A cost-effectiveness analysis evaluating endoscopic surveillance for gastric cancer for populations with low to intermediate risk

10.1371/journal.pone.0083959PLoS ONE812-POLN

Evidence for a common progenitor of epithelial and mesenchymal components of the liver

Tissues of the adult organism maintain the homeostasis and respond to injury by means of progenitor/stem cell compartments capable to give rise to appropriate progeny. In organs composed by histotypes of different embryological origins (e.g. The liver), the tissue turnover may in theory involve different stem/precursor cells able to respond coordinately to physiological or pathological stimuli. In the liver, a progenitor cell compartment, giving rise to hepatocytes and cholangiocytes, can be activated by chronic injury inhibiting hepatocyte proliferation. The precursor compartment guaranteeing turnover of hepatic stellate cells (HSCs) (perisinusoidal cells implicated with the origin of the liver fibrosis) in adult organ is yet unveiled. We show here that epithelial and mesenchymal liver cells (hepatocytes and HSCs) may arise from a common progenitor. Sca+ murine progenitor cells were found to coexpress markers of epithelial and mesenchymal lineages and to give rise, within few generations, to cells that segregate the lineage-specific markers into two distinct subpopulations. Notably, these progenitor cells, clonally derived, when transplanted in healthy livers, were found to generate epithelial and mesenchymal liver-specific derivatives (i.e. hepatocytes and HSCs) properly integrated in the liver architecture. These evidences suggest the existence of a 'bona fide' organ-specific meso-endodermal precursor cell, thus profoundly modifying current models of adult progenitor commitment believed, so far, to be lineage-restricted. Heterotopic transplantations, which confirm the dual differentiation potentiality of those cells, indicates as tissue local cues are necessary to drive a full hepatic differentiation. These data provide first evidences for an adult stem/precursor cell capable to differentiate in both parenchymal and non-parenchymal organ-specific components and candidate the liver as the instructive site for the reservoir compartment of HSC precursors as yet non-localized in the adult. © 2013 Macmillan Publishers Limited All rights reserved

Burnout and work-related stressors in gastroenterology: a protocol for a multinational observational study in the ASEAN region.

BACKGROUND: Clinician burnout is an important occupational hazard that may be exacerbated by the novel COVID-19 pandemic. Within Southeast Asia, burnout in gastroenterology is understudied. The primary objective of this study is to estimate the prevalence of burnout symptoms within gastroenterology, in member states of the Associations of Southeast Asian Nations (ASEAN), during and after the COVID-19 pandemic. The secondary objective is to identify work-related stressors that contribute to burnout in ASEAN gastroenterologists. METHODS AND ANALYSIS: This is an observational study that will use anonymised online surveys to estimate the prevalence of burnout symptoms at two time points: during the COVID-19 pandemic in 2020 and in 2022 (assumed to be after the pandemic). Gastroenterologists from Singapore, Malaysia, Thailand, Indonesia, Philippines and Brunei will be invited to participate in the online survey through their national gastroenterology and endoscopy societies. Burnout will be assessed using the Maslach Burnout Inventory-Human Services Survey tool. Supplementary questions will collect demographic and qualitative data. Associations between demographic characteristics and burnout will be tested by multiple regression. RESULTS: The prevalence of burnout symptoms in gastroenterology during the COVID-19 pandemic, and the baseline prevalence after COVID-19, will be established in the above-mentioned countries. Work-related stressors commonly associated with burnout will be identified, allowing the introduction of preventative measures to reduce burnout in the future. ETHICS AND DISSEMINATION: Ethical approval was granted by the Singhealth Centralised Institutional Review Board (2020/2709). Results will be submitted for publication

Empirical evidence of the continuing improvement in cost efficiency of an endoscopic surveillance programme for gastric cancer in Singapore from 2004 to 2010

10.1186/1472-6963-13-139BMC Health Services Research131

The prevalence of burnout, risk factors, and job-related stressors in gastroenterologists: A systematic review.

