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Functional circular RNAs have been extensively studied in eukaryotes and progressively discovered in archaea, but not been identified in bacteria except some byproducts of self-spliced introns, devoid of biological function. In this study, using an experimental and computational pipeline, we confirm that a regulatory noncoding RNA DucS exists in both linear and circular conformations in Bacillus altitudinis. The 3’ end sequences of linear RNA are critical to RNA circularization. DucS promotes the tolerance of host to H2O2 stress through its linear forms, partly due to upregulating the translation of a stress-responsive gene htrA, whereas its circular forms can promote the degradation of linear cognates. Through re-evaluating published RNA-seq data from 30 bacteria and experimental identification, we demonstrate that circular RNAs also exist in other bacteria, occurred unexpectedly in some well-known noncoding RNAs. Our results reveal firstly a functional circular RNA in bacteria, highlighting the universal existence of functional circular RNAs in all three domains of life.

A novel hot embossing process was used to construct a dense carbon fiber powder (CFP) network in the polydimethylsiloxane (PDMS) matrix of the PDMS/CFP composite, which was investigated experimentally. The results demonstrated that the addition of the filler and the decrease in sample thickness resulted in a significant increase in the thermal conductivity (TC) of the PDMS composites. TC of up to 19.325 W/(mK), which is as high as that of stainless steel (1Cr18Ni9Ti), was achieved at a filler content of 60 wt% and a thickness of 0.2 mm. A mathematical model for predicting TC was established, and the filler content, compression coefficient, and interfacial thermal resistance were systematically discussed. In addition, finite element analyses were performed to predict the TC of the PDMS/CFP composites with various thicknesses and filler contents. The numerical and theoretical results were in agreement with the experimental results. Finally, the PDMS composite was tested as a heat spreader, which significantly reduced the temperature.

With the development of the multi-media internet, visual characteristics have become an important factor affecting user interests. Thus, incorporating visual features is a promising direction for further performance improvements in click-through rate (CTR) prediction. However, we found that simply injecting the image embeddings trained with established pre-training methods only has marginal improvements. We attribute the failure to two reasons: First, The pre-training methods are designed for well-defined computer vision tasks concentrating on semantic features, and they cannot learn personalized interest in recommendations. Secondly, pre-trained image embeddings only containing semantic information have little information gain, considering we already have semantic features such as categories and item titles as inputs in the CTR prediction task. We argue that a pre-training method tailored for recommendation is necessary for further improvements. To this end, we propose a recommendation-aware image pre-training method that can learn visual features from user click histories. Specifically, we propose a user interest reconstruction module to mine visual features related to user interests from behavior histories. We further propose a contrastive training method to avoid collapsing of embedding vectors. We conduct extensive experiments to verify that our method can learn users' visual interests, and our method achieves $0.46\%$ improvement in offline AUC and $0.88\%$ improvement in Taobao online GMV with p-value$

To enhance the thermal conductivity of polymers, a polymer composite system is an effective method, where types of thermally conductive fillers are often introduced into the polymer matrices to form special paths for the phonons or electrons. After years of studies, it can be concluded that selective fillers of different aspect ratio, size, and content and tailoring methods of filler network often result in multiple arrangements of filler network in space, which greatly affect the thermal conductivity of polymer composites. Thus, in this review, we summarize the main affecting factors of filler network, including the types, sizes, and shapes of fillers. Later, we discuss the latest progress of approaches to tailor the filler networks and outline the challenges and prospects of thermally conductive polymer composites.

PurposeTo determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs).MethodsContinuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR.ResultsA total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11–20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079–4.881) and RFS (HR = 2.126, 95% CI 1.038–4.356) compared with the TTR of 10–20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10–20 weeks.ConclusionThere exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.

Background The outbreak of COVID-19 pandemic in China has greatly impacted the radiotherapy (RT) strategy for breast cancer (BC) patients, which might lead to an increased distressing psychological symptom. Thus, we perform a multi-center cross-section survey aiming to investigate the prevalence of fears of cancer recurrence (FCR) and explore predictors for FCR in BC patients referred for RT during pandemic. Methods: 542 BC patients who referred for RT between 24th Jan and 30th April 2020 during pandemic were consecutively enrolled from 14 hospitals around China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ sociodemographic, treatment information as well as psychological characteristics were collected using an information sheet, Fear of progression questionnaire-short form (FoP-Q-SF), Hospital Anxiety and Depression Scale (HADS) and EORTC QLQ-C30. The influence of pandemic on RT schedule was divided into four categories: “delay” was defined as >12 weeks from surgery to RT in patients without chemotherapy or >8 weeks from last time of anti-tumor therapy (including chemotherapy and surgery) to RT in patients with chemotherapy; “Special normal” was defined that patients themselves believed to have delayed RT initiation but actually not; “Interruption” was defined as any unplanned gaps in original RT regime and all other would be classified into “normal”. Another type of influence on RT strategy was that patients had to shift planned RT hospital from Grade-A tertiary hospital to local hospitals. Univariable analyses of FCR were performed in a one-way analysis of variance (ANOVA) or student t-test or Pearson correlation analyses and candidate variables with P Citation Format: Jinrong Xie, Weixiang Qi, Lu Cao, Yuting Tan, Jin Huang, Xiaodong Gu, Bingguang Chen, Peipei Shen, Ying Zhang, Qingwen Zhao, Hecheng Huang, Yubin Wang, Haicheng Fang, Zhenjun Jin, Hui Li, Xuehong Zhao, Xiaofang Qian, Feifei Xu, Dan Ou, Shubei Wang, Cheng Xu, Min Li, Zefei Jiang, Yu Wang, Xiaobo Huang, Jiayi Chen. Predictors for fear of cancer recurrence in breast cancer patients referred for radiation therapy during the COVID-19 pandemic: A multi-center cross-section survey [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-07.

INTRODUCTION Thalassemia traits and iron deficiency anemia are the most common types of hypochromic microcytic anemia with similar clinical and laboratory features. It is vital to establish a new screening model based on HbA2 levels and red cell indices for the differentiation of TT from IDA in hypochromic microcytic anemia cases. METHOD The data comprised of the red blood cell indices and HbA2 prenatal diagnostic test results of 810 individuals who were identified to conform to the following criteria: MCV

A cyclometallated phosphorescent iridium-based probe to detect CN- was prepared through a cyanide alcoholize reaction based on the C^N type main ligand and N^N type ancillary ligand (2-phenyl pyridine and 1,10-phenanthroline-5-carboxaldehyde, respectively). The efficient probe exhibited good sensitivity in response to CN- in an CH3CN and H2O (95/5) mixture within a 1.23 μM detection limit. The response of PL is directly in line with the concentration of CN- from 0 to 2.0 equiv. The PL investigation of other reactive anions proved the great selectivity to CN-. Additionally, upon adding 1.0 equiv. of cyanide, the formation of cyanohydrin was correctly elucidated in 1H NMR, FT-IR, and mass spectra studies. The conspicuous results indicate that the iridium complex has the potential possibility of application in other biosystems related to CN-.

