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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.

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.

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.

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-.

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.

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

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

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