Acceptable Quality Research Articles

Crying wolf, alarm safety and management in paediatrics: A scoping review.

To provide a contemporaneous evidentiary overview of neonatal and paediatric studies investigating alarm-related patient safety and alarm system management. Furthermore, to describe how clinical alarm burden is captured and reported, to identify clinical devices that contribute to alarm burden, to explore alarm-related and patient safety measures and terminologies and to review alarm management initiatives. Scoping review. A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus and EBSCOhost was conducted from 2013 to 2023 using predetermined search terms, index terms, medical subject headings and truncation. Observational and qualitative studies with neonatal and paediatric populations reporting monitoring and alarm practices; and interventional studies reporting the success of alarm safety interventions were included. The quality of the included studies was assessed using the mixed methods appraisal tool. The search yielded 37 studies of acceptable quality. The majority explored alarm burden associated with physiological monitoring (n = 35; 95%). Alarm definitions were reported in 46% (n = 17) of studies, and commonly included what constituted actionable and non-actionable alarms. While 32% (n = 12) of studies considered alarms in relation to clinical outcomes surrounding patient safety, clinician response to alarms was only reported in 19% (n = 7) of studies. Alarm and monitoring interventions were assessed in 51% (n = 19) of included studies, with categorization into six domains: changing alarm parameters, clinician education, communication and planning, technology, alarm ordering and standardization or guidelines. This review has demonstrated the enormity of alarms in clinical settings, heterogeneity of alarm definitions and outlined interventions associated with alarm burden and patient safety. Strategies to ensure appropriate alarm limits are set and clinicians are empowered through education to recognize and respond appropriately to alarms can maximize patient safety. This review adheres to the preferred reporting items for systematic reviews and meta-analysis protocols extension for scoping reviews. No patient or public contribution.

Effects of foliar silicon and nitrogen applications on winter color retention and spring green-up of zoysia grass

Zoysia japonica Steud. (zoysia grass), with its high drought, shade, and salt tolerance, it is an excellent choice for green areas. However, in regions with subtropical climates, it goes into winter dormancy with a loss of green color and functionality, which is a main barrier to its widespread use. The application of silicon and nitrogen in fall was hypothesized to enhance winter color retention of Z. japonica. This study assessed the impact of fall (late-season) nitrogen (0, 2.5, or 5.0 g/m2 ammonium sulfate) and foliar silicon (0, 3, or 6 mL/L potassium silicate) applications on the winter color retention of Z. japonica grown in the field. The experiment was conducted over two consecutive growing seasons in Antalya, Türkiye. Turfgrass quality, color, chlorophyll content, shoot density, and winter dormancy were all improved by late-season nitrogen application. Overall, two sequential nitrogen applications at 5 g/m2 in fall provided 65% to 100% green coverage with acceptable turfgrass quality during fall and winter, indicating the possibility of maintaining the year-round green color of Z. japonica in subtropical climates. However, the silicon treatment did not affect the winter color retention of Z. japonica. The apparent lack of a beneficial response of Z. japonica to the silicon application might be due to the dose, application methods, and silicon source.

IoT Video Delivery Optimization through Machine Learning-Based Frame Resolution Adjustment

Providing acceptable video quality in the Internet of Things (IoT) implementation poses a significant challenge, mainly when the application is performed on low-cost and low-power devices. This research focuses on developing a frame resolution adjustment system that maintains the frame rate value of video delivery in wireless IoT environments with resource-constrained devices. Consistent frame rates prevent motion lag and data loss, improving user experience. The system works by predicting the upcoming throughput values using machine learning methods to adjust the sensing parameter, which is the resolution of the video frame to be captured by camera nodes. Hence, the proposed system is equipped with a file size estimator to estimate the size of the next video frame and then adjust the resolution in accordance with the throughput prediction. In this research, we conducted extensive experiments to evaluate the accuracy of the file size estimator and the throughput prediction. The experiment generated a dataset to evaluate throughput prediction and file size estimator model. The evaluation results for the file size estimator showed a mean absolute percentage error (MAPE) of 6.73% in the experiment using 317 frames with video resolutions between 72p and 720p. Experiments were also conducted to compare several machine learning methods for predicting throughput values. Compared to long short-term memory (LSTM) and autoregressive integrated moving average (ARIMA), simple exponential smoothing (SES) outperforms the others with the lowest root mean squared error (RMSE) and mean absolute error (MAE) values. Building upon these findings, we implemented the frame resolution adjustment system using SES as the method for predicting the upcoming throughput values. Finally, we demonstrated that the proposed system can maintain the frame rate according to the threshold set by the system while the resolution is being maximized, thereby addressing the challenges of maintaining video quality in resource-constrained IoT environments.

