Unlocking the full potential of mesenchymal stromal cell therapy for osteoarthritis through machine learning-based in silico trials.

Despite the potential of mesenchymal stromal cells (MSCs) in osteoarthritis (OA) treatment, the challenge lies in addressing their therapeutic inconsistency. Clinical trials revealed significantly varied therapeutic outcomes among patients receiving the same allogenic MSCs but different treatment regimens. Therefore, optimizing personalized treatment strategies is crucial to fully unlock MSCs' potential and enhance therapeutic consistency. We employed the XGBoost algorithm to train a self-collected database comprising 37 published clinical reports to create a model capable of predicting the probability of effective pain relief and Western Ontario and McMaster Universities (WOMAC) index improvement in OA patients undergoing MSC therapy. Leveraging this model, extensive in silico simulations were conducted to identify optimal personalized treatment strategies and ideal patient profiles. Our in silico trials predicted that the individually optimized MSC treatment strategies would substantially increase patients' chances of recovery compared to the strategies used in reported clinical trials, thereby potentially benefiting 78.1%, 47.8%, 94.4% and 36.4% of the patients with ineffective short-term pain relief, short-term WOMAC index improvement, long-term pain relief and long-term WOMAC index improvement, respectively. We further recommended guidelines on MSC number, concentration, and the patients' appropriate physical (body mass index, age, etc.) and disease states (Kellgren-Lawrence grade, etc.) for OA treatment. Additionally, we revealed the superior efficacy of MSC in providing short-term pain relief compared to platelet-rich plasma therapy for most OA patients. This study represents the pioneering effort to enhance the efficacy and consistency of MSC therapy through machine learning applied to clinical data. The in silico trial approach holds immense potential for diverse clinical applications.

Energy demand forecasting using convolutional neural network and modified war strategy optimization algorithm.

Predicting the electricity demand is a key responsibility for the energy industry and governments in order to provide an effective and dependable energy supply. Traditional projection techniques frequently rely on mathematical models, which are limited in their ability to recognize complex patterns and correlations in data. Machine learning has emerged as a viable tool for estimating electricity in the last decade. In this study, the Modified War Strategy Optimization-Based Convolutional Neural Network (MWSO-CNN) has been provided for electricity demand prediction. To increase the precision of electricity demand prediction, the MWSO-CNN approach integrates the benefits of the modified war strategy optimization technique and the convolutional neural network. To improve efficiency, the modified war strategy optimization technique is employed to adjust the hyperparameters of the CNN algorithm. The suggested MWSO-CNN approach is tested on a real-world electricity demand dataset, and the findings show that it outperforms many state-of-the-art machine learning techniques for predicting electricity demand. In general, the suggested MWSO-CNN approach could offer a successful and cost-effective strategy for predicting energy consumption, which will benefit both the energy business and society as a whole.

Optimization of on-site supervision strategy based on big data of quality risk in drug enterprises / 中国药房

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Biosynthesis of 1,3-Propanediol via a New Pathway from Glucose in Escherichia coli.

1,3-Propanediol (1,3-PDO), an important dihydric alcohol, is widely used in textiles, resins, and pharmaceuticals. More importantly, it can be used as a monomer in the synthesis of polytrimethylene terephthalate (PTT). In this study, a new biosynthetic pathway is proposed to produce 1,3-PDO using glucose as a substrate and l-aspartate as a precursor without the addition of expensive vitamin B12. We introduced a 3-HP synthesis module derived from l-aspartate and a 1,3-PDO synthesis module to achieve the de novo biosynthesis. The following strategies were then pursued that included screening key enzymes, optimizing the transcription and translation levels, enhancing the precursor supply of l-aspartate and oxaloacetate, weakening the tricarboxylic acid (TCA) cycle, and blocking competitive pathways. We also used transcriptomic methods to analyze the different gene expression levels. Finally, an engineered Escherichia coli strain produced 6.41 g/L 1,3-PDO with a yield of 0.51 mol/mol glucose in a shake flask and 11.21 g/L in fed-batch fermentation. This study provides a new pathway for production of 1,3-PDO.

Rolling Bearing Performance Degradation Assessment with Adaptive Sensitive Feature Selection and Multi-Strategy Optimized SVDD.

In light of the problems of a single vibration feature containing limited information on the degradation of rolling bearings, the redundant information in high-dimensional feature sets inaccurately reflecting the reliability of rolling bearings in service, and assessments of the degradation performance being disturbed by outliers and false fluctuations in the signal, this study proposes a method of assessing rolling bearings' performance in terms of degradation using adaptive sensitive feature selection and multi-strategy optimized support vector data description (SVDD). First, a high-dimensional feature set of vibration signals from rolling bearings was extracted. Second, a method combining the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and K-medoids was used to comprehensively evaluate the features with multiple evaluation indicators and to adaptively select better degradation features to construct the sensitive feature set. Next, multi-strategy optimization of the SVDD model was carried out by introducing the autocorrelation kernel regression (AAKR) and a multi-kernel function to improve the ability of the evaluation model to overcome outliers and false fluctuations. Through validation, it could be seen that the method in this study uses samples of rolling bearings in the healthy early stage to establish the evaluation model, which can adaptively determine the starting point of the bearing's degradation. The stability and accuracy of the model were effectively improved.

Tuning metabolic efficiency for increased product yield in high titer fed-batch Chinese hamster ovary cell culture.

High demand in manufactured biologics drives the continued need for increased productivity. In this study elevated lactate metabolization resulted in improved metabolic efficiency and cellular productivity for a readily intensified high titer fed-batch process. Scheduled base or lactate feeds during the stationary growth phase led to increased titers (+9% and +8% respectively) without impacting the overall growth performance. The higher lactate consumption induced by either feed strategy substituted for glutamate catabolism and consequently reduced ammonia build-up. Direct correlation between increased titers and reduced ammonia levels was shown. Product quality attributes were impacted by both feeding strategies but could be matched with the control process by shortening the cell culture duration while maintaining titer constant.

Analysis of the results of colonoscopy in a regional central hospital in Shanghai from the perspective of screening / 上海预防医学

ObjectiveTo compare the differences between residents who did and who did not participate in a community colorectal cancer screening based on the results of their colorectal colonoscopy and explore the reasons. MethodsThe residents who underwent a colonoscopy in a central hospital in Shanghai from 2017 to 2020 were divided into two groups according to whether they had been screened in the community， and t test and χ2 test were used to compare the results of the colonoscopy （detection of lesions） of the examinees with different ages， genders， whether they had a history of colorectal cancer， and whether they had been screened in the community. The correlation between whether they had participated in the community screening and the detection of lesions was analyzed by the logistic regression model. ResultsFrom 2017 to 2020， the hospital had performed a colonoscopy for 6 389 people， and 3 623 lesions were detected， with a detection rate of 56.71%. There were 413 residents who had been screened in the community， accounting for 6.46% of the total number of those receiving a colonoscopy. 243 patients were found with pathological changes， with a detection rate of 58.84%. Compared with the residents who did not participate in the community screening， the proportion of adenoma and polyp was higher in those who had participated in the screening （χ2=50.44， P<0.001）. Among the residents without a history of colorectal cancer， the proportion of adenoma and polyp was higher in those who had participated in the community primary screening （χ2=51.86， P<0.001）. Among the residents who had not participated in the community screening， the proportion of residents with colorectal cancer history was higher （χ2=74.33， P<0.001）. Multivariate regression analysis showed that there was no correlation between participation in community screening and detection of any lesions by colonoscopy （OR=0.905， 95%CI： 0.734‒1.117） or detection of colorectal cancer related lesions （OR=1.113， 95%CI： 0.901‒1.375）. ConclusionThe proportion of residents who have participated in community screening among patients undergoing colonoscopy is low， but the asymptomatic population initially screened by the community and the symptomatic population not initially screened by the community are homogeneous， and the detection rate of precancerous lesions such as adenomas and polyps is high. It is suggested that local measures should be taken to improve residents' colonoscopy response rate， so as to obtain better screening benefits.

The Promotion and Optimization of Bank Financial Products Using Consumers' Psychological Perception.

