The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival...Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.展开更多
How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS consi...How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this paper.First of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight coefficients.The Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed quantitatively.With the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed method.Finally,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.展开更多
The design of mini-missiles(MMs)presents several novel challenges.The stringent mission requirement to reach a target with a certain precision imposes a high guidance precision.The miniaturization of the size of MMs m...The design of mini-missiles(MMs)presents several novel challenges.The stringent mission requirement to reach a target with a certain precision imposes a high guidance precision.The miniaturization of the size of MMs makes the design of the guidance,navigation,and control(GNC)have a larger-thanbefore impact on the main-body design(shape,motor,and layout design)and its design objective,i.e.,flight performance.Pursuing a trade-off between flight performance and guidance precision,all the relevant interactions have to be accounted for in the design of the main body and the GNC system.Herein,a multi-objective and multidisciplinary design optimization(MDO)is proposed.Disciplines pertinent to motor,aerodynamics,layout,trajectory,flight dynamics,control,and guidance are included in the proposed MDO framework.The optimization problem seeks to maximize the range and minimize the guidance error.The problem is solved by using the nondominated sorting genetic algorithm II.An optimum design that balances a longer range with a smaller guidance error is obtained.Finally,lessons learned about the design of the MM and insights into the trade-off between flight performance and guidance precision are given by comparing the optimum design to a design provided by the traditional approach.展开更多
Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,id...Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related genes.Screening for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting outcomes.Additionally,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ARLncRNAs.Results:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC prognosis.Consequently,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC.Patients in the high-risk group showed very poor prognoses in most clinical categories.The Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic processes.Notably,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC.We further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical progression.Conclusion:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC.The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression.With the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.展开更多
Global navigation satellite system-reflection(GNSS-R)sea surface altimetry based on satellite constellation platforms has become a new research direction and inevitable trend,which can meet the altimetric precision at...Global navigation satellite system-reflection(GNSS-R)sea surface altimetry based on satellite constellation platforms has become a new research direction and inevitable trend,which can meet the altimetric precision at the global scale required for underwater navigation.At present,there are still research gaps for GNSS-R altimetry under this mode,and its altimetric capability cannot be specifically assessed.Therefore,GNSS-R satellite constellations that meet the global altimetry needs to be designed.Meanwhile,the matching precision prediction model needs to be established to quantitatively predict the GNSS-R constellation altimetric capability.Firstly,the GNSS-R constellations altimetric precision under different configuration parameters is calculated,and the mechanism of the influence of orbital altitude,orbital inclination,number of satellites and simulation period on the precision is analyzed,and a new multilayer feedforward neural network weighted joint prediction model is established.Secondly,the fit of the prediction model is verified and the performance capability of the model is tested by calculating the R2 value of the model as 0.9972 and the root mean square error(RMSE)as 0.0022,which indicates that the prediction capability of the model is excellent.Finally,using the novel multilayer feedforward neural network weighted joint prediction model,and considering the research results and realistic costs,it is proposed that when the constellation is set to an orbital altitude of 500 km,orbital inclination of 75and the number of satellites is 6,the altimetry precision can reach 0.0732 m within one year simulation period,which can meet the requirements of underwater navigation precision,and thus can provide a reference basis for subsequent research on spaceborne GNSS-R sea surface altimetry.展开更多
Globally,type 2 diabetes mellitus(T2DM)is one of the most common metabolic disorders.T2DM physiopathology is influenced by complex interrelationships between genetic,metabolic and lifestyle factors(including diet),whi...Globally,type 2 diabetes mellitus(T2DM)is one of the most common metabolic disorders.T2DM physiopathology is influenced by complex interrelationships between genetic,metabolic and lifestyle factors(including diet),which differ between populations and geographic regions.In fact,excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM,whereas habitual intakes of plant-based healthy diets usually exert a protective effect.Moreover,genomic studies have allowed the characterization of sequence DNA variants across the human genome,some of which may affect gene expression and protein functions relevant for glucose homeostasis.This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression,some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions.Also,novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations.Furthermore,progresses in other omics areas(epigenomics,metagenomics,proteomics,and metabolomics)are improving current understanding of genetic insights in T2DM clinical outcomes.Although more investigation is still needed,the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening,prevention,diagnosis,management,and prognosis of T2DM through precision nutrition.展开更多
The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trial...The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.展开更多
The paper selected Chinese Cruise Line as the case study. Having based on the survey data of Chinese cruise tourism consumers, the factor analysis method, one-way analysis of variances method, cluster analysis method,...The paper selected Chinese Cruise Line as the case study. Having based on the survey data of Chinese cruise tourism consumers, the factor analysis method, one-way analysis of variances method, cluster analysis method, and other quantitative and qualitative methods were taken to analyze Chinese consumers’ satisfaction differences of cruise tourism service quality with different segmentation markets and clusters markets, and the reasons of satisfaction differences were also explored. Then precision marketing strategy of Chinese cruise tourism with different segmentation markets and clusters markets from the supply-side reform perspective was discussed. The purpose of current research was to provide suggestions of precision management and precision marketing of Chinese cruise tourism for relevant enterprises and government departments.展开更多
New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individua...New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.展开更多
Objective:To explore the impact of a continuous precision nursing model on patients’Knowledge,Attitudes,and Practices(KAP)and cardiac function during the nursing process of patients undergoing percutaneous coronary a...Objective:To explore the impact of a continuous precision nursing model on patients’Knowledge,Attitudes,and Practices(KAP)and cardiac function during the nursing process of patients undergoing percutaneous coronary angiography and stent implantation.Methods:Ninety patients who underwent percutaneous coronary angiography and stent implantation in our hospital from April 2022 to April 2023 were selected and randomly divided into the control group(45 cases),in which routine nursing support was carried out during the treatment process,and the observation group(45 cases),in which continuous precision nursing model was carried out during the treatment process.Comparisons were made between the two groups of patients on their KAP,cardiac function,and quality of life during recovery.Results:There was no difference in the left ventricular ejection fraction(LVEF),cardiac output(CO),and cardiac index(CI)levels before intervention.After the intervention,the levels of cardiac function in the observation group were higher than those of the control group(P<0.05).There was no difference in the Exercise of Self-Care Agency(ESCA)self-care ability scale scores before the intervention.After the intervention,the observation group had higher ESCA scores than the control group(P<0.05).Conclusion:Implementation of a continuous precision nursing model in the care of patients undergoing percutaneous coronary angiography and stent implantation improved the patient’s cardiac function,and KAP,and promoted recovery.展开更多
The research aimed to understand farmers’willingness to adopt(WTA)and willingness to pay(WTP)for precision pesticide technologies and analyzed the determinants of farmers’decision-making.We used a two-stage approach...The research aimed to understand farmers’willingness to adopt(WTA)and willingness to pay(WTP)for precision pesticide technologies and analyzed the determinants of farmers’decision-making.We used a two-stage approach to consider farmers’WTA and WTP for precision pesticide technologies.A survey of 545 apple farmers was administered in Bohai Bay and the Loess Plateau in China.The data were analyzed using the double-hurdle model.The results indicated that 78.72%of respondents were willing to apply precision pesticide technologies provided by service organizations such as cooperatives and dedicated enterprises,and 69.72%were willing to buy the equipment for using precision pesticide technologies.The results of the determinant analysis indicated that farmers’perceived perceptions,farm scale,cooperative membership,access to digital information,and availability of financial services had significant and positive impacts on farmers’WTA precision pesticide technologies.Cooperative membership,technical training,and adherence to environmental regulations increased farmers’WTP for precision pesticide technologies.Moreover,nonlinear relationships between age,agricultural experience,and farmers’WTA and WTP for precision pesticide technology services were found.展开更多