External ear malformations and cardiac and renal anomalies: A systematic review and meta-analysis.

External Ear Malformations (EEM) continue to be a common malformation seen in the pediatric patient population. This study aims to further elucidate the correlation between EEM and cardiac and renal anomalies. A systematic review and meta-analysis to study the incidence of cardiac and renal anomalies associated with syndromic and isolated (EEM). The literature search spanned multiple databases, including Google Scholar, PubMed, Scopus, Web of Science, and MEDLINE. Studies must be focused on EEM and cardiac and/or renal anomalies. Only articles written in English were included. General study characteristics, number of EEM patients, number of cardiac and renal anomalies and whether cases were syndromic were extracted from the studies. Of 1,058 initial studies, 33 were included for meta-analyses. Mean JBI score for all included studies was 92.06%, indicating acceptable study quality. Interrater reliability was high, with a Cohen kappa score for all studies of 0.94. The resulting pooled prevalence of cardiac abnormalities was 20% [95% CI:13-28%], while renal abnormalities were 13% [95% CI: 7-20%]. The most common anomalies were VSD (3.725%) and renal agenesis (2.04%). The presence of syndrome data across studies was not a significant modifier of prevalence rates. Primary limitation is due to heterogeneity in individual study methodology and reporting standards. These results highlight a higher prevalence of cardiac-related conditions than renal anomalies in patients with both syndromic and non-syndromic EEM in the included studies, underscoring the need for thorough clinical evaluations.

Navigating the Ethical Challenges of Clinical Decision-Making for Patients with Mental Illness Presenting with Self-Inflicted Burns

Abstract Complex ethical considerations can arise when patients with severe, persistent mental illness (SPMI) present with critical illness resulting from self-injury. This article presents two clinical cases in which a patient with SPMI was admitted with severe injuries following self-inflicted burns, with substantial impact on their anticipated quality of life and challenges directing their medical care. In both cases, the medical teams held discussions with surrogate decision-makers in order to evaluate the patient's minimal acceptable quality of life and make medical decisions that best reflected the patient's voice and goals. These cases underscore the importance of advance care planning in SPMI, particularly the appointment of a surrogate decision-maker, and highlight the moral distress that can arise among surgical teams and trainees while caring for patients with illness resulting from self-harm. This article offers a framework for approaching decision-making in critical illness resulting from self-harm for patients with SPMI.

Integrated HS-SPME-GC–MS and UHPLC-O-TOF-MS-based metabolomics revealed the characteristics flavor and nonvolatile metabolites during the hydrolysis process of Boletus edulis

This research aimed to investigate the flavor characteristic, metabolites and bioactivities of Boletus edulis hydrolysates via HS-SPME-GC-MS and UHPLC-MS/MS. The Maillard reaction (MR) significantly enhanced the sensory qualities of Boletus edulis, including like-meat, caramel, continuity, and complete acceptance. The accumulation of browning precursors during MR was verified through spectral analysis. We also found that the MR enhanced the antioxidant and hypoglycemic activities of Boletus edulis hydrolysates. Furthermore, 11 VOCs were also identified as key aromatic compounds and had important impact on the flavor characteristics of Maillard reaction products (MRPs). Non-targeted metabolomics analyses revealed that the formation of MRPs was affected through amino acid metabolism, lipid metabolism and plant secondary metabolism. Briefly, the flavor and biological activity of Boletus edulis were improved through enzymolysis and MR. The results provided a theoretical foundation for deep processing and resource utilization of Boletus edulis.

The Legal and Public Health Implications Of Digital Health Technologies

To reduce the negative effects of digitization, normative advice in international human rights legislation incorporates digital health into ethical and human rights frameworks. The use of digital health technology for universal health coverage (UHC) is acknowledged to have benefits, but its implementation must be based on respect for human rights, equity, and ethics, as well as upholding norms of acceptable quality, safety, and morality. The WHA acknowledged the necessity to use digital health technologies in the wake of the COVID-19 pandemic in 2020, but stressed that in doing so, they must "pay particular attention to digital inclusion, patient empowerment, data privacy and security, legal and ethical issues, and the protection of personal data." This paper's goal is to critically assess the proposed legislative framework and policy that regulate digital health technologies in India, as well as the implementation of digital health.

