Dietary habits, commensal microbiome, and nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignant disease characterized by unique geographic distribution endemic to southern China, Southeast Asia, and the Middle East/North Africa. It has been widely accepted that the interaction of Epstein-Barr Virus infection, environmental and lifestyle factors, and genetic susceptibility, contributes to NPC carcinogenesis. In the past two decades, extensive application of intensity-modulated radiotherapy and widespread introduction of chemotherapy have significantly contributed to a desirable prognosis: better survival with fewer toxicities. However, there are still numerous knowledge gaps and unsolved questions about NPC risk and prognosis. In this thesis, we investigated whether dietary habits (Study I), and oral commensal microbiome (Study II) were associated with NPC risk, using a population-based case-control study in endemic southern China. We also conducted a longitudinal hospital-based NPC cohort study (Study III) to deliver proof-of-concept data on the commensal microbiome patterns in patients’ nasopharynx during radiotherapy and their role in NPC prognosis. In Study I/Paper I, we analyzed a total of 4398 study participants (2174 NPC cases and 2224 controls) with data about adolescent diet and 4832 participants (2387 NPC cases and 2445 controls) with data about adulthood diet. We demonstrated a strong positive association between higher consumption of the “animal-foods-based diet” and NPC risk and a strong negative association with higher intake of the “plant-based diet”. Following mutual adjustment for adolescence and adulthood dietary patterns, risk estimates for the former were attenuated and no longer statistically significant, whereas associations with adulthood dietary patterns remained virtually unchanged. In Study II/Paper II, we explored the relationship between NPC status and the oral microbiome using 16S rRNA sequencing in a study of 994 participants (499 NPC cases, 494 controls). We observed a significant reduction in community richness in NPC cases compared to that in controls. We also identified a pair of Granulicatella adiacens amplicon sequence variants (ASVs; Gran-7770 and Gran-5a37), which were strongly associated with NPC status and differed by a single nucleotide. We further revealed that Gran-7770 and Gran-5a37 each formed co-occurring nodes with a dozen ASVs, which were exclusive. These results suggest differences in the oral microbiomes between NPC patients and controls, which may be associated with both a loss of microbial diversity and niche specialization among closely related microorganisms. In Study III/Paper III, we analyzed 445 nasopharyngeal samples longitudinally collected from 39 NPC patients during radiotherapy-based treatment. We addressed stable, temporal changes in the nasopharyngeal microbial community structure among NPC patients during treatment. These changes were associated with patients’ short-term clinical outcomes measured three months after the completion of radiotherapy. We also identified 23 out of 73 abundant ASVs that showed statistically significant changes in the ratio of abundance between early and late responders throughout treatment. These results provided evidence of an association between nasopharyngeal commensal microbiome and NPC patients’ short-term clinical outcome. By studying a range of topics, this thesis provides more insights into NPC in terms of risk and prognosis: plant-based and animal-foods-based diets are differentially associated with NPC risk in endemic southern China, suggesting a possibility of primary prevention of NPC through dietary intervention; oral microbiome is associated with NPC risk; the niche specialization among closely related commensals associated with NPC status calls for future culture-based investigations; moreover, stable, temporal changes of the nasopharyngeal microbiome are associated with NPC patients’ short-term clinical outcome, which calls for more extensive longitudinal studies with long-term follow-up for verification and serves as a base of generating new hypotheses for future studies

Characterization of the Visceral Endoderm Components in Early Post-Implantation Mouse Embryo Development: A Dissertation

Early post-implantation vertebrate embryos are shaped by complex cellular and molecular mechanisms. In mice, the visceral endoderm, an extraembryonic cell lineage that appears before gastrulation, provides several important functions such as nutrition and mechanical protection. My thesis research focused on the role of the visceral endoderm in embryo patterning, a newly discovered function for this tissue. My results showed that an interplay between two subpopulations of visceral endoderm the anterior and posterior visceral endoderm, located on the opposite sides of the developing conceptus, are critical for the establishment of the anteroposterior body axis of the embryo. I also found that senescence-associated β-galactosidase activity delineates the visceral endoderm marking apical vacuole, a lysosomal-like organelle. This however indicates the nutritional function of visceral endoderm cells rather than a senescent population. My studies highlight the fundamental role of extraembryonic tissues in patterning mammalian embryos as opposed to housekeeping roles. They also reveal important difference when conducting studies at the organismal level rather than in cells in culture

Decision-making to switch your ERP system: empirical Japanese evidence

A huge research gap in ERP life cycle, the Decline stage, remains. Not only limited empirical evidence is found to support the Decline stage, but also, the existence of this stage is not acknowledged by the majority. On the other hand, because that the Decline stage is short of theory and data support, organizations which are or will be at this stage have little help to deal with what might happen. This research aims at proposing a practical decision model for organizations facing ERP (Enterprise Resource Planning) switching/reversion. The process model of Rasmussen’s Cognitive Control of Decision Processes was adopted as the theory lens to construct the decision model. Based on the survey results from eighteen organizations, a descriptive model - A2O model - is proposed. This research fulfills the blank in the ERP life cycle, provides the empirical supports on exploring the critical issues, and enlightens vendors and consultants on product development and customer service

The Coordinated Development of Secondary Vocational School Specialty Clusters and Industry Clusters: Citing Longgang No.2 Vocational and Technical School of Shenzhen as a Case Study

With the implementation of the state’s Plan of Constructing High-Level Vocational Schools and Specialties with Chinese Characteristics, the construction of specialty clusters has become a hot topic. They are critical tools for improving the educational quality of vocational schools by promoting vocational education transformation, upgrading, and innovation. To maximize the effectiveness of specialty cluster development in secondary vocational school curriculum reform, we must first identify the rationale for multi-agency involvement in the development of specialty clusters and then formulate action plans. This article examines the definitions and connotations of specialty clusters and discusses the contexts in which specialty clusters emerged. It examines strategies for developing specialty clusters using Shenzhen’s Longgang No. 2 Vocational and Technical School as an example

Endorsement and embodiment of cautiousness-related age stereotypes

Endorsement of implicit age stereotypes was assessed with the propositional evaluation paradigm (PEP) in a high-powered, preregistered study, comprising samples of young ( n  = 89) and older ( n  = 125) adults. To investigate whether implicit age stereotypes shape the behavior via self-stereotyping (“embodiment”), we examined whether implicit endorsement of the belief of older (young) people being cautious (reckless) predicts older (young) individuals’ spontaneous behavior in a speeded response time task. In both age groups, we found significant implicit endorsement effects of age stereotypical beliefs. However, implicit endorsement effects of the cautiousness-related age stereotypes were unrelated to our indicators of spontaneous cautious/reckless behavior in the speeded RT task (as assessed with the parameter a of a diffusion model analysis) for both age groups. The same pattern of results (endorsement of age stereotypic beliefs but no relation with behavioral indicators) was found for explicit measures of age stereotypes. Replicating previous findings, implicit and explicit measures of cautiousness-related age stereotypes were uncorrelated. In sum, our findings provide evidence for the implicit and explicit endorsement of cautiousness-related stereotypical beliefs about old and young people; individual differences in belief endorsement, however, did not predict differences in spontaneous cautiousness-related behavior in a speeded RT task