Funder: Journal of Gastroenterology & Hepatology Foundation (Australia); Id: http://dx.doi.org/10.13039/501100001352Funder: National University of Singapore; Id: http://dx.doi.org/10.13039/501100001352Funder: British Society of GastroenterologyBACKGROUND AND AIMS: Burnout is an important occupational hazard, and the scale of the problem within gastroenterology remains poorly understood. The primary objective of this study was to understand the prevalence of burnout in gastroenterology and ascertain if there was a common prevalence within the field. The secondary objective was to identify factors and job-related stressors that commonly contribute to burnout in gastroenterologists. METHODS: Systematic searches were conducted in PubMed, Scopus, Cochrane, and PsycINFO by two reviewers independently for articles published to 1 September 2020. The primary outcome measure was the reported prevalence of burnout in gastroenterologists. The secondary outcome measures were (i) the prevalence of non-somatic burnout symptoms (emotional exhaustion, depersonalization, and low personal accomplishment) and (ii) the frequency of risk factors and stressors reported in studies. Data were presented, and limited meta-analyses discussed. RESULTS: Data were extracted from 11 studies. 54.5% (6/11) of these studies reported the prevalence of burnout in gastroenterologists; this ranged from 18.3% to 64.4%. Similar to burnout prevalence, burnout symptoms showed geographical variation and were common in gastroenterologists (up to 63.9%). Factors associated with work volume, age, and female gender were the three most frequently reported risk factors for increased levels of stress and burnout in 72.7% (8/11), 54.5% (6/11), and 45.5% (5/11) of studies, respectively. Significant methodological and clinical heterogeneity was observed. CONCLUSIONS: Burnout and its non-somatic symptoms are common in gastroenterologists, but the syndrome is understudied within the field. Further research and good quality data are needed to help address the problem

The impact of the coronavirus disease 2019 pandemic on gastroenterologists in Southeast Asia: A mixed-methods study.

Funder: National University of Singapore; Id: http://dx.doi.org/10.13039/501100001352Funder: University of Cambridge; Id: http://dx.doi.org/10.13039/501100000735Funder: JGH FoundationBACKGROUND AND AIM: The coronavirus disease 2019 pandemic has impacted gastroenterology practices worldwide; however, its protracted effects within Southeast Asia were unknown. The primary aim of the study was to determine the impact of the pandemic on clinical demands including burnout among gastroenterologists within the region. The secondary aim was to identify risk factors for burnout and determine regional stressors. METHODS: This was a mixed-methods study. Gastroenterologists were surveyed electronically between September 1 and December 7, 2020, via gastroenterology and endoscopy societies of Brunei, Indonesia, Malaysia, Philippines, Singapore, and Thailand. Quantitative and qualitative data were collected. The 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to detect burnout. Quantitative data were non-parametric; non-parametric methods were used for statistical comparisons. Logistic regression was used to determine risk factors for burnout. Content analysis method was used to analyze qualitative data. Ethical approval was obtained. RESULTS: A total of 73.0% reported that they were still significantly affected by the pandemic. Of these, 40.5% reported increased workload and 59.5% decreased workload. Statistically significant differences in weekly working hours, endoscopy, and inpatient volumes were present. No differences were observed in outpatient volumes, likely because of telemedicine. Burnout was common; however, 50.1% of gastroenterologists were unaware of or did not have access to mental health support. This, as well as depression, being a trainee, and public sector work, increased burnout risk significantly. CONCLUSION: The effects of the pandemic are multifaceted, and burnout is common among Southeast Asian gastroenterologists. Safeguards for mental health are suboptimal, and improvements are urgently needed

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types

TRAPPC4-ERK2 Interaction Activates ERK1/2, Modulates Its Nuclear Localization and Regulates Proliferation and Apoptosis of Colorectal Cancer Cells

The trafficking protein particle complex 4 (TRAPPC4) is implicated in vesicle-mediated transport, but its association with disease has rarely been reported. We explored its potential interaction with ERK2, part of the ERK1/2 complex in the Extracellular Signal-regulated Kinase/ Mitogen-activated Protein Kinase (ERK-MAPK) pathway, by a yeast two-hybrid screen and confirmed by co-immunoprecipitation (Co-IP) and glutathione S-transferase (GST) pull-down. Further investigation found that when TRAPPC4 was depleted, activated ERK1/2 specifically decreased in the nucleus, which was accompanied with cell growth suppression and apoptosis in colorectal cancer (CRC) cells. Overexpression of TRAPPC4 promoted cell viability and caused activated ERK1/2 to increase overall, but especially in the nucleus. TRAPPC4 was expressed more highly in the nucleus of CRC cells than in normal colonic epithelium or adenoma which corresponded with nuclear staining of pERK1/2. We demonstrate here that TRAPPC4 may regulate cell proliferation and apoptosis in CRC by interaction with ERK2 and subsequently phosphorylating ERK1/2 as well as modulating the subcellular location of pERK1/2 to activate the relevant signaling pathway