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Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process

George M, Farooq M, Dang T, Cortes B, Liu J, Maranga L

Biotechnol Bioeng, 2010 Aug 15;106(6):906-17.
PMID: 20589670 DOI: 10.1002/bit.22753

The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.
Fulltext A mixed method assessment of research productivity on microplastics in various compartments in the environment

Adeniji AO, Okaiyeto K, Mohammed JN, Mabaleha M, Tanor EB, George MJ

Int J Environ Sci Technol (Tehran), 2023 Apr 10.
PMID: 37360561 DOI: 10.1007/s13762-023-04916-7

Microplastic distribution and pollution as emerging contaminants have become a leading environmental issue globally, owing to their ecological and health implications on biota and humans. Although several bibliometric studies have been reported on microplastics, they are mostly restricted to selected environmental media. As a result, the present study aimed at assessing the literature growth trend of microplastics-related research and their distribution in the environment using a bibliometric approach. The Web of Science Core Collection was explored to retrieve published articles on microplastics from 2006 to 2021, and the data were analysed using the Biblioshiny package of RStudio. This study also highlighted filtration, separation, coagulation, membrane technology, flotation, bionanomaterials, bubble barrier devices, and sedimentation as MP remediation techniques. In the present study, a total of 1118 documents were collected from the literature search; the documents/author and authors/document were 0.308 and 3.25, respectively. A significant growth rate of 65.36% was recorded with notable progress between 2018 and 2021. China, the USA, Germany, the UK, and Italy recorded the highest number of publications within the period under consideration. A collaboration index of 3.32 was also relatively high, with the Netherlands, Malaysia, Iran, France, and Mexico having the highest MCP ratios, respectively. It is anticipated that findings from this study will help the policymakers in addressing issues concerning microplastic pollution assist the researchers in identifying areas to concentrate their studies, and where to seek collaboration in their future research plans.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13762-023-04916-7.
Fulltext REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease

Meyer K, Feldman HM, Lu T, Drake D, Lim ET, Ling KH, et al.

Cell Rep, 2019 01 29;26(5):1112-1127.e9.
PMID: 30699343 DOI: 10.1016/j.celrep.2019.01.023

The molecular basis of the earliest neuronal changes that lead to Alzheimer's disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD.
Marine debris in Malaysia: A review on the pollution intensity and mitigating measures

Fauziah SH, Rizman-Idid M, Cheah W, Loh KH, Sharma S, M R N, et al.

Mar Pollut Bull, 2021 Jun;167:112258.
PMID: 33839567 DOI: 10.1016/j.marpolbul.2021.112258

The launch of Roadmap towards Zero Single-use Plastics in 2018 demands baseline data on the management of marine debris in Malaysia. In 2021, Malaysia is placed 28th top plastic polluter in the world with plastic consumption at 56 kg/capita/year, therefore data on mismanaged plastic is imperative. This paper reviews the abundance and distribution of marine debris in selected Malaysian beaches over the last decade (2010-2020) and discusses issue on its management. Plastic debris on beaches in Malaysia, was reported to range from 64 items/m2, to as high as 1930 items/m2, contributing 30-45% of total waste collected. Plastics film was the most dominant, mainly originated from packaging materials. Therefore, appropriate action including improved marine waste management system is crucial to tackle the problem, together with effective governance mechanisms. Various suggestions were proposed based on the statistical-environmental data to reduce the occurrence of marine debris in the country.
Fulltext Barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel in situ analyses

Liu S, Punthambaker S, Iyer EPR, Ferrante T, Goodwin D, Fürth D, et al.

Nucleic Acids Res, 2021 06 04;49(10):e58.
PMID: 33693773 DOI: 10.1093/nar/gkab120

We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method for spatially-resolved, targeted, in situ RNA identification of single or multiple targets. BOLORAMIS was demonstrated on a range of cell types and human cerebral organoids. Singleplex experiments to detect coding and non-coding RNAs in human iPSCs showed a stem-cell signature pattern. Specificity of BOLORAMIS was found to be 92% as illustrated by a clear distinction between human and mouse housekeeping genes in a co-culture system, as well as by recapitulation of subcellular localization of lncRNA MALAT1. Sensitivity of BOLORAMIS was quantified by comparing with single molecule FISH experiments and found to be 11%, 12% and 35% for GAPDH, TFRC and POLR2A, respectively. To demonstrate BOLORAMIS for multiplexed gene analysis, we targeted 96 mRNAs within a co-culture of iNGN neurons and HMC3 human microglial cells. We used fluorescence in situ sequencing to detect error-robust 8-base barcodes associated with each of these genes. We then used this data to uncover the spatial relationship among cells and transcripts by performing single-cell clustering and gene-gene proximity analyses. We anticipate the BOLORAMIS technology for in situ RNA detection to find applications in basic and translational research.
Fulltext Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade

Adeloye D, Agarwal D, Barnes PJ, Bonay M, van Boven JF, Bryant J, et al.

J Glob Health, 2021;11:15003.
PMID: 34737870 DOI: 10.7189/jogh.11.15003

BACKGROUND: The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD.
METHODS: We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.
RESULTS: 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity.
CONCLUSIONS: The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.
ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Mo Y, Ding Y, Cao Y, Hopkins J, Ashley EA, Waithira N, et al.

Wellcome Open Res, 2023;8:179.
PMID: 37854055 DOI: 10.12688/wellcomeopenres.19210.2

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.