Critical success factors for ergonomics programs and their relationship to benefits of health and safety in Mexico’s manufacturing industries

This research determines the critical factors for implementing ergonomics programs related to health and safety benefits in the manufacturing industries of Ciudad Juarez, Mexico, from the middle/upper management perspective. The sample was non-probabilistically selected for convenience, comprising individuals in middle and senior management positions. An original questionnaire containing 105 items measuring five latent variables was developed, reviewed, and validated for data collection. The sample size totalled 206 participants. Structural equation models using partial least squares (PLS) were employed to analyse interrelationships between variables. This research demonstrated acceptable reliability and quality indices. Management commitment emerged as the most significant factor, exerting the highest direct, indirect, and total effects on the work environment and prevention activities, significantly enhancing health and safety benefits. Consequently, manufacturing companies in Juarez City must strive to improve management commitment in the working environment and prevention activities since both strategies can increase employee health and safety benefits.

Citral-thymol based synergistic shellac coatings enhanced shelf life of Kinnow fruit stored under low temperature conditions

Microbial spoilage incurs the main cause of reduced shelf life of Kinnow during storage and transportation. This study aimed to evaluate the postharvest application of plant-derived citral and thymol-based shellac wax coatings on ‘Kinnow’ mandarin under controlled conditions (5–7 °C, 90–95 % relative humidity (RH)) over a 75-day storage period. The fruit were coated with shellac wax (SH) supplemented with citral (1.0 %, CSH), thymol (1.0 %, TSH) and citral-thymol combined formulation (1.0 %, CTSH (1:1)). Rheology studies revealed that the Herschel–Bulkley model was the best fit for all coating solutions, ensuring desirable spreadability and adhesion. The CTSH-coating outperformed all other treatments by reducing mean spoilage to 0.46% as compared to commercial shellac (6.71%) over a period of 75 days under cold store conditions. The treated fruit could control the physiological weight loss to 5.73 % as compared to commercial SH coatings (7.62 %) for 60 days. The study concluded that CTSH-coated Kinnow fruit can be stored up to 60 days under cold store conditions at 5–7 °C and 90–95 % RH with acceptable fruit quality (sensory score 7.83). The activities of cell wall degrading enzymes such as Pectin methylesterase (PME) and cellulase were also found to be retarded, contributing to prolonged shelf life. Therefore, these coatings may offer a green substitute to the synthetic analogues, with no health side effects for extending the postharvest shelf life of Kinnow up to 60 days under cold store conditions.

Assessment of suitability of the Dniester River's water for drinking water supply

The Dniester is a transboundary river between Ukraine and the Republic of Moldova. It is the second longest river in Ukraine and the ninth in Europe. From its source to a town of Staryi Sambir, the Dniester flows through the Carpathian Mountains, then across the flat territory of Ukraine and Moldova. The Dniester Basin extends across seven regions in southwestern Ukraine (Lviv, Ivano-Frankivsk, Ternopil, Khmelnytskyi, Vinnytsia, Chernivtsi and Odesa Regions). A small area of the river in its upper reaches is located in Poland. The basin's shape is a very elongated oval that is curved in the middle, about 700 km long with an average width of 120 km. As it flows into the Black Sea, the Dniester River forms the Dniester estuary in Odesa region (between Ovidiopol and Bilhorod-Dnistrovskyi districts). The estuary area of the Dniester River is a complex landscape system at the sea-river-land contact. Drinking water is an important factor determining a person's health. Due to the intensive development of industry, agriculture and utility services, the number of pollutants that enter the environment and worsen the quality of drinking water in Ukraine keeps increasing. This increases the risk of toxic and infectious diseases spread among the population that consumes such low-quality water. That is why solving the problem of drinking water monitoring and assessment of its quality is a pressing task requiring urgent action. The article examines the quality of water for drinking needs at the water intake site of the Dniester River, a town of Biliaivka, for 2018-2022. Water quality assessment was carried out according to DSTU 4808: 2007 based on average and worst values. The methodology covers 80 indicators and, in accordance with sanitary legislation, is divided into seven separate groups (blocks). According to hygienic standards, the quality of river water is considered suitable for use if it belongs to quality classes 1-3. In this research, the analysis was carried out according to 23 indicators included in three groups, so the assessment is considered as tentative: Group I - organoleptic indicators (chromaticity, turbidity); Group II - general sanitary indicators (dry residue (mineralization), sulfates, chlorides, magnesium, alkalinity, hydrogen index, ammonium nitrogen, nitrite nitrogen, nitrate nitrogen, phosphate phosphorus, dissolved oxygen, bichromate oxidation (COD), BSK5); Group VII – toxicological parameters (total iron, manganese, chromium (VI), zinc, petroleum products, synthetic surface active agents (surfactants), volatile phenols). It was determined that, according to the average values, the water quality of the Dniester at the water intake site is characterized as "good", which means it has clean water of acceptable quality. As for the worst indicators, the water was assessed as transitional in quality from "good" (clean) to "satisfactory" (slightly polluted).

