Taiwan Biobank: a rich biomedical research database of the Taiwanese population

The Taiwan Biobank (TWB) is an ongoing prospective study of over 150,000 individuals aged 30-70 recruited from across Taiwan beginning in 2012. A comprehensive list of phenotypes was collected for each consented participant at recruitment and follow-up visits through structured interviews and physical measurements. Biomarkers and genetic data were also generated for all participants from blood and urine samples. We present here an overview of the genetic data quality, population structure, and familial relationship within TWB, which consists of predominantly Han Chinese-ancestry individuals, and highlight important attributes and genetic findings thus far from the biobank. A linkage to Taiwan's National Health Insurance database of >25 years and other health-related registries is underway that will enrich the phenotypic spectrum of TWB and enable deep and longitudinal genetic investigations. TWB provides one of the largest biobank resources for biomedical and public health research in East Asia that will contribute to our understanding of the genetic basis of human health and disease in global populations through collaborative studies with other biobanks.

A reference induced pluripotent stem cell line for large-scale collaborative studies

Human induced pluripotent stem cells (iPSCs) are a powerful tool for studying development and disease. However, different iPSC lines show considerable phenotypic variation. The lack of common well-characterized cell lines that are used widely frustrates efforts to integrate data across research groups or replicate key findings. Inspired by model organism communities who addressed this issue by establishing a limited number of widely accepted strains, we characterised candidate iPSC lines in unprecedented detail to select a well-performing line to underpin collaborative studies. Specifically, we characterised the morphology, growth rates, and single-cell transcriptomes of iPSC lines in the pluripotent state and assessed their genomic integrity using karyotyping, DNA microarrays, whole genome sequencing, and functional assays for p53 activity. We further tested their ability to be edited by CRISPR/Cas9 and used single-cell RNA sequencing to compare the efficiency with which they could be differentiated into multiple lineages. We found that there was significant variability in the performance of lines across the tested assays that enabled the rational selection of a lead line, KOLF2.1J, which is a gene-corrected derivative of a publicly available line from the Human Induced Pluripotent Stem Cells Initiative (HipSci) resource. We are now using this line in an initiative from the NIH Center for Alzheimer's and Related Dementias to derive hundreds of gene-edited and functionalized sub-clones to be distributed widely through the research community along with associated datasets, with the aim of promoting the standardisation required for large-scale collaborative science in the stem cell field.

Two Decades of Desiccation Biology: A Systematic Review of the Best Studied Angiosperm Resurrection Plants

Resurrection plants have an extraordinary ability to survive extreme water loss but still revive full metabolic activity when rehydrated. These plants are useful models to understand the complex biology of vegetative desiccation tolerance. Despite extensive studies of resurrection plants, many details underlying the mechanisms of desiccation tolerance remain unexplored. To summarize the progress in resurrection plant research and identify unexplored questions, we conducted a systematic review of 15 model angiosperm resurrection plants. This systematic review provides an overview of publication trends on resurrection plants, the geographical distribution of species and studies, and the methodology used. Using the Preferred Reporting Items for Systematic reviews and Meta–Analyses protocol we surveyed all publications on resurrection plants from 2000 and 2020. This yielded 185 empirical articles that matched our selection criteria. The most investigated plants were Craterostigma plantagineum (17.5%), Haberlea rhodopensis (13.7%), Xerophyta viscosa (reclassified as X. schlechteri) (11.9%), Myrothamnus flabellifolia (8.5%), and Boea hygrometrica (8.1%), with all other species accounting for less than 8% of publications. The majority of studies have been conducted in South Africa, Bulgaria, Germany, and China, but there are contributions from across the globe. Most studies were led by researchers working within the native range of the focal species, but some international and collaborative studies were also identified. The number of annual publications fluctuated, with a large but temporary increase in 2008. Many studies have employed physiological and transcriptomic methodologies to investigate the leaves of resurrection plants, but there was a paucity of studies on roots and only one metagenomic study was recovered. Based on these findings we suggest that future research focuses on resurrection plant roots and microbiome interactions to explore microbial communities associated with these plants, and their role in vegetative desiccation tolerance.

