39 research outputs found

    The Quality Literature Quadrant (QLQ): A Reflective Tool for Examining Stereotypes in Texts

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    Because texts often reflect the culture and values of a society and can either disrupt or reinforce stereotypes, it is imperative that faculty and their students alike participate in critical analysis and reflection of the literature and texts used in their classrooms. Critical reflection can reveal whose voices are privileged and whose voices are left out of the literature. In this paper, the authors discuss how faculty and students can use a reflective tool--the Quality Literature Quadrant (QLQ), as a means to examine stereotypes in literature and texts

    Social jetlag and prostate cancer incidence in Alberta\u27s Tomorrow Project: A prospective cohort study

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    We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta\u27s Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-\u3c1 h (from 0 to anything smaller than 1), 1-\u3c2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases

    One-year urinary and sexual outcome trajectories among prostate cancer patients treated by radical prostatectomy: A prospective study

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    BACKGROUND: To examine one-year trajectories of urinary and sexual outcomes, and correlates of these trajectories, among prostate cancer patients treated by radical prostatectomy (RP). METHODS: Study participants were recruited from 2011 to 2014 at two US institutions. Self-reported urinary and sexual outcomes were measured at baseline before surgery, and 5 weeks, 6 months and 12 months after surgery, using the modified Expanded Prostate Cancer Index Composite-50 (EPIC-50). Changes in EPIC-50 scores from baseline were categorized as improved (beyond baseline), maintained, or impaired (below baseline), using previously-reported minimum clinically important differences. RESULTS: Of the 426 eligible participants who completed the baseline survey, 395 provided data on at least one EPIC-50 sub-scale at 5 weeks and 12 months, and were analyzed. Although all mean EPIC-50 scores declined markedly 5 weeks after surgery and then recovered to near (incontinence-related outcomes) or below (sexual outcomes) baseline levels by 12 months post-surgery, some men experienced improvement beyond their baseline levels on each sub-scale (3.3-51% depending on the sub-scale). Having benign prostatic hyperplasia (BPH) at baseline (prostate size ≥ 40 g; an International Prostate Symptom Index Score ≥ 8; or using BPH medications) was associated with post-surgical improvements in voiding dysfunction-related bother at 5 weeks (OR = 3.9, 95% CI: 2.1-7.2) and 12 months (OR = 3.3, 95% CI: 2.0-5.7); and in sexual bother at 5 weeks (OR = 5.7, 95% CI:1.7-19.3) and 12 months (OR = 3.0, 95% CI: 1.2-7.1). CONCLUSIONS: Our findings provide additional support for considering baseline BPH symptoms when selecting the best therapy for early-stage prostate cancer

    ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression.

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    Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX -Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Upregulation of GALNT7 in prostate cancer modifies O-glycosylation and promotes tumour growth.

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    Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression

    PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

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    Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

    The effects of shift work and sleep duration on cancer incidence in Alberta`s Tomorrow Project cohort

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    Introduction: We investigated the main effects of shift work and sleep duration on cancer incidence, and effect modification of the shift work-cancer incidence association by sleep duration. Methods: Shift work and sleep duration were assessed among 21,804 participants from Alberta`s Tomorrow Project. Incident cases of breast, prostate, colorectal and lung cancers were identified through registry linkage. Results: Having worked ≥6 years of rotating shift work (HR = 1.59, 95 % CI = 1.07, 2.37; P = 0.02) and having ever worked night shifts were associated with an increased risk of lung cancer (HR=1.71, 95 % CI=1.18, 2.47; P = 0.01), whereas having ever worked night shifts was associated with a reduced risk of prostate cancer in the latency-adjusted model only (HR=0.70, 95 % CI=0.51, 0.98; P = 0.04). No associations were found between shift work or sleep duration on the risks of breast and colorectal cancers. Some evidence of effect modification by sleep duration for the rotating shift work-lung cancer incidence association was noted (P = 0.06), with stratified analyses revealing borderline increased risk of lung cancer in participants with ≥6 years of rotating shift work and 9 h of sleep/day (HR=2.99, 95 % CI=1.12, 7.97; P = 0.03). No additional evidence of effect modification by sleep duration for shift work and cancer incidence was noted. Discussion: A consistent association between shift work employment and lung cancer risk was noted in this Canadian sample. Furthermore, some evidence of effect modification of the rotating shift work-lung cancer risk association by sleep duration was noted.</p

    Bone Metabolism During Strict Head-Down Tilt Bed Rest and CO2 Exposure

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    International audienceAbstract Objectives Carbon dioxide (CO2) levels on board the International Space Station reach 10× those of outdoor terrestrial levels. We report here studies assessing whether increased levels of ambient CO2 contribute to elevated bone resorption characteristically observed with bed rest as an analog for skeletal unloading during spaceflight. Methods Data are reported from two ground-based studies which included 12 male and 7 female subjects placed in a strict −6° head-down tilt (HDT) position for 30 days at 0.5% ambient CO2 or 60 days with nominal environment (0.04% CO2). Subjects were neither afforded a pillow nor allowed to use an elbow while eating to increase headward fluid pressure. Bone mineral density (BMD) and bone mineral content (BMC) were measured with dual-energy X-ray absorptiometry. Blood and urine were collected before and during HDT for analysis. Results There was no change in BMD or BMC. Excretion of collagen crosslinks increased during HDT (p &lt; 0.001) with no additive effect of CO2. Serum and urine mineral concentrations were not affected by CO2. Serum PTH and 1,25-deoxyhydroxyvitamin D were both reduced during bed rest (p &lt; 0.0001), likely secondary to calcium efflux from bone, but with no additive effect of CO2 exposure. These changes reinforce the impact of decreased mechanical loading on bone and mineral homeostasis and the efficacy of the strict HDT model. Conclusions Exposure to 0.5% CO2 for 30 days did not exacerbate bone resorption during strict HDT bed rest. Future research on bone metabolism at varied CO2 levels is needed to clarify a risk ceiling for bone resorption, especially as missions progress beyond low-Earth orbit. Funding Sources The data reported here were from the NASA Human Research Program Standard Measures Cross-Cutting Project. Funding was provided by the NASA Human Research Program's Human Health Countermeasures Element. ERM was funded through a NASA Summer Science Institute Fellowship
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