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The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma.This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18-65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0-N1 disease (according to International Union Against Cancer-American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66-70 Gy (for the involved cervical lymph nodes), 60-62 Gy (for the high-risk target volume), and 54-56 Gy (for the low-risk target volume) were administered in 30-33 fractions, five fractions per week. Patients with stage II-IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed.Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46-59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7-99·7] in the UNI group vs 96·3% [93·8-98·8] in the WNI group; difference -1·4% [95% CI -4·6 to 1·8]; pElective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0-N1 nasopharyngeal carcinoma.Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation.For the Chinese translation of the abstract see Supplementary Materials section.

Objectives We aimed to develop and validate radiologic scores from [18F]FDG PET/CT and MRI to guide individualized induction chemotherapy (IC) for patients with T3N1M0 nasopharyngeal carcinoma (NPC). Methods A total of 542 T3N1M0 patients who underwent pretreatment [18F]FDG PET/CT and MRI were enrolled in the training cohort. A total of 174 patients underwent biopsy of one or more cervical lymph nodes. Failure-free survival (FFS) was the primary endpoint. The radiologic score, which was calculated according to the number of risk factors from the multivariate model, was used for risk stratification. The survival difference of patients undergoing concurrent chemoradiotherapy (CCRT) with or without IC was then compared in risk-stratified subgroups. Another cohort from our prospective clinical trial (N = 353, NCT03003182) was applied for validation. Results The sensitivity of [18F]FDG PET/CT was better than that of MRI (97.7% vs. 87.1%, p p n = 329) stratified by radiologic score benefited from IC (5-year FFS: IC + CCRT 83.5% vs. CCRT 70.5%; p = 0.0044), while low-risk patients (n = 213) did not. These results were verified again in the validation cohort. Conclusions T3N1M0 patients were accurately staged by both [18F]FDG PET/CT and MRI. The radiologic score can correctly identify high-risk patients who can gain additional survival benefit from IC and it can be used to guide individualized treatment of T3N1M0 NPC. Key Points • [18F]FDG PET/CT was more accurate than MRI in diagnosing histologically proven cervical lymph nodes. • Radiologic lymph node characteristics were reliable independent risk factors for FFS in T3N1M0 nasopharyngeal carcinoma patients. • High-risk patients identified by the radiologic score based on [18F]FDG PET/CT and MRI could benefit from the addition of induction chemotherapy.

Fruits require different planting techniques at different growth stages. Traditionally, the maturity stage of fruit is judged visually, which is time-consuming and labor-intensive. Fruits differ in size and color, and sometimes leaves or branches occult some of fruits, limiting automatic detection of growth stages in a real environment. Based on YOLOV4-Tiny, this study proposes a GCS-YOLOV4-Tiny model by (1) adding squeeze and excitation (SE) and the spatial pyramid pooling (SPP) modules to improve the accuracy of the model and (2) using the group convolution to reduce the size of the model and finally achieve faster detection speed. The proposed GCS-YOLOV4-Tiny model was executed on three public fruit datasets. Results have shown that GCS-YOLOV4-Tiny has favorable performance on mAP, Recall, F1-Score and Average IoU on Mango YOLO and Rpi-Tomato datasets. In addition, with the smallest model size of 20.70 MB, the mAP, Recall, F1-score, Precision and Average IoU of GCS-YOLOV4-Tiny achieve 93.42 ± 0.44, 91.00 ± 1.87, 90.80 ± 2.59, 90.80 ± 2.77 and 76.94 ± 1.35%, respectively, on F. margarita dataset. The detection results outperform the state-of-the-art YOLOV4-Tiny model with a 17.45% increase in mAP and a 13.80% increase in F1-score. The proposed model provides an effective and efficient performance to detect different growth stages of fruits and can be extended for different fruits and crops for object or disease detections.

Background To test the advantages of positron emission tomography and computed tomography (PET/CT) for diagnosing lymph nodes and staging nasopharyngeal carcinoma and to investigate its benefits for survival and treatment decisions. Methods The performance of PET/CT and magnetic resonance imaging (MRI) in diagnosis was compared based on 460 biopsied lymph nodes. Using the propensity matching method, survival differences of T3N1M0 patients with (n = 1093) and without (n = 1377) PET/CT were compared in diverse manners. A radiologic score model was developed and tested in a subset of T3N1M0 patients. Results PET/CT performed better than MRI with higher sensitivity, accuracy, and area under the receiver operating characteristic curve (96.7% vs. 88.5%, p p p p p = 0.006) for the high-risk patients selected by the model but not for those without risk stratification (p = 0.78). Conclusion PET/CT showed advantages in staging nasopharyngeal carcinoma due to a more accurate diagnosis of lymph nodes and this contributed to a survival benefit. PET/CT combined with MRI provided prognostic factors that could identify high-risk patients and guide individualized treatment.

We analyzed the patterns of lymph node (LN) failure and prognosis in patients with regional recurrent nasopharyngeal carcinoma (rNPC) alone after primary intensity-modulated radiotherapy (IMRT).A total of 175 patients who were treated with IMRT between 2010 and 2015 and who experienced regional recurrence alone were included. Recurrent LNs were re-located in the initial pretreatment imaging and IMRT plan and failures were classified as in-field or out-field based on target volume delineation. All patients underwent curative salvage treatment. Independent prognostic factors for overall survival (OS) were selected by multivariate Cox analysis.Level IIb (49.1%, 86/175) was the most frequent recurrence site, followed by level IIa (36%), level III (18.9%), level IVa (12%), the retropharyngeal region (8%), level Va (6.9%), and the parotid region (6.9%). A total of 264 recurrent LNs were recorded: 149 (56.4%) were classified as in-field failure with a prescribed dose ≥66 Gy, 60 (22.7%) with 60 to66 Gy, 32 (12.1%) with 50 to60 Gy, and 23 (8.7%) as an out-field failure, which mainly occurred in the parotid region and level Ib. After a median follow-up of 52.8 months, the estimated 5-year OS rate was 66.9%. Multivariate analysis showed that age, plasma Epstein-Barr virus DNA level, extranodal extension, lower neck involvement, and parotid LN recurrence were independent prognostic factors of OS.In-field failure represented the main pattern of regional recurrence and out-field failure mainly occurred in the parotid gland and level Ib. Patients with regional rNPC alone had a good prognosis after salvage treatment.

