Development of a classification model for Cynanchum wilfordii and Cynanchum auriculatum using convolutional neural network and local interpretable model-agnostic explanation technology.

Cynanchum wilfordii is a perennial tuberous root in the Asclepiadaceae family that has long been used medicinally. Although C. wilfordii is distinct in origin and content from Cynancum auriculatum, a genus of the same species, it is difficult for the public to recognize because the ripe fruit and root are remarkably similar. In this study, images were collected to categorize C. wilfordii and C. auriculatum, which were then processed and input into a deep-learning classification model to corroborate the results. By obtaining 200 photographs of each of the two cross sections of each medicinal material, approximately 800 images were employed, and approximately 3200 images were used to construct a deep-learning classification model via image augmentation. For the classification, the structures of Inception-ResNet and VGGnet-19 among convolutional neural network (CNN) models were used, with Inception-ResNet outperforming VGGnet-19 in terms of performance and learning speed. The validation set confirmed a strong classification performance of approximately 0.862. Furthermore, explanatory properties were added to the deep-learning model using local interpretable model-agnostic explanation (LIME), and the suitability of the LIME domain was assessed using cross-validation in both situations. Thus, artificial intelligence may be used as an auxiliary metric in the sensory evaluation of medicinal materials in future, owing to its explanatory ability.

Chromatographic Method for Monitoring of Pesticide Residues and Risk Assessment for Herbal Decoctions Used in Traditional Korean Medicine Clinics.

The presence of pesticide residues in herbs and the herbal products derived from them raises serious health concerns. This study was conducted to investigate the residual pesticide concentrations and assess potential human health risks from herbal medicines used in traditional Korean medicine clinics. A total of 40 samples of herbal decoctions were collected from 10 external herbal dispensaries. The pesticide residues were analyzed by the multiresidue method for 320 different pesticides using liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS). As a result of the monitoring, carbendazim was detected at 0.01 and 0.03 µg/g in eight samples and no pesticide was detected in the other herbal decoctions. Carbendazim was set for each individual item as less than 0.05 µg/g in Paeoniae radix, less than 0.05 µg/g in Cassiae semen, less than 2.0 µg/g in Lycii fructus, and less than 10 µg/g in Schisandrae fructus (dried). Therefore, the results of this study suggested that the detected pesticide residues in herbal decoctions could not be considered as posing a serious health risk.

Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study.

In this study, we investigated whether the levels of sulfur dioxide (SO2), benzopyrene, and mycotoxins in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for SO2, benzopyrene, and mycotoxins using 10 samples. SO2 and benzopyrene were not detected in any of the herbal decoctions. With regard to mycotoxins, aflatoxin B1 was not detected, but B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). None of these values exceeded the restrictions in prior studies. Thus, we confirm that the amounts of SO2, benzopyrene, and mycotoxins in herbal decoctions are at safe levels and provides the basis of establishing safety management criteria for herbal decoctions.

Monitoring of Heavy Metals and Pesticide Residues of Herbal Decoctions in Traditional Korean Medicine Clinics in Korea.

In this study, we investigated whether the levels of heavy metal and pesticide residues in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for heavy metal content such as lead, arsenic, and cadmium using inductively coupled plasma optical emission spectrometry. For mercury, an automatic mercury analyzer based on the gold amalgamation process was used. For pesticide residues, gas chromatography with electron capture detection and gas chromatography with mass selective detection were used for the analyses. Based on the testing, heavy metals were identified in most of the decoctions (Cd: 0.000-0.003 ppm, Pb: 0.003-0.023 ppm, As: 0.000-0.016 ppm, Hg: 0.000-0.002 ppm). Pesticide residues (e.g., total DDT, total BHC, aldrin, endrin, dieldrin) were not detected at all. All of these were no more than the limit values in preceding studies. Therefore, this study confirms that the contents of heavy metals and pesticides in herbal decoctions are within safe levels based on a previous study and provides evidence for establishing safety management standards for herbal decoctions in Korea.

Time-varying discrimination accuracy of longitudinal biomarkers for the prediction of mortality compared to assessment at fixed time point in severe burns patients.

BACKGROUND: The progression of biomarkers over time is considered an indicator of disease progression and helps in the early detection of disease, thereby reducing disease-related mortality. Their ability to predict outcomes has been evaluated using conventional cross-sectional methods. This study investigated the prognostic performance of biomarkers over time. METHODS: Patients aged > 18 years admitted to the burn intensive care unit within 24 h of a burn incident were enrolled. Information regarding longitudinal biomarkers, including white blood cells; platelet count; lactate, creatinine, and total bilirubin levels; and prothrombin time (PT), were retrieved from a clinical database. Time-dependent receiver operating characteristic curves using cumulative/dynamic and incident/dynamic (ID) approaches were used to evaluate prognostic performance. RESULTS: Overall, 2259 patients were included and divided into survival and non-survival groups. By determining the area under the curve using the ID approach, platelets showed the highest c-index [0.930 (0.919-0.941)] across all time points. Conversely, the c-index of PT and creatinine levels were 0.862 (0.843-0.881) and 0.828 (0.809-0.848), respectively. CONCLUSIONS: Platelet count was the best prognostic marker, followed by PT. Total bilirubin and creatinine levels also showed good prognostic ability. Although lactate was a strong predictor, it showed relatively poor prognostic performance in burns patients.

Trajectories of longitudinal biomarkers for mortality in severely burned patients.

