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Background: The climate crisis and depleting fossil fuel reserves have led to a drive for 'green' alternatives to the way we manufacture chemicals, and the formation of a bioeconomy that reduces our reliance on petrochemical-based feedstocks. Advances in Synthetic biology have provided the opportunity to engineer micro-organisms to produce compounds from renewable feedstocks, which could play a role in replacing traditional, petrochemical based, manufacturing routes. However, there are few examples of bio-manufactured products achieving commercialisation. This may be partially due to a disparity between academic and industrial focus, and a greater emphasis needs to be placed on economic feasibility at an earlier stage. Terpenoids are a class of compounds with diverse use across fuel, materials and pharmaceutical industries and can be manufactured biologically from the key intermediate mevalonate. Results: Here, we report on a method of utilising parallel bioreactors to rapidly map the growth-coupling relationship between the specific product formation rate, specific substrate utilisation rate and specific growth rate. Using mevalonate as an example product, a maximum product yield coefficient of 0.18 gp/gs was achieved at a growth rate (μ ) of 0.34 h−1. However, this process also led to the formation of the toxic byproduct acetate, which can slow growth and cause problems during downstream processing. By using gene editing to knock out the ackA-pta operon and poxB from E. coli BW25113, we were able to achieve the same optimum production rate, without the formation of acetate. Conclusions: We demonstrated the power of using parallel bioreactors to assess productivity and the growth-coupling relationship between growth rate and product yield coefficient of mevalonate production. Using genetic engineering, our resultant strain demonstrated rapid mevalonate formation without the unwanted byproduct acetate. Mevalonate production is quantified and reported in industrially relevant units, including key parameters like conversion efficiency that are often omitted in early-stage publications reporting only titre in g/L. [ABSTRACT FROM AUTHOR]

Background: For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks. A scale-up from those small shaken devices to a stirred tank reactor is barely stated in literature for mammalian cells. Thus, this study aims to address data-driven scale-up for CHO DP12 cells. The oxygen transfer rate is used as a database. Results: The cultivation conditions in microtiter plates and shake flasks are comparable when choosing the maximum oxygen transfer capacity as a scale-up parameter. The minimum cultivation volume was reduced to 400 µL in round and square 96-deep-well microtiter plates. Using a scale-up based on the maximum oxygen transfer capacity to a stirred tank reactor led to conditions with excessive hydromechanical stress. However, cultivation conditions could be reproduced in a stirred tank reactor by utilizing the volumetric power input as a scale-up parameter. Key metabolites behaved the same in all three scales and the final antibody titer was equal. Conclusion: This study presents a successful replication of cultivation results for mammalian cells in microtiter plates, shake flasks and stirred tank reactors. The working volumes ranged from 0.4 to 50 and 600 mL. It offers the opportunity to adapt the method to other, more sensitive mammalian cells and to perform cost- and time-effective experiments in high-throughput. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that parenting behaviours, including the use of violent discipline, can be changed through programmatic interventions. This study seeks to examine how policymakers and service providers in Tanzania perceive the provision of parenting support as a strategy to prevent violence against children and what the enabling and hindering factors are for the scale-up of existing evidence-based parenting supports. It does this by applying Daly's analytical framework for parenting support. Methods: Qualitative research was undertaken, with interviews conducted with 20 key informants consisting of purposively sampled policymakers and service providers. The interview data were analysed using inductive and deductive coding and analysis. Results: The most prominent enabling factors noted for the scale-up of parenting support interventions in Tanzania include the existing supportive political commitment, the interventions currently on offer at the programmatic level, and the perceived understanding of Tanzanian caregivers of the importance of parenting and, thereby, a willingness to change. Current factors hindering the scale-up include the lack of a common understanding of what evidence-based parenting programmes entail, inadequate provision of human and financial capital to implement the programmes using community resources and deeply engrained social norms around adultism and gender. Conclusion: Daly's analytical framework allowed us to examine barriers and facilitators to scale-up the provision of parenting support to prevent violence against children, based on the viewpoints of policymakers and service providers. Understanding these barriers and facilitators will allow Tanzanian policymakers and service providers to further close the gap between the policies and the actual implementation of evidence-based parenting support programmes aimed at preventing violence against children. [ABSTRACT FROM AUTHOR]