Precision Agriculture(PA)has been used in many countries and serving the agricultural sectors.The use of PA solutions intervened with many agricultural businesses and supported decision making using data analytics.Pre...Precision Agriculture(PA)has been used in many countries and serving the agricultural sectors.The use of PA solutions intervened with many agricultural businesses and supported decision making using data analytics.Precision Agriculture depends on weather,soil,plants,and water information that are essential for farming.Precision Agriculture depends on the use of several technologies such as image sensors,vision machines,drones,robots,machine learning,and artificial intelligence.The use of Precision Agriculture Technologies(PAT)depends on integration between devices,sensors,and systems to ensure the proper implementation of activities.This paper is generated from research on the applicability of PA in in Egypt that ended with a proposed framework for proper implementation of it.The conducted research depended on a survey,focus group discussions,and an online questionnaire that reached 271 respondents from 19 Egyptian governorates.The framework has been developed to enhance the role of an initiative leader to promote PAT through collaboration with other stakeholders in the agricultural sector.The proposed framework can be used by governmental,non-governmental entities,universities and private sector institutions and could be used at countries facing issues with land fragmentation,limited access to information,limited access to agricultural extension services,and increase in agricultural input’s prices.展开更多
The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and impro...The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.展开更多
Low-noise high-stability current sources have essential applications such as neutron electric dipole moment measurement and high-stability magnetometers. Previous studies mainly focused on frequency noise above 0.1 Hz...Low-noise high-stability current sources have essential applications such as neutron electric dipole moment measurement and high-stability magnetometers. Previous studies mainly focused on frequency noise above 0.1 Hz while less on the low-frequency noise/drift. We use double resonance alignment magnetometers(DRAMs) to measure and suppress the low-frequency noise of a homemade current source(CS) board. The CS board noise level is suppressed by about 10 times in the range of 0.001-0.1 Hz and is reduced to 100 n A/√Hz at 0.001 Hz. The relative stability of CS board can reach2.2 × 10^(-8). In addition, the DRAM shows a better resolution and accuracy than a commercial 7.5-digit multimeter when measuring our homemade CS board. Further, by combining the DRAM with a double resonance orientation magnetometer,we may realize a low-noise CS in the 0.001-1000 Hz range.展开更多
Presently,precision agriculture processes like plant disease,crop yield prediction,species recognition,weed detection,and irrigation can be accom-plished by the use of computer vision(CV)approaches.Weed plays a vital ...Presently,precision agriculture processes like plant disease,crop yield prediction,species recognition,weed detection,and irrigation can be accom-plished by the use of computer vision(CV)approaches.Weed plays a vital role in influencing crop productivity.The wastage and pollution of farmland's natural atmosphere instigated by full coverage chemical herbicide spraying are increased.Since the proper identification of weeds from crops helps to reduce the usage of herbicide and improve productivity,this study presents a novel computer vision and deep learning based weed detection and classification(CVDL-WDC)model for precision agriculture.The proposed CVDL-WDC technique intends to prop-erly discriminate the plants as well as weeds.The proposed CVDL-WDC technique involves two processes namely multiscale Faster RCNN based object detection and optimal extreme learning machine(ELM)based weed classification.The parameters of the ELM model are optimally adjusted by the use of farmland fertility optimization(FFO)algorithm.A comprehensive simulation analysis of the CVDL-WDC technique against benchmark dataset reported the enhanced out-comes over its recent approaches interms of several measures.展开更多
