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
Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable...Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.展开更多
Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implic...Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implicit computations and full precision for the explicit computations.In this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and efficiency.We develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)methods.The convergence,accuracy,and runtime of these methods are explored.We show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.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
The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil...The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil tends to affect the agricultural coffee production system. Therefore, research related to geoelectrical properties of soil such as resistivity for characterization the region of the study for coffee cultivation purposes can improve and optimize the production. This resistivity method allows to investigate the subsurface through different techniques: 1D vertical electrical sounding and electrical imaging. The acquisition of data using these techniques permitted the creation of 2D resistivity cross section from the study area. The geoelectrical data was acquired by using a resistivity meter equipment and was processed in different softwares. The results of the geoelectrical characterization from 1D resistivity model and 2D resistivity electrical sections show that in the study area of Kabiri, there are 8 varieties of geoelectrical layers with different resistivity or conductivity. Near survey in the study area, the lowest resistivity is around 0.322 Ω·m, while the highest is about 92.1 Ω·m. These values illustrated where is possible to plant coffee for suggestion of specific fertilization plan for some area to improve the cultivation.展开更多
We present a quantitative measurement of the horizontal component of the microwave magnetic field of a coplanar waveguide using a quantum diamond probe in fiber format.The measurement results are compared in detail wi...We present a quantitative measurement of the horizontal component of the microwave magnetic field of a coplanar waveguide using a quantum diamond probe in fiber format.The measurement results are compared in detail with simulation,showing a good consistence.Further simulation shows fiber diamond probe brings negligible disturbance to the field under measurement compared to bulk diamond.This method will find important applications ranging from electromagnetic compatibility test and failure analysis of high frequency and high complexity integrated circuits.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
Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to...Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.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
In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding ma...In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of 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
Offset-tracking is an essential method for deriving glacier flow rates using optical imagery.Sentinel-2(S2)and Landsat-8/9(L8/9)are popular optical satellites or constellations for polar studies,offering high spatial ...Offset-tracking is an essential method for deriving glacier flow rates using optical imagery.Sentinel-2(S2)and Landsat-8/9(L8/9)are popular optical satellites or constellations for polar studies,offering high spatial resolution with relatively short revisit time,wide swath width,and free accessibility.To evaluate and compare the precision of offset-tracking results yielded with these two kinds of data,in this study S2 and L8/9 imagery observed in Petermann Glacier in Greenland,Karakoram in High-Mountains Asia,and Amery Ice Shelf in the Antarctic are analyzed.Outliers and various systematic error sources in the offset-tracking results including orbital and strip errors were analyzed and eliminated at the pre-process stage.Precision at the off-glacier(bare rock)region was evaluated by presuming that no deformation occurred;then for both glacierized and the off-glacier regions,precision of velocity time series was evaluated based on error propagation theory.The least squares method based on connected components was used to solve flow rates time series based on multi-pair images offset-tracking.The results indicated that S2 achieved slightly higher precision than L8/9 in terms of both single-pair derived displacements and least square solved daily flow rates time series.Generally,the RMSE of daily velocity is 26%lower for S2 than L8/9.Moreover,S2 provided higher temporal resolution for monitoring glacier flow rates.展开更多
Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets ...Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.展开更多
Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC pati...Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients.With the advancement of artificial intelligence(AI)technology and the proliferation of medical digital information,AI has demonstrated promising sensitivity and accuracy in assisting precise detection,treatment decision-making,and prognosis assessment of ESCC.It has become a unique opportunity to enhance comprehen-sive clinical management of ESCC in the era of precision oncology.This review examines how AI is applied to the diagnosis,treatment,and prognosis assessment of ESCC in the era of precision oncology,and analyzes the challenges and potential opportunities that AI faces in clinical translation.Through insights into future prospects,it is hoped that this review will contribute to the real-world application of AI in future clinical settings,ultimately alleviating the disease burden caused by ESCC.展开更多
