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PURPOSE To assess the added value of serial blood biomarkers in liver metastasis stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS Eighty-nine patients were retrospectively included. Pre- and midtreatment blood samples were analyzed for potential biomarkers of the treatment response. Three biomarker classes were studied: gene mutation status, complete blood count, and inflammatory cytokine concentration in plasma. One-year local failure (LF) and 2-year overall survival (OS) were chosen as study end points. Multivariate logistic regression was used for response prediction. Added predictive benefit was assessed by quantifying the difference between the predictive performance of a baseline model (clinicopathologic and dosimetric predictors) and that of the biomarker-enhanced model, using three metrics: (1) likelihood ratio, (2) predictive variance, and (3) area under the receiver operating characteristic curve (AUC). RESULTS The most important predictors of LF were mutation in KRAS gene (hazard ratio [HR] = 2.92, 95% CI, [1.17 to 7.28], P = .02) and baseline and midtreatment concentration of plasma interleukin-6 (HR = 1.15 [1.04 to 1.26] and 1.06 [1.01 to 1.13], P = .01). Absolute lymphocyte count and platelet-to-lymphocyte ratio at baseline as well as neutrophil-to-lymphocyte ratio at baseline and before fraction 3 (HR = 1.33 [1.16 to 1.51] and 1.19 [1.09 to 1.30]) had the most significant association with OS ( P = .0003). Addition of baseline GEN and inflammatory plasma cytokine biomarkers in predicting LF, respectively, increased AUC by 0.06 (from 0.73 to 0.79) and 0.07 (from 0.77 to 0.84). In predicting OS, inclusion of midtreatment complete blood count biomarkers increased AUC from 0.72 to 0.80, along with significant boosts in likelihood ratio and predictive variance. CONCLUSION Inclusion of serial blood biomarkers leads to significant gain in predicting response to liver metastasis stereotactic body radiation therapy and can guide treatment personalization.

Background and purpose Clinical targeted volume (CTV) delineation accounting for the patient-specific microscopic tumor spread can be a difficult step in defining the treatment volume. We developed an intelligent and automated CTV delineation system for locally advanced non-small cell lung carcinoma (NSCLC) to cover the microscopic tumor spread while avoiding organs-at-risk (OAR). Materials and methods A 3D UNet with a customized loss function was used, which takes both the patients’ respiration-correlated (“4D”) CT scan and the physician contoured internal gross target volume (iGTV) as inputs, and outputs the CTV delineation. Among the 84 identified patients, 60 were randomly selected to train the network, and the remaining as testing. The model performance was evaluated and compared with cropped expansions using the shape similarities to the physicians’ contours (the ground-truth) and the avoidance of critical OARs. Results On the testing datasets, all model-predicted CTV contours followed closely to the ground truth, and were acceptable by physicians. The average dice score was 0.86. Our model-generated contours demonstrated better agreement with the ground-truth than the cropped 5 mm/8 mm expansion method (median of median surface distance of 1.0 mm vs 1.9 mm/2.0 mm), with a small overlap volume with OARs (0.4 cm3 for the esophagus and 1.2 cm3 for the heart). Conclusions The CTVs generated by our CTV delineation system agree with the physician's contours. This approach demonstrates the capability of intelligent volumetric expansions with the potential to be used in clinical practice.

Imbalances of soil available nutrients and soilborne diseases have seriously restricted the productivity of crops and jeopardized food security worldwide. Pyrroloquinoline quinone (PQQ), a redox cofactor in some bacteria involved in glucose metabolism and phosphorus mineralization, could be anticipated to alter soil ecosystems to a certain extent. However, there is limited information on PQQ defending soilborne pathogens and regulating soil main nutrients. Here, a pot experiment based on mono-cropping soils of pepper was conducted to examine the effects of PQQ amendment on reconstructing soil microbial communities and soil nutrients under aerobic/anaerobic conditions comprising three treatments, namely, control, PQQ (aerobic), and FL-PQQ (anaerobic). The results revealed that soil microbial community composition and soil nutrients were distinctly altered by PQQ regimes. Compared to control, PQQ treatment significantly increased the content of soil available phosphorus (AP), while FL_PQQ treatment strongly improved the content of soil available nitrogen (AN). In terms of pathogens, relative to control, both PQQ treatments suppressed the abundances of pathogens, of which FL_PQQ treatment significantly decreased the abundance of the pathotrophic fungal by 64% and the abundance of Fusarium oxysporum by 57%, largely attributed to the increase of organic acid generators (O

In order to identify the key transport process that determines the Cd concentration in brown rice, this study used 21 hybrid rice varieties as experimental materials and conducted field experiments in Qiyang (cadmium-contaminated site) and Yongding (low-cadmium site). Cd concentrations in 8 organs were measured, and bioconcentration factors and transfer factor were further calculated. The results showed that the Cd concentrations of the organs related to the xylem transport were as follows: root node stem leaf sheath leaf. In the phloem, the Cd concentrations were as follows: rachis brown rice rice husk. And the results of the correlation analysis found that Cd concentration between brown rice and root showed a significant positive correlation in Cd-contaminated site, but no significant correlation in low-cadmium site. Meanwhile, at both experimental sites, the Cd concentration of brown rice showed the most significant correlation with the phloem transfer factor from leaf and leaf sheath to brown rice. Principal Component Analysis (PCA) and stepwise regression analysis likewise found that Cd concentration in leaf and leaf sheath and their phloem transport of Cd to brown rice were significantly and positively correlated with Cd concentration in brown rice. The above results showed that the transport of leaf and leaf sheath to brown rice was a key process, and played a more important role in the accumulation of cadmium in brown rice than in root.