Purpose. A survival benefit of breast-conserving therapy (BCT) over mastectomy has been shown in recent studies. This study aimed to explore differences in recurrence patterns between BCT and mastectomy and clarify the contribution of radiotherapy (RT) to the survival benefit of BCT. Methods. Consecutive patients with pT1-2/pN0-1/M0 breast cancer between 2009 and 2015 in our institution were retrospectively reviewed and compared in matched cohorts using 1 : 1 propensity score matching (PSM). Results. A total of 2370 patients were enrolled with a median follow-up of 75 (3–148) months. In the cohort without regional nodal irradiation (RNI), WBI was associated with significantly increased 10-year relapse-free survival (RFS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS) compared with mastectomy alone. There were 419 pairs in the cohort without RNI and 87 pairs in the cohort with RNI after PSM. In the PSM cohort, improved 10-year RFS (95.4% vs. 82.7%, p < 0.05 ), DMFS (97.4% vs. 84.1%, p < 0.05 ), and RRFS (99.1% vs. 95.5%, p < 0.05 ) were observed in WBI compared with mastectomy alone. Regarding the first recurrence event, WBI demonstrated a significantly lower cumulative rate of distant metastases than mastectomy alone. There was no significant difference in survival outcomes between WBI plus RNI and PMRT before and after the PSM. In patients without RNI, mastectomy alone was significantly associated with unfavorable RFS (HR = 2.3, 95% CI 1.2–4.5, p < 0.05 ) and DMFS (HR = 2.5, 95% CI 1.1–5.8, p < 0.05 ). Conclusion. This study found the benefit of RFS and DMFS in BCT patients compared with those treated with mastectomy without RNI but not in those treated with RNI. We hypothesized that RT played an important role in reducing the risk of regional recurrence and distant metastases.

Multi-scenario Learning to Rank is essential for Recommender Systems, Search Engines and Online Advertising in e-commerce portals where the ranking models are usually applied in many scenarios. However, existing works mainly focus on learning the ranking model for a single scenario, and pay less attention to learning ranking models for multiple scenarios. We identify two practical challenges in industrial multi-scenario ranking systems: (1) The Feedback Loop problem that the model is always trained on the items chosen by the ranker itself. (2) Insufficient training data for small and new scenarios. To address the above issues, we present ZEUS, a novel framework that learns a Zoo of ranking modEls for mUltiple Scenarios based on pre-training on users' spontaneous behaviors (e.g. queries which are directly searched in the search box and not recommended by the ranking system). ZEUS decomposes the training process into two stages: self-supervised learning based pre-training and fine-tuning. Firstly, ZEUS performs self-supervised learning on users' spontaneous behaviors and generates a pre-trained model. Secondly, ZEUS fine-tunes the pre-trained model on users' implicit feedback in multiple scenarios. Extensive experiments on Alibaba's production dataset demonstrate the effectiveness of ZEUS, which significantly outperforms state-of-the-art methods. ZEUS averagely achieves 6.0%, 9.7%, 11.7% improvement in CTR, CVR and GMV respectively than state-of-the-art method.

Patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) were assigned to dose and volume de-escalated intensity-modulated radiation therapy (IMRT) based on response to induction chemotherapy (IC) to limit treatment related toxicity while preserving efficacy.A single-arm de-escalated phase II trial was performed in this study. Patients with LANPC received two cycles of IC with docetaxel 60 mg/mBetween January 2010 and November 2013, 48 and 83 eligible patients with stage III and IVA-B NPC were accrued to this trial. With a median follow-up of 92 months, the 5-year and 8-year estimated PFS were 89.6% and 76.0%, 63.9% and 58.0% for patients with stage III and IVA-B disease, which were all improved in comparison with historical controls. Grade 3 acute mucositis were developed in 27.5% patients. Cranial neuropathy and asymptomatic temporal lobe necrosis were found in 2.3% and 1.5% patients.Dose and volume de-escalated IMRT was associated with high PFS and mild late neurological toxicities for IC responders. Further exploration of de-escalation strategies in appropriate patients is needed.Clinical trials.gov identifier: NCT03389295.

IntroductionShort course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40–42.5 Gy in 15–16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique.Methods and analysisThis is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life.Ethics and disseminationThe study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03829553.

A convenient and efficient strategy for detecting cancer cells at preclinical stages is one of the dominant challenges in early cancer diagnostics. In this work, a sandwich-type cytosensor was structured to analyze cancer cells based on metal organic framework PCN-224 and DNA tetrahedron linked dual-aptamer. Firstly, the tetrahedral DNA nanostructures linked dual aptamers (AS1411 and MUC1) immobilizing on the gold electrode (GE) surface as bio-recognition elements can capture the MCF-7 cancer cells and improve the density and orientation of surface nanoprobes. Then, the novel metal organic framework PCN-224 homogeneously decorated by Pt nanoparticles was modified by the G-quadruplex/hemin DNAzyme, horseradish peroxidase (HRP) and dual-aptamer. The fabricated nanoprobes were applied to catalyze the oxidation of hydroquinone (HQ) with hydrogen peroxide (H2O2) for amplifying the electrochemical signal. The results indicated that the linear response of the aptasensor ranged from 20 to 1 × 107 cells/mL and the detection limit was 6 cells/mL. Finally, we performed an electrochemical reductive desorption to break gold thiol bond and release all compounds on the electrode surface for analyzing the viability of collected cells and regenerating the cytosensor. This work can be extended to other cancer cells by using specific type aptamers and has widely applications prospect in point-of-care cancer diagnosis.

Developing highly sensitive and selective detection strategies for biomarkers is beneficial for fundamental research and disease diagnosis. Herein, we constructed a sandwich-type electrochemical aptasensor to detect the breast cancer cell biomarker Human Epidermal Growth Factor Receptor 2 (HER2). The aptasensor was a combination of tetrahedral DNA nanostructures (TDNs)–aptamer as recognition probes and flower-like nanozymes/horseradish peroxidase (HRP) as signal nanoprobes. In the process of assembling the biosensor, the TDN–aptamer 1 as a bio-recognition element was immobilized on the gold electrode (GE) surface for capturing the biomarker HER2. The nanozyme Mn3O4 was decorated by Pd@Pt nanozymes which were linked by the aptamer 2 and natural enzyme HRP. The designed Mn3O4/Pd@Pt/HRP nanoprobe (nanoprobe 1) was used to amplify the biosensor signal via catalyzing the oxidation of hydroquinone (HQ) with hydrogen peroxide (H2O2). After binding HER2, an aptamer–protein–nanoprobe sandwich system was fabricated on the GE surface. Lastly, a Pd@Pt/HRP/complementary DNA (cDNA) nanoprobe (nanoprobe 2) was added on the surface of nanoprobe 1 through DNA hybridization of aptamer 2 and cDNA to form a dendritic DNA nanostructure to further amplify the signal significantly. The results indicate that the aptasensor shows a broad linear response from 0.1 to 100.0 ng mL−1 and the low detection limit is 0.08 ng mL−1. The designed approach holds great potential for the construction of various aptasensors for the effective and convenient detection of different biomarkers.