This study aimed to investigate the differences in the trajectory of blood biomarkers routinely assessed through forward- and backward-looking approaches among burn patients. This cohort study included patients above 18 years of age from February 2007 to December 2018. All the biomarkers were estimated from admission to discharge from the intensive care unit. Significant differences were observed in the platelet count at 40 days, prothrombin time (PT) at 32 days, white blood cell count at 26 days, creatinine levels at 22 days, and lactate and total bilirubin levels at 19 days before death. In reverse order, significant differences were observed in the fitted model in platelet count at 44 days and in the platelet count and PT at 33 days. We obtained more valuable information from the longitudinal biomarker trajectory using the backward-looking method than using the forward-looking method. The platelet count served as the earliest predictor of mortality among burn patients.

Development of Hazardous Materials Management Standard for Decoction Type of Personalized Herbal Medicine.

OBJECTIVES: This study was conducted to development of hazardous materials management standards for the decoction type of personalized herbal medicines (PHMs). METHODS: This study was conducted in two stages. We searched documents about criteria to use words such as 'Herb', 'Herbal medicine', and 'Botanical Drug' and summarized the results. We organized the committee consisted of seven experts, and held two meetings to reach an agreement on hazardous management standards of the decoction type of PHMs. RESULTS: The seven documents were presented in the literature review and six items related to hazardous management standards of decoction were identified. The second expert meeting brought that a total of six items, including heavy metal, pesticide residues, sulfur dioxide, benzopyrene, mycotoxin, and micro-organism limits, were selected for safety management of decoction type of PHMs. Also, the criteria and test methods for each standard were suggested for monitoring the decoction type of PHMs. CONCLUSION: The study suggested hazardous material management standards and criteria for the decoction types of PHMs. In the future, it would be necessary to conduct a pilot test to ensure the validity and credibility of the safety management standard and criteria. Furthermore, the government level safety management system should be introduced to verify the safety of decoction medicines.

Clinical features, treatment and outcomes of colorectal mucosa-associated lymphoid tissue (MALT) lymphoma: literature reviews published in English between 1993 and 2017.

BACKGROUND: Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma (cMALToma) is rare and comprises only 2.5% of the MALT lymphomas. Its etiology and treatment have not been well established. The aim of this systematic literature review was to try to characterize cMALToma and analyze the risk factors for treatment failure with various therapeutic strategies. METHODS: We retrospectively reviewed 50 case reports from 1993 to 2017 through a PubMed search of English medical literature, describing cMALToma. We included 67 patients from previous case reports and we added 6 patients treated for cMALToma in our multicenter institutes. Risk factor analysis was done for treatment failure, defined as remission failure and recurrence. RESULTS: Of 73 patients diagnosed with cMALToma, tumors were located in 54 patients (74.0%) in the rectum, in 10 patients (13.6%) in the right colon, in 3 patients (4.1%) in the transverse colon, and in 6 patients (8.2%) in the sigmoid colon. In first-line treatment, patients achieved complete remission (CR) with surgery (18/19 cases), local resection (18/19 cases), chemotherapy (12/13 cases), radiation therapy (4/5 cases), antibiotics therapy including Helicobacter pylori eradication (12/15 cases), and no treatment (1/2 cases). Among these, eight cases (10.9%) needed second-line treatment, and there was overall remission failure in 3 cases (4.1%). Of the remaining 70 patients with CR, the tumor recurred in 5 patients (6.8%). The multivariable analysis showed that male sex, multiple tumors, and first-line treatment failure were significantly related to treatment failure (p=0.03, p=0.05, p=0.03, respectively). CONCLUSION: CR of primary cMALToma was achieved using various therapeutic strategies. First-line treatment failure and multiple tumors were associated with treatment failure, although the numbers of cases that failed are too small to draw definitive conclusions.

Evaluation of bilirubin interference and accuracy of six creatinine assays compared with isotope dilution-liquid chromatography mass spectrometry.

OBJECTIVES: The aim of this study was to estimate bilirubin interference and accuracy of six routine methods for measuring creatinine compared with isotope dilution-liquid chromatography mass spectrometry (ID-LC/MS). DESIGN AND METHODS: A total of 40 clinical serum samples from 31 patients with serum total bilirubin concentration >68.4µmol/L were collected. Serum creatinine was measured using two enzymatic reagents and four Jaffe reagents as well as ID-LC/MS. Correlations between bilirubin concentration and percent difference in creatinine compared with ID-LC/MS were analyzed to investigate bilirubin interference. Bias estimations between the six reagents and ID-LC/MS were performed. Recovery tests using National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 967a were also performed. RESULTS: Both the enzymatic methods showed no bilirubin interference. However, three of the four Jaffe methods demonstrated significant bilirubin concentration-dependent interference in samples with creatinine levels <53µmol/L, and two of them showed significant bilirubin interference in samples with creatinine levels ranging from 53.0 to 97.2µmol/L. Comparison of these methods with ID-LC/MS using patients' samples with elevated bilirubin revealed that the tested methods failed to achieve the bias goal at especially low levels of creatinine. In addition, recovery test using NIST SRM 967a showed that bias in one Jaffe method and two enzymatic methods did not achieve the bias goal at either low or high level of creatinine, indicating they had calibration bias. One enzymatic method failed to achieve all the bias goals in both comparison experiment and recovery test. CONCLUSIONS: It is important to understand that both bilirubin interference and calibration traceability to ID-LC/MS should be considered to improve the accuracy of creatinine measurement.