Control Step Research Articles

P-1774. Order sets paired with facilitation training to effectively reduce postoperative surgical prophylaxis

Abstract Background Inappropriate surgical antibiotic prophylaxis occurs in up to 40% of cases, primarily reflecting unnecessary postoperative doses ( >24hrs) in clean or clean-contaminated cases. It accounts for approximately 20% of all inappropriate use in children’s hospitals. We described order set outcomes from the Operatic Trial to compare two strategies, order set changes versus order set change with facilitation, to reducing excessive postoperative prophylaxis.Figure 1.Stepped-wedge trial design comparing order set change only (control) versus order set change plus a facilitation workshop (intervention) attended by the ASP team at the beginning of each step. Nine children’s hospitals were randomized to 1 of 3 cluster. Each cluster included 3 hospitals and each step was 6 months in duration. Methods The operatic trial was a stepped-wedge cluster randomized control trial with nine US children’s hospitals (11/1/2020-10/31/2023), with 6 steps lasting 6 months each (Figure 1). Antimicrobial stewardship teams were recruited and enrolled. After 6 months of all hospitals starting in control (step 0) of changing order sets, 3 hospital ASP teams in steps 1-3 participated in a virtual facilitation workshop (int). Facilitation is a strategy that supports people in health services organizations develop the means to change the structure and processes within settings, and clinicians can be educated on the skills and expertise to become an effective facilitator. Hospital ASP teams were surveyed every 2 months to evaluate order set changes. Results Approximately 75% of order set changes attempted were completed (65/85). Table 1 describes completed order set changes demonstrating a variety of specialties targeted and a focus on reducing prophylaxis duration. Importantly, only 4 were initiated and completed in the pre-intervention period, while the remaining were either initiated pre-intervention and completed post-intervention or initiated and completed post-intervention suggesting that facilitation training supported order set change completion. The median time to complete an order set change was 5 months. Individuals also reported other activities to support change, for example data dashboards and paper-based guidance. Conclusion Changing order sets is an effective approach to reduce excess antibiotic use in children’s hospitals. Facilitation played a role in the successful completion of order sets, including potentially assisting teams to complete order set changes that were initiated prior to facilitation training. Disclosures Jason G. Newland, MD, MEd, Moderna: Grant/Research Support|Pfizer: Grant/Research Support

Autonomous aircraft maneuvering under unknown CG variations through a robust adaptive backstepping control

The objective of the present article is to address the hitherto unaddressed problem of executing demanding autonomous aircraft maneuvers mitigating significant uncertainties in lateral center of gravity (c.g.) position. As a major contribution, it is shown that, under a reasonable simplifying assumption, a strict feedback form of the dynamics with affine in c.g. position can be derived from the highly coupled equations of motion that is caused by asymmetric c.g. variations. Thereafter, a two-step adaptive backstepping control is proposed adapting to the c.g. position automatically. Also, the useful nonlinearities in the dynamics are identified from the aircraft’s dataset and are retained to prevent a conservative control design. To provide further robustness to the aforementioned model simplification as well as to aerodynamic uncertainties, a fast adaptive sliding mode control is integrated with each of the two steps of the baseline adaptive backstepping control and the asymptotic stability of the overall system is proved using Lyapunov’s method. To validate the efficacy of the proposed control, the high angle of attack Herbst maneuver is simulated for the F18-HARV aircraft and nearly identical maneuver performance is achieved over a wide range of lateral c.g. variations on either side of the fuselage centerline. Real time hardware in loop simulations are also performed to establish the real time applicability of the proposed control.

Protocol for genetic analysis of population-scale ultra-low-depth sequencing data.

Non-invasive prenatal testing (NIPT) not only enables the detection of chromosomal anomalies in fetuses but also generates vast amounts of ultra-low-depth sequencing data, which can be leveraged for population genomic studies. Here, we present a protocol designed for massive ultra-low-depth sequencing datasets. We detail the steps for data processing, quality control, and genotype imputation, followed by genome-wide association study (GWAS) and post-GWAS analyses. This protocol applies to a wide range of ultra-low-depth sequencing studies, extending beyond data from NIPT. For complete details on the use and execution of this profile, please refer to Xiao etal.1.

Enhancing Acclimatization Conditions for Vriesea splendens 'Fire': A Comparative Analysis of Substrate Effects on Growth and Survival.

This study investigates the acclimatization success of Vriesea splendens 'Fire', a popular ornamental bromeliad, through in vitro propagation on various substrates. Due to the increasing demand for V. splendens, micropropagation offers a promising solution to overcome the limitations of traditional propagation methods. In this research, acclimatization was conducted in two trial types: in the one-step greenhouse conditions, and in two-step acclimatization, which introduced a controlled laboratory step before transferring plants to the greenhouse. The substrates examined included pure and mixed forms of turf, perlite, coco coir, pine bark (hereafter referred to as bark), moss, and vermiculite. Morphological traits such as plant height, leaf length, number and length of roots, and fresh weight were evaluated, together with physiological parameters, such as chlorophyll and carotenoid concentrations and survival percentage, to test the effectiveness of acclimatization. Coco coir-based substrates significantly enhanced plant height, root development, and survival percentages in both experiments compared with other substrates, thus proving its suitability for the propagation of V. splendens. Vermiculite had the highest survival rate during one-step acclimatization, whereas turf showed a very good performance in two-step acclimatization. On the opposite side, substrates containing bark and moss showed a reduced effect on plant growth and survival, which indicated the vital role of substrates for best development. Statistical analyses confirmed the superiority of some combinations of substrates related to physiological health, showing that optimal acclimatization results could be improved by a chosen substrate. These results strengthen the present in vitro propagation protocols of the Vriesea species by confirming the relevance of substrate choice in producing hardy plants with good commercial prospects.

Young people's preferences and motivations for STI partner notification: observational findings from the 2024 Sex, Drugs and Rock 'n' Roll survey.

Background Partner notification is an important step in the control of sexually transmissible infections (STIs). STIs remain at high rates among young people and can have serious reproductive consequences if left untreated. This study aimed to determine the preferences and motivations for partner notification among young people in Australia. Methods Quantitative and free-text qualitative data were collected through the 2024 Sex, Drugs and Rock 'n' Roll survey, an annual cross-sectional survey conducted among people aged 15-29years old in Victoria, Australia. Respondents were recruited using convenience sampling through social media advertisements. Counts and proportions were calculated for the preferences and motivations for partner notification by regular and casual sexual partners as well as methods of communication. Inductive content analysis was used to analyse free-text responses. Results The partner notification module of the survey was completed by 1163 people (60.3% identified as women, 40.2% as heterosexual) who provided a total of 1720 free-text responses. The majority, 1056 (90.8%) stated that they would notify their sexual partners and 1142 (98.2%) would want to be notified by a sexual partner of an STI risk. Qualitative analysis highlighted that respondents felt that partner notification is the responsible thing to do to look after their own and their partner's health and protect others by reducing transmission. Few stated that embarrassment and fear of repercussions may make them less likely to notify their partners or that it would depend on the type of relationship. Most preferred to notify regular partners face-to-face (941, 80.9%) and casual partners via text message (785, 67.5%). Conclusion Almost all young people want to notify and be notified by partners of an STI risk regardless of age, gender or sexual identity. Tailoring resources by communication method and partner type is one way in which practitioners and public health authorities can support young people in undertaking this important step in STI control.

Combining Short- and Long-Read Transcriptomes for Targeted Enzyme Discovery.

The discovery of genes that code for a specific enzymatic activity is important in various fields of life science and provides valuable biotechnological tools. Many genes that contribute to the production of secondary metabolites and specialized metabolic pathways are still not identified. Due to the great diversity of metabolic functions found in nature and their rapid evolutionary adaptation, we need precise but high-throughput approaches for a targeted search based on minimal prior knowledge. In this chapter, we describe a transcriptomics pipeline that was used to search for candidate genes coding for a specific enzymatic activity in a nonmodel species. We generated and combined short- and long-read transcriptomic data to obtain reliable full-length transcript sequences along with information on allelic variation, isoform expression, and condition-specific expression. Based on protein domain annotations of coding sequences and transcriptomic data, we selected candidate genes for activity assays. We provide detailed instructions for analysis and quality control steps in our pipeline that can be applied to other biological questions.

Central venous pressure as a method of optimising atrio-ventricular delay after cardiac surgery.

Haemodynamic atrioventricular delay (AVD) optimisation has primarily focussed on signals that are not easy to acquire from a pacing system itself, such as invasive left ventricular catheterisation or arterial blood pressure (ABP). In this study, standard clinical central venous pressure (CVP) signals are tested as a potential alternative. Sixteen patients with a temporary pacemaker after cardiac surgery were studied. AV delay optimisation was performed by alternating between a reference AVD of 120ms and tested settings ranging from 40 to 280ms, with 8 replicates for each setting. Alongside (a) the raw data, three methods of correcting for respiration were tested: (b) limiting analysis to a respiratory cycle, (c) asymmetric least squares (ALS) and (d) discrete wavelet transform (DWT). The utility of a quality control step was tested. CVP signals were a mirror image of the systolic ABP signals: The four R values were -0.674, -0.692, -0.631, -0.671 respectively (all p<0.001). With quality control, the mirror image was best for DWT (R = -0.76, p<0.001), with the CVP and ABP optima agreeing well (R = 0.78, p<0.001). The automated quality control signal correctly predicted the gap between the AVD optima calculated from ABP and CVP (R = 0.8, p<0.001). Central venous pressure signals could be used to optimise AVD, because they have a reliable inverse relationship with ABP when pacemaker settings undergo protocolised testing. However, protocols need careful design to circumvent spontaneous biological variability.

Detection and Characterization of Clonal Hematopoiesis.

Clonal hematopoiesis (CH) is the age-related expansion of hematopoietic stem cell clones resulting from the acquisition of somatic point mutations or mosaic chromosomal alterations (mCAs). It is linked to adverse systemic effects, including hematologic malignancies, cardiovascular diseases, metabolic disorders, as well as liver and kidney ailments, ultimately contributing to elevated overall mortality.Given its diverse biological and clinical implications, the identification of clonal hematopoiesis holds significance in various contexts. While traditionally centered on mutations associated with myeloid malignancies, stem/progenitor cell involvement has been documented for various lymphoid malignancies, including T-cell lymphoma, chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL). Lymphoid CH (L-CH) involves a broader spectrum of genes and occurs at a lower prevalence, resulting in reduced mutation prevalences per gene. This characteristic poses challenges for efficient CH detection.The major strategies to identify CH are whole exome sequencing (WES), whole genome sequencing (WGS), or targeted sequencing. Targeted sequencing allows for much higher sequencing depth compared to WES and WGS because of the focus on genes known to be associated with CH and therefore allows detecting potential variants at low frequencies with high precision. Here, we describe an error-corrected targeted sequencing approach for detection of CH in bone marrow (BM) or peripheral blood (PB) samples, which we have successfully established and used in various cohorts. This protocol includes the process of DNA isolation from PB and BM samples, library preparation with molecular tags including quality control steps and computational analysis including variant filtering.

Advancing nuclear transfer cloning in zebrafish (Danio rerio) into a translational pathway using interdisciplinary tools.

The Zebrafish International Resource Center (ZIRC) is an NIH-funded national stock center and germplasm repository that maintains and distributes genetically modified and wild-type zebrafish (Danio rerio) lines to the biomedical research community. The ZIRC and its community would benefit from incorporating somatic cell nuclear transfer (SCNT) cloning which would allow the preservation of diploid genomes. The goal of this study was to advance a zebrafish SCNT cloning protocol into a reproducible community-level pathway by use of process mapping and simulation modeling approaches to address training requirements, process constraints, and quality management gaps. Training, for most steps in the SCNT protocol, could be completed within two months; however, steps that involved micromanipulation of eggs required more than four months of training. Dechorionation of embryos and egg micromanipulation were identified as major constraints because the processes were performed manually and required advanced operator manual skills. Chemical dechorionation and microfluidic devices to aid micromanipulation were identified as ways to eliminate these constraints. Finally, quality control steps to record the initial quality of collected germplasm were recommended to prevent production defects and harmonize the SCNT pathway across multiple facilities. By beginning to enhance the reproducibility of the SCNT cloning pathway, this technique can be implemented across zebrafish research facilities and facilities that work with other biomedical models.