BACKGROUND: Radiotherapy is the mainstay of treatment for nasopharyngeal carcinoma. Radiation-induced temporal lobe injury (TLI) can regress or resolve in the early phase, but it is irreversible at a later stage. However, no study has proposed a risk-based follow-up schedule for its early detection. Planning evaluation is difficult when dose-volume histogram (DVH) parameters are similar and optimization is terminated. METHODS: This multicenter retrospective study included 6065 patients between 2014 and 2018. A 3D ResNet-based deep learning model was developed in training and validation cohorts and independently tested using concordance index in internal and external test cohorts. Accordingly, the patients were stratified into risk groups, and the model-predicted risks were used to develop risk-based follow-up schedules. The schedule was compared with the Radiation Therapy Oncology Group (RTOG) recommendation (every 3 months during the first 2 years and every 6 months in 3–5 years). Additionally, the model was used to evaluate plans with similar DVH parameters. FINDINGS: Our model achieved concordance indexes of 0.831, 0.818, and 0.804, respectively, which outperformed conventional prediction models (all P

Extracellular accumulation of β amyloid peptides of 40 (Aβ40) and 42 residues (Aβ42) has been considered as one of the hallmarks in the pathology of Alzheimer’s disease. In this work, we are able to prepare oligomeric aggregates of Aβ with uniform size and high structural homogeneity. Our experimental design is to incubate Aβ peptides in reverse micelles (RMs) so that the peptides could aggregate only through a single nucleation process and the size of the oligomers is confined by the physical dimension of the reverse micelles. The hence obtained Aβ oligomers (AβOs) are 23 nm in diameter and they belong to the category of high molecular-weight (MW) oligomers. The solid-state NMR data revealed that Aβ40Os adopt the structural motif of β-loop-β but the chemical shifts manifested that they are structurally different from low-MW AβOs and mature fibrils. From the thioflavin-T results, we found that high-MW Aβ42Os can seed the fibrillization of Aβ40 monomers. Our protocol allows performing cross-seeding experiments among oligomeric species. By comparing the chemical shifts of Aβ40Os cross seeded by Aβ42Os and those of Aβ40Os prepared in the absence of Aβ42Os, we observed that the structures of E11, K16, and E22 were altered, whereas the backbone conformation of the β-sheet region near the C-terminus is structurally invariant. The use of reverse micelles allows hitherto the most detailed characterization of the structural variability of Aβ40Os.

Background To explore the prognostic value of early radiological response (ERR) to first‐line platinum‐containing chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC), as well as its correlation with the best radiological response (BRR). Patients and methods A total of 756 mNPC patients with measurable lesions who received first‐line platinum‐containing chemotherapy were enrolled in this study. ERR was defined as complete or partial response after 6 weeks of chemotherapy according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. We performed survival analyses according to the radiological response after repeated chemotherapy. Log‐rank test and Cox regression were used to analyze the survival data. Results About 470 patients achieved ERR and 78 patients achieved subsequent response (objective response after repeated chemotherapy). ERR patients had better OS (P, The radiological response to chemotherapy is a critical feature in the clinical evaluation of antitumor effects and associated with survival outcome. Our study suggested that early radiological response is helpful in giving prognostic information for both physicians and patients, and also valuable in selecting patients for more intensive multidisciplinary treatments.

We report a systematic study of carbon fibre (CF)-supported NiCo layered double hydroxide nanosheets (LDHNs) with and without heat treatment at 200 and 400 °C (CF-NiCo LDHN

In this study, a preservation package that can extend the shelf life of Agaricus bisporus was developed using plasma modification combined with low-density polyethylene (LDPE), collagen (COL), and carboxymethyl cellulose (CMC). Out results showed that the selectivity of LDPE to gas can be controlled by plasma modification combined with coating of different concentrations of CMC and COL. Packaging test results applied to A. bisporus showed that 3% and 5% of CMC and COL did not significantly inhibit polyphenol oxidase and β-1,3-glucanase, indicating no significant effect on structural integrity and oxidative browning. The use of 0.5% and 1.0% CMC and COL can effectively inhibit the polyphenol oxidase and β-1,3-glucanase activity of A. bisporus, leading to improved effects in browning inhibition and structural integrity maintenance. P-1.0COL can effectively maintain gas composition in the package (carbon dioxide: 10–15% and oxygen: 8–15%) and catalase activity during storage, thereby reducing the oxidative damage caused by respiration of A. bisporus. The current study confirmed that the use of plasma modification technology combined with 1.0% COL can be used in preservation packaging by regulating the respiration of A. bisporus, thus extending its shelf life from 7 to 21 days.

Background We aimed to testify the advantage of positron emission tomography and computed tomography(PET/CT) in diagnosing cervical lymph nodes and staging nasopharyngeal carcinoma, and investigate whether PET/CT could bring about benefit in survival and serve for individualized treatment. Methods A total of 2759 patients were enrolled in this study. 460 biopsied cervical lymph nodes were named cohort A. Cohort B consisted of 1093 T3N1M0 patients who received both PET/CT and magnetic resonance imaging(MRI), while Cohort C contained 1377 T3N1M0 patients who underwent MRI alone. Cohort D enrolled 838 patients receiving concurrent chemoradiotherapy(CCRT) with or without induction chemotherapy(IC) to develop radiologic score model to guide IC. Results In cohort A, the sensitivity, accuracy, and area under the curve of PET/CT were much higher than those of MRI (96.7%versus88.5%, p

In this study, a preservation package that can extend the shelf life of Agaricus bisporus was developed using plasma modification combined with low-density polyethylene (LDPE), collagen (COL), and carboxymethyl cellulose (CMC). Out results showed that the selectivity of LDPE to gas can be controlled by plasma modification combined with coating of different concentrations of CMC and COL. Packaging test results applied to A. bisporus showed that 3% and 5% of CMC and COL did not significantly inhibit polyphenol oxidase and β-1,3-glucanase, indicating no significant effect on structural integrity and oxidative browning. The use of 0.5% and 1.0% CMC and COL can effectively inhibit the polyphenol oxidase and β-1,3-glucanase activity of A. bisporus, leading to improved effects in browning inhibition and structural integrity maintenance. P-1.0COL can effectively maintain gas composition in the package (carbon dioxide: 10–15% and oxygen: 8–15%) and catalase activity during storage, thereby reducing the oxidative damage caused by respiration of A. bisporus. The current study confirmed that the use of plasma modification technology combined with 1.0% COL can be used in preservation packaging by regulating the respiration of A. bisporus, thus extending its shelf life from 7 to 21 days.

Concave Pd core/ island Pt shell nanoparticles (Pd@Pt CINPs) were successfully synthesised and used as catalysts for the glucose oxidation reaction (GOR) and to directly sense D-glucose in phosphate-buffered solutions. The results measured by an electrochemical quartz crystal microbalance (EQCM) indicate that the GOR accelerates from -0.3 V (vs. Ag/AgCl) to 0.2 V and at least 1.0067 μg of glucose reacted with the Pd@Pt CINPs for each catalysis. A favourable comparison shows that 12.9 nm Pd@Pt CINPs have high sensitivity (15.14 μAmM−1 cm-2), which is four times greater than the 3.7 μAmM−1 cm-2 of 9 nm Pt NPs. The greater sensitivity within a linear range of 1–8.5 mM and high stability during repeated GORs indicate that Pd@Pt CINPs are potential non-enzymatic glucose sensors.