5538 Background: To assess the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma (Chinese Clinical Trial Registry number, ChiCTR2000032879). Methods: Twenty-two locally advanced cervical cancer patients, regardless of programmed death ligand-1 status, received toripalimab treatment combined with concurrent chemoradiotherapy. Concurrent chemoradiotherapy(CCRT) includes cisplatin (40 mg/m2, once a week for 5 weeks), radiotherapy (external irradiation 45-50.4Gy/25-28Fx, 5 fractions a week, followed by brachytherapy 24-30Gy/3-5Fx) and toripalimab (240mg on days 1, 22 and 43). The primary end-point was safety and feasibility. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), overall survival (OS). Results: The median age was 55 years old (range, 42 to 72 years old), with 2 patients in FIGO stage II, 15 patients in stage IIIC, and 5 patients in stage IVA. All patients have received CCRT successfully. Grade III and higher adverse events (AEs) were observed in 10 patients (10/22, 45.5%), and no patient had a grade V AE. The most frequent grade III AE was leukopenia (8/22, 36.4%). The most common immunotherapy-related adverse reaction was hypothyroidism (2/22, 9.1%). The 3-month ORR rate was 95.5%. At data cutoff (Jan 31, 2022), the median follow-up was 10 months (range, 3.30 to 16.73 months). One patient developed multiple metastases 3 months after treatment, and 1 patient developed lung metastasis 6 months after treatment. The ORR was 100%, while the PFS rate was 90.1%, and the OS rate was 95.5%. Conclusions: Toripalimab combined with concurrent chemoradiotherapy demonstrated a manageable safety profile and promising anti-tumor activity in patients with locally advanced cervical cancer, thus might represent a novel treatment option for this patient population. Longer follow-up results and further phase II/III studies are expected. Clinical trial information: ChiCTR2000032879.

ObjectiveThe outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic.Methods542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed.Results488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (pConclusionsRT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.

Radiation-induced heart disease (RIHD) leads to myocardial dysfunction and metabolic abnormalities in patients treated with thoracic irradiation which restricts the long-term survival benefits of radiotherapy. There is no specific or effective manner of intervention currently available. Asparaginyl endopeptidase (AEP) plays a pivotal role in the maintenance of cellular functions through regulating proteolytic cleavage as peptidase enzyme. We aimed to investigate the role of unique cardiac AEP in cardiac function by modulating key signaling elements in the myocardium. The murine heart was exposed to a single dose of 14 Gy radiation. Cellular signaling and apoptosis was analyzed in human and rat cardiomyocytes treated with various doses of radiation, we observed expression of AEP was increased by immunohistochemical staining in murine heart exposed to radiation. The AEP production along with its increased level of mRNA expression was associated with increased doses of radiation (0, 2, 5, 10 Gy) in cardiomyocytes. The myocardial cells transfected with AEP overexpression showed overall cellular viability enhancement, DNA damage inhibition, the foci formation of γ-H2AX suppressed and DNA repair enhancement significantly after radiation exposure. Small interfering RNA-mediated AEP knockdown was with reduced cardiomyocyte viability, elevated apoptotic rate, increased γ-H2AX foci formation and inhibited DNA repair as well after irradiation. After radiation exposure of 10 Gy, the expression of AEP increased in P53 overexpressing cardiomyocytes and decreased in the P53 knockdown cells, indicates that radiation-induced expression of AEP might be regulated by P53. Moreover, treatments with either AEP overexpression or knockdown showed enhanced NRF2 activity in the nuclear or suppressed NRF2 expression in the cytoplasm of myocardial cells after irradiation, respectively, defined a possible regulatory effect of AEP associated with diminished NRF2 translocation and activation by radiation exposure, including impair myocardium and myocardial apoptosis. These findings suggest that increased levels of AEP in failing myocardium after irradiation is mediated by P53 and regulate a novel pathway that involves NRF2 activation. AEP is essential for maintaining cellular redox homeostasis of cardiac function.

OBJECTIVES: To evaluate long-term survival outcomes and late toxicities of the sequential chemotherapy regimen of gemcitabine plus cisplatin (GP) compared with cisplatin plus fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From June 2005 to December 2014, 235 patients with pathologically confirmed NPC treated with intensity-modulated radiotherapy (IMRT) combined with GP (n = 144) or PF (n = 91) were retrospectively analyzed. RESULTS: After a median follow-up of 61 months, the 5-year overall survival (OS) rates were not significantly different between GP and PF groups (84.2% vs. 74.4%, P = .208). The 5-year local control rates were significantly improved in the GP group (96.3% vs 84.1%, P = .010). Subgroup analysis demonstrated that the increased benefits of GP were from T1-3 classification (99% vs. 87.8%, P = .013) and stage III patients (100% vs. 82.4%, P = .017). The most common late adverse events were xerostomia and hearing impairment. The incidences of grade 3 to 4 late toxicities were relatively low and were similar in the two groups. CONCLUSIONS: Sequential chemotherapy combined with IMRT achieved satisfactory survival outcomes in locoregionally advanced NPC with acceptable late toxicities. The GP regimen significantly improved local control compared with PF regimen. Further phase III randomized clinical studies were warranted.

Purpose The aim of this study was to evaluate the impact of time to radiotherapy (TTR) after completion of chemotherapy (CT), and TTR after surgery, in breast cancer (BC) patients. Patients and Methods Continuous breast cancer patients treated with surgery and CT followed by radiotherapy (RT) from 2009 through 2015 were retrospectively reviewed. Patients were categorized into four groups with respect to TTR after CT, i.e. 12 weeks, and TTR after surgery, i.e. 202 days. The Cox proportional hazards model was used to identify the independent effect of TTRs. Results Overall, 989 patients were enrolled. Patients with a TTR of >12 weeks after CT showed significantly worse breast cancer-specific survival (BCSS) and overall survival (OS) compared with those who had a TTR of 12 weeks remained an independent predictor for adverse BCSS and OS. Conclusion Initiation of RT beyond 12 weeks after CT might compromise survival outcomes. Efforts should be made to avoid delaying RT, especially after completion of CT and in patients with HR-positive tumors, positive lymph nodes, and those receiving mastectomy.