The quantization algorithm compresses the original network by reducing the numerical bit width of the model,which improves the computation speed. Because different layers have different redundancy and sensitivity to d...The quantization algorithm compresses the original network by reducing the numerical bit width of the model,which improves the computation speed. Because different layers have different redundancy and sensitivity to databit width. Reducing the data bit width will result in a loss of accuracy. Therefore, it is difficult to determinethe optimal bit width for different parts of the network with guaranteed accuracy. Mixed precision quantizationcan effectively reduce the amount of computation while keeping the model accuracy basically unchanged. In thispaper, a hardware-aware mixed precision quantization strategy optimal assignment algorithm adapted to low bitwidth is proposed, and reinforcement learning is used to automatically predict the mixed precision that meets theconstraints of hardware resources. In the state-space design, the standard deviation of weights is used to measurethe distribution difference of data, the execution speed feedback of simulated neural network accelerator inferenceis used as the environment to limit the action space of the agent, and the accuracy of the quantization model afterretraining is used as the reward function to guide the agent to carry out deep reinforcement learning training. Theexperimental results show that the proposed method obtains a suitable model layer-by-layer quantization strategyunder the condition that the computational resources are satisfied, and themodel accuracy is effectively improved.The proposed method has strong intelligence and certain universality and has strong application potential in thefield of mixed precision quantization and embedded neural network model deployment.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
This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivo...This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.展开更多
Accurate localization is paramount for unmanned aerial vehicles (UAVs) spanning various technical and industrial domains, necessitating a comprehensive assessment of global navigation satellite system (GNSS) precision...Accurate localization is paramount for unmanned aerial vehicles (UAVs) spanning various technical and industrial domains, necessitating a comprehensive assessment of global navigation satellite system (GNSS) precision. This study investigates the performance of distinct GNSS constellations in determining the precise location of a building utilizing a high-precision GNSS receiver. The receiver, incorporating advanced multi-frequency and full-constellation positioning capabilities, was integrated with a smartphone via Bluetooth to enable the UAV’s acquisition of centimeter-level positioning data. Sequential utilization of single satellite systems—such as GPS-only, GLONASS-only, Galileo-only, SBAS-only, and BeiDou-only—facilitated the documentation of latitude and longitude coordinates for the designated building. Subsequent comparison of these coordinates with a specialized Geographic Information System (GIS) was conducted to evaluate their positional accuracy. The comparative analysis underscores significant variability in the precision offered by each satellite constellation, providing valuable insights for optimizing UAV navigation across GIS, IoT, construction, and other sectors requiring high-precision localization. This research underscores the significance of high-precision GNSS receivers in enhancing UAV-based geospatial assessments, emphasizing the critical selection of appropriate satellite systems for tailored localization tasks. The study contributes to advancing UAV navigation strategies, ensuring robust and accurate geospatial data collection within diverse operational frameworks.展开更多
Artificial intelligence, often referred to as AI, is a branch of computer science focused on developing systems that exhibit intelligent behavior. Broadly speaking, AI researchers aim to develop technologies that can ...Artificial intelligence, often referred to as AI, is a branch of computer science focused on developing systems that exhibit intelligent behavior. Broadly speaking, AI researchers aim to develop technologies that can think and act in a way that mimics human cognition and decision-making [1]. The foundations of AI can be traced back to early philosophical inquiries into the nature of intelligence and thinking. However, AI is generally considered to have emerged as a formal field of study in the 1940s and 1950s. Pioneering computer scientists at the time theorized that it might be possible to extend basic computer programming concepts using logic and reasoning to develop machines capable of “thinking” like humans. Over time, the definition and goals of AI have evolved. Some theorists argued for a narrower focus on developing computing systems able to efficiently solve problems, while others aimed for a closer replication of human intelligence. Today, AI encompasses a diverse set of techniques used to enable intelligent behavior in machines. Core disciplines that contribute to modern AI research include computer science, mathematics, statistics, linguistics, psychology and cognitive science, and neuroscience. Significant AI approaches used today involve statistical classification models, machine learning, and natural language processing. Classification methods are widely applicable to problems in various domains like healthcare, such as informing diagnostic or treatment decisions based on patterns in data. Dean and Goldreich, 1998, define ML as an approach through which a computer has to learn a model by itself from the data provided but no specification on the sort of model is provided to the computer. They can then predict values for things that are different from the values used in training the models. NLP looks at two interrelated concerns, the task of training computers to understand human languages and the fact that since natural languages are so complex, they lend themselves very well to serving a number of very useful goals when used by computers.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
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financially supported by the National Natural Science Foundation of China(Grants 52172276)fund from Anhui Provincial Institute of Translational Medicine(2021zhyx-B15)。
文摘Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.
基金supported by ONR UMass Dartmouth Marine and UnderSea Technology(MUST)grant N00014-20-1-2849 under the project S31320000049160by DOE grant DE-SC0023164 sub-award RC114586-UMD+2 种基金by AFOSR grants FA9550-18-1-0383 and FA9550-23-1-0037supported by Michigan State University,by AFOSR grants FA9550-19-1-0281 and FA9550-18-1-0383by DOE grant DE-SC0023164.
