Parameterized SVM for Personalized Drug Concentration Prediction

This paper proposes a parameterized Support Vector Machine (ParaSVM) approach for modeling the Drug Concentration to Time (DCT) curves. It combines the merits of Support Vector Machine (SVM) algorithm that considers various patient features and an analytical model that approxi- mates the predicted DCT points and enables curve calibrations using occasional real Therapeutic Drug Monitoring (TDM) measurements. The RANSAC algorithm is applied to construct the parameter library for the relevant basis functions. We show an example of using ParaSVM to build DCT curves and then calibrate them by TDM measurements on imatinib case study

Drug concentration prediction and delivery

In medical practice, the decision-making process regarding drug dose is critical to patients’ health and recovery. For drugs with narrow therapeutic ranges, the medical doctor decides the quantity (dose amount) and frequency (dose interval) on the basis of a set of patients’ parameters. Computer-aided tools for drug dose administration makes the prescription procedure faster, more accurate, more objective, and less expensive. We describe an advanced integrated Drug Administration Decision Support System (DADSS) to help clinicians/patients with the dose/frequency computing. Based on a support vector machine (SVM) algorithm, enhanced with the random sample consensus technique, this system is able to predict the drug concentration values and computes the ideal dose amount and dose interval for a new patient. With an extension to combine the SVM method and the explicit analytical model, the advanced integrated DADSS system is able to compute drug concentration-to-time curves for a patient under different conditions

Safe Implementation of Embedded Software for a Portable Device Supporting Drug Administration

Poor adherence to medical regimen causes approximately 33% to 69% of medication-related hospitalizations and accounts for $100 billion in annual health care costs. In this paper we address the problem of unintentional non adherence, when patient fails to take a medication due to forgetfulness or carelessness. We present the safe approach to software implementation of a portable reminder device with enabled personalization of medical regimen. The presented prototype is designed for imatinib administration, a drug used to treat Chronic Myeloid Leukemia (CML). However, thanks to the component-based structure of the software, the method can be applied to other cases by replacing implementation of certain components

Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China

Background/Aims: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status. Methods: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples. Results: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States. Conclusion: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Herbicidal action of root -applied glufosinate -ammonium

Glufosinate-ammonium (GLA) is a post-emergence herbicide that inhibits glutamine synthetase (GS), synthesis of glutamine from glutamate. This inhibition results in NH4+ accumulation and ultimate plant death. GLA is usually effective as foliar spray at concentrations over 200 mg/L. Research on root applied GLA is lacking. The current research studied the effects of root-application of GLA on tomato plant growth, foliar NH 4+ accumulation, and ethylene evolution. In a dose-response experiment under hydroponics, phytotoxicity symptoms appeared on tomato seedling with 25 or 50 mg GLA X at 6 days after treatment (DAT). Under soil conditions, GLA higher than 7.5 mg/pot caused toxicity symptoms in 2 days. With 3 and 5 mg/pot symptoms appeared at 4 DAT. 1.5 mg GLA/pot at 5 DAT. With an increase of GLA rate, shoot NH4+ concentration increased in hydroponics or soil experiments. In a time course experiment, at 4 DAT, GLA at 25 mg/L caused foliar toxicity symptoms and overall stunting, and ethylene evolution increased dramatically. At 9 DAT, plants died. Accumulation of NH4+ caused by GLA was mainly in the foliage and increased with time; that caused by exogenously supplied NH4+ was in roots and non-phytotoxic during the duration of the experiments. If AOA or STS was added into nutrient solution with GLA at 25 mg/L, AOA delayed the appearance of toxicity and NH4+ accumulation but STS had no suppressive effects on their presence. AOA completely inhibited ethylene evolution during the experiment but STS did not low ethylene evolution by plant receiving GLA. Effects of foliarly applied GLA and soil-applied GLA were compared. At 3 DAT, tomato plants sprayed with 1.5 or 3 mg GLA/kg soil started showing symptoms on top leaves. At 5 DAT, all foliarly treated plants became poisoned by GLA, and those receiving 1.5 or 3 mg GLA from soil started showing poisoning. Tomato plant growth was retarded slightly by GLA applied at more than 1.5 mg/plant during 5 days of growth. Effect of degradation time of efficacy on GLA in soil was studied. At 4 days after transplanting, GLA induced toxicity symptoms and reduced biomass. GLA after 5-days degradation in soil caused higher shoot NH4 + accumulation than 10–20 days degradation. Root-applied GLA under hydrophonics or soil conditions can cause foliar toxicity symptoms, foliar accumulation of NH4+, and ethylene evolution on tomato plants

miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis

Objective Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. Methods We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments. Results miR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression. Conclusion In type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy