Exposure-Response and Subgroup Analyses to Support Body Weight-Based Dosing of Brentuximab Vedotin in Children and Young Adults with Newly Diagnosed High-Risk Classical Hodgkin Lymphoma.

PURPOSE: To evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma (cHL) in the phase 3 AHOD1331 study. PATIENTS AND METHODS: Overall, 296 patients (age 2-21 years) in the overall population were randomized to and received BV + chemotherapy; the pharmacokinetic subpopulation comprised 24 patients (age <13 years). Age- and/or BW-based (pharmacokinetic surrogates) subgroup analyses of efficacy and safety were conducted for the overall population. Exposure-response analyses were limited to the pharmacokinetic subpopulation. RESULTS: There were no visible trends in disease characteristics across pediatric age subgroups, while BW increased with age. Observed antibody-drug conjugate exposures in patients aged <12 years were lower than those in adults administered BV 1.8 mg/kg every 3 weeks (Q3W), as exposure increased with BW. Nevertheless, no detrimental impact on event-free survival (EFS) was seen in younger subgroups: 3-year EFS was 96.2% (2-<12-years) and 92.0% (12-<18-years), with no events observed in those aged <6 years. Neither early response nor lack of need for radiation therapy was associated with high pharmacokinetic exposure. No evidence of exposure-driven grade ≥2 or ≥3 peripheral neuropathy or grade ≥3 neutropenia was seen in exposure-safety and BW-based subgroup analyses; the incidence of these safety events was comparable across pediatric age subgroups, despite lower exposure in younger children. CONCLUSIONS: No further adjustments based on age or BW are required for the BV dose (1.8 mg/kg Q3W) approved in children.

Detection of chlorophyll content based on optical properties of maize leaves.

The chlorophyll content reflects plants' photosynthetic capacity, growth stage, and nitrogen status. Maize is one of the three widely planted gain crops in the world. In order to offer useful information for the development of chlorophyll content detectors of maize leaves, a single integrating sphere system was used to measure the transmittance and reflectance spectra of maize leaves over the wavelength range of 500-950 nm. The linear relationships of transmittance and reflectance with chlorophyll content were investigated. The feature wavelengths (FWs) sensitive to chlorophyll content were extracted from the full transmittance and reflectance spectra using the successive projections algorithm (SPA). The partial least squares regression (PLSR) models for predicting the chlorophyll content were established using the full spectra and extracted FWs. The results showed that there were obvious linear relationships between transmittance and reflectance with chlorophyll content of maize leaves and the best linear relationships were found at 709 nm and 714 nm, respectively, with the linear correlation coefficients of 0.801 and 0.696, and the root-mean-squares error (RMSEP) of 0.321 mg·g-1 and 0.405 mg·g-1, respectively. Eight and 6 FWs were extracted from the transmittance and reflectance spectra, respectively. The PLSR model established using the selected FWs from transmittance spectra had better prediction performance with RMSEP of 0.208 mg·g-1 than using full transmittance spectra. The built PLSR models using the full reflectance spectra and extracted FWs had poor robustness. This research offers some theoretical basis for developing a maize leaf chlorophyll content detector based on transmittance or reflectance.

Effect of forchlorfenuron and thidiazuron on kiwifruits' internal qualities, optical properties and their relationship during growth.

Forchlorfenuron (1-(2-chloropyridin-4-yl)-3-phenylurea, CPPU) and thidiazuron (N-Phenyl-N'-1,2,3-thiadiazol-5-ylurea, TDZ) are two widely used plant growth regulators in kiwifruit cultivation. They can promote fruit size, but it is unclear whether they have same effect on internal qualities, optical properties and cell structure of kiwifruit, and whether the kiwifruits treated with CPPU and TDZ can be identified based on optical properties. To answer these questions, the kiwifruits treated with 20 mg/L CPPU and 2 mg/L TDZ solutions were used as samples, and the untreated kiwifruits were used as control to investigate the optical properties (absorption coefficient µa and reduced scattering coefficient µs'), internal qualities (soluble solids content (SSC), firmness and moisture content) and microstructure of pulp tissue during the growth. Moreover, the relationship between the optical properties and internal qualities were analyzed, and the potential for identifying the kiwifruits treated with CPPU and TDZ based on optical properties was evaluated. The results showed that CPPU and TDZ increased the SSC and reduced the firmness of kiwifruits, but had some different effects on the moisture content and cell size. CPPU and TDZ did not influence the change trend of µa and µs' with wavelength, but affected their values and the relationship with internal qualities. In general, the mean µa of the kiwifruits treated with CPPU and with TDZ was the largest and the smallest at the absorption peaks (980 nm, 1190 nm and 1420 nm), respectively. The linear discriminant analysis modeling results showed that the spectra of µa with µs' had greater potential in identifying the kiwifruits treated with CPPU/TDZ with accuracy of 75.76 %.

