•The effective segregation coefficient of Ce in Cs2LiYCl6 (CLYC) crystals is 0.22.•The scintillation properties of Ce-doped CLYC crystals are nonuniform across the length of the ingot.•Appropriate Ce ...doping concentration (2 %) was proposed.
Ce-doped Cs2LiYCl6 (CLYC) has widespread applications in homeland security owing to its excellent neutron/gamma discrimination ability. Ce3+ ions, as luminescent centers of CLYC, have a significant difference in effective ionic radius compared with Y3+, hinting at the severe inhomogeneous distribution of Ce3+ in CLYC. Still, only the relation between scintillation properties and nominal doping concentrations in CLYC crystals has been reported. The segregation behavior of Ce3+ ions along the ingot are still open for research. Herein, we measured the actual Ce3+ doping concentration along the CLYC ingot. Gamma-ray energy spectrum and powder XRD patterns of different samples were utilized to study the effects of Ce segregation on CLYC crystals. The effective segregation coefficient of Ce in CLYC crystals, keff = 0.22, was calculated. In most part of the ingots, the concentration of Ce3+ ions was lower than the nominal doping amount and rose rapidly at the tail. The scintillation properties of CLYC crystals along the ingot were affected by the distribution of Ce concentrations. This work may guide the optimization of properties for large-size CLYC crystals by modifying the distribution of Ce3+ ions.
Circular RNA (circRNA) has been recently identified as a critical regulator during carcinogenesis. However, the biological function and potential underlying mechanisms of circRNAs in lung cancer ...remain to be further elucidated.
Here, we first evaluated the differentially expressed circRNAs between tumor and the matched adjacent nontumor tissues (3 pairs) of lung cancer patients via circRNA microarray. The expression of top five dysregulated circRNAs were tested in lung cancer cell lines and the circSCAP with concordant alteration in microarray data and cell lines was selected for further investigation. Then we validated the expression level of circSCAP in tumor and corresponding adjacent tissues (161 pairs) from a lung cancer cohort by RT-PCR analysis followed by correlation and prognosis analysis between circSCAP and clinical characteristics. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnosis (about 80% in the cohort used in this study). Therefore, we focused the role of circSCAP in NSCLC in the present study. In vitro and in vivo assays were performed to study the biological function of circSCAP in NSCLC. Biotin-labeled RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to identify the proteins directly interacting with circSCAP. The molecular mechanism of circSCAP-driven tumor suppression was demonstrated by immunoblotting, immunoprecipitation and luciferase reporter assays. In vitro and in vivo rescue experiments were conducted to verify the role of the circSCAP/SF3A3/p53 signaling axis in NSCLC.
We screened the expression profiles of human circRNAs in lung cancer tissues and found that hsa_circ_0065214 (termed as circSCAP) was significantly decreased. Kaplan-Meier analysis showed that patients with low level of circSCAP had a significantly poor prognosis. Gain- and loss-of-function experiments suggested that circSCAP played an important role in NSCLC cell proliferation, cell migration and apoptosis. Mechanistically, circSCAP directly binds to the SF3A3 protein, facilitating the reduction of SF3A3 by promoting its ubiquitin-proteasome-mediated degradation, which enhances the expression of MDM4-S to finally activate its downstream p53 signaling.
These findings illustrate a novel circSCAP/SF3A3/p53 signaling axis involved in suppressing the malignance of NSCLC and provide a promising target for NSCLC prognosis prediction and treatment.
To explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal ...carcinoma (LA-NPC).
TILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs-LYM% score = 0), middle-risk group (MRG) (TILs-LYM% score = 1), and low-risk group (LRG) (TILs-LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs-LYM% status with clinicopathological factors and survival, were evaluated.
As a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan-Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs-LYM% score of 0, 1, and 2 (all
0.05). Further multivariate analyses showed that TILs-LYM% score was an independent factor affecting survival of the patients, and HRG (TILs-LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89,
0.001), death (HR = 8.08,
= 0.008), distant metastasis (HR = 7.66,
= 0.001), and local relapse (HR = 5.18,
= 0.013) compared with LRG (TILs-LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs-LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone.
A positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs-LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.
Carotid artery invasion (CAI) has been demonstrated to be an important prognosticator in some head and neck cancers. This study aimed to examine the prognostic value of radiologic CAI (rCAI) by ...cervical lymphadenopathy in nasopharyngeal carcinoma (NPC).
NPC patients treated between January 2013 and December 2016 were included. Pre-treatment MRIs were reviewed for cervical rCAI according to the radiologic criteria. Univariate and multivariate models were constructed to assess the association between cervical rCAI and clinical outcomes. A new N classification system was proposed and compared to the 8th AJCC system.
The percentage of patients with MRI-positive lymph nodes was 84.7% (494/583), of whom cervical rCAI cases accounted for 42.3% (209/494). Cervical rCAI was associated with significantly poorer OS, DFS, DFFS and RFFS compared to non-rCAI (P < 0.05). Multivariate analyses confirmed that cervical rCAI was an independent prognosticator for DFS and DFFS, surpassing other nodal features, such as laterality, size, cervical node necrosis (CNN) and radiologic extranodal extension (rENE), while location of positive LNs remained independently associated with OS, DFS and DFFS. We propose a refined N classification: New_N1: upper neck LNs only without cervical rCAI; New_N2: upper neck LNs only with cervical rCAI; New_N3: upper and lower LNs. The proposed classification broadened the differences in OS, DFS and DFFS between N1 and N2 disease, and achieved a higher c-index for DFS and DFFS.
Cervical rCAI was an independent unfavorable indicator of NPC. Compared to the AJCC system, the proposed N category showed satisfactory stratification between N1 and N2 disease, and better prediction of distant metastasis and disease failure.