Meta-analysis of bone mineral density in adults with phenylketonuria

BackgroundLifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.MethodsStudies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.ResultsBMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).ConclusionsAdults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

Developing a Machine Learning 'Smart' Polymerase Chain Reaction Thermocycler Part 2: Putting the Theoretical Framework into Practice.

The introduction of PCR into forensic science and the rapid increases in the sensitivity, specificity and discrimination power of DNA profiling that followed have been fundamental in shaping the field of forensic biology. Despite these developments, the challenges associated with the DNA profiling of trace, inhibited and degraded samples remain. Thus, any improvement to the performance of sub-optimal samples in DNA profiling would be of great value to the forensic community. The potential exists to optimise the PCR performance of samples by altering the cycling conditions used. If the effects of changing cycling conditions upon the quality of a DNA profile can be well understood, then the PCR process can be manipulated to achieve a specific goal. This work is a proof-of-concept study for the development of a smart PCR system, the theoretical foundations of which are outlined in part 1 of this publication. The first steps needed to demonstrate the performance of our smart PCR goal involved the manual alteration of cycling conditions and assessment of the DNA profiles produced. In this study, the timing and temperature of the denaturation and annealing stages of the PCR were manually altered to achieve the goal of reducing PCR runtime while maintaining an acceptable quality and quantity of DNA product. A real-time feedback system was also trialled using an STR PCR and qPCR reaction mix, and the DNA profiles generated were compared to profiles produced using the standard STR PCR kits. The aim of this work was to leverage machine learning to enable real-time adjustments during a PCR, allowing optimisation of cycling conditions towards predefined user goals. A set of parameters was found that yielded similar results to the standard endpoint PCR methodology but was completed 30 min faster. The development of an intelligent system would have significant implications for the various biological disciplines that are reliant on PCR technology.

Serum Selenium Levels and Lipid Profile: A Systematic Review and Meta-analysis of Observational Studies.

Selenium is a trace element with pivotal roles in metabolic processes. Studies suggested that selenium deficiency could lead to impaired lipid profiles. However, inconsistent results have been reported regarding the association between serum selenium concentrations and lipid profile (triglycerides, LDL, HDL, VLDL, and total cholesterol). Thus, we aimed to review the correlation between them. A systematic literature search was conducted in PubMed, Embase, Web of Science, Scopus, and Google Scholar until 31 December 2023. The relevant correlation coefficients were used as desired effect sizes to assess the correlation between selenium level and lipid profile. Among 8291 records found in the primary search, 47 and 34 articles were included in the systematic review and meta-analysis, respectively. All included studies were observational investigations and had acceptable quality. Our results failed to reach strong evidence supporting the correlation between serum selenium level and lipid profiles, except for HDL, which showed a weak correlation among both adults (r = 0.1 [0.03:0.17]; I2 = 71%) and pediatrics (r = 0.08 [0.03:0.14]; I2 = 38%). Subgroup analyses based on gender did not reveal a significant or strong correlation with selenium levels (except for total cholesterol in males (r = 0.12 [0.01:0.22]; I2 = 52%)). The results did not change after the sensitivity analysis. Although some previous studies have suggested that selenium deficiency could lead to impaired lipid profile, the findings of this study indicate no strong correlation between serum selenium levels and lipid profile.