Three-dimensional(3D)printing technology is expected to solve the organ shortage problem.However,owing to the accuracy limitations,it is difficult for the current bioprinting technology to achieve an accurate control ...Three-dimensional(3D)printing technology is expected to solve the organ shortage problem.However,owing to the accuracy limitations,it is difficult for the current bioprinting technology to achieve an accurate control of the spatial position and distribution of a single cell or single component droplet.In this study,to accurately achieve the directional deposition of different cells and biological materials in the spatial position for the construction of large transplantable tissues and organs,a high-precision multichannel 3D bioprinter with submicron-level motion accuracy is designed,and concurrent and synergistic printing methods are proposed.Based on the high-precision motion characteristics of the gantry structure and the requirements of concurrent and synergistic printing,a 3D bioprint-ing system with a set of 6 channels is designed to achieve six-in-one printing.Based on the Visual C++environ-ment,a control system software that integrates the programmable multi-axis controller(PMAC)motion,pneumatic,and temperature control subsystems was developed and designed.Finally,based on measurements and experiments,the 3D bioprinter and its control system was verified to fulfil the requirements of multichannel,concurrent,and syn-ergistic printing with submicron-level motion accuracy,significantly shortening the printing time and improving the printing efficiency.This study not only provides an equipment basis for printing complex heterogeneous tissue structures,but also improves the flexibility and functionality of bioprinting,and ultimately makes the construction of complex multicellular tissues or organs possible.展开更多
The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapi...The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies.Over the past few decades,the emergence of transcriptome analysis tools,including real-time quantitative reverse transcription PCR,microarrays,and RNA sequencing,has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures.In recent years,the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment,which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets.In the present article,we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains:primary cancer cells;carcinogenic stimuli;and tumor microenvironment.We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics,surveillance,and treatment of HCC recurrence.展开更多
The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does...The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.展开更多
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82173182)the Sichuan Science and Technology Program(Grant No.2021YJ0117 to Weiya Wang+1 种基金Grant No.2023NSFSC1939 to Dan Liu)the 1·3·5 project for Disciplines of Excellence–Clinical Research Incubation Project,West China Hospital,Sichuan University(Grant Nos.2019HXFH034 and ZYJC21074)。
文摘Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.
基金National Natural Science Foundation of China(Grant Nos.11972193 and 92266201)。
文摘How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this paper.First of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight coefficients.The Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed quantitatively.With the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed method.Finally,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.
文摘The design of mini-missiles(MMs)presents several novel challenges.The stringent mission requirement to reach a target with a certain precision imposes a high guidance precision.The miniaturization of the size of MMs makes the design of the guidance,navigation,and control(GNC)have a larger-thanbefore impact on the main-body design(shape,motor,and layout design)and its design objective,i.e.,flight performance.Pursuing a trade-off between flight performance and guidance precision,all the relevant interactions have to be accounted for in the design of the main body and the GNC system.Herein,a multi-objective and multidisciplinary design optimization(MDO)is proposed.Disciplines pertinent to motor,aerodynamics,layout,trajectory,flight dynamics,control,and guidance are included in the proposed MDO framework.The optimization problem seeks to maximize the range and minimize the guidance error.The problem is solved by using the nondominated sorting genetic algorithm II.An optimum design that balances a longer range with a smaller guidance error is obtained.Finally,lessons learned about the design of the MM and insights into the trade-off between flight performance and guidance precision are given by comparing the optimum design to a design provided by the traditional approach.
文摘Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related genes.Screening for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting outcomes.Additionally,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ARLncRNAs.Results:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC prognosis.Consequently,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC.Patients in the high-risk group showed very poor prognoses in most clinical categories.The Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic processes.Notably,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC.We further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical progression.Conclusion:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC.The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression.With the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.
基金the National Natural Science Foundation of China under Grant(42274119)the Liaoning Revitalization Talents Program under Grant(XLYC2002082)+1 种基金National Key Research and Development Plan Key Special Projects of Science and Technology Military Civil Integration(2022YFF1400500)the Key Project of Science and Technology Commission of the Central Military Commission.