This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions.
...In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%;
= 224) and a validation set (ca. 30%;
= 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan-Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors.
Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12-63.86) in the high-risk group and 83.0% (95%CI, 76.31-90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model.
The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.
Two cycles of induction chemotherapy (IC) followed by 2 cycles of platinum-based concurrent chemoradiotherapy (CCRT) (2IC+2CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is ...widely adopted but not evidence-confirmed. This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy, toxicity and cost-effectiveness.
This real-world study from two epidemic centers used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. The enrolled patients were divided into three groups based on treatment modality: Group A (2IC+2CCRT), Group B (3IC+2CCRT or 2IC+3CCRT) and Group C (3IC+3CCRT). Long-term survival, acute toxicities and cost-effectiveness were compared among the groups. We developed a prognostic model dividing the population into high- and low-risk cohorts, and survivals including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared among the three groups according to certain risk stratifications.
Of 4,042 patients, 1,175 were enrolled, with 660, 419, and 96 included in Groups A, B and C, respectively. Five-year survivals were similar among the three groups after PSM and confirmed by IPTW. Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A (52.1%
41.5%
25.2%; 41.7%
32.7%
25.0%) as were grade 3-4 nausea/vomiting and oral mucositis (29.2%
15.0%
6.1%; 32.3%
25.3%
18.0%). Cost-effective analysis suggested that 2IC+2CCRT was the least expensive, while the health benefits were similar to those of the other groups. Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients, while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals, mainly reflected by LRRFS.
In LA-NPC patients, 2IC+2CCRT was the optimal choice regarding efficacy, toxicity and cost-effectiveness; however, 2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high- and low-risk populations, respectively.
We aimed to develop a nomogram integrating MRI-based tumor burden features (MTBF), nodal necrosis, and some clinical factors to forecast the distant metastasis-free survival (DMFS) of patients ...suffering from non-metastatic nasopharyngeal carcinoma (NPC). A total of 1640 patients treated at Sun Yat-sen University Cancer Center (Guangzhou, China) from 2011 to 2016 were enrolled, among which 1148 and 492 patients were randomized to a training cohort and an internal validation cohort, respectively. Additionally, 200 and 257 patients were enrolled in the Foshan and Dongguan validation cohorts, respectively, which served as independent external validation cohorts. The MTBF were developed from the stepwise regression of six multidimensional tumor burden variables, based on which we developed a nomogram also integrating nodal necrosis and clinical features. This model divided the patients into high- and low-risk groups by an optimal cutoff. Compared with those of patients in the low-risk group, the DMFS hazard ratio (HR): 4.76, 95% confidence interval (CI): 3.39–6.69;
p
< 0.0001, and progression-free survival (PFS; HR: 4.11, 95% CI: 3.13–5.39;
p
< 0.0001) of patients in the high-risk group were relatively poor. Furthermore, in the training cohort, the 3-year DMFS of high-risk patients who received induction chemotherapy (ICT) combined with concurrent chemoradiotherapy (CCRT) was better than that of those who were treated with CCRT alone (
p
= 0.0340), whereas low-risk patients who received ICT + CCRT had a similar DMFS to those who only received CCRT. The outcomes we obtained were all verified in the three validation cohorts. The survival model can be used as a reliable prognostic tool for NPC patients and is helpful to determine patients who will benefit from ICT.
Gamma/neutron dual detection has occupied significant territory in the field of homeland security and nuclear energy development. Cs 2 LiLaBr 6 (CLLB) has shown both neutron/gamma dual-mode detection ...capability and excellent scintillation properties. Herein, we explored the Cs 2 LaBr 5 -LiBr phase diagram through powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) tests of synthesized polycrystalline materials. The Cs 2 LaBr 5 -rich side of the phase diagram is similar to a binary peritectic phase diagram, where the peritectic line (447 °C) extends to a LiBr content of 61%. The LiBr-rich side of the phase diagram resembles a binary eutectic phase diagram, where the eutectic point (395 °C) is located at 80% LiBr concentration. Guided by the phase diagram, CLLB ingots were designed to grow from the LiBr-rich side with different concentrations of LiBr. The scintillator properties of CLLB crystals were found to be deteriorated by the increasing defects with elevated LiBr contents. A concentration of LiBr around 55% was a preference for the growth of high-quality CLLB. A better understanding of the Cs 2 LaBr 5 -LiBr phase diagram benefits the growth of CLLB crystals and provides considerations for other halide double perovskites.
Purpose
To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing ...induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis.
Methods
SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (
n
= 204) and an external independent cohort (
n
= 272).
Results
SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy time dependent area under the curve (tAUC) at 5 years: 0.70, and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival.
Conclusions
Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population.
•The dendrites and peritectic reaction were discovered during CLLB crystal growth.•The mechanism of dendrite growth was discussed though its evolution process.•A modified phase diagram was proposed ...to understand the growth processes of CLLB.
The lanthanum crystal Cs2LiLaBr6 (CLLB) has excellent scintillation properties for gamma/neutron discrimination. The initial melt with hyper-peritectic ratios (55 < LiBr/mol.% < 61) was found beneficial for CLLB crystal growth. The hyper-peritectic melt would pass though the peritectic point. However, the detailed process was still unknown. Herein, the dendrite growth and peritectic reaction were discovered near the peritectic point in CLLB single crystal ingots for the first time. The mechanism of dendrite growth was analyzed. The Cs2LaBr5-LiBr phase diagram was modified according to these results. The understanding of phase transition and dendrite evolution can guide crystal growth of CLLB and other similar elpasolite crystals.
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