Several N,O-coordinate half-sandwich iridium complexes, 1-5, containing constrained bulky β-enaminoketonato ligands were prepared and clearly characterized. Single-crystal X-ray diffraction characterization of these complexes indicates that the iridium center adopts a distorted octahedral geometry. Complexes 1-5 showed good catalytic efficiency in the oxidative homocoupling of primary amines, dehydrogenation of secondary amines, and the oxidative cross-coupling of amines and alcohols, which furnished various types of imines in good yields and high selectivities using O2 as an oxidant under mild conditions. No distinctive substituent effects of the iridium catalysts were observed in these reactions. The diverse catalytic activity, broad substrate scope, mild reaction conditions, and high yields of the products made this catalytic system attractive in industrial processes.

Thalassemia traits and iron deficiency anemia are the most common types of hypochromic microcytic anemia with similar clinical and laboratory features. It is vital to establish a new screening model based on HbAThe data comprised of the red blood cell indices and HbAWe put forward a new model and compared it with 5 efficient formulas. The new model exhibited the highest accuracy (0.918), with its sensitivity and specificity calculated as 0.917 and 0.921, respectively. Our new model's Youden index was 0.838, which is higher than the other formulas' Youden indices.The new screening model, based on HbA

For better user experience and business effectiveness, Click-Through Rate (CTR) prediction has been one of the most important tasks in E-commerce. Although extensive CTR prediction models have been proposed, learning good representation of items from multimodal features is still less investigated, considering an item in E-commerce usually contains multiple heterogeneous modalities. Previous works either concatenate the multiple modality features, that is equivalent to giving a fixed importance weight to each modality; or learn dynamic weights of different modalities for different items through technique like attention mechanism. However, a problem is that there usually exists common redundant information across multiple modalities. The dynamic weights of different modalities computed by using the redundant information may not correctly reflect the different importance of each modality. To address this, we explore the complementarity and redundancy of modalities by considering modality-specific and modality-invariant features differently. We propose a novel Multimodal Adversarial Representation Network (MARN) for the CTR prediction task. A multimodal attention network first calculates the weights of multiple modalities for each item according to its modality-specific features. Then a multimodal adversarial network learns modality-invariant representations where a double-discriminators strategy is introduced. Finally, we achieve the multimodal item representations by combining both modality-specific and modality-invariant representations. We conduct extensive experiments on both public and industrial datasets, and the proposed method consistently achieves remarkable improvements to the state-of-the-art methods. Moreover, the approach has been deployed in an operational E-commerce system and online A/B testing further demonstrates the effectiveness., Accepted to WWW 2020, 10 pages

Objective To observe the local regression and control in T1‐2 nasopharyngeal carcinoma (NPC) patients treated with intensity‐modulated radiotherapy (IMRT) and to analyze the related influencing factors. Methods Between January 2006 and June 2014, 247 consecutive T1‐2 NPC patients treated with IMRT were retrospectively analyzed, with 126 (51.0%) N0‐1 disease and 121 (49.0%) N2‐3 disease. Among them, 72.9% received platinum‐based chemotherapy. The prescribed dose to gross tumor volume was 66 Gy/30 fractions. Results By the end of IMRT, the chemoradiotherapy (CRT) group had higher local complete response (CR) rate compared with IMRT alone group (92.2% vs 74.6%, P

Highlights • In locally advanced HNSCC, baseline leukocytosis predicts OS and PFS. • Respectively 24% and 20% patients displayed baseline leukocytosis or neutrophilia. • This independent biomarker could help identifying patients with high risk of tumor relapse., Objective To study the prognostic value of leukocyte increase in a retrospective cohort of locally advanced head and neck squamous cell carcinoma (HNSCC) patients receiving definitive concurrent cisplatin and radiation. Materials and methods Clinical records of consecutive previously untreated locally advanced HNSCC patients treated in our Institution between March 2006 and October 2012 by concurrent cisplatin (100 mg/m2, every 3 weeks) and radiation (70 Gy in 7 weeks) were collected. The prognostic value of pretreatment leukocyte increase was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as a leukocyte count or a neutrophils count exceeding 10 and 7.5 G/L, respectively. Results We identified 193 patients, all treated with concurrent cisplatin-based chemoradiotherapy. Respectively 24% and 20% patients displayed baseline leukocytosis or neutrophilia. Mean leukocyte count were significantly more elevated in current smokers, patients with performance status (PS) >0, T4 and less in HPV + tumor. The 5-year actuarial overall survival (OS) and progression-free survival (PFS) were 56% and 51% respectively. In univariate analysis, both leukocytosis and neutrophilia were strongly associated with worse OS and PFS (p

Objectives: We investigated the prognostic value of pre-treatment hematological parameters in patients with p16-positive oropharyngeal squamous-cell carcinoma (OPSCC). Material and methods: Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and hemoglobin concentration measurement (Hb), were collected on day one of treatment. Endpoints were overall survival (OS) and progression-free survival (PFS). All patients were planned to receive concurrent chemoradiation. Staging were reviewed according to the recent AJCC 8th edition. Results: We included 167 patients in this study. In multivariate analyses, a smoking history > 30 packyears was associated with decreased OS (p = 0.009; HR, 3.4827) and PFS (p = 0.042; HR, 2.421); Hb < 12 g/dL was associated with impaired OS (p = 0.007; HR, 6.527) and PFS (p = 0.014; HR, 4.092); an NLR > 5 before treatment was associated with decreased OS (p = 0.042; HR, 2.945). Hemoglobin concentration and the NLR were not correlated (p = 0.577), nor anemia and an NLR > 5 (p = 0.167). Patients with an NLR > 5 had a significantly higher rate of disease recurrence (30.8% vs. 8.4%, p = 0.0299, RR = 3.922, 95% CI 1.351–11.386). Discussion: We found hemoglobin level and the NLR to be independent prognostic factors in p16-positive OPSCC patients. This approach is to be considered for further clinical investigations, and its significance in treatment decision-making should be further explored. Keywords: Oropharyngeal carcinoma, P16, Papillomavirus, Smoking, Hemoglobin, Neutrophil-to-lymphocyte ratio

Background and purpose The aim of the present study was to investigate the role of three hypoxia-related biomarkers in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiotherapy (3-weekly cisplatin) or bioradiotherapy (weekly cetuximab). Material and methods In tumor tissue material from 100 patients with known HPV status, we evaluated the extent of tumor necrosis, the expression level of CA-IX and the microvascular density (MVD) measured as the density of CD34+ vascular structures. The correlations between biomarker expressions and clinicopathological characteristics and treatment outcomes were analyzed. Results We found a significant correlation of MVD with UICC stage (p = 0.02) and T classification (p = 0.05), of CA-IX with UICC stage (p = 0.03) and N classification (p = 0.04) and a significant inverse correlation of MVD with CA-IX expression (r = −0.22, p = 0.03). Multivariate analysis showed that low MVD combined with high CA IX-expression was a significant independent prognostic factor for worse loco-regional control (HR = 2.6, 95%CI 1.1–5.0, p = 0.02) in the whole population but not in the p16+ subgroup. Patients treated with CRT had a better LRC than those with BRT independent of MVD or CA-IX expression. Conclusions The combination of MVD and CA-IX expression might give additional prognostic information in HNSCC patients with known HPV status.