文摘Global navigation satellite system-reflection(GNSS-R)sea surface altimetry based on satellite constellation platforms has become a new research direction and inevitable trend,which can meet the altimetric precision at the global scale required for underwater navigation.At present,there are still research gaps for GNSS-R altimetry under this mode,and its altimetric capability cannot be specifically assessed.Therefore,GNSS-R satellite constellations that meet the global altimetry needs to be designed.Meanwhile,the matching precision prediction model needs to be established to quantitatively predict the GNSS-R constellation altimetric capability.Firstly,the GNSS-R constellations altimetric precision under different configuration parameters is calculated,and the mechanism of the influence of orbital altitude,orbital inclination,number of satellites and simulation period on the precision is analyzed,and a new multilayer feedforward neural network weighted joint prediction model is established.Secondly,the fit of the prediction model is verified and the performance capability of the model is tested by calculating the R2 value of the model as 0.9972 and the root mean square error(RMSE)as 0.0022,which indicates that the prediction capability of the model is excellent.Finally,using the novel multilayer feedforward neural network weighted joint prediction model,and considering the research results and realistic costs,it is proposed that when the constellation is set to an orbital altitude of 500 km,orbital inclination of 75and the number of satellites is 6,the altimetry precision can reach 0.0732 m within one year simulation period,which can meet the requirements of underwater navigation precision,and thus can provide a reference basis for subsequent research on spaceborne GNSS-R sea surface altimetry.
文摘Globally,type 2 diabetes mellitus(T2DM)is one of the most common metabolic disorders.T2DM physiopathology is influenced by complex interrelationships between genetic,metabolic and lifestyle factors(including diet),which differ between populations and geographic regions.In fact,excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM,whereas habitual intakes of plant-based healthy diets usually exert a protective effect.Moreover,genomic studies have allowed the characterization of sequence DNA variants across the human genome,some of which may affect gene expression and protein functions relevant for glucose homeostasis.This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression,some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions.Also,novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations.Furthermore,progresses in other omics areas(epigenomics,metagenomics,proteomics,and metabolomics)are improving current understanding of genetic insights in T2DM clinical outcomes.Although more investigation is still needed,the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening,prevention,diagnosis,management,and prognosis of T2DM through precision nutrition.
基金National Science and Technology Council,No.NSTC 112-2314-B-039-048.
文摘The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.
基金National Natural Science Foundation of China(72074053).
文摘The paper selected Chinese Cruise Line as the case study. Having based on the survey data of Chinese cruise tourism consumers, the factor analysis method, one-way analysis of variances method, cluster analysis method, and other quantitative and qualitative methods were taken to analyze Chinese consumers’ satisfaction differences of cruise tourism service quality with different segmentation markets and clusters markets, and the reasons of satisfaction differences were also explored. Then precision marketing strategy of Chinese cruise tourism with different segmentation markets and clusters markets from the supply-side reform perspective was discussed. The purpose of current research was to provide suggestions of precision management and precision marketing of Chinese cruise tourism for relevant enterprises and government departments.
文摘New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.
文摘Objective:To explore the impact of a continuous precision nursing model on patients’Knowledge,Attitudes,and Practices(KAP)and cardiac function during the nursing process of patients undergoing percutaneous coronary angiography and stent implantation.Methods:Ninety patients who underwent percutaneous coronary angiography and stent implantation in our hospital from April 2022 to April 2023 were selected and randomly divided into the control group(45 cases),in which routine nursing support was carried out during the treatment process,and the observation group(45 cases),in which continuous precision nursing model was carried out during the treatment process.Comparisons were made between the two groups of patients on their KAP,cardiac function,and quality of life during recovery.Results:There was no difference in the left ventricular ejection fraction(LVEF),cardiac output(CO),and cardiac index(CI)levels before intervention.After the intervention,the levels of cardiac function in the observation group were higher than those of the control group(P<0.05).There was no difference in the Exercise of Self-Care Agency(ESCA)self-care ability scale scores before the intervention.After the intervention,the observation group had higher ESCA scores than the control group(P<0.05).Conclusion:Implementation of a continuous precision nursing model in the care of patients undergoing percutaneous coronary angiography and stent implantation improved the patient’s cardiac function,and KAP,and promoted recovery.