Semblans: automated assembly and processing of RNA-seq data.

Recent advancements in parallel sequencing methods have precipitated a surge in publicly available short-read sequence data. This has encouraged the development of novel computational tools for the de novo assembly of transcriptomes from RNA-seq data. Despite the availability of these tools, performing an end-to-end transcriptome assembly remains a programmatically involved task necessitating familiarity with best practices. Aside from quality control steps, including error correction, adapter trimming, and chimera filtration needing to be correctly used, moving data between programs often requires manual reformatting or restructuring, which can further impede throughput. Here, we introduce Semblans, a tool for streamlining the assembly process that efficiently and consistently produces high-quality transcriptome assemblies. Semblans abstracts the key quality control, reconstitution, and postprocessing steps of transcriptome assembly from raw short-read sequences to annotated coding sequences. Evaluating its performance against previously assembled transcriptomes on the basis of assembly quality, we find that Semblans produced higher quality assemblies for 98 of the 101 short-read runs tested. Semblans is written in C++ and runs on Unix-compliant operating systems. Source code, documentation, and compiled binaries are hosted under the GNU General Public License at https://github.com/gladshire/Semblans.

Normalization Strategies for Lipidome Data in Cell Line Panels

ABSTRACTSample collection can significantly affect lipid concentration measurements in cell line panels, concealing intrinsic differences between cancer subtypes. Most quality control steps in lipidomic data analysis focus on controlling technical variation. Correcting for the total amount of biological material remains an additional challenge for cell line panels. Here, we investigated how we can normalize lipidomic data acquired from multiple cell lines to correct for differences in sample biomass. We studied how commonly used data normalization and transformation strategies influence the resulting lipid data distributions. We compared normalization by biological properties including cell count and total protein concentration, to statistical and data‐based approaches, such as median, mean, or probabilistic quotient‐based normalization. We used intraclass correlations to estimate how normalization influenced the similarity between replicates. Normalizing lipidomic data by cell count improved the similarity between replicates but only for cell lines with similar morphologies. When comparing cell line panels with diverse morphologies neither cell count nor protein concentration was sufficient to increase the similarity of lipid abundances between cell line replicates. Data‐based normalizations increased these similarities but resulted in a bias towards the large and variable lipid class of triglycerides. These artifacts are reduced by normalizing for the abundance of only structural lipids. We conclude that there is a delicate balance between improving the similarity between replicates and avoiding artifacts in lipidomic data and emphasize the importance of an appropriate normalization strategy in studying biological phenomena using lipidomics.

The whole process control algorithm of inflatable dustproof shed construction in substation engineering based on graph neural network

Abstract During the construction of an inflatable dust-proof shed in substation engineering, it is one of the key issues in power system research to use scientific whole-process control algorithms to complete substation engineering decisions. At present, the control algorithm has some problems, such as low control accuracy and poor convergence speed. Therefore, the whole process control algorithm of inflatable dust shed construction in substation engineering based on a graph neural network is proposed. The control indexes of the whole process of inflatable dust-proof shed construction in substation engineering are divided into the highest level, the middle level, and the lowest level. The discriminant matrix is established to obtain the single-factor fuzzy evaluation matrix of the middle-level index. Thus, the control indexes are constructed. According to this index, the basic operation flow of the graph neural network is constructed, the objective function of the graph neural network is set, the control steps of the whole process of inflatable dust-proof shed construction in substation engineering is analyzed, and the algorithm research is realized. The experimental results show that the convergence steps are greatly reduced, the control accuracy is high, and the convergence speed is significantly improved after applying the algorithm proposed in this paper.

Mathematical Modeling of Salmonella Inactivation During Apple Drying and Pre-Drying Heating in Closed Environments.