We present a new second-order oracle bound for the expected risk of a weighted majority vote. The bound is based on a novel parametric form of the Chebyshev- Cantelli inequality (a.k.a. one-sided Chebyshev's), which is amenable to efficient minimization. The new form resolves the optimization challenge faced by prior oracle bounds based on the Chebyshev-Cantelli inequality, the C-bounds [Germain et al., 2015], and, at the same time, it improves on the oracle bound based on second order Markov's inequality introduced by Masegosa et al. [2020]. We also derive a new concentration of measure inequality, which we name PAC-Bayes-Bennett, since it combines PAC-Bayesian bounding with Bennett's inequality. We use it for empirical estimation of the oracle bound. The PAC-Bayes-Bennett inequality improves on the PAC-Bayes-Bernstein inequality of Seldin et al. [2012]. We provide an empirical evaluation demonstrating that the new bounds can improve on the work of Masegosa et al. [2020]. Both the parametric form of the Chebyshev-Cantelli inequality and the PAC-Bayes-Bennett inequality may be of independent interest for the study of concentration of measure in other domains., Comment: aligned with the camera-ready version published at NeurIPS 2021

Background Due to the occult anatomic location of the nasopharynx and frequent presence of adenoid hyperplasia, the positive rate for malignancy identification during biopsy is low, thus leading to delayed or missed diagnosis for nasopharyngeal malignancies upon initial attempt. Here, we aimed to develop an artificial intelligence tool to detect nasopharyngeal malignancies under endoscopic examination based on deep learning. Methods An endoscopic images-based nasopharyngeal malignancy detection model (eNPM-DM) consisting of a fully convolutional network based on the inception architecture was developed and fine-tuned using separate training and validation sets for both classification and segmentation. Briefly, a total of 28,966 qualified images were collected. Among these images, 27,536 biopsy-proven images from 7951 individuals obtained from January 1st, 2008, to December 31st, 2016, were split into the training, validation and test sets at a ratio of 7:1:2 using simple randomization. Additionally, 1430 images obtained from January 1st, 2017, to March 31st, 2017, were used as a prospective test set to compare the performance of the established model against oncologist evaluation. The dice similarity coefficient (DSC) was used to evaluate the efficiency of eNPM-DM in automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images, by comparing automatic segmentation with manual segmentation performed by the experts. Results All images were histopathologically confirmed, and included 5713 (19.7%) normal control, 19,107 (66.0%) nasopharyngeal carcinoma (NPC), 335 (1.2%) NPC and 3811 (13.2%) benign diseases. The eNPM-DM attained an overall accuracy of 88.7% (95% confidence interval (CI) 87.8%–89.5%) in detecting malignancies in the test set. In the prospective comparison phase, eNPM-DM outperformed the experts: the overall accuracy was 88.0% (95% CI 86.1%–89.6%) vs. 80.5% (95% CI 77.0%–84.0%). The eNPM-DM required less time (40 s vs. 110.0 ± 5.8 min) and exhibited encouraging performance in automatic segmentation of nasopharyngeal malignant area from the background, with an average DSC of 0.78 ± 0.24 and 0.75 ± 0.26 in the test and prospective test sets, respectively. Conclusions The eNPM-DM outperformed oncologist evaluation in diagnostic classification of nasopharyngeal mass into benign versus malignant, and realized automatic segmentation of malignant area from the background of nasopharyngeal endoscopic images.

Hollow core-shell Pt-Ag nanoparticles (NPs) with discontinuous Ag shells were successfully synthesized using a Pt-seed-mediated growth method and used to catalyze electroless copper deposition (ECD). The activities and resulting ECD kinetics of hollow NPs and solid-core Pt-Ag NPs with sizes of 5.9, 9.6, 14.7, and 20.6 nm were compared. The deposition kinetics was investigated using an electrochemical quartz crystal microbalance (EQCM). The induction period for the 7.3 nm hollow NPs, as observed using a potential-deposition time curve, was 5 s, significantly shorter than that of the 5.9 nm solid Pt-Ag NPs (13 s). At a deposition time of 500 s, the mean mass activities in terms of the weight of the catalyst for the hollow NPs and 5.9 nm NPs were determined to be 4.591 and 3.065, respectively. The large hollow NPs with discontinuous Ag shells show a 1.5-fold higher mass activity than that of the 5.9 nm NPs. In a careful comparison based on the same electrochemical surface area (ESA), the specific activities were in the order: hollow NPs > 20.6 nm NPs > 6 nm NPs > 14.7 nm NPs > 9.6 nm NPs, where the hollow NPs show faster deposition (5.88 × 10−9 g m−2 s−1) than the 20.6 nm NPs (5.2 × 10−9 g m−2 s−1).

Background and purpose To evaluate the prognostic value of MRI-detected residual retropharyngeal lymph node (RRLN) at three months after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and second, to establish a nomogram for the pretherapy prediction of RRLN. Materials and methods We included 1103 patients with NPC from two hospitals (Sun Yat-Sen University Cancer Center [SYSUCC, n = 901] and Dongguan People's Hospital [DGPH, n = 202]). We evaluated the prognostic value of RRLN using Cox regression model in SYSUCC cohort. We developed a nomogram for the pretherapy prediction of RRLN using logistic regression model in SYSUCC training cohort (n = 645). We assessed the performance of this nomogram in an internal validation cohort (SYSUCC validation cohort, n = 256) and an external independent cohort (DGPH validation cohort, n = 202). Results RRLN was an independent prognostic factor for OS (HR 2.08, 95% CI 1.32–3.29), DFS (HR 2.45, 95% CI 1.75–3.42), DMFS (HR 3.31, 95% CI 2.15–5.09), and LRRFS (HR 3.04, 95% CI 1.70–5.42). We developed a nomogram based on baseline Epstein–Barr virus DNA level and three RLN status-related features (including minimum axial diameter, extracapsular nodal spread, and laterality) that predicted an individual's risk of RRLN. Our nomogram showed good discrimination in the training cohort (C-index = 0.763). The favorable performance of this nomogram was confirmed in the internal and external validation cohorts. Conclusion MRI-detected RRLN at three months after IMRT was an unfavorable prognostic factor for patients with NPC. We developed and validated an easy-to-use nomogram for the pretherapy prediction of RRLN.

