Interactions of trace organic compounds (TOrCs) with polymeric nanofiltration (NF) membrane can affect their rejection. It is desirable to investigate whether solubility which depends on the free ...energy of interaction between these solutes and water correlates with rejection/adsorption and the potential to be incorporated in the partitioning terms of current NF model. A total of ten neutral disinfection by-products (DBPs) were selected as the model compounds for TOrCs to comprehensively investigate the role of solubility on rejection and adsorption. Pearson correlation analysis indicated that the correlation between MW and rejection ratio was highly significant (
r
= 0.778,
p
= 0.008) and that between solubility and rejection ratio was moderately significant (
r
= −0.636,
p
= 0.48) in a cross-flow system. By fitting Freundlich equation from adsorption isotherm experiment, the adsorption affinity (
K
f
) of DBPs was roughly correlated with their solubility with regard to the comparison of
n
value with 1.
α
was then introduced as a parameter of solute-membrane interaction from the perspective of partitioning term in the hydrodynamic model. Exponential relationship can be observed between the solubility and
α
, demonstrating the possibility of incorporating solubility into the partitioning terms in NF model to accurately predict the rejection of DBPs.
Background. The aim of the study was to evaluate the dosimetric benefit of applying volumetric modulated arc therapy (VMAT) on the post-mastectomy left-sided breast cancer patients, with the ...involvement of internal mammary nodes (IMN).
Patients and methods. The prescription dose was 50 Gy delivered in 25 fractions, and the clinical target volume included the left chest wall (CW) and IMN. VMAT plans were created and compared with intensity-modulated radiotherapy (IMRT) plans on Pinnacle treatment planning system. Comparative endpoints were dose homogeneity within planning target volume (PTV), target dose coverage, doses to the critical structures including heart, lungs and the contralateral breast, number of monitor units and treatment delivery time.
Results. VMAT and IMRT plans showed similar PTV dose homogeneity, but, VMAT provided a better dose coverage for IMN than IMRT (p = 0.017). The mean dose (Gy), V
(%) and V
(%) for the heart were 13.5 ± 5.0 Gy, 9.9% ± 5.9% and 50.2% ± 29.0% by VMAT, and 14.0 ± 5.4 Gy, 10.6% ± 5.8% and 55.7% ± 29.6% by IMRT, respectively. The left lung mean dose (Gy), V
(%), V
(%) and the right lung V
(%) were significantly reduced from 14.1 ± 2.3 Gy, 24.2% ± 5.9%, 42.4% ± 11.9% and 41.2% ± 12.3% with IMRT to 12.8 ± 1.9 Gy, 21.0% ± 3.8%, 37.1% ± 8.4% and 32.1% ± 18.2% with VMAT, respectively. The mean dose to the contralateral breast was 1.7 ± 1.2 Gy with VMAT and 2.3 ± 1.6 Gy with IMRT. Finally, VMAT reduced the number of monitor units by 24% and the treatment time by 53%, as compared to IMRT.
Conclusions. Compared to 5-be am step-and-shot IMRT, VMAT achieves similar or superior target coverage and a better normal tissue sparing, with fewer monitor units and shorter delivery time.
Whole-exome sequencing (WES), one of the next-generation sequencing (NGS), has become a powerful tool to identify exonic variants. Investigating causality of the sequence variants in human disease ...becomes an important part in NGS for the research and clinical applications. Recently, important guidelines on them have been published and will keep on updating. In our study, two Chinese families, with the clinical diagnosis of "Epilepsy", which presented with seizures, psychomotor retardation, hypotonia and etc. features, were sequenced by Trio-WES (including the proband and the unaffected parents), and a standard interpretation of the identified variants was performed referring to the recently updated guidelines. Finally, we identified three novel mutations (c.71 C > T, p.P24L; c.1387-1389delGAG, p.E463-; c.134 G > A, p.W45*; NM_000026) in ADSL in the two Chinese families, and confirmed them as the causal variants to the disease-Adenylosuccinate Lyase Deficiency. Previous reported specific therapy was also introduced to the patients after our refined molecular diagnosis, however, the effect was very limited success. In summary, our study demonstrated the power and advantages of WES in exploring the etiology of human disease. Using the constantly updated guidelines to conduct the WES study and to interpret the sequence variants are a necessary strategy to make the molecular diagnosis and to guide the individualized treatment of human disease.
The cone beam CT (CBCT) guided radiation can reduce the systematic and random setup errors as compared to the skin-mark setup. However, the residual and intrafractional (RAIF) errors are still ...unknown. The purpose of this paper is to investigate the magnitude of RAIF errors and correction action levels needed in cone beam computed tomography (CBCT) guided accelerated partial breast irradiation (APBI).
Ten patients were enrolled in the prospective study of CBCT guided APBI. The postoperative tumor bed was irradiated with 38.5 Gy in 10 fractions over 5 days. Two cone-beam CT data sets were obtained with one before and one after the treatment delivery. The CBCT images were registered online to the planning CT images using the automatic algorithm followed by a fine manual adjustment. An action level of 3 mm, meaning that corrections were performed for translations exceeding 3 mm, was implemented in clinical treatments. Based on the acquired data, different correction action levels were simulated, and random RAIF errors, systematic RAIF errors and related margins before and after the treatments were determined for varying correction action levels.