Objectives To evaluate long-term results of a phase II study of induction and adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Materials and methods One hundred and twelve patients (Stage III: 65, IVA-B: 47) with locoregionally advanced NPC were enrolled in this study. All patients received induction chemotherapy consisting of 1000 mg/m2 gemcitabine on day 1 and 8, and cisplatin 25 mg/m2 on day 1–3, every 3 weeks for 2 cycles. Adjuvant chemotherapy for 2 cycles of the same regime was given 28 days after the end of IMRT. The IMRT technique was utilized for all patients. Results In total, 97.3% patients completed 2 cycles of induction chemotherapy. The overall response rate (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1–2 myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant chemotherapy. All patients finished IMRT with RR at the end of IMRT for nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and 97.7%, respectively. The 5-year local control, regional control, distant metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%, respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and 75.5%, respectively. The incidence of grade 3–4 acute radiotherapy-related mucositis was 28.6%. Severe late toxicities were uncommon. Conclusion IMRT combined with GP for locoregionally advanced NPC is well tolerated, effective, and convenient, and warrants further studies.

Objectives: To explore prognostic and predictive value of radiomics in patients with locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated with concurrent chemoradiotherapy (CRT) or bioradiotherapy (BRT).Materials and Methods: Data of 120 patients (CRT vs. BRT matched 2: 1) were retrospectively analyzed. A total of 544 radiomics features of the primary tumor were extracted from radiotherapy planning computed tomography scans. Cox proportional hazards models were used to examine the association between survival and radiomics features with false discovery rate correction. The discriminatory performance was evaluated using receiver operating characteristic curve analysis.Results: Multivariate analysis showed a 24-feature based signature significantly predicted for OS (HR = 0.3, P = 0.02) and progression-free survival (PFS) (HR = 0.3, P = 0.01). Combining the radiomics signature with p16 status showed a significant improvement of prognostic performance compared with p16 (AUC = 0.78 vs. AUC = 0.64 at 5 years, P = 0.01) or radiomics signature (AUC = 0.78 vs. AUC = 0.67, P = 0.01) alone. When patients were stratified according to this combination, OS and PFS were significantly different according to the 4 sub-types (p16+ with low/high signature score; p16-with low/high signature score) (P Conclusion: Our analysis suggests an added value of radiomics features as prognostic and predictive biomarker in HNSCC treated with CRT/BRT. Moreover, the radiomics signature provided additional information to HPV/p16 status to further stratify patients. External validation of such findings is mandatory given the risk of overfitting. (C) 2017 Elsevier Ltd. All rights reserved.

This study aimed to explore the prognostic value of extensive invasion of primary tumor volume for local control in patients with T3-4 NPC receiving intensity-modulated radiotherapy (IMRT).Between January 2009 and December 2015, initial volume of GTV-P, the confined and extensive invasion part of GTV-P (GTV-C and GTV-E) were obtained from 159 prospectively enrolled non-metastatic T3-4 NPC patients. GTV-E included the tumor with infiltration of bony structures at skull base, cervical vertebra, paranasal sinuses or with intracranial extension. GTV-C was calculated by the subtraction of GTV-E from GTV-P. The effects of tumor volume levels on local control rate (LC) were evaluated by Kaplan-Meier method and multivariate analysis.GTV-P (P = 0.015) and GTV-E (P = 0.001) were significantly correlated with local failure, while GTV-C (P = 0.494) was not. Then optimal cut-off values of GTV-P (43 mL) and GTV-E (22 mL) were determined by receiver operating characteristic curve analysis. Patients with small (22 mL) GTV-E achieved better 5-year LC rate than those with large (≥22 mL) GTV-E (96.3% vs.76.1%, P 0.001), but no significant difference was found between patients with small (43 mL) and large (≥43 mL) GTV-P (95.9% vs. 85.5%, P = 0.094). Multivariate analysis also demonstrated large (≥22 mL) GTV-E to be an independent unfavorable prognostic factor for LC (hazard ratio [HR], 3.805; 95% CI, 1.100-13.166; P = 0.035).GTV-E is an independent prognostic factor for LC in T3-4 NPC and may further assist in the optimization of treatment strategies.

MicroRNAs, essential for gene expression and physiological regulation, are considered to be reliable biomarkers for the early diagnosis and treatment of cancers. Herein, a sensitive biosensor that uses a synergistically catalytic nanoprobe and improved toehold strand displacement reaction (TSDR) has been fabricated, and successfully applied to microRNA-155 (miR-155) detection. A nanoscale copper-based metal organic framework assembled by Pt nanoparticles and horseradish peroxidase (Cu-NMOF@PtNPs/HRP) served as a co-catalytic nanoprobe and was coupled with improved TSDR to achieve multiple amplifications. In the absence of miR-155, the tetrahedral DNA nanostructures (TDNs) immobilized on the gold electrode were independent of the TSDR system because of the binding of the shielding region of the locked probe (LP) with the template probe (TP). Instead, the target would initiate the TSDR system, leading to the conformational change of TDNs and hybridization of the nanoprobe. Cu-NMOF@PtNPs/HRP exhibited extraordinary catalytic property towards the hydroquinone-hydrogen peroxide system, demonstrating that the nanoprobe exerted a concerted effect on the electrochemical performance of the biosensor. Under optimal conditions, the cathodic current exhibited a logarithmic relation over 0.50–1.0 × 105fM miR-155, with a detection limit of 0.13 fM, indicating that the constructed biosensor has considerable potential in the field of clinical disease diagnostics for miR-155.