Hydration dominates dielectric spectroscopy-based high accuracy quantification of lactose content in cow's milk.

BACKGROUND: Lactose is a critical factor in the quality of milk and dairy products. Achieving high accuracy and rapid detection of lactose content in cow's milk remains a challenge. Dielectric spectroscopy has emerged as a promising tool for detecting food components. We explored the effect of lactose content on the dielectric spectra of cow's milk and we propose a rapid analytical method for the quantitative determination of lactose content in cow's milk with high accuracy based on dielectric spectra. RESULTS: We obtained the dielectric spectra of 316 cow's milk samples in the frequency range 20-4500 MHz and noticed a strong negative correlation between the lactose content and the value of the dielectric loss factor (ε″) below 1500 MHz. Lactose does not affect cow's milk dielectric properties by excluded volume effect, but dominates the effect on the dielectric properties of cow's milk by hydration. The support vector regression model based on the variable importance in projection has the best prediction performance for lactose content. Its root-mean-square error of prediction set and residual prediction deviation is 0.29 g kg-1 and 6.968, respectively, and its prediction performance is better than that of the currently reported near-infrared (NIR) method and other methods. CONCLUSION: Despite the weak polarity of lactose molecules, its hydration is a significant factor affecting the dielectric properties of milk. The present study provides a basis for high accuracy and rapid quantitative detection of lactose in cow's milk based on dielectric spectra. © 2023 Society of Chemical Industry.

Simultaneous electrochemical detection of multiple heavy metal ions in milk based on silica-modified magnetic nanoparticles.

A sensitive and simple analytical method integrated with Fe3O4@SiO2-based extraction with direct electrochemical detection was applied to individually and simultaneously analyze heavy metal ions, including Cd2+, Pb2+, Cu2+, and Hg2+. The Fe3O4@SiO2-based electrochemical sensor was developed through the mixture of heavy metal ions with Fe3O4@SiO2 after alkali treatment, which was modified onto the working electrode surface. The Fe3O4@SiO2 with negative charges after alkali treatment could easily interact with heavy metal ions with positive charges by electrostatic force. Under the optimized conditions, the developed analytical method could be applied to individually and simultaneously detect heavy metal ions with good sensitivity. The detection limits were all in the nanomolar range, and the recoveries ranged from 96.0 to 104.3% for heavy metal ions in milk. Therefore, the proposed analytical method exhibited great potential for quantitatively analyzing multiple heavy metal ions in milk.

Comparison of near-infrared and dielectric spectra for quantitative identification of bovine colostrum adulterated with mature milk.

The nonhomogeneity of bovine colostrum leads to strong scattering effects for electromagnetic waves, which affects the application of electromagnetic spectroscopy in detecting colostrum. This work aimed to compare the performance of near-infrared spectroscopy (NIRS) and dielectric spectroscopy (DS) in quantitatively predicting the content of mature milk as an adulterant in colostrum. The near-infrared spectra in the range of 833 to 2,500 nm and the dielectric spectra in the range of 20 to 4,500 MHz of 150 adulterated colostrum samples containing 0 to 50% mature milk were analyzed. The different proportions of mature milk in colostrum significantly changed near-infrared and dielectric spectra. The principal component analysis score plot showed that both NIRS and DS could identify the proportion of mature milk in colostrum, but the 2 methods had different characteristics. Linear partial least squares regression and nonlinear least squares support vector machine (LSSVM) models based on near-infrared and dielectric spectra were established to identify doping proportions. The results showed that DS had better identification performance with a root-mean-square error of prediction of 4.9% and a residual prediction deviation of 3.441 by successive projection algorithm LSSVM, whereas NIRS was relatively weak with a root-mean-square error of prediction of 7.3% and a residual prediction deviation of 2.301 by full-spectra LSSVM. This work provides important insights for the quantitative prediction of nonhomogeneous liquid food by DS.