Osteosarcoma: novel prognostic biomarkers using circulating and cell-free tumour DNA

Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents. Despite treatment with curative-intent, many patients die of this disease. Biomarkers for assessment of disease burden and prognoses for osteosarcoma are not available. Circulating-free (cfDNA) and -tumour DNA (ctDNA) are promising biomarkers for disease surveillance in several major cancer types, however only two such studies are reported for OS. In this combined discovery and validation study, we identified four novel methylation-based biomarkers in 171 OS tumours (test set) and comprehensively validated our findings in silico in two independent osteosarcoma sample datasets (n= 162, n=107) and experimentally using digital droplet PCR (ddPCR, n=20 OS tumours). Custom ddPCR assays for these biomarkers were able to detect ctDNA in 40% of pre-operative plasma samples (n=72). ctDNA was detected in 5/17 (29%) post-operative plasma samples from patients who experienced a subsequent relapse post-operatively. Both cfDNA levels and ctDNA detection independently correlated with overall survival, p=0.0015, p=0.0096, respectively. Combining both assays increased the prognostic value of the data. Our findings illustrate the utility of mutation-independent methylation-based markers, broadly applicable ctDNA assays for tumour surveillance and prognostication. This study lays the foundation for multi-institutional collaborative studies to explore the utility of plasma-derived biomarkers for predicting clinical outcome of OS.

Novel gene discovery for hearing loss and other routes to increased diagnostic rates

Despite decades of research, there is much to be learned about the genetic landscape of sensorineural hearing loss. Novel genes for hearing loss remain to be identified while ‘secrets’ of the known genes need to be uncovered. These ‘secrets’ include regulatory mechanisms of gene activity and novel aspects of gene structure. To obtain a more complete picture of the genetics of hearing loss, the available experimental and bioinformatic tools need to be fully exploited. This is also true for data resources such as ENCODE. For the inner ear, however, such data resources and analytical tools need to be developed or extended. Collaborative studies provide opportunities to achieve this and to optimally use those tools and resources that are already available. This will accelerate the discoveries that are necessary for improving molecular genetic diagnostics and genetic counselling and for the development of therapeutic strategies.

Collaborative research in Australasian plastic surgery

Many specialist groups have developed clinical trial initiatives in response to the growing need for more collaborative research, and these are proliferating in multiple countries across the globe. The Royal Australasian College of Surgeons (RACS), under the direction of Professor John Windsor, established the clinical trials network of Australia and New Zealand (CTANZ). CTANZ supports the Australasian clinical trials in plastic, reconstructive and aesthetic surgery (ACTPRAS) research group which has already facilitated two multicentre, international, collaborative studies.

Investigating the Views of Academic Staff on Academic Synergy

The aim of this study is to examine academics' views on academic synergy. Academic synergy can be defined as the process by which two or more academics work together to achieve more than what they can individually. This study focuses on how academics can combine their knowledge and experience to achieve more efficiency/work (publications, articles, papers, projects, etc.) with the same effort they would spend alone. It is designed as a case study, applying a qualitative research method. The interviews were conducted with 21 academic staff members working at a public university. The results indicate that having a higher or lower academic title does not have a significant effect on the willingness to work together. Most of the participants stated that, for joint studies, they prefer to work with colleagues who have "academic background in the field of study". The results also revealed that academics' positive personal characteristics such as being open to cooperation, acting responsibly, and being sincere are considered as some important criteria for joint studies. The results also show that the majority prefer to collaborate with other academics rather than conducting individual studies. The academics prefer to collaborate to increase productivity and to compensate for their shortcomings. Most of them further stated that the academic incentive program introduced by the Council of Higher Education (CoHE) has increased the number of collaborative studies and the motivation to work together, but at the same time, decreased the research quality and led to some unethical behaviors. The paper is concluded with some suggestions on how to achieve academic synergy among academics through conducting joint studies.