To explore the temporal profile of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and the potential prognostic value of its dynamic changes.Complete blood count of 112 patients from a previous phase II study were retrospectively collected at the timepoints of the initiation of induction chemotherapy (pre-IC), within 1 week before radiotherapy started (pre-RT), and within 1 week after radiotherapy finished (post-RT). Data of 103 patients were fully recorded and Cox regression analysis was used to analyze the correlations of potential risk factors with 5‑year overall survival (OS). The performance of the prognostic factor was validated in another independent cohort of 103 matched (by T and N stage) patients selected from 236 consecutive NPC patients treated with IC and concurrent chemoradiation.Multivariate analysis (MVA) identified patient age50 years old (hazard ratio [HR] = 3.4, p = 0.02), weight loss during RT7.5% (HR = 3.2, p = 0.03), and post-RT peripheral NLR7.05 (vs. NLR ≤7.05, HR = 2.5, p = 0.04, 5‑year OS 71.4% vs. 87.8%) as unfavorable prognostic factors for OS. There was also a non-significant trend in the MVA that patients with post-RT peripheral NLR7.05 showed worse progression-free survival (PFS; HR = 1.9, p = 0.06, 5‑year PFS 64.1% vs. 81.8%). Post-RT NLR had a good prognostic performance in the validation cohort (concordance index = 0.73, standard error 0.10; p = 0.02, Wilcoxon test).Post-RT NLR is an independent prognostic factor for OS in LANPC patients. The dynamic change of the routinely tested inflammatory variable could help selection of appropriate treatment options and follow-up strategies.ZWECK: Untersuchung des zeitlichen Verlaufs der peripheren NLR („neutrophil-to-lymphocyte ratio“) bei Patienten mit lokal fortgeschrittenem Nasopharynxkarzinom (LANPC) und des potenziellen prognostischen Werts seiner dynamischen Veränderungen.Das vollständige Blutbild von 112 Patienten aus einer früheren Phase-II-Studie wurde zum Zeitpunkt des Beginns der Induktionschemotherapie (Pre-IC), innerhalb einer Woche vor Beginn der Strahlentherapie (Pre-RT) und innerhalb einer Woche nach beendeter Strahlentherapie (post-RT) retrospektiv erhoben. Die Daten von 103 Patienten wurden vollständig aufgezeichnet und die Cox-Regressionsanalyse wurde verwendet, um die Korrelationen des potenziellen Risikofaktors mit dem 5‑Jahres-Gesamtüberleben (OS) zu analysieren. Die Leistung des Prognosefaktors wurde in einer anderen unabhängigen Kohorte von 103 (nach T‑ und N‑Stadium) passenden Patienten validiert, die aus 236 konsekutiven NPC-Patienten ausgewählt wurden, die mit IC und gleichzeitiger Radiochemotherapie behandelt wurden.Die multivariate Analyse (MVA) identifizierte ein Patientenalter50 Jahre (Hazard Ratio [HR] = 3,4; p = 0,02), einen Gewichtsverlust während RT7,5% (HR = 3,2; p = 0,03) und eine periphere NLR nach RT7,05 (NLR ≤7,05; HR = 2,5; p = 0,04; 5‑Jahres-OS 71,4% vs. 87,8%) als ungünstige Prognosefaktoren für das OS. Es gab auch einen nichtsignifikanten Trend in der MVA, dass Patienten mit peripherer NLR nach RT7,05 ein schlechteres progressionsfreies Überleben (PFS) zeigten (HR = 1,9; p = 0,06; 5‑Jahres-PFS 64,1% vs. 81,8%). Post-RT-NLR zeigte eine gute Prognoseleistung in der Validierungskohorte (Konkordanzindex = 0,73, Standardfehler 0,10; p = 0,02, Wilcoxon-Test).Post-RT-NLR ist ein unabhängiger Prognosefaktor für das OS bei LANPC-Patienten. Die dynamische Änderung der routinemäßig getesteten entzündlichen Variablen könnte dazu beitragen, geeignete Behandlungsoptionen und Follow-up-Strategien zu entwickeln.

To investigate the prognostic value of tumor-associated macrophages (TAM) and HLA class I expression according to HPV status in patients with head and neck squamous cell carcinoma treated with definitive radiotherapy combining cisplatin (CRT) or cetuximab (BRT).Ninety-five patients were enrolled. The density of CD68+ cells and CD68+ CD163+ cells (further referred as M2) in the intraepithelial and the stromal compartments, respectively, as well as HLA class I expression in tumor cells, were evaluated semi-quantitatively. Correlations between biomarker expression and treatment outcomes were analyzed.Multivariate analysis showed that the intraepithelial macrophage density (IEMD) was prognostic for favorable progression-free survival (PFS) and there was a non-significant trend for improved overall survival (OS). HLA class I down-regulation was not an independent prognostic factor. Subgroup analysis showed that in p16+ population, patients with high IEMD had improved 5-year PFS vs. patients with low IEMD (81.2% vs. 25.0%, p 0.001), while in p16- population, no difference was observed. Similarly, when stratified by primary tumor site, IEMD showed prognostic value in oropharyngeal cancer patients (OPC) but not non-OPC patients. Five-year PFS of patients with low stromal M2 macrophage density treated with CRT was significantly improved vs. those with BRT (54.5% vs. 36.1%, p = 0.03), while in tumors with high M2, there was no significant difference (50.3% vs. 42.9%, p = 0.67).The prognostic role of TAM phenotype and distribution depends on HPV status and might predict treatment response. They prompt further validation in prospective studies.

This article aims to investigate whether there is a difference in audiovisual integration in school-aged children (aged 6 to 13 years; mean age = 9.9 years) between the selective attention condition and divided attention condition. We designed a visual and/or auditory detection task that included three blocks (divided attention, visual-selective attention, and auditory-selective attention). The results showed that the response to bimodal audiovisual stimuli was faster than to unimodal auditory or visual stimuli under both divided attention and auditory-selective attention conditions. However, in the visual-selective attention condition, no significant difference was found between the unimodal visual and bimodal audiovisual stimuli in response speed. Moreover, audiovisual behavioral facilitation effects were compared between divided attention and selective attention (auditory or visual attention). In doing so, we found that audiovisual behavioral facilitation was significantly difference between divided attention and selective attention. The results indicated that audiovisual integration was stronger in the divided attention condition than that in the selective attention condition in children. Our findings objectively support the notion that attention can modulate audiovisual integration in school-aged children. Our study might offer a new perspective for identifying children with conditions that are associated with sustained attention deficit, such as attention-deficit hyperactivity disorder.

To compare the treatment outcomes between young and adult patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT).We conducted a retrospective case-matched analysis of all patients with non-metastatic NPC ≤20 years treated in our institution between January 2010 and July 2016. Adult patients ≥35 years treated over the same time period were included and matched at a ratio of 1:1 according to N classification, T classification, treatment modality, year of diagnosis, and gender. Survival outcomes and late toxicities were compared between the two groups.Overall 112 young patients with NPC were included, and 112 out of 3105 consecutive patients with NPC aged ≥35 years were matched. The 5-year overall survival (OS), progression-free survival, locoregional control and distant control of young and control cohorts were 89.1% vs. 79.3% (p = 0.03), 80.3% vs. 67.0% (p = 0.02), 96.4% vs. 84.3% (p 0.01), and 82.9% vs. 82.8% (p = 0.94), respectively. Multi-variate analysis showed that age ≤20 years was the only significant factor predicting for better OS (HR = 0.5, CI 0.3-0.97, p = 0.04). A trend of higher rate of hypothyroidism (grade 1-2) was observed in the young cohort (67.9% vs. 46.2%, p = 0.08).Young patients with NPC treated with modern multimodality therapy have better survival outcomes. Age was an independent favorable prognostic factor for NPC in the IMRT era. Further prospective studies are needed to establish optimal management for the young population to minimize and manage long-term side-effects without compromising survival.