Drying is one of the most effective preservation methods for extending the shelf-life of perishable foods. The microbial safety of low-moisture food products had not been recognized as a concern until outbreaks reported over the past decade in products contaminated with bacterial pathogens, in particular Salmonella. There is now an urgent need to understand the influence of process conditions on the thermal inactivation of pathogens in various drying operations. This study aimed to develop a predictive model for Salmonella inactivation in diced apples during hot air drying and in high-humidity heating in closed environments. Fresh-cut apple cubes (6 mm) inoculated with a cocktail of Salmonella enterica strains (Enteritidis PT30, Montevideo 488275, and Agona 447967) were placed in a customized box inside an oven for three different treatments: (1) open-box drying at oven temperature 90 °C (Drying-90); (2) close-box pre-drying heating at 90 °C (PD heating-90); and (3) close-box pre-drying heating at 70 °C (PD heating-70). Air temperature, relative humidity (RH), and sample temperatures were monitored, and Salmonella survival was measured at multiple time intervals. After 10 min, the air RH reached 66% in PD heating-90 and 74% in PD heating-70, versus 30% in Drying-90. A 5-log reduction in Salmonella was achieved in 8.5 min in PD heating-90, and 14 min in PD heating-70, compared to 28.7 min in Drying-90. A mathematical model using sample surface RH and sample temperature profiles accurately predicted Salmonella inactivation across all treatments (RMSE = 0.92 log CFU/g, R2 = 0.86), with thermal death parameters comparable to isothermal studies. This study underscores the role of humidity in enhancing microbial reduction during drying and proposes high-humidity pre-drying heating as an effective control step. The developed model shows promise for real-time prediction of microbial inactivation in complex drying environments with dynamic temperature and humidity conditions.

Electronic health record data analysis on the impact of rescue-triggered inhaled corticosteroids on controller therapy in Black and Latinx individuals from a pragmatic, open-label, patient-level randomised trial

ObjectiveThe Person Empowered Asthma Relief (PREPARE) study found that as-needed inhaled corticosteroid (ICS) supplementation combined with participants’ usual controller and rescue therapy reduced asthma exacerbations for Black and Hispanic/Latinx individuals....

Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing

Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet’s weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.

Accelerating chiller sequencing using dynamic programming

Effective management of heating, ventilation, and air conditioning (HVAC) systems is crucial for enhancing building energy efficiency. Chillers, a significant component of HVAC systems, are responsible for more than 50 % of energy usage of the whole cooling plant, underscoring the importance of optimizing chiller sequencing. Although Model Predictive Control (MPC) has demonstrated efficacy in enhancing chiller performance, its widespread adoption is hindered by its high computational complexity. This study introduces a dynamic programming approach coupled with a 2-step optimization method to expedite chiller sequencing optimization while upholding MPC’s real-time control capabilities. The MPC method implemented in this study integrates a load forecasting model with an artificial neural network (ANN) based chiller model. Through simulation tests utilizing historical HVAC operational data from a commercial building located in Shanghai, the proposed chiller sequencing strategy achieves a 9.73 % decrease in energy consumption. Moreover, the dynamic programming approach, especially in conjunction with the 2-step optimization process, significantly reduces the MPC solution time at each control step from 165 min to 3.61 s, making it a viable solution for real-time MPC deployment. Additionally, the research delves into the influence of the chiller model’s complexity, the optimization strategy, and control horizon on computational efficiency. This research provides a feasible solution to implement chiller sequencing in real buildings to pick up the low-hanging fruits in an effective way.

Synchronous DTC for torque sub-harmonic reduction in low switching frequency induction motor drives

A direct torque control (DTC) algorithm with synchronous modulation for high-power induction motors is presented in this paper. While maintaining the dynamic response and robustness of a PI-based DTC operating in the stationary reference frame, the proposed scheme is able to keep an integer PWM modulation ratio, adjusting the stator flux angle and the switching period at each control step so that the synchronicity condition is always satisfied. In this way, it is possible to achieve an improvement of the very low-frequency harmonic spectrum of the torque, in particular by reducing torque sub-harmonics. These represent one of the main problems associated with low-frequency modulation typical of high-power drives and their reduction allows to avoid drawbacks such as resonance and mechanical stresses. The performance of the proposed algorithm is evaluated with experimental tests on a small-scale test bench.