A total of 75 pairs of CBCT data sets were analyzed. The systematic and random setup errors based on skin-mark setup prior to treatment delivery were 2.1 mm and 1.8 mm in the lateral (LR), 3.1 mm and 2.3 mm in the superior-inferior (SI), and 2.3 mm and 2.0 mm in the anterior-posterior (AP) directions. With the 3 mm correction action level, the systematic and random RAIF errors were 2.5 mm and 2.3 mm in the LR direction, 2.3 mm and 2.3 mm in the SI direction, and 2.3 mm and 2.2 mm in the AP direction after treatments delivery. Accordingly, the margins for correction action levels of 3 mm, 4 mm, 5 mm, 6 mm and no correction were 7.9 mm, 8.0 mm, 8.0 mm, 7.9 mm and 8.0 mm in the LR direction; 6.4 mm, 7.1 mm, 7.9 mm, 9.2 mm and 10.5 mm in the SI direction; 7.6 mm, 7.9 mm, 9.4 mm, 10.1 mm and 12.7 mm in the AP direction, respectively.
Residual and intrafractional errors can significantly affect the accuracy of image-guided APBI with nonplanar 3DCRT techniques. If a 10-mm CTV-PTV margin is applied, a correction action level of 5 mm or less is necessary so as to maintain the RAIF errors within 10 mm for more than 95% of fractions. Pre-treatment CBCT guidance is not a guarantee for safe delivery of the treatment despite its known benefits of reducing the initial setup errors. A patient position verification and correction during the treatment may be a method for the safe delivery.
Purpose:
For patients with metastatic castration-resistant prostate cancer (CRPC), the efficacy and safety of molecular targeted agents (MTAs) in combination with docetaxel are still unclear. We ...conducted this meta-analysis to assess the efficacy and toxicity of the addition of MTAs to docetaxel-based chemotherapy for the treatment of metastatic CRPC.
Methods:
Databases from PubMed, Web of Science, and abstracts presented at American Society of Clinical Oncology meeting up to 31 June 2014 were searched to identify relevant studies. Eligible studies included prospective phase III randomized controlled trials (RCTs) evaluating docetaxel with or without MTAs in patients with metastatic CRPC. The primary aim was to assess overall survival (OS). Secondary aims were to assess progression-free survival (PFS); overall response rates (ORRs), and grade 3-5 toxicities. Statistical analyses were conducted by using either random effects or fixed-effect models according to the heterogeneity of included studies.
Results:
A total of 5886 patients from five phase III RCTs were identified. No statistically significant difference in OS hazard ratio (HR): 0·98, 95% confidence interval (CI): 0·91-1·04, P = 0·44, ORR relative risk (RR): 1·32, 95% CI: 0·94-1·84, P = 0·11, and PSA response rate (RR: 1·22, 95% CI: 0·86-1·74, P = 0·27) was found between the two groups. The addition of MTAs to docetaxel significantly improved PFS (HR: 0·92, 95% CI: 0·86-0·98, P = 0·011). However, the benefits in PFS was accompanied by increasing the risk of developing grade 3-4 (RR: 1·19, 95% CI: 0·99-1·42, P = 0·062) and fatal (RR: 1·30, 95% CI: 1·01-1·66, P = 0·039) adverse events.
Conclusions:
The findings of this study suggest that the palliation of CRPC with MTAs and docetaxel does not provide a significant survival benefit and is associated with increased severe toxicities.
Transition metal-free cascade reactions of alkynols with imines have been achieved using potassium tert-butoxide as catalyst. Switching the reaction solvent gives two kinds of products in good yield: ...isoquinolin-1(2H)-one derivatives and dihydroisobenzofuran derivatives. This approach was used to generate the natural product 8-oxypseudopalmatine in a two-step procedure from commercially available starting materials. Additionally, multicomponent reactions of alkynols, aldehydes, and amines were also successfully achieved to afford isoquinolin-1(2H)-one derivatives.
Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface ...markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.
Human papillomavirus (HPV) detection based on cervical cytology specimens is useful for cervical cancer screening. The aim of this study was to compare Mojin HPV kit (a newly developed HPV genotyping ...assay) with the Cobas 4800 HPV test in detecting high-risk (HR) HPV.
A total of 347 cervical exfoliated cell specimens were tested using the Mojin HPV kit and Cobas 4800 HPV test. When the results from the two tests were inconsistent, gene sequencing was performed for correction.
For HR-HPV, the results of the two assays agreed by 96.3% Kappa = 0.911; 95% confidence interval (CI): 0.863 - 0.958). The positive and negative coincidence rates between the two tests were 96.0% (95% CI: 92.7% - 98.0%) and 97.0% (95% CI: 91.5% - 99.4%), respectively. Of the 13 samples with discordant results, 3 samples were false positive and 10 samples were true negative for Mojin HPV test, according to the identification by sequencing. For HPV16 genotyping, the total coincidence rate between the 2 tests was 100% (Kappa = 1.000), and 99.7% (Kappa = 0.973; 95% CI: 0.905 - 1.000) for HPV18.
Mojin HPV kit may be as effective as Cobas 4800 HPV assay in detecting the total HR-HPV, especially HPV16 or HPV18.
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