A simple molecular phosphorescent Ru(II) probe P1 has been synthesized by the reaction of 5-aldehyde-2,2′-bipyridine with ruthenium(II) chlorides under mild conditions. The probe upon interaction with different cation and anion showed high selectivity and sensitivity for cyanide ion (CN‒) through phosphorescence “turn-on” response in aqueous solution (60% water) with a detection limit of 0.75 μM. The significant phosphorescence enhancement (~ 30-fold) is attributed to the nucleophilic addition of cyanide ion to the aldehyde groups of the ruthenium complex in 3 : 1 stoichiometry, in which a naked-eye sensitive orange red color of solution changed to a yellow. The generation of cyanohydrin species through nucleophilic addition has been confirmed by 1H NMR, FT-IR and mass spectra. Based on the color change of the solution, a visual colorimetric strip was prepared, which also showed good detection performance on cyanide ion with quick response time. The prominent efficiency of the Ru(II) probe proved the potential possibility of application in biosystems relating with cyanide ion.

Purpose The current standard treatment for locally advanced nasopharyngeal carcinoma (LANPC) is intensity-modulated radiation therapy (IMRT) plus cisplatin concurrent chemoradiotherapy (CCRT). However, this regimen has well-known hematological and gastrointestinal toxicities. Many studies have reported that S-1 was effective in the treatment of multiple solid cancers with mild toxicities. However, knowledge regarding IMRT plus S-1 CCRT in LANPC is lacking. Therefore, we conducted this prospective phase II trial to evaluate the efficacy and safety of this regimen in LANPC. Patients and Methods Eligible patients with histologically confirmed LANPC were enrolled in this study. IMRT was given in 30–32 fractions five times per week. Concurrently, S-1 was administrated twice per day orally based on the body surface area (BSA 1.5 m2, 50 mg). The primary endpoints were progression-free survival (PFS) and adverse events. Results From August 1, 2013, to December 15, 2017, 131 patients were enrolled in this study. The distribution of disease stages among the patients was as follows: 21 patients were in stage II (16.0%), 42 patients were in stage III (32.0%), and 68 patients were in stage IV (52.0%). After CCRT, the 3-year PFS, overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates were 87.4%, 95.7%, 94.7%, and 91.5%, respectively. The severity of most toxicities was mild. Approximately two-thirds of patients had no hematological toxicity. Grade 2 hematological toxicities included leukopenia (11.5%), anemia (1.5%), and thrombocytopenia (0.8%). Grade 3 hematological toxicities were rarely observed. Conclusion The results demonstrated that IMRT plus S-1 CCRT was effective with mild toxicity for patients with LANPC.

In this study, we attempted to assess the efficacy of upfront brain radiotherapy (RT) in breast cancer (BC) patients with brain metastases (BM). Medical records of 111 consecutive BC patients treated with WBRT or SRS between August 2009 and November 2017 in single center were retrospectively reviewed. Eighty patients received upfront brain RT after BM diagnosis and 31 had delayed RT. The median age at BM was 54 years (22-77), with median KPS 80 (50-90). The molecular BC subtypes of Luminal A, Luminal B, triple-negative and HER2 overexpression were 16, 47, 27, and 19, respectively, with 2 unknown. Of them, 83 received WBRT after BM and 28 SRS. Median overall survival (OS) was significantly related to Breast-GPA, as following: 6.5, 9.9, 14.4, and 24.5 months in 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 subgroups, respectively (P = 0.007). Univariate and multivariate analysis showed that KPS ≤70, infratentorial involvement, extracranial metastases, and no continuing systemic therapy were independent risk factors for OS. In the whole group, no significant difference in OS was found between upfront or delayed RT. For Breast-GPA 0-2.0 subgroup, upfront RT was associated with increased median OS (3.3 vs 9.8 months, P = 0.04). In GPA 2.5-4.0 subgroup, the median OS for upfront and delayed RT was 13.8 and 16.5 months, respectively (P = 0.58). In conclusion, BCBM patients with better KPS, systemic therapy, without infratentorial involvement and extracranial metastases are associated with better OS. Patients with Breast-GPA 0-2.0 might benefit from upfront brain RT.

The role of regional nodal irradiation (RNI) in patients with cN1 breast cancer following neoadjuvant treatment (NAT) is still controversial. The Neo-Bioscore staging system has shown promising prospect in assessing individual prognosis after NAT, and we sought to evaluate the role of Neo-Bioscore in guiding RNI following NAT. Medical records of 163 women with cN1 and ypN0–1 disease treated with NAT between 2009 and 2014 were retrospectively reviewed and a Neo-Bioscore was assigned to each patient. Survivals were calculated using the Kaplan–Meier method and compared with the log-rank test. Multivariate analysis was used to identify independent predictors by using Cox proportional hazards models. The median follow-up after surgery was 59.4 months. Of all 163 patients, 119 received RNI. At surgery, 36 patients (22.1%) had pathological complete response (pCR), while 89 patients (54.6%) achieved ypN0. In the whole cohort, RNI significantly improved distant metastasis-free survival (DMFS) on multivariable analysis. In the subgroup of patients with a Neo-Bioscore of 1–3, RNI significantly improved the 5-year DMFS rate of 97.0% versus 76.9% (p = 0.002), 5-year regional node recurrence-free survival rate of 95.5% versus 76.9% (p = 0.007), and 5-year overall survival rate of 100% versus 89.2% (p = 0.005). No significant difference in outcomes was found between the RNI and non-RNI groups in patients with a score of 4–6. In patients with cN1 and ypN0–1, RNI was found to significantly improve DMFS following NAT. Patients with a Neo-Bioscore of 1–3 are more likely to benefit from RNI, however a large prospective study is needed to confirm this finding.

Tasks such as search and recommendation have become increas- ingly important for E-commerce to deal with the information over- load problem. To meet the diverse needs of di erent users, person- alization plays an important role. In many large portals such as Taobao and Amazon, there are a bunch of di erent types of search and recommendation tasks operating simultaneously for person- alization. However, most of current techniques address each task separately. This is suboptimal as no information about users shared across di erent tasks. In this work, we propose to learn universal user representations across multiple tasks for more e ective personalization. In partic- ular, user behavior sequences (e.g., click, bookmark or purchase of products) are modeled by LSTM and attention mechanism by integrating all the corresponding content, behavior and temporal information. User representations are shared and learned in an end-to-end setting across multiple tasks. Bene ting from better information utilization of multiple tasks, the user representations are more e ective to re ect their interests and are more general to be transferred to new tasks. We refer this work as Deep User Perception Network (DUPN) and conduct an extensive set of o ine and online experiments. Across all tested ve di erent tasks, our DUPN consistently achieves better results by giving more e ective user representations. Moreover, we deploy DUPN in large scale operational tasks in Taobao. Detailed implementations, e.g., incre- mental model updating, are also provided to address the practical issues for the real world applications., 10 pages, accepted an oral paper in sigKDD2018(industry track)