文摘Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implicit computations and full precision for the explicit computations.In this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and efficiency.We develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)methods.The convergence,accuracy,and runtime of these methods are explored.We show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.
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.
文摘The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil tends to affect the agricultural coffee production system. Therefore, research related to geoelectrical properties of soil such as resistivity for characterization the region of the study for coffee cultivation purposes can improve and optimize the production. This resistivity method allows to investigate the subsurface through different techniques: 1D vertical electrical sounding and electrical imaging. The acquisition of data using these techniques permitted the creation of 2D resistivity cross section from the study area. The geoelectrical data was acquired by using a resistivity meter equipment and was processed in different softwares. The results of the geoelectrical characterization from 1D resistivity model and 2D resistivity electrical sections show that in the study area of Kabiri, there are 8 varieties of geoelectrical layers with different resistivity or conductivity. Near survey in the study area, the lowest resistivity is around 0.322 Ω·m, while the highest is about 92.1 Ω·m. These values illustrated where is possible to plant coffee for suggestion of specific fertilization plan for some area to improve the cultivation.
基金Project supported by the National Key Research and Development Program of China (Grant No.2021YFB2012600)。
文摘We present a quantitative measurement of the horizontal component of the microwave magnetic field of a coplanar waveguide using a quantum diamond probe in fiber format.The measurement results are compared in detail with simulation,showing a good consistence.Further simulation shows fiber diamond probe brings negligible disturbance to the field under measurement compared to bulk diamond.This method will find important applications ranging from electromagnetic compatibility test and failure analysis of high frequency and high complexity integrated circuits.
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Supported by Rumah Program 2024 of Research Organization for Health,National Research and Innovation Agency of Indonesia2023 Grant of The Fondazione Veronesi,Milan,Italy(Caecilia H C Sukowati)2023/2024 Postdoctoral Fellowship of The Manajemen Talenta,Badan Riset dan Inovasi Nasional,Indonesia(Sri Jayanti).
文摘Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.
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%.
基金Supported by the National Natural Science Foundation of China,No.82100599 and No.81960112the Jiangxi Provincial Department of Science and Technology,No.20242BAB26122+1 种基金the Science and Technology Plan of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2023Z021the Project of Jiangxi Provincial Academic and Technical Leaders Training Program for Major Disciplines,No.20243BCE51001.
文摘In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of 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.
基金supported by the National Natural Science Foundation of China(Grant no.42371136)the Guangdong Basic and Applied Basic Research Foundation(Grant no.2021B1515020032)the Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(Grant no.311022003).
文摘Offset-tracking is an essential method for deriving glacier flow rates using optical imagery.Sentinel-2(S2)and Landsat-8/9(L8/9)are popular optical satellites or constellations for polar studies,offering high spatial resolution with relatively short revisit time,wide swath width,and free accessibility.To evaluate and compare the precision of offset-tracking results yielded with these two kinds of data,in this study S2 and L8/9 imagery observed in Petermann Glacier in Greenland,Karakoram in High-Mountains Asia,and Amery Ice Shelf in the Antarctic are analyzed.Outliers and various systematic error sources in the offset-tracking results including orbital and strip errors were analyzed and eliminated at the pre-process stage.Precision at the off-glacier(bare rock)region was evaluated by presuming that no deformation occurred;then for both glacierized and the off-glacier regions,precision of velocity time series was evaluated based on error propagation theory.The least squares method based on connected components was used to solve flow rates time series based on multi-pair images offset-tracking.The results indicated that S2 achieved slightly higher precision than L8/9 in terms of both single-pair derived displacements and least square solved daily flow rates time series.Generally,the RMSE of daily velocity is 26%lower for S2 than L8/9.Moreover,S2 provided higher temporal resolution for monitoring glacier flow rates.
基金supported by the National Natural Science Foundation of China(Grant No.:82174246)the National Key R&D Program of China(Grant No.:2019YFC1708701)the Postdoctoral Innovation Talent Support Program(Grant No.:BX20220329).
文摘Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.