Qualitative identification of mature milk adulteration in bovine colostrum using noise-reduced dielectric spectra and linear model.

BACKGROUND: The rapid and accurate identification of colostrum, a strong non-homogeneous food, remains a challenge. In the present study, the dielectric spectra including the dielectric constant (ε') and loss factor (ε″) of 154 colostrum samples adulterated with 0-50% mature milk were measured from 20 to 4500 MHz. RESULTS: The results showed that the noise-reducing spectral preprocessing, including Savitzky-Golay (S-G), second derivative (SD), and S-G + SD, was significantly better than scattering-eliminating, including standard normal variate (SNV), multiplicative scatter correction (MSC), and SNV + MSC. The combination of S-G and SD was the best. Principal component analysis results demonstrated that dielectric spectroscopy is less susceptible to the inhomogeneity of colostrum and can be used to identify doped colostrum. The identification performance of linear models was better than that of non-linear models. The established linear discriminant analysis model based on full spectra had the best accuracy rates of 99.14% and 97.37% in the calibration and validation sets, respectively. Confirmatory tests on samples from different sources confirmed the satisfactory robustness of the proposed model. CONCLUSION: We found that the main unfavorable effect on the identification based on dielectric spectroscopy was noise interference, rather than scattering effect caused by inhomogeneity of colostrum. The satisfactory results undoubtedly cast light on rapid detection of strongly non-homogeneous foods based on dielectric spectroscopy. © 2022 Society of Chemical Industry.

Electrochemical detection of aminoglycoside antibiotics residuals in milk based on magnetic molecularly imprinted particles and metal ions.

This work proposed a cost-effective, simple, and highly sensitive magnetic molecularly imprinted particles (MMIPs) electrochemical sensor to indirectly detect kanamycin (KAN), tobramycin (TOB), and gentamicin (GEN). The MMIPs electrochemical sensor was prepared by a complex of metal ions and the MMIPs of rebinding the template, which modified on the magnetic glassy carbon electrode surface. Here, metal ions were used as the signal tracers and amplifiers of the MMIPs electrochemical sensor. Then the response peak currents of metal re-oxidized to metal ion was recorded by differential pulse voltammetry and used to monitor the level of aminoglycoside antibiotics. Under the optimal conditions, the MMIPs electrochemical sensors showed a high sensitivity toward KAN, TOB, and GEN with detection limits of 4.88, 1.28, and 1.07 nmol/L, respectively. Furthermore, the MMIPs electrochemical sensors showed high selectivity for determining KAN, TOB, and GEN, and they were successfully used to detect KAN, TOB, and GEN in milk.

Quantitatively determining the somatic cell count of raw milk using dielectric spectra and support vector regression.

To investigate the potential of dielectric spectroscopy in quantitatively determining the somatic cell count (SCC) of raw milk, the dielectric spectra of 301 raw milk samples at different SCC were collected using coaxial probe technology in the frequency range of 20 to 4,500 MHz. Standard normal variate, Mahalanobis distance, and joint x-y distances sample division were used to pretreat spectra, detect outliers, and divide samples, respectively. Principal component analysis and variable importance in projection (VIP) methods were used to reduce data dimension and select characteristic variables (CVR), respectively. The full spectra, 16 principal components obtained by principal component analysis, and 86 CVR selected by VIP were used as inputs, respectively, to establish different support vector regression models. The results showed that the nonlinear support vector regression models based on the full spectra and selected CVR using VIP had the best prediction performance, with the standard error of prediction and residual predictive deviation of 0.19 log SCC/mL and 2.37, respectively. The study provided a novel method for online or in situ detection of the SCC of raw milk in production, processing, and consumption.

Recent developments on rapid detection of main constituents in milk: a review.