基金supported by the National Key Research and Development Program of China(2017YFE0122500)the UK BBSRC-Innovate UK–China Agritech Challenge Funded Project(RED-APPLE,BB/S020985/1)the project supported by the Fundamental Research Funds for the Central Universities,China(2662022JGQD001).
文摘The research aimed to understand farmers’willingness to adopt(WTA)and willingness to pay(WTP)for precision pesticide technologies and analyzed the determinants of farmers’decision-making.We used a two-stage approach to consider farmers’WTA and WTP for precision pesticide technologies.A survey of 545 apple farmers was administered in Bohai Bay and the Loess Plateau in China.The data were analyzed using the double-hurdle model.The results indicated that 78.72%of respondents were willing to apply precision pesticide technologies provided by service organizations such as cooperatives and dedicated enterprises,and 69.72%were willing to buy the equipment for using precision pesticide technologies.The results of the determinant analysis indicated that farmers’perceived perceptions,farm scale,cooperative membership,access to digital information,and availability of financial services had significant and positive impacts on farmers’WTA precision pesticide technologies.Cooperative membership,technical training,and adherence to environmental regulations increased farmers’WTP for precision pesticide technologies.Moreover,nonlinear relationships between age,agricultural experience,and farmers’WTA and WTP for precision pesticide technology services were found.
文摘Precision Agriculture(PA)has been used in many countries and serving the agricultural sectors.The use of PA solutions intervened with many agricultural businesses and supported decision making using data analytics.Precision Agriculture depends on weather,soil,plants,and water information that are essential for farming.Precision Agriculture depends on the use of several technologies such as image sensors,vision machines,drones,robots,machine learning,and artificial intelligence.The use of Precision Agriculture Technologies(PAT)depends on integration between devices,sensors,and systems to ensure the proper implementation of activities.This paper is generated from research on the applicability of PA in in Egypt that ended with a proposed framework for proper implementation of it.The conducted research depended on a survey,focus group discussions,and an online questionnaire that reached 271 respondents from 19 Egyptian governorates.The framework has been developed to enhance the role of an initiative leader to promote PAT through collaboration with other stakeholders in the agricultural sector.The proposed framework can be used by governmental,non-governmental entities,universities and private sector institutions and could be used at countries facing issues with land fragmentation,limited access to information,limited access to agricultural extension services,and increase in agricultural input’s prices.
文摘The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 12174446 and 61671458)。
文摘Low-noise high-stability current sources have essential applications such as neutron electric dipole moment measurement and high-stability magnetometers. Previous studies mainly focused on frequency noise above 0.1 Hz while less on the low-frequency noise/drift. We use double resonance alignment magnetometers(DRAMs) to measure and suppress the low-frequency noise of a homemade current source(CS) board. The CS board noise level is suppressed by about 10 times in the range of 0.001-0.1 Hz and is reduced to 100 n A/√Hz at 0.001 Hz. The relative stability of CS board can reach2.2 × 10^(-8). In addition, the DRAM shows a better resolution and accuracy than a commercial 7.5-digit multimeter when measuring our homemade CS board. Further, by combining the DRAM with a double resonance orientation magnetometer,we may realize a low-noise CS in the 0.001-1000 Hz range.