Silicon (Si) plays a pivotal role in mitigating phytotoxicity caused by cadmium (Cd). However, few former reports focused on the internal mechanism how Si assisted in alleviating Cd stress in rice under different durations of Cd exposure. Herein, the effects of Si on subcellular distribution of Cd in rice roots under short-term (12 h) and long-term (20 d) Cd exposure were explored. Results showed that Si decreased shoot Cd concentration but had little impact on root Cd levels. Under short-term Cd exposure, subcellular distribution analysis showed that Si increased the ratio of Cd in root cell wall by 23.2~24.0%, and decreased the ratio of Cd in root soluble fraction by 20.6~21.5%. This suggested that Si supply improved root retention of Cd by fixing it on the cell wall and thus restricted intracellular transportation of Cd. Further analysis unraveled that pectin (especially ionic-soluble pectin) of the cell wall was the main binding component, and Si supply induced more Cd accumulation in covalent-soluble pectin and hemicellulose. Moreover, the overexpression of germin-like proteins (GLPs) proved the role of cell wall in moderating Cd toxicity. Under long-term Cd exposure, Si promoted phytochelatin 2 (PC2) and phytochelatin 3 (PC3) synthesis in cytosol, at the same time, Si down-regulated the expression of the Cd efflux-related protein multidrug resistance-associated protein-like ATP-binding cassette transporters (MRP-like ABC transporters) and limited Cd transportation from vacuole to cytosol. Taken together, Si rather predominates in limiting Cd translocation by the cell wall of root under short-term Cd exposure and promoting vacuole compartmentalization to mitigate the Cd toxicity under long-term exposure, instead of reducing the absorption of Cd in rice roots, thereby decreasing Cd delivery into shoots.

Mutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.

In this study, the accurate effectiveness of CaO in mitigating Cd bioavailability in paddy soil-rice system was investigated and moreover, the potential for reversibility of CaO liming process was provided. Increasing soil pH to ≥6.5 by CaO was determined to be the minimal threshold for minimizing Cd transfer into rice in historically contaminated soils across light to severe Cd levels, while an elevated CaO ratio was needed for soil with recent input of Cd. In CaO remediation treatment, a reduced pool of bioavailable Cd in rhizosphere soil coupled with an increased Cd retention by Fe plaque and an inhibited planta Cd transfer was determined consistently and proposed to be largely responsible for the significant reduction in brown rice Cd. Under continuous simulated acid precipitation test, a negligible level of Cd in eluate with ∼1 unit higher pH than control was recorded with CaO. Significant acidification, however, increased Cd solubilization in the limed soil than in unlimited control, notably at pH 5.5–6.5. As indicated by Visual MINTEQ, a higher Cd-carbonate solubility and much decreased Cd complexation on Fe-(hydr)-oxides across this pH range occurred as a result of elevated Ca input. This suggests that a high soil pH (≥6.5) needs to be permanently maintained once liming has been performed to minimize Cd mobilization. Therefore, amending Cd-contaminated soils with CaO is a cost-effective remedial measure for reducing Cd bioavailability to paddy rice, while a high soil pH need to be permanently maintained to sustain this beneficial effect.

Objectives: Prompt gamma (PG) imaging has previously been demonstrated for use in proton range verification of a brain treatment with a homogeneous target region. In this study, the feasibility of PG imaging to detect anatomic change within a heterogeneous region is presented. Methods: A prompt gamma camera recorded several fractions of a patient treatment to the base of skull. An evaluation CT revealed a decrease in sinus cavity filling during the treatment course. Comparison of PG profiles between measurement and simulation was performed to investigate range variations between planned and measured pencil beam spot positions. Results: For one field, an average over range of 3 mm due to the anatomic change could be detected for a subset of spots traversing the sinus cavity region. The two other fields appeared less impacted by the change but predicted range variations could not be detected. These results were partially consistent with the simulations of the evaluation CT. Conclusion: We report the first clinical application of PG imaging that detected some of the expected small regional proton range deviations due to anatomic change in a heterogeneous region. However, several limitations exist with the technology that may limit its sensitivity to detect range deviations in heterogeneous regions. Advances in knowledge: We report on the first detection of range variations due to anatomic change in a heterogeneous region using PGI. The results confirm the feasibility of using PG-based range verification in highly heterogeneous target regions to identify deviations from the treatment plan.

A search for charged massive stable particles has been performed with the D0 detector using 1.1 fb{sup -1} of data. The speed of the particle has been calculated based on the time-of-flight and position information in the muon system. The present research is limited to direct pair-production of the charged massive long-lived particles. We do not consider CMSPs that result from the cascade decays of heavier particles. In this analysis, the exact values of the model parameters of the entire supersymmetric particle mass spectrum, relevant for cascade decays, are not important. We found no evidence of the signal. 95% CL cross-section upper limits have been set on the pair-productions of the stable scaler tau lepton, the gaugino-like charginos, and the higgsino-like charginos. The upper cross section limits vary from 0.31 pb to 0.04 pb, for stau masses in the range between 60 GeV and 300 GeV. We use the nominal value of the theoretical cross section to set limits on the mass of the pair produced charginos. We exclude the pair-produced stable gaugino-like charginos with mass below 206 GeV, and higgsino-like charginos below 171 GeV, respectively. Although the present sensitivity is insufficient to test the model of the pair produced stable staus, we do set cross section limits which can be applied to the pair production of any charged massive stable particle candidates with similar kinematics. These are the most restrictive limits to the present on the cross sections for CMSPs and the first published from the Tevatron Collider Run II. The manuscript has been published by Physical Review Letters in April 2009 and is available at arXiv as.