Background: The role of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma (mNPC) patients is unclear. Methods: mNPC patients with biopsy-proven disease, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and 5-fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. The chemotherapy regimens were 5-fluorouracil continuous intravenous infusion at 5 gm/m2 over 120 h and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for six cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Primary endpoint of the study was overall survival (OS). Findings: 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median follow-up duration was 26.7 months (IQR 17.2-33.5). The study met its primary end-point of improved OS (stratified hazard ratio [HR] = 0.42; 95% confidence interval [CI], 0.23-0.77; P = 0.004) in favor of chemotherapy plus radiotherapy. PFS was also improved in the chemotherapy plus radiotherapy group compared to the chemotherapy alone group (stratified HR = 0.36; 95% CI 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxicities were observed between the treatment arms. The frequency of acute ≥grade 3 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 hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Interpretation: Radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive mNPC patients. Trial Registration: This trial was registered as NCT02111460. Funding Statement: Funding was provided by the Program of Sun Yat-Sen University for Clinical Research 5010 Program (No.201310), the National Natural Science Foundation of China (No.81572912, 81772895, 81874134), Guangdong Province Science and Technology Development Special Funds (Frontier and Key Technology Innovation Direction – Major Science and Technology Project) (No. 703040078088), Guangzhou Science and Technology Planning Project - Production and Research Collaborative Innovation Major Project (No. 201505012235268). MC is supported by the National Medical Research Council Singapore Clinician-Scientist Award - #NMRC/CSA/0027/2018 and the Duke-NUS Oncology Academic Program Proton Research Program. This research is also supported by the National Research Foundation Clinical Research Programme Grant (NRF-CRP17-2017-05). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Sun Yat-sen University Cancer Center (SYSUCC). The trial was performed in accordance with the Declaration of Helsinki, and the results are reported according to the CONSORT statement. All participants provided written informed consent.

Pao-Yen Lin,* Yi-Shan Wu* Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan *These authors contributed equally tothis work Background: Studies have examined the association between heroin dependence and serotonin transporter gene polymorphisms but yielded inconsistent results. The purpose of current study is to determine the overall effect of these polymorphisms on the risk for heroin dependence through a meta-analytic method.Methods: A meta-analysis was conducted to examine the association of heroin dependence with two common polymorphisms of serotonin transporter gene, in the promoter (5-hydroxytryptamine transporter-linked promotor region [5-httlpr]) and intron 2 (a various number tandem repeat in serotonin transporter intron 2 [STin2]). Data from studies with 5-httlpr (6 studies) and STin2 (8 studies) were synthesized by random effects model.Results: In the analysis, heroin dependence was found to be significantly associated with the S allele of 5-httlpr (odds ratio [OR] =1.22, 95% confidence interval [CI] =1.08–1.41, P=0.002). The association between the S allele of 5-httlpr and heroin dependence was significant in Caucasian subjects (OR =1.37, 95% CI =1.12–1.68, P=0.003), but not in non-Caucasian subjects. On the other hand, no association with STin2 polymorphism was found (OR =1.14, 95% CI =0.91–1.42, P=0.242).Conclusion: The results suggest an ethnic-specific effect of the 5-httlpr polymorphism on the risk for heroin dependence, but the influence of the genetic variance in the patients with comorbidities or intermediate phenotypes of heroin dependence needs to be further examined. Keywords: ethnicity, heroin, polymorphism, serotonin transporter, STin2

Heterostructured Pd-Pt core-shell nanocubes (NCs) are shown to display catalytic activity in the glucose oxidation reaction (GOR), and were employed as non-enzymatic glucose sensors in 0.1 M NaOH(aq) solution. High-angle annular dark-field transmission electron microscopy and line-scanned energy-dispersive X-ray spectroscopy analyses show that the growth of the Pt shell initially occurs via a layer-by-layer mode, but then switches to the island mode. The voids formed between Pt islands contribute to an increase in the electrochemically active surface area. Based on the same catalyst loading mass, the results of Tafel measurements and cyclic voltammetry indicate that the heterostructured Pd-Pt core-shell NCs (typically 32.7 nm in size) display an exchange current density of 1.81 × 10−2 mA cm−2 for chemisorption and dehydrogenation of glucose at the onset of the GOR, and an activity of 0.322 mA in the subsequent reaction that causes the formation gluconolactone on the Pt-OH surface. These values are larger than those observed for 7.5-nm Pt nanoparticles (1.51 × 10−2 mA cm−2 and 0.187 mA cm-2, respectively). Additionally, the core-shell NCs exhibit a sensitivity of 170 μA∙mM−1∙cm−2 under GOR catalysis conditions, require a potential as low as −0.05 V (vs. Ag/AgCl) which favors selectivity, and have a linear response range that extends from 0.3 to 6.8 mM. The potential of these NCs for use in non-enzymatic sensing of glucose is further exemplified by a successful analysis of spiked calf serum. In our perception, this sensor also has a large potential in glucose fuel cells.

A new eocrinoid locality of the Balang Formation (Cambrian Series 2) near Kaili City is reported. The fauna is associated with index trilobites, such as Redlichia ( Pteroredlichia ) murakamii Resser and Endo in Kobayashi, 1935 and Arthricocephalus chauveaui Bergeron, 1899 , that are common in the Balang Biota (Cambrian Series 2) but absent in the younger Kaili Biota (Cambrian Series 3). This new locality contains a new eocrinoid fauna ( n = 22) that is different from Guizhoueocrinus yui Zhao, Parsley and Peng, 2007a in bearing a smaller theca, a shorter stalk, and a robust attachment disk; thus, a taxon Globoeocrinus zhaoyuanlongensis n. sp. is proposed.

An electrostatic attraction method is utilized for successfully attaching 10 nm Pd nanocubes on reduced graphene nanosheet (RGN) surfaces. The RGNs used to support the Pd nanocubes are prepared via both a sonoelectrochemical method (RGNSECM) and a chemical reduction method (RGNCM). X-ray photoelectron spectroscopic analyses indicate the domination of physical defects and C-OH groups on the surfaces of RGNSECM and RGNCM, respectively. The linear scanning voltammograms, taken using rotating ring-disk electrode analyses in alkaline oxidation-reduction reactions (ORRs), show that the Pd nanocubes supported by RGNSECM (Pd cubes/RGNSECM) and RGNCM (Pd cubes/RGNCM) show improved onset potentials of 0.1 V on the order of Pd cubes/RGNSECM > Pd cubes/RGNCM > Pt/C ∼ Pd/C > Pd nanocubes for their catalytic disk currents in the electron-transfer region. Mass-transfer-corrected Tafel diagrams demonstrate that RGNSECM, which contains a greater number of physical defects, facilitated greater active sites of these Pd nanocubes due to its greater surface area, and thus better promoted ORRs. In terms of the kinetic current density, a greater mass activity (7.85 × 10−2 mA·μg−1) is observed for the Pd cubes/RGNSECM composite. Additionally, the durability test reveals that RGNSECM could provide good strength to stabilize Pd nanocubes during a long ORR period.