Milk is a good source of quality fats, proteins, carbohydrates, minerals, and vitamins. Determining milk constituents is very important in dairy production and is usually conducted by means of physical or chemical processes in laboratories. These methods are time-consuming and cannot satisfy the need in practice. Developing simple, quick, cost-effective, reliable, and sensitive methods on the detection of main constituents in milk is useful for dairy farmers, manufacturers and consumers. In last decades, many rapid detection techniques such as chromatography, spectroscopy, dielectric properties, and sensors, have emerged and shown great potential in the detection of main constituents in liquid milk. In this review, the rapid detection techniques applied to determine the main constituents in milk have been reviewed. Meanwhile, the potential advantages and limitations of these techniques and recommendations for future research have also been proposed.

Effect of CPPU on bulk optical properties of kiwifruit during storage in near-infrared range.

BACKGROUND: Investigating the effect of N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU) on the bulk optical properties of postharvest kiwifruit is helpful in understanding the mechanism of identification of CPPU-treated kiwifruit using spectroscopy and to develop effective optical sensing techniques. In this study, the absorption coefficient µa and reduced scattering coefficient µ s ' of flesh and skin of kiwifruit treated with CPPU solutions at CPPU concentration levels (CCLs) of 0, 5, 10 and 15 mg L-1 were measured by using a single integrating sphere setup over the range 950-1650 nm during 12 weeks' storage. RESULTS: Generally, at the same storage period, there was no significant difference (P ≤ 0.05) on flesh's µa among the kiwifruit treated with different CCLs at absorption peaks of 970, 1190, and 1390 nm. The average flesh's µ s ' of kiwifruit treated with higher CCLs at 1190 nm were larger than those treated with lower CCLs, and there was a significant difference (P ≤ 0.05) between the kiwifruit treated with 0, 5 and 15 mg L-1 CPPU solutions except for week 6. Contrasted with the µa and µ s ' of kiwifruit flesh, the µa and µ s ' of skin had bigger standard deviations and larger fluctuations with storage time. Additionally, the CPPU-treated kiwifruit had higher moisture content, lower firmness, and larger cells than CPPU-untreated kiwifruit. CONCLUSIONS: This study indicates that the µ s ' of flesh has potential in identifying kiwifruit treated with different CCLs during storage. © 2020 Society of Chemical Industry.

Quantitatively determining the total bacterial count of raw goat milk using dielectric spectra.

The objective of this study was to evaluate dielectric spectra as a means of quantitatively determining total bacterial count (TBC) of raw goat milk. The dielectric spectra, including dielectric constant (ε') spectra and dielectric loss factor (ε″) spectra, and TBC of 154 raw goat milk samples were measured using network analyzer and plate count methods, respectively. Owing to the poor linear relationship between TBC in logarithm and permittivities at a single frequency, chemometrics was used to reduce noise, identify outliers, select effective variables, and divide sample sets. Several linear models, such as multiple linear regression, ridge regression, and least absolute shrinkage and selection operator, were established to determine TBC based on the effective spectra of ε', ε″, and their combination (ε'+ε″). The results indicated that the models built using the spectra of ε'+ε″ and ε' had excellent TBC prediction performance. The best model was multiple linear regression based on ε'+ε″ spectra with the residual predictive deviation of 3.26. This study shows that the dielectric spectra had great potential to quantitatively and rapidly determine TBC of raw milk.

A novel identification method for CPPU-treated kiwifruits based on images.

BACKGROUND: The application of exogenous plant growth regulator, for example forchlorfenuron (CPPU), on kiwifruits has become an important factor that influences kiwifruit economic efficiency and the health development of the kiwifruit industry. Owing to the slight difference in calyx shape between the kiwifruits treated with CPPU (CPPU-treated kiwifruits) and the kiwifruits without CPPU treatment (CPPU-untreated kiwifruits), this study aims to provide a cheap, quick, convenient, and non-destructive method for identifying CPPU-treated kiwifruits based on the images of kiwifruits captured at visible lights. RESULTS: The identification method includes three steps. Firstly, the kiwifruit was extracted from the background by using Otsu algorithm, hole filling operation and 'bwareaopen' function. Secondly, the calyx was extracted by using corrosion, image enhancement, hole filling and closing operations. Finally, the length/width ratio of the minimum enclosing rectangle of calyx region was calculated. The kiwifruit was regarded as a CPPU-treated kiwifruit if the length/width ratio of the rectangle was higher than 1.6. Otherwise, the kiwifruit was regarded as a CPPU-untreated one. The method had the total identification accuracy rate of 90.0% when the kiwifruit images were captured either by utilizing a smartphone at normal lighting condition or by using an image acquisition system. CONCLUSION: The programs run on computer and smartphone were developed, and they could realize kiwifruit identification in 0.6 s and 2 s, respectively. The study makes identifying CPPU-treated kiwifruits in online processing be realizable, and offers a convenient method for kiwifruit consumers. © 2019 Society of Chemical Industry.