With the rapid economic growth and increased national income year by year, individuals and families have an increasingly greater demand for financial products. Banks' sales of financial products have become a new economic profit growth point for major banks. Based on consumers' psychological perception, the influencing factors of consumers' behavior in purchasing bank financial products are studied. The influencing factor model path of consumer purchase behavior is constructed to find out the factors affecting consumers' purchase of bank financial products and formulate appropriate promotion strategies according to the influencing factors. Through the research methods of literature analysis, small-scale in-depth interview, questionnaire surveys, and statistical analysis, this exploration selects four variables: independent variable, mediator, control variable, and dependent variable. They are influencing factors of purchasing bank financial products (perceived convenience, risk value of bank financial products, satisfaction of purchasing communication process), consumers' willingness to buy bank financial products, consumers' personal characteristics and consumers' behavior of purchasing bank financial products. Meanwhile, based on 196 valid questionnaires, regression analysis is carried out through a regression model. The results show that the three influencing factors of consumers' purchase of bank financial products-perceived convenience, risk value of bank financial products, and satisfaction with the purchase communication process significantly impact consumers' purchase of bank financial products. They can put forward specific promotion suggestions for banks. This exploration aims to study the optimization of bank financial product promotion strategy from the perspective of consumer psychological perception to provide a reference for subsequent related research.

How low can you go? Examining the effects of brief online training and post-training consultation dose on implementation mechanisms and outcomes for measurement-based care.

BACKGROUND: Initial training and ongoing post-training consultation (i.e., ongoing support following training, provided by an expert) are among the most common implementation strategies used to change clinician practice. However, extant research has not experimentally investigated the optimal dosages of consultation necessary to produce desired outcomes. Moreover, the degree to which training and consultation engage theoretical implementation mechanisms-such as provider knowledge, skills, and attitudes-is not well understood. This study examined the effects of a brief online training and varying dosages of post-training consultation (BOLT+PTC) on implementation mechanisms and outcomes for measurement-based care (MBC) practices delivered in the context of education sector mental health services. METHODS: A national sample of 75 clinicians who provide mental health interventions to children and adolescents in schools were randomly assigned to BOLT+PTC or control (services as usual). Those in BOLT+PTC were further randomized to 2-, 4-, or 8-week consultation conditions. Self-reported MBC knowledge, skills, attitudes, and use (including standardized assessment, individualized assessment, and assessment-informed treatment modification) were collected for 32 weeks. Multilevel models were used to examine main effects of BOLT+PTC versus control on MBC use at the end of consultation and over time, as well as comparisons among PTC dosage conditions and theorized mechanisms (skills, attitudes, knowledge). RESULTS: There was a significant linear effect of BOLT+PTC over time on standardized assessment use (b = .02, p < .01), and a significant quadratic effect of BOLT+PTC over time on individualized assessment use (b = .04, p < .001), but no significant effect on treatment modification. BOLT + any level of PTC resulted in higher MBC knowledge and larger growth in MBC skill over the intervention period as compared to control. PTC dosage levels were inconsistently predictive of outcomes, providing no clear evidence for added benefit of higher PTC dosage. CONCLUSIONS: Online training and consultation in MBC had effects on standardized and individualized assessment use among clinicians as compared to services as usual with no consistent benefit detected for increased consultation dosage. Continued research investigating optimal dosages and mechanisms of these established implementation strategies is needed to ensure training and consultation resources are deployed efficiently to impact clinician practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT05041517 . Retrospectively registered on 10 September 2021.

Evaluation of comprehensive benefits of sponge cities using meta-analysis in different geographical environments in China.

With the rapid progress in urbanization, frequent urban waterlogging and non-point source pollution are threatening the living and health of human beings. Sponge city construction has become an effective means to curb urban waterlogging. Although related studies have explored the comprehensive benefits of sponge cities, few studies have been conducted on the effects of different geographical environments on runoff control and suspended solid (SS) removal. Based on 76 cities with sponge cities in China, this study used the meta-analysis method to evaluate the relationships of climate, terrain, underlying surface conditions, and construction area with the increase in the total annual runoff control rate and SS removal rate. The results reveal that the runoff control benefit can be significantly improved by sponge cities under the combined conditions of average annual precipitation of approximately 1000 mm, high fractional vegetation cover, sufficient soil fertility, a terrain slope i of ≤2%, and a permeability coefficient of strata of 100-200 m/d, especially in northern China, where the weight representing the quantity of comprehensive benefits was calculated to be 25.5%. In addition, the study results assist in reforming unfavorable geographical environments in the construction of sponge city, thus providing more effective solutions for tackling SS pollution. The most significant benefits of SS removal were obtained in north central China, where the weight was 21.4%. This study comprehensively investigated the effects of geographical environmental factors on the comprehensive benefits of sponge city reflected by the improvement in the total annual runoff control rate and the SS removal rate. The results will provide guidance for the planning and design of global sponge cities and effectively optimize the practice, scale, and location of existing construction based on specific geographical environments.