Importance The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants 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. Interventions The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2over 120 hours and 100 mg/m2intravenous 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. Main Outcomes and Measures The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results 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. Conclusions and Relevance In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration ClinicalTrials.gov Identifier:NCT02111460

This research is mainly focused on preparing gallic acid (GA) coated, antimicrobial, active packaging, low density polyethylene (LDPE) films by capacitively coupled plasma. Firstly, the suitable plasma treatment condition was 30 W treated for 60 s from the result of appearance and tensile strength. From the result of SEM and ATR-FTIR, the surface roughness increased which facilitated the GA coating and the surface turn smoother after GA coating. In the result of antimicrobial activity, these films is able to reduce the growth of Gram-negative bacterium Escherichia coli and Gram-positive bacterium Staphylococcus aureus about 0.5–0.6 log CFU/mL when GA concentration is above 1%. Between these two microorganisms, the film has more significant inhibition on E. coli than S. aureus due to cell membrane structure differences. These results are first stage in developing antibacterial active packaging for foods preservation.

Nitrogen-doped carbon nanofibers (CNFs) were prepared by an electrospinning method, this followed by a hydrothermal reaction or nitrogen plasma treatment to obtain electrode for non-enzymatic amperometric sensing of H2O2. The hydrothermally treated electrode performs better. Its electrochemical surface is 3.7 × 10-3 mA cm-2, which is larger than that of a nitrogen plasma treated electrode (8.9 × 10-4) or a non-doped CNF (2.45 × 10-4 mA cm-2). The hydrothermally treated CNF with rough surface and a complex profile with doped N has a higher sensitivity (357 μA∙mM-1∙cm-2), a lower detection limit (0.62 μM), and a wider linear range (0.01-0.71 mM) than N-CNFP at a working potential of -0.4 V (vs. Ag/AgCl). The electrode gave high recoveries when applied to the analysis of milk samples spiked with H2O2. Graphical abstract Nitrogen-doped carbon nanofibers prepared by an electrospinning method followed by a hydrothermal reaction (N-CNFht) or nitrogen plasma treatment (N-CNFP) are directly used as non-enzymatic amperometric H2O2 sensors.

Supplemental material, T-Supplementary_Material for The plasma Epstein–Barr virus DNA level guides precision treatment for nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: a large population-based cohort study from an endemic area by Hu Liang, Xing Lv, Lin Wang, Yi-Shan Wu, Rui Sun, Yan-Fang Ye, Liang-Ru Ke, Qin Yang, Ya-Hui Yu, Wen-Ze Qiu, Guo-Ying Liu, Xin-Jun Huang, Wang-Zhong Li, Shu-Hui Lv, Xiang Guo, Yan-Qun Xiang and Wei-Xiong Xia in Therapeutic Advances in Medical Oncology

Nitrogen-doped graphene nanosheet (N-SEGN) with pyrrolic nitrogen and 5-9 vacancy defects has been successfully prepared from a hydrothermal reaction of tetra-2-pyridinylpyrazine and sonoelectrochemistry-exfoliated graphene nanosheet, with point defects. Additionally, based on the same reaction using chemically reduced graphene oxide, nitrogen-doped chemically reduced graphene oxide (N-rGO) with graphitic nitrogen was prepared. The N-SEGN and N-rGO were used as a non-enzymatic H2O2 sensors. The sensitivity of the N-SEGN was 231.3 μA·mM−1·cm−2, much greater than 57.3 μA·mM−1·cm−2 of N-rGO. The N-SEGN showed their potential for being a H2O2 sensor.

Summary Background Cisplatin-based concurrent chemoradiotherapy is currently considered to be the standard treatment regimen for patients with advanced nasopharyngeal carcinoma, but has well known side-effects such as gastrointestinal reactions, nephrotoxicity, and ototoxicity. Nedaplatin was developed to decrease the toxic effects induced by cisplatin, and in this trial we assessed whether a nedaplatin-based concurrent chemoradiotherapy regimen was non-inferior to a cisplatin-based regimen in patients with locoregional, stage II–IVB nasopharyngeal carcinoma. Methods We did an open-label, non-inferiority, phase 3, randomised, controlled trial at two centres in China. Patients aged 18–65 years with non-keratinising stage II–IVB (T1–4N1–3 or T3–4N0) nasopharyngeal carcinoma, a Karnofsky score of at least 70, and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either nedaplatin 100 mg/m 2 or cisplatin 100 mg/m 2 on days 1, 22, and 43 for three cycles concurrently with intensity-modulated radiotherapy. Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre and clinical stage. Patients and clinicians were not masked to treatment allocation. The primary endpoint was progression-free survival at 2 years; non-inferiority was shown if the upper limit of the 95% CI for the difference in 2-year progression-free survival between the two groups did not exceed 10%. Analyses were by both intention to treat and per protocol, including all patients who received at least one complete cycle of chemotherapy. This trial is registered with ClinicalTrials.gov, number NCT01540136, and is currently in follow-up. Findings Between Jan 16, 2012, and July 16, 2014, we randomly assigned 402 patients to nedaplatin-based (n=201) or cisplatin-based (n=201) concurrent chemoradiotherapy. In the intention-to-treat population, 2-year progression-free survival was 89·9% (95% CI 85·8–94·0) in the cisplatin group and 88·0% (83·5–94·5) in the nedaplatin group, with a difference of 1·9% (95% CI −4·2 to 8·0; p non-inferiority =0·0048). In the per-protocol analysis (cisplatin group, n=197; nedaplatin group, n=196), 2-year progression-free survival was 89·7% (95% CI 85·4–94·0) in the cisplatin group and 88·7% (84·2–94·5) in the nedaplatin group, with a difference of 1·0% (95% CI −5·2 to 7·0; p non-inferiority =0·0020). A significantly higher frequency of grade 3 or 4 vomiting (35 [18%] of 198 in the cisplatin group vs 12 [6%] of 200 in the nedaplatin group, p vs four [2%], p=0·0021), and anorexia (53 [27%] vs 26 [13%], p=0·00070) was observed in the cisplatin group compared with the nedaplatin group. 11 (6%) patients in the nedaplatin group had grade 3 or 4 thrombocytopenia compared with four (2%) in the cisplatin group (p=0·065). Patients in the cisplatin group had a higher frequency of any grade or grade 3 or 4 late auditory or hearing toxicities than did patients in the nedaplatin group (grade 3 or 4: three [2%] in the nedaplatin group vs 11 [6%] in the cisplatin group, p=0·030). No patients died from treatment-related causes. Interpretation Our findings show that nedaplatin-based concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy for patients with locoregional, advanced nasopharyngeal carcinoma. Further investigations are needed to explore the potential use of this treatment as induction or adjuvant chemotherapy or in combination with other agents. Funding National Key R&D Program of China, National Natural Science Foundation of China, Sun Yat-sen University Clinical Research 5010 Program, Sci-Tech Project Foundation of Guangzhou City, National Key Basic Research Program of China, Special Support Plan of Guangdong Province, Sci-Tech Project Foundation of Guangdong Province, Health & Medical Collaborative Innovation Project of Guangzhou City, National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, PhD Start-up Fund of Natural Science Foundation of Guangdong Province, Cultivation Foundation for the Junior Teachers in Sun Yat-sen University, and Fundamental Research Funds for the Central Universities.