Background: Investment in scale-up and sustainment of effective health-promoting programs is often hampered by competing demands on scarce health dollars. Thus, optimizing programs to reduce resource use (e.g., delivery costs) while maintaining effectiveness is necessary to promote health at scale. Using a phased approach (2015–2024), we adapted and scaled-up an evidence-based, health-promoting program for older adults (Choose to Move; CTM). For CTM Phase 4 we undertook a systematic, data-driven adaptation process to reduce resource use. In this paper we: 1) describe the CTM Phase 4 program ('CTM Phase 4') and assess its 2) implementation and 3) effectiveness. Methods: For CTM Phase 4 (30-min one-on-one consultation and 8, 60-min group meetings with an activity coach), we reduced activity coach hours by 40% compared to Phase 3. To evaluate effectiveness of CTM Phase 4 we conducted a type 2 hybrid effectiveness-implementation study involving 137 programs (1126 older adults; 59–74 years, 75 + years) delivered by 29 activity coaches. We assessed implementation indicators (e.g., dose, fidelity, adaptation, participant responsiveness, self-efficacy) via survey in activity coaches and older adults. We assessed older adults' physical activity (PA), mobility, social isolation, and loneliness before and after (0, 3 months) the program. Results: Implementation indicators demonstrated that CTM Phase 4 was delivered successfully. Post-intervention, PA (+ 1.4 days/week; 95% CI 1.3, 1.6), mobility limitations (-6.4%), and scores for mobility (+ 0.7; 95% CI: 0.4, 1.3), social isolation (+ 0.9; 95% CI: 0.67, 1.17), and loneliness (-0.23; 95% CI: -0.34, -0.13) were improved in those < 75 years. Among those ≥ 75 years, PA (+ 1.0 days/week; 95% CI, 0.7, 1.2), mobility score (+ 1.1; 95% CI: 0.4, 1.8), and social isolation score (+ 0.5; 95% CI: 0.08, 0.86) were improved post-intervention. Participant-level benefits were comparable to, or greater (PA and social isolation in those < 75) than, those observed in Phase 3. Conclusions: CTM was co-designed as a flexible program, adapted over time based on user group needs and preferences. This flexibility enabled us to reduce activity coach delivery hours without compromising implementation or benefits to older adults' health. Optimizing effective health-promoting programs to enhance their scalability and sustainability provides an important pathway to improved population health. Trial Registration: ClinicalTrials.gov, NCT05678985. Registered 10 January 2023 – Retrospectively registered, https://clinicaltrials.gov/study/NCT05678985. [ABSTRACT FROM AUTHOR]