Factors associated with North–South research collaboration focusing on HIV/AIDS: lessons from ClinicalTrials.gov

Background A North–South (N–S) research collaboration is one way through which research capacity of developing countries can be strengthened. Whereas N–S collaboration in HIV/AIDS area may result in research capacity strengthening of Southern partners, it is not clear what factors are associated with this type of collaboration. The study aims to characterize N–S research collaboration focusing on HIV/AIDS and to determine factors associated with such N–S research collaborations. Methods Clinical trial data on HIV/AIDS-related studies conducted between 2000 and 2019 were obtained from ClinicalTrials.gov. Using these data, we characterized N–S collaborative studies focusing on HIV/AIDS and summarized them using frequencies and percentages. To determine factors associated with these studies, we used logistic regression and reported results as adjusted odds ratios with Wald 95% confidence intervals. Results and discussion Of the 4,832 HIV/AIDS-related studies retrieved from the registry, less than one-quarter (n = 1133, 23%) involved a Southern institution, with 77% of these studies classified as N–S collaborations. Majority of these studies have single PI (50%), are conducted at single location (39%); have large sample sizes (41%); are federally-funded (32%) or receive funding from other sources (32%); are intervention studies (64%); and involve a mixture of male and female participants (58%) and adult participants (54%). Single PIs (as opposed to multiple PIs) were more likely to be from the North than South institution (odds ratio = 5.59, 95%CI: 4.16 – 11.57). Trend analyses showed that N–S research collaborations produced HIV/AIDS-related studies at a faster rate than S–S research collaborations. N–S collaborations involving female or children produced HIV/AIDS-related studies between 2000 and 2019 at a significantly faster rate than S–S collaborations involving females and children during the same period. Holding other factors constant, N–S collaborative research focusing on HIV/AIDS are associated with: multiple PIs as opposed to single PI, multiple institutions as opposed to a single institution, multiple locations as opposed to a single location, large number of participants as opposed to small sample sizes, and public funding as opposed to industry funding. Almost half of these studies had a Northern PI only, about one-third had a Southern PI only, and much fewer had PIs from both North and South. However, these studies were less likely to receive funding from other sources than industry funding. Conclusions HIV/AIDS-related research is increasingly becoming a more collaborative global research involving more N–S collaborations than S–S collaborations. Factors associated with N–S collaborative studies focusing on HIV/AIDS include multiple PIs, institutions, and locations; large sample sizes; publicly funded; and involve vulnerable populations such as women and children. Whereas almost half of these studies have a Northern PI only, about one-third have a Southern PI only, and much fewer have PIs from both North and South. Our results inform future design and implementation of N–S research collaborations in this area. Suggestions for improvement of ClinicalTrials.gov registry are provided.

Higher Education Institutions as Partners in Growing Innovation of Local Economy

Higher education institutions (HEIs) are constantly evolving how they operate and their areas of academic interest. What remains unchanged is the fact that the raison d’être of a university is to fulfill the role of a citadel of knowledge to its environment. The aim of this paper is to show the relationship between HEIs and entities that have an impact on the growth of the local economy, in particular the possibilities of shaping local partnerships for innovation. The paper thus outlines the nature of individual sectors, the special role played by local governments, and the activities of universities related to innovation in the economy, based on the results of two collaborative studies co-sponsored by the Ministry of Science and Higher Education and teams of researchers at the WSB University in Dąbrowa Górnicza. One of the projects was under the framework of the DIALOG program of 2019–2020 and the other used the framework of the Regional Excellence Initiative program of 2019–2022. The main part of this study was based on a survey of representatives of local governments; the survey was oriented towards identifying the opinions of local managers on the current and postulated roles of universities in the development of the local economy. The results presented in this study indicate, among other things, a significant differentiation of expectations concerning the cooperation of entities in the process of local development based on innovation and changes in the areas of this cooperation.