Closed reduction followed by percutaneous fixation of acute femoral neck fractures in young adults: a retrospective cohort study

OBJECTIVES: To evaluate the surgical outcomes of femoral neck fractures (FNF) in young adults treated with a closed reduction technique as it pertains to reduction quality, rates of union and risk factors for complication. METHODS: Design: Retrospective cohort study with radiograph and electronic medical record review. Setting: Level 1 Swiss Trauma center. Patient Selection Criteria: Between 2012 and 2021, young adults with isolated FNF (AO/OTA 31-B1) treated with percutaneous screw fixation were selected. Exclusion criteria were open reduction technique, age over 65 or under 16, pathologic fractures, associated femoral head or shaft fractures. Outcome Measures and Comparisons: Primary outcome was quality of reduction, as assessed by three experienced trauma surgeons’ evaluation of, intraoperative and/or first postoperative radiographs using the overall impression, the Garden’s alignment index, and Lowell`s criteria. Additionally, clinical outcomes, conversion to arthroplasty and complications following closed reduction and fixation of femoral neck fractures was reviewed. RESULTS: A total of 54 patients with a median (IQR) age of 57.5 (48-60) years were included. Among them, 22 (41%) were female and 32 (59%) were male. The closed reduction technique demonstrated satisfactory reduction results in up to 87% of cases. Major complications occurred in 19%, with 17% requiring conversion to total hip arthroplasty. Unacceptable or borderline acceptable reduction quality correlated significantly with the need for later conversion (p=0.03). CONCLUSIONS: The study supported the use of the closed reduction technique for acute FNF in patients under 65, achieving satisfactory reduction results in up to 87% of cases with comparable complication rates to treatment of young femoral neck fractures with open reduction. Furthermore, it underscored the significance of the surgeon's overall impression of reduction quality, alongside the established reduction criteria, the Garden alignment index and Lowell’s criteria, in evaluating the quality of the reduction. Additionally, risk of conversion to total hip arthroplasty was associated with worse closed reduction quality. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

SELECTION OF POTENTIAL CHIPPING ADVANCED POTATO CLONES FOR THE PROCESSING INDUSTRY IN SOUTHERN AND EASTERN INDIA

A multi-location evaluation of 60 advanced processing clones was undertaken in the selected locations of south viz., Karnataka (Rabi and Kharif), Tamil Nadu (Kharif), Telangana (Rabi) and in Rabi crop season of West Bengal. Based on four-year trials, among advanced clones, viz., MP/12-126 consistently outperformed others during 2020-21, 2021-22 and 2022-23 in the Rabi season at different locations in Karnataka. However, MP/12-126 had almost similar yield but acceptable quality parameters as compared to controls in the Kharif seasons of Karnataka and Tamil Nadu. MP/14-171 was found to have higher yield and acceptable quality traits during 2020-21, 2021-22 in the rabi season of Karnataka and Kharif season of Tamil Nadu during 2023. During the rabi season of West Bengal (2020-21, 2022-23) and the rabi season of Karnataka (2022-23) advanced clone MP/15-698 had superior performance. MP/15-651 was found to be the most widely adapted clone as it has superior performance in all states either in Rabi/Kharif or both. Based on a four-year field trial at multiple locations (6 locations) and seasons (rabi and kharif), advanced clones namely MP/12-126, MP/14-171, MP/15-651 and MP/15-698 have the potential to provide a suitable alternative to the potato growers of south and eastern India as against the existing variety/varieties with acceptable chip colour, high dry matter (&gt;20%) and lesser total potato defects including higher process grade potato yield as compared to controls.

Improving sensory quality and properties of stirred high-protein yogurts with a rotor/stator device

This study investigated the impact of post-fermentation processing and fat content on the quality of stirred high-protein yogurts (6 wt% protein) during 13 weeks of storage. A rotor/stator device was used to apply two post-fermentation treatments (119W and 296W, 290 L-1h) to yogurts containing 0 or 3 wt % fat, while a control yogurt did not undergo post-fermentation processing. Sensory quality was analyzed by Quantitative descriptive analysis (QDA) and Quality control (QC). QC results showed significant effects of post-fermentation processing on appearance, consistency, and odor/flavor. Post-fermentation processing significantly reduced whey separation, stickiness, thickness, sticky mouthfeel and mealiness, and increased shininess and smooth mouthfeel according to QDA results. Confocal laser scanning microscopy and darkfield microscopy revealed larger protein aggregates in the control samples compared to the post-processed samples. The post-processed yogurts maintained acceptable quality after 13 weeks of storage, contrasting with the control samples that had unacceptable quality throughout the storage period.

Enhancing Public Healthcare Security: Integrating Cutting-Edge Technologies into Social Medical Systems

To reduce the negative effects of digitization, normative advice in international human rights legislation incorporates digital health into ethical and human rights frameworks. The use of digital health technology for universal health coverage (UHC) is acknowledged to have benefits, but its implementation must be based on respect for human rights, equity, and ethics, as well as upholding norms of acceptable quality, safety, and morality. The WHA acknowledged the necessity to use digital health technologies in the wake of the COVID-19 pandemic in 2020, but stressed that in doing so, they must "pay particular attention to digital inclusion, patient empowerment, data privacy and security, legal and ethical issues, and the protection of personal data." This paper's goal is to critically assess the proposed legislative framework and policy that regulate digital health technologies in India, as well as the implementation of digital health.

