. Some adjustments to training may be warranted to encourage a more positive shift in attitudes.
545 Background: Population-based linked datasets are vital tools to generate real-world evidence (RWE) that can inform interventions and policies to improve cancer care quality and outcomes. The novel University of North Cancer Information & Population Health Resource (CIPHR) links statewide cancer registry data, public and private health insurance claims, and provider- and area-level data since 2003, representing more than 80% of North Carolina’s large, diverse cancer patient population. This scoping review included all articles that have used CIPHR data (N=44) to characterize the breadth of RWE generated and to identify further opportunities for population-based care quality surveillance. Methods: Articles published between 2012-2022 were categorized by cancer site(s) of focus, exposure variables, and outcomes examined across the cancer care continuum. For each article, notable results and conclusions were extracted and summarized, including statistically significant associations between patient-level factors (e.g., demographics, clinical variables, insurance type, distance to providers), provider-level factors (e.g., specialties, facility type, networks), system/policy-level factors and outcomes. Results: Of the 44 articles included, findings were reported across 23 unique cancer sites; 9 articles reported results aggregated across multiple cancer sites. Across the cancer care continuum, the majority of articles’ outcomes were categorized as focused on treatment and survivorship (n=25), with most examining treatment initiation and/or adherence (n=13). Other common outcomes included costs of care (n=8) and mortality/survival (n=8). Fewer articles focused on cancer screening (n=2), recurrence (n=1), long-term care use (n=1), or incidence (n=1). The cancer site most frequently examined was breast cancer (n=19), followed by colorectal (n=6), cervical (n=5), and uterine cancers (n=5). The majority of articles focused on racial/ethnic, rural/geographic, and socioeconomic inequities in care and outcomes, as well as multilevel predictors of observed trends. Conclusions: These findings demonstrate the value of creating and sustaining robust, longitudinal, population-based databases to facilitate the generation of RWE that can be used to monitor cancer care delivery trends, including cancer inequities that warrant intervention and policy attention. Lessons learned from more than a decade of analytics utilizing this unique data resource highlight opportunities to explore less frequently studied cancers and outcomes; motivate targeted implementation of equity-focused interventions and policies responding to trends; and inform development of similar resources in other states.
107 Background: Clinical trials are essential for developing novel cancer treatments and improving survival. However, Black women with breast cancer have higher cancer mortality rates compared to non-Black women and are less likely to be enrolled in clinical trials. This study aimed to understand barriers and facilitators to clinical trial participation among Black women with breast cancer to inform the design of a mobile health application (app). Methods: Semi-structured interviews lasting 45-60 minutes were conducted between May and September 2022 with a purposive sample of 20 Black women with breast cancer receiving care in academic and community practices in North Carolina. Participants were asked open-ended questions about their perspective on clinical trial participation. Interviews were digitally recorded, transcribed, and analyzed following a consensus coding-based thematic analysis. Results: Participants represented various age groups ranging from 33 to 76 years, breast cancer hormone receptor/HER 2 status, and stage. Several themes related to facilitators and barriers to clinical trial participation emerged from the interviews. Facilitators included prior experience with participating in clinical trials (cancer treatment, behavioral, and symptom management trials); desire to increase representation of Black women in cancer research to better understand how treatments may affect them differently; benefitting others; and potential for less intensive treatment regimens. Barriers included concern with adverse health effects; fear of new drugs and uncertain therapeutic effect; historical exploitation of Black people participating in research and medical care; lack of representation of Black people participating in clinical research; lack of clinical trial opportunities; concern with the term “trial” and being treated as a guinea pig; and concern with getting a placebo. Most participants were willing to use a mobile health app to obtain trusted information about clinical trials. Recommended content for the app included clinical trial risks and benefits, personal testimonials, link to available clinical trials, and resources to address logistical barriers such as transportation. Most participants also reported the importance of having Black people represented in their healthcare team and health messaging to improve trust in clinical trials. Conclusions: Several barriers and facilitators to clinical trial participation were identified. These findings will inform the content of a mobile health app designed to improve engagement of Black women with breast cancer in clinical trial discussions. Presence of racially representative clinicians and research staff was also noted to improve participation of Black women with breast cancer in clinical trials.
Lifetime imaging microscopy with sub-micron resolution provides essential understanding of living systems by allowing both the visualisation of their structure, and the sensing of bio-relevant analytes in vivo using external probes. Chemistry is pivotal for the development of the next generation of bio-tools, where contrast, sensitivity, and molecular specificity facilitate observation of processes fundamental to life. A fundamental limitation at present is the nanosecond lifetime of conventional fluorescent probes which typically confines the sensitivity to sub-nanosecond changes, whilst nanosecond background autofluorescence compromises the contrast. High-resolution visualization with complete background rejection and simultaneous mapping of bio-relevant analytes including oxygen – with sensitivity orders of magnitude higher than that currently attainable – can be achieved using time-resolved emission imaging microscopy (TREM) in conjunction with probes with microsecond (or longer) lifetimes. Yet the microsecond timescale has so far been incompatible with available multiphoton excitation/detection technologies. Here we realize for the first time microsecond-imaging with multiphoton excitation whilst maintaining the essential sub-micron spatial resolution. The new method is background-free and expands available imaging and sensing timescales 1000-fold. Exploiting the first engineered water-soluble member of a family of remarkably emissive platinum-based, microsecond-lived probes amongst others, we demonstrate (i) the first instance of background-free multiphoton-excited microsecond depth imaging of live cells and histological tissues, (ii) over an order-of-magnitude variation in the probe lifetime in vivo in response to the local microenvironment. The concept of two-photon TREM can be seen as "FLIM + PLIM" as it can be used on any timescale, from ultrafast fluorescence of organic molecules to slower emission of transition metal complexes or lanthanides/actinides, and combinations thereof. It brings together transition metal complexes as versatile emissive probes with the new multiphoton-excitation/microsecond-detection approach to create a transformative framework for multiphoton imaging and sensing across biological, medicinal and material sciences.
The formation of epithelial tissues allows organisms to specialise and form tissues with diverse functions and compartmentalised environments. The tight controls on cell growth and migration required to maintain epithelia can present problems such as the development and spread of cancer when normal pathways are disrupted. By attaining a deeper understanding of how cell migration is suppressed to maintain the epithelial organisation and how it is reactivated when epithelial tissues become mesenchymal, new insights into both cancer and development can be gained. Here we discuss recent developments in our understanding of epithelial and mesenchymal regulation of the actin cytoskeleton in normal and cancerous tissue, with a focus on the pancreas and intestinal tract.
The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised.
Aims: To review the efficacy of near and distance stereotests in current use and to question the functional benefits of stereopsis based on current evidence.Method: A literature review was carried out to analyse the current reports of what is a normal level of stereopsis and how and why this varies according to the test used. In addition the role of stereopsis in many aspects of life is evaluated.Results: The values reported for the normal limits of near stereo-acuity vary greatly with only a weak correlation. Some of the variation can be attributed to test difficulties, such as monocular cues, or the population tested. There is no consensus as to whether near and distance stereo-acuity are equal or vary, and if so which is better. In terms of functional ability stereopsis has been shown to be beneficial in many areas such as academic ability, driving and sports.Conclusions: The values reported for stereo-acuity continue to pose questions with regard to the best approach for screening and clinical care. With tests now available to assess stereo-acuity in the distance it is anticipated that knowledge of conditions, and subsequent treatment, will improve in conditions such as intermittent distance esotropia. The answer to the question 'Do we need stereopsis?' is that it is beneficial but not essential. However, it may be more pertinent to ask 'What is the precise nature of the benefit?'
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