The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.
To investigate the efficacy and safety of locoregional radiotherapy in de novo ...mNPC.
Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months.
The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy.
The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.
Overall, 126 patients were enrolled (105 men 83.3% and 21 women 16.7%; median IQR age, 46 39-52 years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio HR, 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group.
In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.
ClinicalTrials.gov Identifier: NCT02111460.
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•dGN-supported Pt NPs are prepared and successfully catalyse neutral GOR.•Pt/dGN600 with point vacancy, 5–8-5, and 5–9 vacancy defect exhibit a remarkable activity.•In-situ GOR ...kinetics by Pt/dGNs and their activities are studied by EQCM.•Electron transfer numbers for the catalysis of GORs on the various Pt/dGNs were determined.•Pt/dGN600 showed its potential for being a non-enzymatic glucose sensor.
Significantly improving the dispersion of platinum nanoparticles (NPs) over the support is critical to boosting their performance in electrocatalysis. Herein, an effective method is reported to synthesise well-dispersed Pt NPs (∼3 nm) on defective graphene nanosheets (Pt/dGNs) through a self-regulation reduction method of sodium n-dodecyl sulphate (SDS). The dGNs (dGN600, dGN400, and dGN200) were rapidly exfoliated and prepared using a sonoelectrochemical method with sonication powers of 600, 400, and 200 W. Consequently, highly dispersed and dense Pt NPs formed on dGN600 (Pt/dGN600) with point vacancy, 5–8-5 defect, and 5–9 vacancy defect were obtained. The Pt/dGN600 exhibited a significant mass activity (5.80 × 1020 molecules· g-1Pt) for the sequential catalysis of neutral D-glucose oxidation reaction (GOR), where the electron transfer number was 1.13, suggesting that the element step to form gluconolactone. Additionally, amperometric sensor studies for transient catalysis clearly showed the potential of Pt/dGN600 for use as a non-enzymatic glucose sensor.
Patients with infertility are a high risk group in depression and anxiety. However, an existing theoretically and empirically validated model of stressors, stress, and mental symptoms specific for ...infertile patients is still a void. This study aimed to determine the related factors and their relational structures that affect the level of depressive and anxiety symptoms among infertile patients.
A cross-sectional sample of 400 infertility outpatients seeking reproduction treatments in three teaching hospitals across Taiwan participated in the structured questionnaire survey in 2011. The hypothesized model comprising 10 latent variables was tested by Structural Equation Modeling using AMOS 17.
Goodness-of-fit indexes, including χ2/DF = 1.871, PGFI = 0.746, PNFI = 0.764, and others, confirmed the modified model fit the data well. Marital stressor, importance of children, guilt-and-blame, and social stressor showed a direct effect on perceived stress. Instead of being a factor of stress, social support was directly and positively related to self-esteem. Perceived stress and self-esteem were the two major mediators for the relationships between stressors and mental symptoms. Increase in social support and self-esteem led to decrease in mental symptoms among the infertile patients.
The relational structures were identified and named as the Stressors Stress Symptoms Model, clinically applied to predict anxiety and depression from various stressors. Assessing sources and level of infertility-related stress and implementing culturally-sensitive counseling with an emphasis on positive personal value may assist in preventing the severity of depression and anxiety.
Epidermal growth factor receptor (EGFR) and activin A are both overexpressed in oral cavity squamous cell carcinoma (OSCC). We evaluated their clinical correlation and activin A-mediated EGFR ...regulation in this study. Overexpression of both transcripts/proteins indicated a poorer prognosis in OSCC patients. Knockdown of endogenous INHBA repressed the expression of EGFR and inhibited activin A-mediated canonical Smads, noncanonical phosphorylation of AKT (ser473) (p-AKT ser473) and SP1. Inhibition of PI3K signaling via its inhibitor attenuated p-AKT ser473 and in turn reduced SP1 and EGFR expression in the presence of recombinant activin A (rActivin A) in OSCC cells, as revealed via a luciferase assay and western blotting. However, canonical Smad signaling repressed the EGFR promoter, as revealed by a luciferase assay. The transcription factor SP1, its coactivator CBP/p300, and Smad proteins were recruited to the EGFR proximal promoter following rActivin A treatment, as revealed by chromatin immunoprecipitation (ChIP). Smad2/3/4 dramatically outcompeted SP1 binding to the EGFR proximal promoter following mithramycin A treatment. Activin A activates the PI3K and Smad pathways to compete for binding to overlapping SP1 consensus sequences on the EGFR proximal promoter. Nevertheless, canonical p-Smad2 was largely repressed in OSCC tumor tissues, suggesting that the activin A-mediated noncanonical pathway is essential for the carcinogenesis of OSCC.
