A machine learning-based radiomics model for prediction of tumor mutation burden in gastric cancer

Purpose: To evaluate the potential of machine learning (ML)-based radiomics approach for predicting tumor mutation burden (TMB) in gastric cancer (GC).Methods: The contrast enhanced CT (CECT) images with corresponding clinical information of 256 GC patients were retrospectively collected. Patients were separated into training set (n = 180) and validation set (n = 76). A total of 3,390 radiomics features were extracted from three phases images of CECT. The least absolute shrinkage and selection operator (LASSO) model was used for feature screening. Seven machine learning (ML) algorithms were employed to find the optimal classifier. The predictive ability of radiomics model (RM) was evaluated with receiver operating characteristic. The correlation between RM and TMB values was evaluated using Spearman’s correlation coefficient. The explainability of RM was assessed by the Shapley Additive explanations (SHAP) method.Results: Logistic regression algorithm was chosen for model construction. The RM showed good predictive ability of TMB status with AUCs of 0.89 [95% confidence interval (CI): 0.85–0.94] and 0.86 (95% CI: 0.74–0.98) in the training and validation sets. The correlation analysis revealed a good correlation between RM and TMB levels (correlation coefficient: 0.62, p < 0.001). The RM also showed favorable and stable predictive accuracy within the cutoff value range 6–16 mut/Mb in both sets.Conclusion: The ML-based RM offered a promising image biomarker for predicting TMB status in GC patients

Breakfast Consumption Is Positively Associated with Usual Nutrient Intakes among Food Pantry Clients Living in Rural Communities

Background: Breakfast consumption has declined over the past 40 y and is inversely associated with obesity-related diet and health outcomes. The breakfast pattern of food pantry clients and its association with diet is unknown. Objective: The objective is to investigate the association of breakfast consumption with diet quality and usual nutrient intakes among food pantry clients (n = 472) living in rural communities. Methods: This was an observational study using cross-sectional analyses. English-speaking participants ≥18 y (or ≥19 y in Nebraska) were recruited from 24 food pantries in rural high-poverty counties in Indiana, Michigan, Missouri, Nebraska, Ohio, and South Dakota. Participants were surveyed at the pantry regarding characteristics and diet using 24-h recall. A second recall was self-completed or completed via assisted phone call within 2 wk of the pantry visit. Participants were classified as breakfast skippers when neither recall reported breakfast ≥230 kcal consumed between 04:00 and 10:00; breakfast consumers were all other participants. The Healthy Eating Index-2010 was modeled with breakfast pattern using multiple linear regression. Mean usual intake of 16 nutrients was estimated using the National Cancer Institute Method and compared across breakfast pattern groups. Usual nutrient intake was compared with the Estimated Average Requirement (EAR) or Adequate Intake (AI) to estimate the proportion of population not meeting the EAR or exceeding the AI. Results: A total of 56% of participants consumed breakfast. Compared with breakfast skippers, breakfast consumers had 10–59% significantly higher usual mean intakes of all nutrients (P ≤ 0.05), and had 12–21% lower prevalence of at-risk nutrient intakes except for vitamin D, vitamin E, and magnesium. Conclusions: Adult food pantry clients living in rural communities experienced hardships in meeting dietary recommendations. Breakfast consumption was positively associated with usual nutrient intakes in this population. This trial was registered at clinicaltrials.gov as NCT03566095

Comparative study of the composition and genetic diversity of the picoeukaryote community in a Chinese aquaculture area and an open sea area

Picoeukaryotes (<2–3 μm) perform key roles for the functioning of marine ecosystems, but little is known regarding the composition and diversity of picoeukaryotes in aquaculture areas. In this study, the Illumina MiSeq platform was used for sequencing the V4 variable region within the 18S rDNA gene to analyse genetic diversity and relative abundance of picoeukaryotic communities in the Qinhuangdao scallop cultivation area of the Bohai Sea. The community was dominated by three super groups, the alveolates (54%), stramenopiles (41%) and chlorophytes (3%), and three groups, dinoflagellates (54%), pelagomonadales (40%) and prasinophytes (3%). Furthermore, a contrasting station with open water away from the eutrophic aquaculture area was chosen. The communities collected from the two stations exhibited significant differences, with higher diversity in the aquaculture area. These results provide the first snapshot of the picoeukaryotic diversity in surface waters of the Qinhuangdao scallop cultivation area, and basic data for future studies on picoeukaryote community in an aquaculture region

Adsorption of virus-like particles on ion exchange surface: Conformational changes at different pH detected by dual polarization interferometry