In this study, wastewater from a sewage treatment plant was used to culture the microalga, Verrucodesmus verrucosus. The ability of microalgae to adapt to adverse environments and produce high lipid concentrations was evaluated using different media, including sterile and non-sterile media and a control medium. The analysis showed that the control medium (distilled water sample enriched with fertilizer) removed 80.35% ammonium, 32.71% phosphate, and 83.86% nitrate. The sterile raw effluent removed 78.91% of ammonium, 83.44% of phosphate, and 98.82% of nitrate. The optimal conditions for biomass production were sterile raw wastewater, which produced 383.3 mg L−1 of biomass, 2.5% of total lipids, and an average lipid production of 9.31 mg L−1. Microalgae can grow and consume inorganic nutrients under adverse environmental conditions such as in raw wastewater, which is of great importance because it is a pollutant that negatively affects the environment and society. However, wastewater may represent a viable alternative substrate, allowing the generation of high-value products, such as lipids. Furthermore, the specificity of microalgal morphotypes must be evaluated, because each has specific metabolic plasticity. Verrucodesmus verrucosus is a microalga that has not been evaluated in bioremediation processes of wastewater with and without the presence of biotic factors. Therefore, the present study provides a viable alternative for this biological process, with the potential to store metabolites of interest in the industry. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has brought global attention towards the readiness of biotechnology platforms for rapid development of immunogens to be used as vaccine antigens, in diagnostics and in fundamental research. In the present study we provide a bioprocess that is both robust and industry-compatible for high level expression, efficient purification, and scale-up of IMT-CVAX, a prefusion-stabilized trimeric spike protein of SARS-CoV-2. The recombinant IMT-CVAX protein was produced using stable cell pool of Chinese Hamster Ovary (CHO-S) cells that were banked in compliance with cGMP (Current Good Manufacturing Practices) regulations. High quantity expression of IMT-CVAX was achieved through optimization of the shake flask-based process with regards to media, nutrient feeding regimen, incubation temperature, viable cell density and cell viability. We employed refined expression procedures to scale up IMT-CVAX using bioreactor, resulting in a significantly higher yield of around 500 mg/L. Subsequently, a straightforward and simple purification process was developed to produce high-quality IMT-CVAX protein. This procedure consisted of centrifugation, tangential flow filtration (TFF), and either one- or two-step liquid chromatography. A robust anti-spike IgG response was observed in mice after immunization with purified adjuvanted IMT-CVAX. In pseudoviral neutralization assay, mice-generated anti-IMT-CVAX sera could neutralize various SARS-CoV-2 variants. The human convalescent sera from COVID-19-recovered patients recognized IMT-CVAX effectively, which confirms the conformational integrity of IMT-CVAX epitopes. The bioprocess demonstrated here is able to produce sufficient quantities of biopharmaceutical-quality spike protein, which can be used as immunogen against emerging SARS-CoV-2 variants, and can aid in the rapid response to any other pandemic-potential pathogens. [Display omitted] • Bioprocess for high level expression of recombinant, prefusion-stabilized trimeric spike protein (named IMT-CVAX) of SARS-CoV-2 in CHO cells. • Scale-up of IMT-CVAX expression using bioreactor and simple purification process using tangential flow filtration and liquid chromatography. • In mice, IMT-CVAX was found to have a high immunogenic response, and antisera was able to effectively neutralize SARS-Cov-2 variants. • IMT-CVAX maintains its stability at a variety of temperatures and has also been recognized by human convalescent sera. • IMT-CVAX has potential of clinical development of protein-subunit based vaccine against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Female lumpfish (Cyclopterus lumpus) are a primary target of commercial fishery for their roe, a substitute for caviar. The remaining carcasses are underutilized rest raw material. The pre-treatment and acid extraction conditions of collagen from lumpfish skins were optimized. Full factorial design was used to optimize the alkali pre-treatment conditions with NaOH. The optimal conditions were X1 = 0.1 M (NaOH concentration), X2 = 6 h (NaOH treatment time), X3 = 4 °C (treatment temperature) and X4 = 1:5 (w/v, solid to liquid ratio). Optimized conditions for collagen extraction with acetic acid were investigated using a Box–Behnken design. The result suggested a concentration of 0.9 M acetic acid, treatment temperature of 21 °C, a treatment time of 36 h in a total of 2 volumes of acid. Combined optimized effects resulted in a collagen yield of 45% (DW/DW) with high purity (>90%) and a high hydroxyproline content (7.9%). A scale-up experiment (starting with 45 kg) showed that the yield was somewhat lower (18–25%). Enzyme hydrolysis of skin after acetic acid extraction added another 23% (DW/DW) to the yield and enzyme hydrolysis of precleaned skins resulted in 60% (DW/DW). [ABSTRACT FROM AUTHOR]

Large quantities of artificial single-stranded DNA (ssDNA) with user-defined sequences are increasingly required to exploit the potential of DNA nanotechnology. Cross-contamination-free ssDNA production can be achieved using Escherichia coli with an optimized helper plasmid in high-cell-density cultivation via the secretion of phagemid particles containing ssDNA with user-defined sequences. In our study, we aimed to reduce the number of phagemid particles for the initiation of ssDNA production. We tested different infection densities, ranging from a multiplicity of infection (MOI) of 10−6–10−2 tfu cfu−1 at the start of the initial batch phase in a 2.5 L stirred tank bioreactor. A MOI of 10−3 tfu cfu−1 was the best compromise between process time and ssDNA concentration. Early initiation of ssDNA production with low MOI reduced the number of phagemid particles by a factor of 250,000. The early infection strategy was successfully scaled up to the 25 L scale, resulting in ssDNA concentrations of >100 mg L−1 within a process time of one day. Transferring the infection strategy to a 1000 L scale gained 65 mg L−1 ssDNA because of incomplete initial infection. The versatility of the early infection strategy was further proven with a second prolonged, user-defined ssDNA sequence. [ABSTRACT FROM AUTHOR]

Vitamin E succinate has gained substantial attention as a potential therapeutic agent for cancer treatment due to its biomedical activities. One of the prominent methods of synthesizing vitamin E succinate is through enzymatic processes, which, although advantageous, presents inherent challenges related to optimization, scalability, and particularly, the poor stability of lipases in organic solvents. Our study addresses these challenges by conducting a comprehensive comparative analysis between Lipase UM1 and three other immobilized commercial lipases, demonstrating Lipase UM1's enhanced resistance to organic solvents and its superior efficiency in vitamin E succinate production. Further optimization experiments with Lipase UM1 led to an unprecedented conversion of 99%. Additionally, we scaled the reaction to a proof‐of‐concept industrial level. The synthesized product was verified using Fourier transform infrared spectroscopy and nuclear magnetic resonance analysis, ensuring its quality and consistency. This study validates Lipase UM1 as an efficient catalyst for vitamin E succinate synthesis, offering a promising avenue for industrial production with potential applications in cancer therapy and beyond. [ABSTRACT FROM AUTHOR]