The Evaluation of Mean-Detrended Cross-Correlation Analysis Portfolio Strategy for Multiple risk Assets.

The fractal characteristics of the security market were considered in portfolio strategy optimization. First, the detrended cross-correlation analysis was adopted to measure the fractal correlation of different securities. Second, the fractal correlation was embedded into the mean-variance criterion of the modern portfolio theory. Third, the mean-detrended cross-correlation analysis portfolio strategy of multiple risk assets was constructed, and the analytic solution of the strategy was given. Finally, the evaluation results revealed that the constructed the mean-detrended cross-correlation analysis portfolio strategy clearly improved investment performance, thus achieving the goal of optimizing the multiple risk asset portfolio strategy.

Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy.

Alzheimer's disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood-brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients. Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-ß peptides (Aß40/42) or activated astrocyte-conditioned medium (Aß40/42/IL-1ß/TNFα-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. We found that all patients' CSF significantly reduced hmNGF release from NGC0211 cells in vitro. Aß40/42, inflammatory molecules, and activated astrocytes significantly affected NGC0211 cell proliferation without altering hmNGF release or other parameters important for essential functions of the NGC0211 cells. Long-term constant cell proliferation within the ECB device is critically important to maintain a steady cell population needed for stable mNGF release. These data show hampered proliferation of NGC0211 cells, which may lead to a decline of the NGC0211 cell population in ECBs, thereby reducing hmNGF release. Our study highlights the need for future studies to strengthen ECB-mediated long-term drug delivery approaches.

Improved esophageal squamous cell carcinoma screening effectiveness by risk-stratified endoscopic screening: evidence from high-risk areas in China.

BACKGROUND: Risk-stratified endoscopic screening (RSES), which offers endoscopy to those with a high risk of esophageal cancer, has the potential to increase effectiveness and reduce endoscopic demands compared with the universal screening strategy (i.e., endoscopic screening for all targets without risk prediction). Evidence of RSES in high-risk areas of China is limited. This study aimed to estimate whether RSES based on a 22-score esophageal squamous cell carcinoma (ESCC) risk prediction model could optimize the universal endoscopic screening strategy for ESCC screening in high-risk areas of China. METHODS: Eight epidemiological variables in the ESCC risk prediction model were collected retrospectively from 26,618 individuals aged 40-69 from three high-risk areas of China who underwent endoscopic screening between May 2015 and July 2017. The model's performance was estimated using the area under the curve (AUC). Participants were categorized into a high-risk group and a low-risk group with a cutoff score having sensitivities of both ESCC and severe dysplasia and above (SDA) at more than 90.0%. RESULTS: The ESCC risk prediction model had an AUC of 0.80 (95% confidence interval: 0.75-0.84) in this external population. We found that a score of 8 (ranging from 0 to 22) had a sensitivity of 94.2% for ESCC and 92.5% for SDA. The RSES strategy using this threshold score would allow 50.6% of endoscopies to be avoided and save approximately US$ 0.59 million compared to universal endoscopic screening among 26,618 participants. In addition, a higher prevalence of SDA (1.7% vs. 0.9%), a lower number need to screen (60 vs. 111), and a lower average cost per detected SDA (US$ 3.22 thousand vs. US$ 5.45 thousand) could have been obtained by the RSES strategy. CONCLUSIONS: The RSES strategy based on individual risk has the potential to optimize the universal endoscopic screening strategy in ESCC high-risk areas of China.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

X-architecture Steiner minimal tree algorithm based on multi-strategy optimization discrete differential evolution.

Global routing is an important link in very large scale integration (VLSI) design. As the best model of global routing, X-architecture Steiner minimal tree (XSMT) has a good performance in wire length optimization. XSMT belongs to non-Manhattan structural model, and its construction process cannot be completed in polynomial time, so the generation of XSMT is an NP hard problem. In this paper, an X-architecture Steiner minimal tree algorithm based on multi-strategy optimization discrete differential evolution (XSMT-MoDDE) is proposed. Firstly, an effective encoding strategy, a fitness function of XSMT, and an initialization strategy of population are proposed to record the structure of XSMT, evaluate the cost of XSMT and obtain better initial particles, respectively. Secondly, elite selection and cloning strategy, multiple mutation strategies, and adaptive learning factor strategy are presented to improve the search process of discrete differential evolution algorithm. Thirdly, an effective refining strategy is proposed to further improve the quality of the final Steiner tree. Finally, the results of the comparative experiments prove that XSMT-MoDDE can get the shortest wire length so far, and achieve a better optimization degree in the larger-scale problem.