Development of a qPCR assay for the quantification of canine autosomal DNA recovered from livestock attacks

The absence of a standardised method to quantify canine DNA recovered from livestock attacks leaves forensic providers without an important quality control step to help support their decision making. Typically used to normalise the amount of DNA for STR amplification, modern forensic DNA quantification approaches use qPCR of target genes and can also include an Internal Positive Controls (IPC) to determine the presence of PCR inhibitors. The co-amplification of livestock DNA alongside canine DNA has meant that previously developed qPCR methods are not suitable for use so a standardised approach is needed. This research describes the development of a Taq-man multiplex qPCR assay that simultaneously quantifies the autosomal MC1R and Y-specific SRY gene to determine the concentration of canine DNA recovered from attacked livestock. Data suggests that the method is robust and reproducible with no significant difference in the standard curves produced from multiple runs or from different DNA standards derived from different canines. Assay sensitivity of between 15 and 31 pg is consistent with other forensic quantification assays and also in line with the sensitivity of the two tested canine STR kits, Canine Genotype 2.1 Kit and CaDNAP Panels 1 and 2. The assay is highly specific to canines when tested against 163 different dogs representing 33 different breeds and no cross-amplification of non-target species’ DNA was observed even from livestock DNA tested at 31.25 ng/µl. This strongly suggests that any DNA detected on evidence collected from attacked livestock is canine. The assay also shows robust tolerance to common livestock inhibitors continuing to amplify when inhibitor-spiked DNA samples were tested. Both mixed and inhibited DNA samples underwent STR typing using two canine forensic STR kits with data showing the Canine Genotype 2.1 Kit displaying pronounced cross-amplification of livestock DNA and and/or extensive PCR inhibition leading to the complete loss of amplification when using this kit. Conversely the CaDNAP Panels 1 and 2 showed little cross-amplification of livestock DNA and improved inhibitor tolerance suggesting that this approach was better suited for the analysis of livestock attack samples. Findings are discussed and the impact of the observations on future work in this area are explored.

Preparation of CYCU‐3/MCM‐41 Composites and Adsorption Properties for n‐Hexane

AbstractAdsorption method is one of the effective technologies for treating VOCs. Compared with activated carbon, silicon‐based materials have well‐ordered pore structure, good thermal stability and non‐flammability. In this paper, CYCU‐3/MCM‐41 composites were prepared by hydrothermal method through mixing MCM‐41 powder in situ. The nitrogen adsorption isotherms, saturation adsorption and cyclic adsorption/desorption curves of n‐hexane on CYCU‐3/MCM‐41 composites were experimentally measured. The results displayed that the CYCU‐3/MCM‐41 (3) exhibited the largest BET specific surface area (1631 m2/g). And its n‐hexane adsorption capacity was 776 mg/g, which was 19.4 % higher than that of MCM‐41, 1.42 times that of activated carbon, and 2.64 times that of molecular sieve. The kinetic fitting results showed that the pseudo‐first order kinetic model can more precisely embody the n‐hexane adsorption process on CYCU‐3/MCM‐41 composites, and the W‐M intraparticle diffusion model confirmed that intraparticle diffusion was not the only control step for the adsorption rate of n‐hexane on CYCU‐3/MCM‐41 composites. In addition, the regenerative rate of CYCU‐3/MCM‐41 (3) was over 98.9 % after ten adsorption and desorption cycles of n‐hexane, showing good desorption performance and excellent structural stability, and proving its broad application prospect in the field of VOCs treatment.

Process Control of Multistep Surface Functionalization on Hydroxyethyl Starch Nanocapsules Determines the Reproducibility of the Biological Efficacy.

Nanocarrier synthesis is highly process-dependent, leading to potential batch-to-batch variability if it is not controlled at each step. This variability affects the reproducibility of subsequent biomodification, resulting in unpredictable biological effects, particularly for bioactive molecules such as interleukin-2 (IL-2). Inconsistent conjugation can lead to variable treatment outcomes and severe side effects. Therefore, precise control of each synthesis step is critical for ensuring a consistent quality and biological performance. Our study demonstrates that dividing nanocarrier synthesis into smaller, controlled steps improves reproducibility. Using this method, we achieved highly reproducible, concentration-dependent growth of CTLL-2 cells with hydroxyethyl starch (HES) nanocapsules functionalized with defined amounts of IL-2. We believe that such detailed, stepwise control in nanocarrier synthesis enhances batch consistency, improving the clinical applicability of the drug delivery systems.