文摘Presently,precision agriculture processes like plant disease,crop yield prediction,species recognition,weed detection,and irrigation can be accom-plished by the use of computer vision(CV)approaches.Weed plays a vital role in influencing crop productivity.The wastage and pollution of farmland's natural atmosphere instigated by full coverage chemical herbicide spraying are increased.Since the proper identification of weeds from crops helps to reduce the usage of herbicide and improve productivity,this study presents a novel computer vision and deep learning based weed detection and classification(CVDL-WDC)model for precision agriculture.The proposed CVDL-WDC technique intends to prop-erly discriminate the plants as well as weeds.The proposed CVDL-WDC technique involves two processes namely multiscale Faster RCNN based object detection and optimal extreme learning machine(ELM)based weed classification.The parameters of the ELM model are optimally adjusted by the use of farmland fertility optimization(FFO)algorithm.A comprehensive simulation analysis of the CVDL-WDC technique against benchmark dataset reported the enhanced out-comes over its recent approaches interms of several measures.
基金Supported by National Key Research and Development Program of China(Grant No.2018YFA0703000)National Natural Science Foundation of China(Grant No.51875518)Fundamental Research Funds for the Central Universities of China(Grant Nos.2019XZZX003-02,2019FZA4002).
文摘Three-dimensional(3D)printing technology is expected to solve the organ shortage problem.However,owing to the accuracy limitations,it is difficult for the current bioprinting technology to achieve an accurate control of the spatial position and distribution of a single cell or single component droplet.In this study,to accurately achieve the directional deposition of different cells and biological materials in the spatial position for the construction of large transplantable tissues and organs,a high-precision multichannel 3D bioprinter with submicron-level motion accuracy is designed,and concurrent and synergistic printing methods are proposed.Based on the high-precision motion characteristics of the gantry structure and the requirements of concurrent and synergistic printing,a 3D bioprint-ing system with a set of 6 channels is designed to achieve six-in-one printing.Based on the Visual C++environ-ment,a control system software that integrates the programmable multi-axis controller(PMAC)motion,pneumatic,and temperature control subsystems was developed and designed.Finally,based on measurements and experiments,the 3D bioprinter and its control system was verified to fulfil the requirements of multichannel,concurrent,and syn-ergistic printing with submicron-level motion accuracy,significantly shortening the printing time and improving the printing efficiency.This study not only provides an equipment basis for printing complex heterogeneous tissue structures,but also improves the flexibility and functionality of bioprinting,and ultimately makes the construction of complex multicellular tissues or organs possible.
基金Linkou Chang Gung Memorial Hospital,Taiwan,No.CORPG3L0271,No.CORPG3L0281,No.CMRPG3K2292,and No.CORPG3L0301Ministry of Science and Technology,No.MOST111-2314-B-182A-126.
文摘The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies.Over the past few decades,the emergence of transcriptome analysis tools,including real-time quantitative reverse transcription PCR,microarrays,and RNA sequencing,has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures.In recent years,the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment,which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets.In the present article,we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains:primary cancer cells;carcinogenic stimuli;and tumor microenvironment.We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics,surveillance,and treatment of HCC recurrence.
基金supported by the Anhui Famous Traditional Chinese Medicine Liu Jian Studio Construction Project(Traditional Chinese Medicine Development Secret[2018]No.11)the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(No.2018YFC1705204)+1 种基金Anhui Province Traditional Chinese Medicine Leading Talent Project(Traditional Chinese Medicine Development Secret[2018]No.23)the Anhui Key Research and Development Program Foreign Science and Technology Cooperation Project(No.201904b11020011).
文摘The pathophysiology of osteoarthritis(OA)is multifactorial,with the primary risk factors being obesity,age,environmental variables,and genetic predisposition.The available evidence suggests that genetic diversity does not adequately account for all clinical characteristics and heterogeneity of OA.Genetics has emerged as a nascent and crucial area of research in OA.The epigenetic module presents a potential link between genetic and environmental risk factors and the susceptibility and pathogenesis of OA.As a critical epigenetic alteration,DNA methylation has been shown to have an important role in the etiology of OA and is a viable biomarker for predicting disease progression and medication response,as shown in this research.This review aims to update knowledge in the field of DNA methylation associated with OA to better identify the essential features of OA subtypes and pathological conditions,hence accelerating individualized treatment and precision medicine.