Disassembling of virus-like particles (VLPs) like hepatitis B virus surface antigen (HB-VLPs) during chromatographic process has been identified as a major cause of loss of antigen activity. In this study, dual polarization interferometry (DPI) measurement, together with chromatography experiments, were performed to study the adsorption and conformational change of HB-VLPs on ion exchange surface at three different pHs. Changes in pH values of buffer solution showed only minimal effect on the HB-VLPs assembly and antigen activity, while significantly different degree of HB-VLPs disassembling was observed after ion exchange chromatography (IEC) at different pHs, indicating the conformational change of HB-VLPs caused mainly by its interactions with the adsorbent surface. By creating an ion exchange surface on chip surface, the conformational changes of HB-VLPs during adsorption to the surface were monitored in real time by DPI for the first time. As pH increased from 7.0 to 9.0, strong electrostatic interactions between oppositely charged HB-VLPs and the ion exchange surface make the HB-VLPs spread thinly or even adsorbed in disassembled formation on the surface as revealed by significant decrease in thickness of the adsorbed layer measured by DPI. Such findings were consistent with the results of IEC experiments operated at different pHs, that more disassembled HB-VLPs were detected in the eluted proteins at pH 9.0. At low pH like pH 5.0, however, possible hi-layer adsorption was involved as evidenced by an adsorbed layer thickness higher than average diameter of the HB-VLPs. The &quot;lateral&quot; protein protein interactions might be unfavorable and would make additional contribution to the disassembling of HB-VLPs besides the primary mechanism related to the protein surface interactions; therefore, the lowest antigen activity was observed after IEC at pH 5.0. Such real-time information on conformational change of VLPs is helpful for better understanding the real mechanism for the disassembling of VLPs on the solid liquid interface. (C) 2015 Elsevier B.V. All rights reserved

Ultra-Narrow-Band Filter Based on High Q Factor in Metallic Nanoslit Arrays

Here we propose a novel high Q ultra-narrow-band filter in the optical regime. Multiple high Q resonances are achieved in ultra-thin metallic nanoslit arrays on stacked low index&ndash;high index dielectric (LID&ndash;HID) substrate. Based on the cooperative effect of suppressed modes and transmission modes, the high spectral resolution of transmission peaks is obtained. The number and Q factor of transmission peaks can be freely manipulated by a simple combination of the stacked LID&ndash;HID. It is demonstrated that the linewidths of the transmission peaks can be reduced down to the extreme limit of 1 nm and the Q factor is up to 700 by optimizing the structure parameter of the three-layer LID&ndash;HID. The results provide a theoretical basis to design a multi-band nanophotonic device with a high Q factor and have potential applications in the next generation of high-resolution plasmonic biosensing and filtering

Performance of agarose and gigaporous chromatographic media as function of pore-to-adsorbate size ratio over wide span from ovalbumin to virus like particles

Two commercially available agarose ion exchange media, DEAE-Capto and DEAE-Sepharose FF (DEAE-FF), and two gigaporous media DEAE -AP-120 nm and DEAE-AP-280 nm were evaluated for their applicability in adsorption of five proteins with large span of radius ranges from 2.9 nm to 14.1 nm, which include ovalbumin, bovine serum albumin (BSA), haptoglobin, thyroglobulin and hepatitis B surface antigen (HBsAg) virus like particle. The average pore radius of the four media was determined to be 6.9 nm, 18.5 nm, 59.4 nm and 139.3 nm, respectively, which was obtained by log normal distribution for DEAE-Capto and DEAE-FF and by bimodal Gaussian distribution for the two DEAE-AP media. The performance of these four media including phase ratio, static and dynamic binding capacity, and transport properties for the adsorption of these five model proteins as function of pore-to-adsorbate size ratio were investigated and compared. The best ratio of pore-to-adsorbate size was found dependent on the protein size. For protein with radius from 2.9 nm (ovalbumin) to 5.4 nm (BSA), the agarose media was superior to gigaporous media. Both the static and dynamic adsorption capacities reduced with the increase of pore size, and the highest values were obtained at the smallest pore-to-adsorbate size of about 2 times in this study, although the highest accessible surface area was obtained at pore-to-adsorbate size ratio about 16 to 20. For proteins with radius of 5.4 nm or larger than that, their adsorption capacities decreased firstly and then increased with the increase of ratio of pore-to-adsorbate size, and the highest values were obtained on the gigaporous media DEAE-AP-280 nm, which could provide faster diffusivity and larger accessible surface area. However, protein with radius of 14.1 nm (HBsAg) had much lower capacities compared to other proteins at the same pore-to-adsorbate size ratio, implying large protein needs greater pore-to-adsorbate size ratio to achieve a satisfactory capacity. For all the five tested proteins, the DEAE-Capto media having the smallest pore radius and branched dextran chains, was found superior to DEAE-FF in terms of both higher adsorption capacities and uptake kinetics, which suggested that the "chain delivery effect" took place on proteins over large size span from ovalbumin to HBsAg, though the effect on the larger proteins was much less significant than that on the smaller ones. Results from the present work provided more information on how do the relationships of pore size of chromatography media and adsorbate size interactively affect the chromatography behaviors, thus will provide general guidance for selection of suitable adsorbent for biologics of a given size. (C) 2021 Elsevier B.V. All rights reserved