Background Available data in the literature comparing different induction chemotherapy (IC) regimens on locoregionally advanced nasopharyngeal carcinoma (NPC) are scarce. The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane, cisplatin and 5-fluorouracil (TPF) or cisplatin and 5-fluorouracil (PF) as IC followed by concurrent chemoradiotherapy (CCRT). Methods In total, 1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study. We compared overall survival (OS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival, using the propensity score method. Results In total, 1256 patients received TPF or PF as IC backbone. The TPF group showed significantly better OS (hazard ratio [HR], 0.660; 95% confidence interval [CI] 0.442–0.986; P = 0.042), DSS (HR, 0.624; 95% CI 0.411–0.947; P = 0.027) and DMFS (HR, 0.589; 95% CI 0.406–0.855; P = 0.005) compared with the PF group in multivariable analyses. Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS (88.1% vs. 80.7%; P = 0.042), DSS (88.5% vs. 80.7%; P = 0.021) and DMFS (87.9% vs. 78.6%; P = 0.012) rates compared with the PF group. There were no significant differences in locoregional relapse-free survival before or after matching. Conclusions In our study, IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen. However, a prospective randomized clinical trial to validate these findings is necessary.

Background: Brain-derived neurotrophic factor (BDNF) is known related to the psychopathology of bipolar disorder. However, the results of the relationship between BDNF levels and bipolar disorder were inconsistent. In this study, we aimed to investigate the relationship between BDNF levels, the different phases and clinical phenotypes of bipolar disorder. Methods: Over a 4-year period, bipolar patients in different disease phases, including mania phase, depressive phase and remission, were recruited. All participants had peripheral blood drawn to analyze the serum BDNF levels. We also investigated the relationships between serum BDNF levels, violence, suicidal behavior and Young Mania Rating Scale score (YMRS) before and after 4-week treatment. Results: A total of 102 participants in different disease phases, including acute mania (n=44), acute depressive episode (n=20) and remission (n=38) of bipolar disorder were invited for this study. The serum BDNF levels of patients with acute mania or depressive phases were significantly lower than bipolar patients in remission phases using ANCOVAs with age and sex adjustment (mania: p=0.013, depression: p=0.003, respectively). Bipolar mania patients with violence had lower BDNF levels than those without violence (p=0.025). Among 42 followedup patients, increased BDNF level from baseline was noted after one-month treatment, but there is not statistically significant by means of paired t test (mania: p=0.845 and depression: p=0.931, respectively). Conclusions: Our study found that lower serum BDNF levels are strongly associated with the depressive and manic phase of bipolar disorder than remission phase. In addition, bipolar mania patients with violence had lower BDNF levels than those without violence. In the future, it needs a large sample to prove these results.

Background: Bilateral lesions of nucleus tractus solitarii in rat result in acute hypertension, pulmonary edema, and death within hours. The hypertension results from excessive catecholamine release. Catecholamine can activate connexin43 to regulate cell death. There is no study investigating the cardiopulmonary impacts of different adrenergic blockers and apoptosis mechanism in rat model. Methods: The authors microinjected 6-hydroxydopamine into nucleus tractus solitarii of the rat (n = 8 per group) and evaluated the cardiopulmonary changes after treatment with different concentrations of α1-blockers, α2-blockers, β-blockers, and α-agonists. Results: In the rat model, the authors found that prazosin (0.15 mg/kg) treatment could preserve cardiac output and reverse neutrophil infiltrations in lungs and lead to prevent pulmonary hemorrhagic edema. The time-dependent increases in connexin43 and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells induced by 6-hydroxydopamine lesions were decreased after prazosin treatment (terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells at 6 h: 64.01 ± 2.41% vs. 24.47 ± 3.10%; mean ± SD, P < 0.001, in heart, and 80.83 ± 2.52% vs. 2.60 ± 1.03%, P < 0.001, in lung). However, propranolol caused further compromise of the already impaired cardiac output with consequence of rapid death. Phenylephrine enhanced the phenotype in the link between connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells but not yohimbine. Connexin43 expressions and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells were more decreased with prazosin (0.15 and 0.3 mg/kg) than that with prazosin (0.05 mg/kg) treatment. Conclusions: α1-Receptors are the keystones of the phenotype. In some brainstem encephalitis and brain injury with nucleus tractus solitarii involvement, early α1-receptor blockade treatment may prevent acute death from tissue apoptosis. α-Blockers can also decrease cerebral perfusion pressure, and further studies are needed in translation to brain injury with increased intracranial pressure.

Among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. However, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. We investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model.Treatment study.Research laboratory.Sprague-Dawley rats.We microinjected 6-hydroxydopamine or vitamin C into nucleus tractus solitarii of the rat and evaluated the cardiopulmonary changes after treatment with ganglionic blocker.The time course of changes in the heart and lungs of rats with brainstem lesions were investigated. Rats were administered 6-hydroxydopamine to induce brainstem lesions, causing acute hypertension in 10 minutes and acute elevations of catecholamines accompanied by acute cardiac dysfunction and increased strong expressions of connexin 43 gap junction protein in heart and lung specimens by immunohistochemical staining within 3 hours. Severe pulmonary hemorrhagic edema was produced within 6 hours, and the rats expired rapidly within 7 hours. After hexamethonium treatment, it was found that the acute hypertension induced by 6-hydroxydopamine lesions was immediately reversed and the acute high rise of catecholamine serum level was significantly attenuated within 3 hours, accompanied by preserved cardiac output and decreased expressions of connexin 43 in the heart and lungs. No pulmonary edema occurred and the rats survived for more than 14 hours.Early hexamethonium treatment attenuates acute excessive release of catecholamines to prevent cardiac dysfunction and pulmonary edema for increasing survival rate.

