Project description:Background: Gastric intestinal metaplasia (IM) is a pre-cancerous stage spanning a morphological spectrum that is poorly represented by human cell line models.
Objective: We aim to establish and characterize human IM cell models to better understand IM progression along the cancer spectrum.
Design: A large human gastric IM organoid (IMO) cohort (n=28), their clonal derivatives and normal gastric organoids (n=42) for comparison were established. Comprehensive multi-omics profiling and functional characterization were performed.
Results: Single-cell transcriptomes revealed IMO cells spanning a spectrum from hybrid gastric/intestinal to advanced intestinal differentiation. Their lineage trajectories connected different cycling and quiescent stem and progenitors, highlighting differences in gastric to IM transition and the potential origin of IM from STMN1 cycling isthmus stem cells. Hybrid IMOs showed impaired differentiation potential, high lineage plasticity beyond gastric or intestinal fates, and reactivation of a fetal gene program.
Cell populations in gastric IM and cancer tissues were highly similar to those derived from IMOs and exhibited a fetal signature. Genomically, IMOs showed elevated mutation burden, frequent chromosome 20 gain, and epigenetic de-regulation of many intestinal and gastric genes. Functionally, IMOs were FGF10 independent and showed downregulated FGFR2. Several IMOs exhibited a cell-matrix adhesion independent (CMi) subpopulation that displayed chromosome 20 gain but lacked key cancer driver mutations, potentially representing the earliest neoplastic precursor of IM-induced gastric cancer.
Conclusions: Overall, our IM organoid biobank captured the heterogeneous nature of IM, revealing mechanistic insights on IM pathogenesis and progression, offering an ideal platform for studying early gastric neoplastic transformation and chemoprevention.
Project description:BackgroundWaterpipe smoking has gained global popularity in recent years, especially among young people. However, there is a lack of empirical investigation into waterpipe smoking in East Asia. This study aimed to investigate the demographical and psycho-social characteristics and patterns of waterpipe smoking (WPS) among university students in Hong Kong.MethodsA cross-sectional survey was conducted via online questionnaires administered to 1288 Hong Kong university students (mean age: 22.4 [SD = 3.8]). Logistic regressions were used to compute adjusted odd ratios (aOR) for waterpipe ever-smoking in relation to respondents' characteristics. Moreover, multinomial logistic regression yielded adjusted RR (aRR) for four different smoking status (i.e., never, waterpipe-only, cigarette-only, and dual smoking) regarding the characteristics.Results23.8% of participants reported having ever smoked a waterpipe (vs. cigarette ever-smoking: 21.1%). Factors including being female (aOR:1.57; 95% CI: 1.22-2.02), older age (≥24 years: 4.17; 1.35-12.93), frequent alcohol consumption (>monthly: 26.02; 10.91-62.09), and higher sensation-seeking behaviours (high level: 2.98;1.46-6.08) were associated with waterpipe ever-smokers. The study also identified that demographical and psycho-social characteristics were variably associated with students' smoking status. Particularly, more frequent alcohol consumption was most significantly associated with waterpipe-only smoking (aRR:45.73; 95% CI:11.44-182.73) (vs. cigarette-only smoking: 3.01; 1.76-5.14).ConclusionsWPS is the most common form of tobacco smoking among university students in Hong Kong, and characteristics unique to the population were identified. There is no legislation of relevant policies on WPS despite its concerning significance in public health among young people, therefore immediate action to monitor and control WPS is needed in Hong Kong.
Project description:ImportanceCOVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination.ObjectiveTo quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong.Design, setting, and participantsA cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs.Main outcomes and measuresA mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block.ResultsAmong 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (β = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (β = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (β = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (β = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (β = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (β = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4).Conclusions and relevancePreference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.