Infection with dengue virus (DENV) causes an increase in proinflammatory responses, such as nitric oxide (NO) generation and TNF-αexpression; however, the molecular mechanism underlying this inflammatory activation remains undefined, although the activation of the transcription factor NF-κB is generally involved. In addition to TNF-αproduction in DENV-infected murine macrophage RAW264.7 cells, inducible NO synthase was transcriptionally and posttranslationally elevated and accompanied by NO generation. NF-κB is known to be activated by DENV infection. Pharmacologically inhibiting NF-κB activation abolishes iNOS/NO biosynthesis and TNF-αproduction. With inhibition, the potential role of NF-κB in oxidative signaling regulation was prevented during DENV infection. Heat-inactivated DENV failed to cause the identified inflammatory responses. Pharmacological inhibition of TLR3 partly decreased NF-κB activation; however, it effectively abolished inducible iNOS/NO biosynthesis but did not inhibit TNF-αproduction. In contrast to TLR3, viral protein NS2B3 also independently contributed to NF-κB activation to regulate TNF-αproduction. These results show the distinct pathways for NF-κB activation caused by DENV infection individually for the regulation of iNOS/NO and TNF-αexpression.

Hippocampus avoidance in whole brain radiotherapy (HA-WBRT) offers the feasibility of less-impaired cognitive function than conventional WBRT. The study aims to assess the radiological distribution of brain metastases (BMs) with relation to the hippocampus and peri-hippocampus region as defined by the RTOG 0933 for better understanding of margin definition in HA-WBRT treatment planning.Consecutive patients with diagnosis of BM from enhanced MRI between March 2011 and July 2016 were analysed. The pre-treatment TA total of 226 patients with 1080 visible metastatic sites were reviewed. The origin of the primary tumors was in 72.6% lung (n = 164), in 45 cases (19.9%) breast cancer and in 7.5% other malignancies (n = 17). There were 758 (70.2%) lesions situated beyond the tentorium. The median size of single lesion was 13.9 ± 14.7 mm. Impossible, it seems that more of the patients are with only one lesion, to verify. The hippocampus involvement was found in 3.1% (n = 7, 95% CI 0.01-0.05) within 5 mm, 5.7% (n = 13, 95% CI 0.03-0.09) within 10mm and 8.4% (n = 19, 95% CI 0.05-0.12) within 20 mm. In multivariate analysis, the number 6 BM or higher was found to be an independent risk factor for hippocampal involvement (HI) (OR: 5.2, 5.38 and 3.84 in 5, 10 and 20 mm).This radiological study found that the incidence of hippocampus involvement is low in patients with BM. HA-WBRT can be delivered under the context of complete radiological diagnosis after careful delineation, proper margin definition and individual planning optimization. Advances in knowledge: The incidence of HI in patients with initial diagnosis of BM from solid tumours impacts the radiotherapeutic decision. Our radiological data analysed the incidence of HI not only to the conventional 5 mm margin definition, but also expanded to wider margins as 10 and 20 mm from hippocampus, which will help the treatment planning optimization with different technique.

Objective To investigate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) as a noninvasive tool to assess salivary gland function for follow-up of patients with radiation-induced xerostomia. Materials and Methods This study included 23 patients with nasopharyngeal carcinoma who had been treated with parotid-sparing radiotherapy (RT). Salivary function was assessed by DW-MRI pre-treatment and one week and one year post-RT, respectively. The maximum apparent diffusion coefficient (ADC) of parotid glands (pADCmax) and the time to peak ADC of parotid glands (pTmax) during stimulation were obtained. Multivariate analysis was used to analyze factors correlated with the severity of radiation-induced xerostomia. Results The ADCs of parotid and submandibular glands (1.26 ± 0.10 × 10-3 mm2/s and 1.32 ± 0.07 × 10-3 mm2/s pre-RT, respectively) both showed an increase in all patients at one week post-RT (1.75 ± 0.16 × 10-3 mm2/s, p < 0.001 and 1.70 ± 0.16 × 10-3 mm2/s, p < 0.001, respectively), followed by a decrease in parotid glands at one year post-RT(1.57 ± 0.15 × 10-3 mm2/s, p < 0.001) but not in submandibular glands (1.69 ± 0.18 × 10-3 mm2/s, p = 0.581). An improvement in xerostomia was found in 13 patients at one year post-RT. Multivariate analysis revealed 4 significant predictors for the improvement of xerostomia, including dose to parotid glands (p = 0.009, odds ratio [OR] = 0.639), the ADC of submandibular glands (p = 0.013, OR = 3.295), pADCmax (p = 0.024, OR = 0.474), and pTmax (p = 0.017, OR = 0.729) at one week post-RT. Conclusion The ADC value is a sensitive indicator for salivary gland dysfunction. DW-MRI is potentially useful for noninvasively predicting the severity of radiation-induced xerostomia.

Functional foods targeting the ubiquitin-activating enzyme (E1) of the ubiquitin–proteasome pathway as anti-tumour agents are considered to be important for cancer chemoprevention. The low-toxicity Panax ginseng was used in traditional herbal medicine or food use for either treating or preventing cancer for more than 1000 years. In this study, we constructed an ubiquitin-tagged protein as a substrate to analyze the six ginsenosides Rb1, Rb2, Rc, Rd, Re, and Rg1 by ubiquitination assay. More ubiquitinated E1 levels were induced by increasing concentrations of ubiquitin-activating enzyme. Ginsenosides Re and Rg1 inhibited ubiquitin-activating enzyme. Unlike ginsenosides Re and Rg1, ginsenosides Rb1, Rb2, Rc, and Rd increased ubiquitination on E1 enzyme. Interestingly, ginsenoside Rg1 inhibits both the chymotrypsin-like activity of 26S proteasome and E1 activity. These results suggest that ginsenoside Rg1 is a potential functional food application for cancer prevention because of its specific E1 inhibitory effects. Furthermore, the 6-O-Glu position of the ginsenoside may play a role in its E1 inhibitory property. Ginsenosides could be further developed as a useful drug for cancer therapy.

In this paper, a nonlinear compressed sensing-based LDA Topic (NCSLT) model is proposed for the classification of polarimetric synthetic aperture radar (PolSAR) images. The CS theory shows that when a signal is sparsely rendered on some basis, it can be recovered exactly by a relatively small set of random measurements of the original signal. In this paper, such notion is applied to a more general case to analyze nonlinear PolSAR data. Therefore, the NCSLT model is presented with the following two objectives: to capture the nonlinear structure of PolSAR data on a manifold surface using the CS theory and to provide a generative explanation for the relationship between the image pixels and high-level complex scenes for image classification by establishing a Texture-CS-Topic model. Compared with the other traditional SAR image-classification methods, the proposed method displayed potential achievements when applied to two sets of PolSAR image data.

Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.