A Trajectory Privacy Preserving Scheme in the CANNQ Service for IoT.

Nowadays, anyone carrying a mobile device can enjoy the various location-based services provided by the Internet of Things (IoT). 'Aggregate nearest neighbor query' is a new type of location-based query which asks the question, 'what is the best location for a given group of people to gather?' There are numerous, promising applications for this type of query, but it needs to be done in a secure and private way. Therefore, a trajectory privacy-preserving scheme, based on a trusted anonymous server (TAS) is proposed. Specifically, in the snapshot queries, the TAS generates a group request that satisfies the spatial K-anonymity for the group of users-to prevent the location-based service provider (LSP) from an inference attack-and in continuous queries, the TAS determines whether the group request needs to be resent by detecting whether the users will leave their secure areas, so as to reduce the probability that the LSP reconstructs the users' real trajectories. Furthermore, an aggregate nearest neighbor query algorithm based on strategy optimization, is adopted, to minimize the overhead of the LSP. The response speed of the results is improved by narrowing the search scope of the points of interest (POIs) and speeding up the prune of the non-nearest neighbors. The security analysis and simulation results demonstrated that our proposed scheme could protect the users' location and trajectory privacy, and the response speed and communication overhead of the service, were superior to other peer algorithms, both in the snapshot and continuous queries.

Analysis of rapid detection of Treponema pallidum antibody before voluntary blood donation and strategy optimization / 国际检验医学杂志

Objective To evaluate the performance of fast Treponema pallidum(TP) detection in voluntary blood donors and optimize the strategy for pre-donation screening.Methods Before blood donation,the gold standard TP test strip was used to make a fast detection.After blood donation,the TP-ELISA was used to test the blood.Then,analyze the donors′ anti-TP positive rate,times and intervals of donating,false positive and negative of TP fast detection.Results From 2014 to 2015,among 73 990 donors who were tested by using fast TP detection,0.71% of them(529 donors) were positive.Among the positive donors,89.2% of them(472 donors) were first-time blood donors.35 donors′ donating intervals were more than 3 years,who accounted for 61.4% of the donors who had donated for more than once.The numbers of the false positive obtained from fast TP detection were 5 and the false negative was 15.By applying the fast TP detection before blood donation,the rate of anti-TP positive had been declined from 0.71% to 0.17%.Conclusion The rejection rate of TP positive can be significantly reduced by using fast TP detection before blood donation.The fast TP detection can be used to optimize the pre-donation screening and promote blood donation service efficiency and level,while donating times and intervals of the blood donors were also considered.

Two-phase analysis in consensus genetic mapping.

Numerous mapping projects conducted on different species have generated an abundance of mapping data. Consequently, many multilocus maps have been constructed using diverse mapping populations and marker sets for the same organism. The quality of maps varies broadly among populations, marker sets, and software used, necessitating efforts to integrate the mapping information and generate consensus maps. The problem of consensus genetic mapping (MCGM) is by far more challenging compared with genetic mapping based on a single dataset, which by itself is also cumbersome. The additional complications introduced by consensus analysis include inter-population differences in recombination rate and exchange distribution along chromosomes; variations in dominance of the employed markers; and use of different subsets of markers in different labs. Hence, it is necessary to handle arbitrary patterns of shared sets of markers and different level of mapping data quality. In this article, we introduce a two-phase approach for solving MCGM. In phase 1, for each dataset, multilocus ordering is performed combined with iterative jackknife resampling to evaluate the stability of marker orders. In this phase, the ordering problem is reduced to the well-known traveling salesperson problem (TSP). Namely, for each dataset, we look for order that gives minimum sum of recombination distances between adjacent markers. In phase 2, the optimal consensus order of shared markers is selected from the set of allowed orders and gives the minimal sum of total lengths of nonconflicting maps of the chromosome. This criterion may be used in different modifications to take into account the variation in quality of the original data (population size, marker quality, etc.). In the foregoing formulation, consensus mapping is considered as a specific version of TSP that can be referred to as "synchronized TSP." The conflicts detected after phase 1 are resolved using either a heuristic algorithm over the entire chromosome or an exact/heuristic algorithm applied subsequently to the revealed small non-overlapping regions with conflicts separated by non-conflicting regions. The proposed approach was tested on a wide range of simulated data and real datasets from maize.