Efficient optimization of robust project scheduling for industry 4.0: A hybrid approach based on machine learning and meta-heuristic algorithms

This research contributes significantly to the domain of Industry 4.0 by offering a nuanced approach to the multi-objective optimization of the resource-constrained project scheduling problem (RCPSP) under uncertainty. Focused on the context of smart product platforming, this study introduces a novel methodology that not only considers traditional factors like time and cost but also incorporates quality and risk aspects, crucial for personalized product fulfillment. In this regard, a comprehensive four-objective mathematical model is proposed to minimize project completion time, total project costs, and project risks while simultaneously enhancing overall project quality. Real-world uncertainty is acknowledged through the incorporation of uncertain parameters for the time, risk, and quality associated with each project activity. To address this uncertainty, a robust optimization method is applied based on Bertsimas and Sim's approach. Moreover, to optimize the proposed model, the Hybrid Red Deer and Genetic Algorithm (HRDGA) is proposed, which is leveraging a machine learning approach for clustering solutions. The numerical results demonstrate that increasing the project budget by 30% leads to an upward trend in total project costs and a reduction in the minimum acceptable quality by 10%–30% results in a decreasing trend in the total project cost. This research emphasizes the adoption of Industry 4.0 enabling technology within the project scheduling platform, particularly highlighting its significance for personalized product fulfillment.

Strategies for improving expression of recombinant human chorionic gonadotropin in Chinese Hamster Ovary (CHO) cells

Optimizations of the gene expression cassette combined with the selection of an appropriate signal peptide are important factors that must be considered to enhance heterologous protein expression in Chinese Hamster Ovary (CHO) cells. In this study, we investigated the effectiveness of different signal peptides on the production of recombinant human chorionic gonadotropin (r-hCG) in CHO-K1 cells. Four optimized expression constructs containing four promising signal peptides were stably transfected into CHO-K1 cells. The generated CHO-K1 stable pool was then evaluated for r-hCG protein production. Interestingly, human serum albumin and human interleukin-2 signal peptides exhibited relatively greater extracellular secretion of the r-hCG with an average yield of (16.59 ± 0.02 μg/ml) and (14.80 ± 0.13 μg/ml) respectively compared to the native and murine IgGκ light chain signal peptides. The stably transfected CHO pool was further used as the cell substrate to develop an optimized upstream process followed by a downstream phase of the r-hCG. Finally, the biological activity of the purified r-hCG was assessed using in vitro bioassays. The combined data highlight that the choice of signal peptide can be imperative to ensure an optimal secretion of a recombinant protein in CHO cells. In addition, the stable pool technology was a viable approach for the production of biologically active r-hCG at a research scale with acceptable bioprocess performances and consistent product quality.

A small secret of big rheumatology

Current recommendations for RA treatment determine the need to reduce the dose and duration of glucocorticoid(GC) use. This is due to the wide spectrum and high frequency (up to 100%) of serious adverse events (AE) during GC treatment. However, in real practice GCs in RA are used very often (in Russia, Western Europe and the USA they are used in about 50% of patients), and often in long-term courses. This is explained by the fact that the combination of disease-modifying antirheumatic drugs (DMARDs), including biologics (bDMARDs) and Janus kinase inhibitors (JAK), with GCs allows to achieve faster improvement of patients’ condition and therefore is very “convenient” for many patients and physicians.However, it is very difficult to ensure dose reduction and (especially!) complete discontinuation of GC administration afterwards. Clinical and observational studies show that 30–40% of patients manage to discontinue the use of GCs during treatment with bDMARDs and JAK. In addition, discontinuation of GCs may significantly increase the risk of RA flare, even with complex pathogenetic therapy.Nevertheless, prolonged use of GCs, including low doses (less than 7.5 mg/day of prednisolone) should be considered as an indicator of the severity of the disease course and inadequacy of the current therapy. Therefore, we should strive for personalization of RA therapy, selection of DMARDs based on the assessment of the disease phenotype and predictors of response to treatment with different drugs, achieving the main goal of therapy – remission/low disease activity and achievement of acceptable quality of life, without the use of GCs.