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway

Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Injury of bone microvascular endothelial cells (BMECs) caused by glucocorticoid administration is one of the important causes of ONFH, and there is currently a lack of effective clinical treatments. Extracellular vesicles derived from bone stem cells (BMSC-EVs) can prevent ONFH by promoting angiogenesis and can inhibit cell apoptosis by regulating autophagy via the PI3K/Akt/mTOR signaling pathway. The present study aimed to investigate the effect of extracellular vesicles derived from bone marrow stem cells (BMSC) on a glucocorticoid-induced injury of BMECs and possible mechanisms. We found that BMSC-EVs attenuated glucocorticoid-induced viability, angiogenesis capacity injury, and the apoptosis of BMECs. BMSC-EVs increased the LC3 level, but decreased p62 (an autophagy protein receptor) expression, suggesting that BMSC-Exos activated autophagy in glucocorticoid-treated BMECs. The protective effects of BMSC-EVs on the glucocorticoid-induced injury of BMECs was mimicked by a known stimulator of autophagy (rapamycin) and could be enhanced by co-treatment with an autophagy inhibitor (LY294002). BMSC-EVs also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated BMECs. In conclusion, the results indicate that BMSC-EVs prevent the glucocorticoid-induced injury of BMECs by regulating autophagy via the PI3K/Akt/mTOR pathway

Microcalorimetric study of adsorption and disassembling of virus-like particles on anion exchange chromatography media

Chromatographic purification of virus-like particles (VLPs) is important to the development of modern vaccines. However, disassembly of the VLPs on the solid-liquid interface during chromatography process could be a serious problem. In this study, isothermal titration calorimetric (ITC) measurements, together with chromatography experiments, were performed on the adsorption and disassembling of multi-subunits hepatitis B virus surface antigen virus-like particles (HB-VLPs). Two gigaporous ion-exchange chromatography (IEC) media, DEAE-AP-280 nm and DEAE-POROS, were used. The application of gigaporous media with high ligand density led to significantly increased irreversible disassembling of HB-VLPs and consequently low antigen activity recovery during IEC process. To elucidate the thermodynamic mechanism of the effect of ligand density on the adsorption and conformational change of VLPs, a thermodynamic model was proposed. With this model, one can obtain the intrinsic molar enthalpy changes related to the binding of VLPs and the accompanying conformational change on the liquid-solid interface during its adsorption. This model assumes that, when intact HB-VLPs interact with the IEC media, the total adsorbed proteins contain two states, the intact formation and the disassembled formation; accordingly, the apparent adsorption enthalpy, Delta H-app, which can be directly measured from ITC experiments, presents the sum of three terms: (1) the intrinsic molar enthalpy change associated to the binding of intact HB-VLps s Delta H-bind(intact), 1 (2) the intrinsic molar enthalpy change associated to the binding of HB-VLPs disassembled formation ( Delta H-bind(dis)), and (3) the enthalpy change accompanying the disassembling of HB-VLPs (Delta H-conf(dis)). The intrinsic binding of intact HB-VLPs and the disassembled HB-VLPs to both kinds of gigaporous media (each of which has three different ligand densities), were all observed to be entropically driven as indicated by positive values of Delta H-bind(intact) and Delta H-bind(dis) while the nagative Delta H-conf(dis) values suggested a spontenous enthalpy-driven process for the forming of HB-VLPs disassembled formation at all conditions studied. As ligand density increases, Delta H-conf(dis) became more negative, which was in agreement with the findings from chromatography experiments, that higher ligand density leads to more serious disassembling of HB-VLPs. Results from thermodynamic studies provided us insight understanding on the mechanism of adsorption and conformational change of VLPs, as well as the effect of ligand densities on the structural stability of VLPs during IEC process. (C) 2015 Elsevier B.V. All rights reserved.</p