An Arabidopsis thaliana mutant defective in chloroplast protein import was isolated and the mutant locus, cia5, identified by map-based cloning. CIA5 is a 21-kD integral membrane protein in the ...chloroplast inner envelope membrane with four predicted transmembrane domains, similar to another potential chloroplast inner membrane protein-conducting channel, At Tic20, and the mitochondrial inner membrane counterparts Tim17, Tim22, and Tim23. cia5 null mutants were albino and accumulated unprocessed precursor proteins. cia5 mutant chloroplasts were normal in targeting and binding of precursors to the chloroplast surface but were defective in protein translocation across the inner envelope membrane. Expression levels of CIA5 were comparable to those of major translocon components, such as At Tic110 and At Toc75, except during germination, at which stage At Tic20 was expressed at its highest level. A double mutant of cia5 At tic20-I had the same phenotype as the At tic20-I single mutant, suggesting that CIA5 and At Tic20 function similarly in chloroplast biogenesis, with At Tic20 functioning earlier in development. We renamed CIA5 as Arabidopsis Tic21 (At Tic21) and propose that it functions as part of the inner membrane protein-conducting channel and may be more important for later stages of leaf development.
Recessive variants of the SLC26A4 gene are an important cause of hereditary hearing impairment. Several transgenic mice with different Slc26a4 variants have been generated. However, none have ...recapitulated the auditory phenotypes in humans. Of the SLC26A4 variants identified thus far, the p.T721M variant is of interest, as it appears to confer a more severe pathogenicity than most of the other missense variants, but milder pathogenicity than non-sense and frameshift variants. Using a genotype-driven approach, we established a knock-in mouse model homozygous for p.T721M. To verify the pathogenicity of p.T721M, we generated mice with compound heterozygous variants by intercrossing Slc26a4
mice with Slc26a4
mice, which segregated the c.919-2A > G variant with abolished Slc26a4 function. We then performed serial audiological assessments, vestibular evaluations, and inner ear morphological studies. Surprisingly, both Slc26a4
and Slc26a4
showed normal audiovestibular functions and inner ear morphology, indicating that p.T721M is non-pathogenic in mice and a single p.T721M allele is sufficient to maintain normal inner ear physiology. The evidence together with previous reports on mouse models with Slc26a4 p.C565Y and p.H723R variants, support our speculation that the absence of audiovestibular phenotypes in these mouse models could be attributed to different protein structures at the C-terminus of human and mouse pendrin.
In this study, hysteresis-free double-layer gate-all-around stacked poly-Si nanosheet channel ferroelectric Hf x Zr 1-x O 2 negative capacitance field-effect transistors (DL GAA NS FE-HZO NC-FETs) ...with an internal metal gate (IMG) and NH 3 plasma nitridation were experimentally investigated and comprehensively discussed for the first time. The results revealed that NH 3 plasma nitridation at both the ZrO 2 /TiN and TiN/HZO interfaces can effectively enhance the HZO ferroelectricity and quality by suppressing the generation of oxygen vacancies (<inline-formula> <tex-math notation="LaTeX">{V}_{o}{)} </tex-math></inline-formula>. Furthermore, the SiON interfacial layer quality can be enhanced by passivating bulk defects within the SiON interfacial layer through NH 3 plasma nitridation at the ZrO 2 /TiN interface. When NH 3 plasma nitridation is performed at both the ZrO 2 /TiN and TiN/HZO interfaces, the devices exhibit excellent electrical characteristics: 1) an extremely low subthreshold swing (SS) of 45.77 mV/decade; 2) an ultrasteep average SS (ASS) of 61.39 mV/decade; 3) a relatively high ON/OFF current ratio (<inline-formula> <tex-math notation="LaTeX">{I}_{ \mathrm{\scriptscriptstyle ON}} / {I}_{ \mathrm{\scriptscriptstyle OFF}}{)} </tex-math></inline-formula> of <inline-formula> <tex-math notation="LaTeX"> > 5\,\,\times \,\,10^{{7}} </tex-math></inline-formula>; and 4) a quite high effective breakdown voltage (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {EBD}} </tex-math></inline-formula>) of 6.7 V at <inline-formula> <tex-math notation="LaTeX">{V}_{D} </tex-math></inline-formula> = 0.1 V. Thus, these devices are promising candidates for low-power-consumption monolithic 3-D integrated circuit (IC) applications.
This study proposes a conceptual dynamic latent Dirichlet allocation (CDLDA) model for topic detection and tracking in conversational content. Topic detection and tracking is vital for conversational ...communication, especially for spoken interactions. Because topic transitions occur frequently during conversational communication (i.e., a conversation usually contains many topics), language processors must detect different topics in conversational content. Considering the structure of spoken dialogue, the dynamic model was employed in this study to capture the sequence of two adjacent topics in spoken content. The proposed model applies the proportions of verbs and nouns to analyze the similarity between utterances. An agglomerative clustering algorithm, based on an ontology defined in E-HowNet, clusters conversational utterances. Because the topic structure of conversational content is friable, E-HowNet uses hypernym relationships of speech acts to obtain robust solutions, even for sparse data. Compared with the traditional latent Dirichlet allocation (LDA) model, which detects topics only through a bag-of-words technique, the proposed model considers temporal features by introducing dynamic concepts. Experimental results revealed that the proposed approach outperformed the traditional DLDA and LDA and support vector machine models, in addition to achieving excellent performance for topic detection and tracking in conversations.
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