To investigate the relationship between the pretreatment body mass index (BMI) and the clinical outcomes in patients with locoregionally advanced nasopharyngeal carcinoma treated with combination of chemotherapy and radiotherapy.From August 2002 to April 2005, 400 patients with stage III or stage IVa nasopharyngeal carcinoma were recruited for a randomised clinical trial of induction chemotherapy combined with radiotherapy or concurrent chemoradiotherapy. The patients were divided into four groups of underweight (BMI18.5kg/m(2)), normal weight (BMI 18.5-22.9kg/m(2)), overweight (BMI 23.0-27.4kg/m(2)) or obese (BMI≥27.5kg/m(2)) according to the World Health Organization classifications for Asian populations. The differences in the long-term survival, of these four BMI groups were analysed.The 5-year failure-free survival rates for the underweight, normal weight, overweight and obese groups were 44%, 61%, 68% and 73%, respectively (p=0.014), and the 5-year overall survival rates were 51%, 68%, 80% and 72% (p=0.001), respectively. BMI was a strongly favoured prognostic factor of overall survival and failure-free survival in a Cox regression model.Pretreatment body mass index was a simple, reliable independent prognostic factor for patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Yu Lee,1 Yi-Shan Wu,1 Chih-Yen Chien,2 Fu-Min Fang,3 Chi-Fa Hung1 1Department of Psychiatry, 2Department of Otolaryngology, 3Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China Objective: The purposes of this study are 1) to estimate the prevalence of common mental disorders including depressive disorder in patients with head and neck cancer (HNC) at baseline and at the 6-month follow-up and 2) to test the validity of two self-reported questionnaires, theHospital Anxiety and Depression Scale (HADS) and the Taiwanese Depression Questionnaire (TDQ), for screening depression in patients with HNC. Methods: Participants were recruited from the outpatient collaborative care clinic for HNC of a tertiary hospital in Taiwan between January 2010 and January 2011. Ninety-three patients with HNC were enrolled and assessed using the HADS, TDQ, and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Patient edition, at baseline and at the 6-month follow-up. Conventional validity indices of the HADS and TDQ were examined. Results: Our results showed that the validity of the TDQ was satisfactory and comparable to that of both the HADS depression subscale and the HADS total scale. The cutoff scores of the HADS and TDQ for screening possible depressive disorders were 8 and 15, respectively. The areas under the receiver operating characteristic curve of the HADS and TDQ were mean 0.975±0.015 and 0.966±0.019, respectively. Thirteen participants (14%) were diagnosed with depressive disorders at the 6-month follow-up, compared with 8.5% at baseline. Conclusion: Our results indicate that both the HADS and TDQ are valid instruments for screening depression in patients with HNC. Keywords: head and neck cancer, Hospital Anxiety and Depression Scale, Taiwanese Depression Questionnaire, validity, prevalence

Background The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. Methods Patients with stage III–IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m2 cisplatin every 3 weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m2 d1) and fluorouracil (800 mg/m2 civ d1–5) every 3 weeks for two cycles before CCRT. The primary end-point was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary end-point was overall survival (OS). Survival curves for the time-to-event endpoints were analyzed by the Kaplan–Meier method and compared using the log-rank test. The P value was calculated using the 5-year endpoints. Results Four hundred seventy six patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77–0.87) than the control arm (74.1%, 95% CI = 0.68–0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% versus 88.5%, P = 0.815; LRRFS: 94.3% versus 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P Conclusion NACT improved tumour control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in OS. Longer follow-up is needed to determine the eventual therapeutic efficacy.

Yi-Shan Wu,1 Pao-Yen Lin,1,2 Chih-Yen Chien,3 Fu-Min Fang,4 Nien-Mu Chiu,1 Chi-Fa Hung,1 Yu Lee,1 Mian-Yoon Chong11Department of Psychiatry, 2Institute for Translational Research in Biomedical Sciences, 3Department of Otolaryngology, 4Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, TaiwanObjective: We aimed to assess psychiatric morbidities of patients with head and neck cancer (HNC) in a prospective study at pretreatment, and 3 and 6 months after treatment, and to compare their health-related quality of life (HRQL) between those with and without depressive disorders (depression).Materials and methods: Patients with newly diagnosed HNC from a tertiary hospital were recruited into the study. They were assessed for psychiatric morbidities using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Their HRQL was simultaneously evaluated using the quality of life questionnaire of the European Organisation for Research and Treatment of Cancer with a specific module for head and neck cancer; and depressed and nondepressed HNC patients were compared by using the generalized mixed-effect model for repeated measurements.Results: A total of 106 patients were recruited into this study. High rates of anxiety were found at pretreatment, but steadily declined over time (from 27.3% to 6.4%, and later 3.3%). A skew pattern of depression was observed, with prevalence rates from 8.5% at pretreatment to 24.5% and 14% at 3 and 6 months, respectively, after treatment. We found that loss of sense (P=0.001), loss of speech (P

The authors applied independent component analysis to oscillations of heart rate and blood pressure and obtained a new index of sympathovagal balance. The performance of this index was tested in patients with carotid artery stenting and in the EuroBavar data set according to the following criteria: (1) the index should vary similarly among subjects in response to different autonomic conditions; (2) the variability in the index among subjects exposed to the same autonomic conditions should be small; and (3) the response of the index to various autonomic conditions should reflect the underlying changes in the physiological state and have a meaningful interpretation. The new index from independent component analysis better fulfilled the criteria than the commonly used sympathovagal index, the ratio of low-to-high frequency spectra power of heart rate variability, and had higher discrimination power in distinguishing the autonomic status of the patients who had undergone carotid artery stenting from that of the control subjects.

Downregulation of hSSB1, a single-stranded DNA-binding protein, causes increased radiosensitivity, defective checkpoint activation and genomic instability. However, the mechanisms of hSSB1 function in these responses remain to be uncovered. Here, we present evidence that hSSB1 directly binds p21 and this interaction may prevent p21 from ubiquitin-mediated degradation. Furthermore, both promotion of the G1/S transition and abrogation of the G2/M checkpoints induced by hSSB1 knockdown are partially dependent on p21. Most importantly, hSSB1 and p21 levels are positively correlated in human hepatocellular carcinomas (HCC), as determined by immunostaining. Therefore, hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as HCC.

Baroreflex sensitivity is recognized for its prognostic relevance to cardio-vascular and cerebro-vascular risks. However, little is known about the long-term outcome of baroreflex function in patients with carotid stenosis undergoing carotid stenting. Heart rate variability and cardio-vascular autonomic function, including baroreflex sensitivity, were examined using non-invasive methods in 22 adult patients who underwent carotid stenting. They were compared with the normal control group with 22 sex- and age-matched normal volunteers and the risk control group with 10 adult patients with severe stenosis or even total occlusion of the carotid artery without stenting. The groups of patients with stenting and risk controls had significantly reduced valsalva ratio and baroreflex sensitivity measured by the valsalva method compared to normal controls. However, there was no significant difference between patients with stenting and risk controls. There was significant decrease in heart rate response to deep breathing and to head-up tilt in patients with carotid stenting compared to normal controls. Other parameters of cardio-vascular autonomic function showed no difference among the three groups. Reduced baroreceptor function in patients with carotid stenting may be due to underlying diseases rather than the stenting itself. There was no short-term parasympathetic hyperactivity after the stenting, suggesting that the effect is transient rather than permanent.