Background: Intervention trials that have demonstrated significant effects may not always replicate those effects when scaled up. This study aimed to test whether scaling-up a successful cluster randomized trial (the COMMUNICATE study, 9 intervention communities), which promoted population-level physical activity (PA), could promote PA in a broader citywide setting (29 communities) after two years, as a mid-term evaluation of the six-year scaled-up trial. Methods: This is a single-arm, pre-post comparison of a multi-strategic community-wide intervention covering the entire Unnan City, Japan. The intervention for middle-aged and older people consisted of three components: information delivery, education, and support delivery. The intervention method followed the COMMUNICATE study but adapted and introduced new initiatives tailored to local resources. A baseline survey (n = 3,718) among randomly selected residents aged 40–79 years in 2016 and a follow-up survey with the same respondents two years later were conducted. The primary outcome was the change in the percentage of people who practiced the recommended levels of PA, analyzed with a generalized linear mixed model to account for clusters at individual and community levels. Additionally, we examined the dose–response relation of the effect based on the intervention doses in each community. The RE-AIM framework assessed intervention dissemination and implementation. Results: The two-year intervention was implemented in all communities, reaching and involving various groups. The rate of people engaged in PA significantly increased in two years (adjusted change: + 8.0 percentage points [95% confidence interval: 6.1, 10.0]). Based on the type of PA, only muscle-strengthening activity showed a significant increase (+ 11.5% points [9.6, 13.5]), whereas walking (-1.8% points [-3.6, 0.1]) and flexibility activities (+ 0.3% points [-1.5, 2.0]) did not. The increase in PA in higher-dose areas was not significantly different but slightly larger than that in lower-dose areas (+ 8.4% points vs. + 7.6% points, adjusted difference in change: 0.8% points [-3.8, 5.5]). Conclusion: The scaled-up citywide intervention promoted PA, especially muscle-strengthening activity. Collaboration with diverse organizations in different settings is crucial for multi-faceted interventions and requires balancing uncertainty in its implementation quality and quantity owing to collaborative decision-making. Trial registration: UMIN-CTR, UMIN000024682. Registered 02 November 2016, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000028377 [ABSTRACT FROM AUTHOR]

Halogenation reactions are a vital area of study for the pharmaceutical industry. The study of the reaction conditions along with the reactors and their scale-up is a thrust area in drug synthesis and manufacturing. There is a shift in the research community towards accommodating renewable energy sources which has driven scientists to include energy sources that are sustainable and aid in making the overall process efficient. This review provides a comprehensive overview of the challenges in selecting the best catalyst, light source and reaction conditions for the fluorination, chlorination and bromination reactions. This paper goes a step further to explain the photoreactors’ design and modelling as well as the scale-up of the same. Overall, it provides a comprehensive view of diverse scientific areas, from halogenation in drug synthesis to the potential of photochemical batch and flow approaches in halogenation reactions. [ABSTRACT FROM AUTHOR]

Lactic acid (LA), the starting material for polylactic acid, is currently in high demand owing to rising bioplastic production. Large‐scale production of LA typically uses a first‐generation feedstock, namely food‐grade sugars, owing to the absence of contaminants and ease of processing. However, it is not ethically correct to grow crops exclusively for LA production as the available land, water and resources should be utilized for food. Utilizing biowaste as a feedstock, which does not compete with the supply of the food chain, is a more responsible strategy. This review intends to address the most critical aspect of recent advances in laboratory‐ and pilot‐scale LA production that utilizes biowaste as the substrate. Based on the review, the biowastes used for LA fermentation can be categorized into four main groups: starchy materials, lignocellulosic materials, food and dairy wastes. A flowchart that summarizes the process of developing a pilot scale LA production is proposed. It covers essential parameters to be considered, such as the substrate, fermentation process and inoculum. The future insights concerning LA production are critically addressed at the end of this review. [ABSTRACT FROM AUTHOR]