Frequency, moisture content, and temperature dependent dielectric properties of potato starch related to drying with radio-frequency/microwave energy.

To develop advanced drying methods using radio-frequency (RF) or microwave (MW) energy, dielectric properties of potato starch were determined using an open-ended coaxial-line probe and network analyzer at frequencies between 20 and 4,500 MHz, moisture contents between 15.1% and 43.1% wet basis (w.b.), and temperatures between 25 and 75 °C. The results showed that both dielectric constant (ε') and loss factor (ε″) were dependent on frequency, moisture content, and temperature. ε' decreased with increasing frequency at a given moisture content or temperature. At low moisture contents (≤25.4% w.b.) or low temperatures (≤45 °C), ε″ increased with increasing frequency. However, ε″ changed from decrease to increase with increasing frequency at high moisture contents or temperatures. At low temperatures (25-35 °C), both ε' and ε″ increased with increasing moisture content. At low moisture contents (15.1-19.5% w.b.), they increased with increasing temperature. The change trends of ε' and ε″ were different and dependent on temperature and moisture content at their high levels. The penetration depth (d p ) decreased with increasing frequency. RF treatments may provide potential large-scale industrial drying application for potato starch. This research offers useful information on dielectric properties of potato starch related to drying with electromagnetic energy.

Nonparametric Regularized Regression for Phenotype-Associated Taxa Selection and Network Construction with Metagenomic Count Data.

We use a metagenomic approach and network analysis to investigate the relationships between phenotypes across taxa under different environmental conditions. The network structure of taxa can be affected by the disease-associated environmental conditions. In addition, taxa abundance is differentiated under conditions. Therefore, knowing how the correlation or relative abundance changes with these factors would be of great interest to researchers. We develop a nonparametric regularized regression method to construct taxa association networks under different clinical conditions. We let the coefficients be unknown functions of the environmental variable. The varying coefficients are estimated by using regression splines. The proposed method is regularized with concave penalties, and an efficient group descent algorithm is developed for computation. We also apply the varying coefficient model to estimate taxa abundance to see how it changes across different environmental conditions. Moreover, for conducting inference, we propose a bootstrap method to construct the simultaneous confidence bands for the corresponding coefficients. We use different simulated designs and a real data set to demonstrate that our method can identify the network structures successfully under different environmental conditions. As such, the proposed method has potential applications for researchers to construct differential networks and identify taxa.

Dielectric properties of honeydew melons and correlation with quality.

Dielectric properties of three honeydew melon cultivars, grown and harvested to provide a range of maturities, were measured with an open-ended coaxial-line probe and impedance analyzer over the frequency range from 10 MHz to 1.8 GHz. Probe measurements were made on the external surface of the melons and also on tissue samples from the edible internal tissue. Moisture content and soluble solids content (SSC) were measured for internal tissue samples, and SSC (sweetness) was used as the quality factor for correlation with the dielectric properties. Individual dielectric constant and loss factor correlations with SSC were low, but a high correlation was obtained between the SSC and permittivity from a complex-plane plot of dielectric constant and loss factor, each divided by SSC, for both the external surface and internal tissue measurements. However, SSC prediction from the dielectric properties by these relationships was not as high as expected. Permittivity data (dielectric constant and loss factor) for the melons are presented graphically to show their relationships with frequency for external surface and internal tissue measurements. A dielectric relaxation for the external surface measurements, which is attributable to bound water and Maxwell-Wagner relaxations, is also illustrated. Coefficients of determination for complex-plane plots, moisture content and SSC relationship, and penetration depth are also shown graphically. Further studies are needed for determining the practicality of sensing melon quality from the dielectric properties.