Background: In the intensity-modulated radiotherapy (IMRT) era, the survival benefit of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains undetermined. This study aimed to evaluate the benefits of IMRT with concurrent chemotherapy compared with IMRT alone for LA-NPC patients with different plasma Epstein–Barr virus (EBV) DNA levels. Methods: Patients were identified from a prospectively maintained database in an endemic area between November 2002 and December 2013. Cox proportional hazards models, propensity score matching, and inverse probability weighting models were established for survival analysis. Stratification analysis was performed based on interaction effects analysis. Finally, sensitivity analysis was performed considering unmeasured confounders. Results: A total of 1357 eligible patients were enrolled (median follow up 62.4 months; range 3.5–155.8 months). No significant survival differences were observed between groups in the entire cohort. Notably, a significant interaction effect was observed between treatment regimens and EBV DNA levels. In patients with high EBV DNA levels (>4000 copies/ml), all three models showed that IMRT with concurrent chemotherapy significantly improved overall survival [hazard ratio (HR) 2.521, 95% confidence interval (CI) 1.218–5.216], disease-free survival (HR 2.168, 95% CI 1.349–3.483), and distant metastasis-free survival (HR 2.331, 95% CI 1.194–4.551) compared with IMRT alone. No differences were found in patients with low EBV DNA levels. Sensitivity analysis confirmed the robustness of the results. Conclusion: In the IMRT era, concurrent chemotherapy treatment of LA-NPC patients with high EBV DNA levels is reasonable. However, the optimal regimen for LA-NPC patients with low EBV DNA levels needs further validation in randomized clinical trials.

This research intends to investigate the patent activity on water pollution and treatment in China (1985-2007), and then compares the results with patents data about Triadic patents, South Korea, Brazil and India over the same periods, patents data were collected from Derwent World Patents Index between 1985 and May 2008. For this study, 169,312 patents were chosen and examined. Total volume of patents, technology focus, assignee sector, priority date and the comparison with other countries are analyzed. It is found that patents on water pollution and treatment filed at China have experienced a remarkable increase and the increase rate of patents filed at China change simultaneous with the percentage of domestic applications. However, the number of high quality Triadic patents with priority country as China remains small. Furthermore, in addition to individual patent assignees, both Chinese universities and enterprises also play important roles in patent activity of water pollution and treatment. In addition, the pattern of South Korea's development can provide short-term implications for China and the regularity in Triadic patents' development can provide some guidance to China's long-term development. In contrast, the development pattern of Brazil and India is less influential to China's devel- opment. Furthermore, China's technology focuses on water pollution and treatment seem to parallel global and triadic patent trends. This research provides a comprehensive picture of China's innovation capability in the area of water pollution and treatment. It will help China's local governments to improve their regional S&T capability and will provide support the National Water Pollution Control and Treatment Project in China.

GNPs (gold nanoparticles) as an eye-catching sensor rely on the high extinction coefficients and the shift of the surface plasmon band which signals the disperse-to-aggregate transformation. The selectivity of the sensors is dictated by the surface functionality whose density presumably has a positive correlation with the sensitivity toward the targeted analyte. To improve the analytical performance, most efforts in this research field focus on the design and synthesis of the sensing elements as well as on the increase in density on GNPs. Proposed here is an alternative rationale that the further improvement of the GNP sensitivity can be achieved by minimizing the electrostatic repulsion and hence the energy barrier for the recognition event to take place. Our model system begins with thioctic acid-stabilized GNPs which are subsequently modified with 15-crown-5 ether for the recognition toward K (+). For a given coverage of 15-crown-5 ether, the limits of detection (LODs) can be improved by more than 3 orders of magnitude via adjusting the solution pH and ionic strength which we suggest a general guideline for the optimization of a new GNP sensing scheme. Following this guideline, satisfactory performance with LODs at the micromolar level can be systematically and efficiently found for GNPs with a range of 15-crown-5 ether coverage.

A large number of patients with neurosyphilis present dementia with a progressive course and psychiatric symptoms such as depression, mania, and psychosis. Despite prompt and proper antibiotic treatment, the recovery is often incomplete, especially when tissue damage has occurred. We reported a patient with persisted cognitive decline associated with neurosyphilis that improved substantially after donepezil therapy. A 43-year-old man manifested significant psychiatric symptoms such as mania, psychosis, and cognitive impairment due to neurosyphilis. Subsequently, the patient was treated with antipsychotics and donepezil concurrent with an adequate antibiotic treatment for neurosyphilis. During the 1-year follow-up, his rapid plasma reagin titer approached from 1:256 to 1:64. His Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale scores improved from 12 to 25 and 42.3 to 6.3, respectively, after a 6-month donepezil treatment. Donepezil was discontinued. Three months later, worsening of cognitive impairment (MMSE score, 23) was noted. After donepezil was started again for 3 months, his MMSE score improved to 26. Persistent cognitive impairment is commonly associated with neurosyphilis despite adequate penicillin treatment. Treatment of the cognitive impairment is important but difficult. Cholinergic pathways are considered as involving in the cognitive deficit induced by neurosyphilis and donepezil, a cholinesterase inhibitor, which may be useful for the improvement of cognition. In this case report, we described for the first time the successful use of donepezil in treating cognitive impairment associated with neurosyphilis. The role of cholinesterase inhibitors in the treatment of cognitive impairments caused by neurosyphilis needs further studies.

BACKGROUND This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC). METHODS The nomogram was based on a retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided. RESULTS Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort. CONCLUSIONS The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.

We report a novel missense mutation, D678H, in the APP gene in a Taiwanese patient who had progressive cognitive decline beginning in middle age. Brain MRI showed leukoencephalopathy, cortical microhemorrhages and focal superficial cortical hemosiderosis, which are consistent with cerebral amyloid angiopathy. A phenotype of combined dementia and cerebral microvasculopathy suggested concurrent increases in brain parenchymal and cerebrovascular beta-amyloid peptide (Aβ) deposition in this patient. The promotion of Aβ aggregation has been postulated to underlie the pathogenic mechanism of the mutation.

Restricted sensory syndrome provides an excellent chance for the understanding of neuroanatomic correlation. The trigeminal nerve has been shown to convey buccal sensory impulse to central compartment. However, the pathway between cortex and the trigeminal sensory nucleus remains largely unknown.A patient presented with cheirobuccopedal syndrome, or objective sensory impairment confined to the left intraoral cheek, hand and foot, was reported.Decrease in pinprick pain and fine touch sensation was detected at the left intraoral cheek, hand and foot. A recent infarction was disclosed at the left paramedian pons. The foregoing hypalgesia and hypesthesia recovered within one month after onset.The trigeminobuccal sensory tracts are deemed to run in parallel with other spinothalamic and trigeminothalamic tracts within the brainstem. The rarity of buccal sensory deficit upon brainstem damage may be due to dispersion of the trigeminobuccal sensory tracts on their way of ascending, or their relatively high tolerance to different insults.