Numerous influential policy and scientific bodies are calling for more rapid advances in the scale-up of child and youth mental health services (CYMHS). A number of CYMHS innovations hold promise for advancing scale-up but little is known about how real-world efforts are progressing. We conducted a scoping review to identify promising approaches to CYMHS scale-up across the globe. Searches were completed in six databases (Academic Search Complete, CINAHL, MEDLINE, PsychInfo, PubMed, and Web of Science). Article selection and synthesis were conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist. A second search focused on low-and-middle-income countries (LMIC) was conducted based on the Cochrane Library recommended search filters of the World Bank listed LMIC countries. Authors used a double coding strategy during the title/abstract and full-text review. Twenty-eight articles meeting the eligibility criteria were identified that described 22 initiatives (in 11 different countries). Our review found the majority of published scale-up studies in CYMHS were not informed by scale-up frameworks in design or reporting. The methods and outcomes used in the identified articles were highly variable and limited our ability to draw conclusions about comparative effectiveness although promising approaches emerged. Successes and failures identified in our review largely reflect consensus in the broader literature regarding the need for strategies to better navigate the complexities of system and policy implementation while ensuring CYMHS interventions fit local contexts. [ABSTRACT FROM AUTHOR]

The design of a mineral slurry transportation system is difficult because of the non-Newtonian nature of the flow at high slurry concentrations. The behavior of the slurry depends on many physio-chemical properties such as particle density, particle size distribution (PSD), particle shape, chemical composition, pH etc. This work presents a comparative study between three preferred methods of scale-up of the head loss in larger diameter pipelines, namely Bowen's Method, rheological method and Wilson's Method. The performance of each method is validated with the pipe loop test data in a 200 DN pipeline. A high concentration (>50% by weight) iron ore concentrate slurry was used for carrying out the above study. This work would be beneficial for engineers involved in the design and maintenance of the slurry pipelines with respect to the choice of the scale-up methods available for estimation of the head loss for a time independent, homogenous, non-Newtonian particulate slurry for both laminar and turbulent regime. [ABSTRACT FROM AUTHOR]

Microbial fermentations are widely used for the production of chemicals used as pharmaceuticals, food ingredients, materials, solvents, and biofuels. Technoeconomic analysis of a given fermentation process is important to perform before scaling the process to levels that enable commercial production. Titer, rate, and yield (TRY) of the fermentation process are key metrics that are used for technoeconomic analysis. TRY metrics have different impacts on the technoeconomic analysis, and it is important to be aware of these differences. Microbial fermentations offer the opportunity to produce a wide range of chemicals in a sustainable fashion, but it is important to carefully evaluate the production costs. This can be done on the basis of evaluation of the titer, rate, and yield (TRY) of the fermentation process. Here we describe how the three TRY metrics impact the technoeconomics of a microbial fermentation process, and we illustrate the use of these for evaluation of different processes in the production of two commodity chemicals, 1,3-propanediol (PDO) and ethanol, as well as for the fine chemical penicillin. On the basis of our discussions, we provide some recommendations on how the TRY metrics should be reported when new processes are described. [ABSTRACT FROM AUTHOR]

α-Galactosidase (α-GAL) is a class of hydrolase that releases galactose from galacto-oligosaccharides and synthetic substrates such as pNPG. In this study, the production of α-GAL by Actinoplanes utahensis B1 in submerged fermentation was enhanced by using statistical methods. The effects of temperature, pH, and inoculum percentage on enzyme secretion were optimized using BBD of RSM. The optimized process was scaled up from the shake flask to the laboratory scale (5 L) and to pilot scale (30 L) using KLa based scale-up strategy. By using BBD, a maximum yield of 62.5 U/mL was obtained at a temperature of 28 °C, a pH of 6.9, and an inoculum of 6.4%. Scale-up was performed successfully and achieved a yield of 74.4 U/mL and 76.8 U/mL in laboratory scale and pilot scale fermenters. The TOST was performed to validate the scale-up strategy and the results showed a confidence level of 95% for both scales indicating the perfect execution of scale-up procedure. Through the implementation of BBD and scale-up strategy, the overall enzyme yield has been significantly increased to 76%. This is the first article to explore the scale-up of α-GAL from the A. utahensis B1 strain and provide valuable insights for industrial applications. [ABSTRACT FROM AUTHOR]

Anthocyanins are natural pigments, known for their antioxidant, anti‐inflammatory properties, and health benefits. One method to extract anthocyanins uses natural deep eutectic solvents (NADES). NADES are mixtures of two or more natural compounds that result in a liquid with a lower melting point than any of its individual components. NADES are nontoxic, biodegradable solvents that can be obtained from renewable sources, making them an attractive alternative to traditional solvents; therefore, they are known as the "21st century solvents." This review provides a comprehensive and critical assessment of the use of NADES as a sustainable solvent system for anthocyanins extraction. It also discusses the main properties of anthocyanins, NADES, process parameters, and economic and environmental analysis to efficiently extract anthocyanins. Current state of knowledge focusing on its applicability within the industrial context was evaluated and identified gaps in knowledge, highlighting its advantages and challenges to provide recommendations for future research. [ABSTRACT FROM AUTHOR]