文摘Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients.With the advancement of artificial intelligence(AI)technology and the proliferation of medical digital information,AI has demonstrated promising sensitivity and accuracy in assisting precise detection,treatment decision-making,and prognosis assessment of ESCC.It has become a unique opportunity to enhance comprehen-sive clinical management of ESCC in the era of precision oncology.This review examines how AI is applied to the diagnosis,treatment,and prognosis assessment of ESCC in the era of precision oncology,and analyzes the challenges and potential opportunities that AI faces in clinical translation.Through insights into future prospects,it is hoped that this review will contribute to the real-world application of AI in future clinical settings,ultimately alleviating the disease burden caused by ESCC.
文摘The quantization algorithm compresses the original network by reducing the numerical bit width of the model,which improves the computation speed. Because different layers have different redundancy and sensitivity to databit width. Reducing the data bit width will result in a loss of accuracy. Therefore, it is difficult to determinethe optimal bit width for different parts of the network with guaranteed accuracy. Mixed precision quantizationcan effectively reduce the amount of computation while keeping the model accuracy basically unchanged. In thispaper, a hardware-aware mixed precision quantization strategy optimal assignment algorithm adapted to low bitwidth is proposed, and reinforcement learning is used to automatically predict the mixed precision that meets theconstraints of hardware resources. In the state-space design, the standard deviation of weights is used to measurethe distribution difference of data, the execution speed feedback of simulated neural network accelerator inferenceis used as the environment to limit the action space of the agent, and the accuracy of the quantization model afterretraining is used as the reward function to guide the agent to carry out deep reinforcement learning training. Theexperimental results show that the proposed method obtains a suitable model layer-by-layer quantization strategyunder the condition that the computational resources are satisfied, and themodel accuracy is effectively improved.The proposed method has strong intelligence and certain universality and has strong application potential in thefield of mixed precision quantization and embedded neural network model deployment.
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.
文摘This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.
文摘Accurate localization is paramount for unmanned aerial vehicles (UAVs) spanning various technical and industrial domains, necessitating a comprehensive assessment of global navigation satellite system (GNSS) precision. This study investigates the performance of distinct GNSS constellations in determining the precise location of a building utilizing a high-precision GNSS receiver. The receiver, incorporating advanced multi-frequency and full-constellation positioning capabilities, was integrated with a smartphone via Bluetooth to enable the UAV’s acquisition of centimeter-level positioning data. Sequential utilization of single satellite systems—such as GPS-only, GLONASS-only, Galileo-only, SBAS-only, and BeiDou-only—facilitated the documentation of latitude and longitude coordinates for the designated building. Subsequent comparison of these coordinates with a specialized Geographic Information System (GIS) was conducted to evaluate their positional accuracy. The comparative analysis underscores significant variability in the precision offered by each satellite constellation, providing valuable insights for optimizing UAV navigation across GIS, IoT, construction, and other sectors requiring high-precision localization. This research underscores the significance of high-precision GNSS receivers in enhancing UAV-based geospatial assessments, emphasizing the critical selection of appropriate satellite systems for tailored localization tasks. The study contributes to advancing UAV navigation strategies, ensuring robust and accurate geospatial data collection within diverse operational frameworks.
文摘Artificial intelligence, often referred to as AI, is a branch of computer science focused on developing systems that exhibit intelligent behavior. Broadly speaking, AI researchers aim to develop technologies that can think and act in a way that mimics human cognition and decision-making [1]. The foundations of AI can be traced back to early philosophical inquiries into the nature of intelligence and thinking. However, AI is generally considered to have emerged as a formal field of study in the 1940s and 1950s. Pioneering computer scientists at the time theorized that it might be possible to extend basic computer programming concepts using logic and reasoning to develop machines capable of “thinking” like humans. Over time, the definition and goals of AI have evolved. Some theorists argued for a narrower focus on developing computing systems able to efficiently solve problems, while others aimed for a closer replication of human intelligence. Today, AI encompasses a diverse set of techniques used to enable intelligent behavior in machines. Core disciplines that contribute to modern AI research include computer science, mathematics, statistics, linguistics, psychology and cognitive science, and neuroscience. Significant AI approaches used today involve statistical classification models, machine learning, and natural language processing. Classification methods are widely applicable to problems in various domains like healthcare, such as informing diagnostic or treatment decisions based on patterns in data. Dean and Goldreich, 1998, define ML as an approach through which a computer has to learn a model by itself from the data provided but no specification on the sort of model is provided to the computer. They can then predict values for things that are different from the values used in training the models. NLP looks at two interrelated concerns, the task of training computers to understand human languages and the fact that since natural languages are so complex, they lend themselves very well to serving a number of very useful goals when used by computers.
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.
