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Shanshan Hou,1,2 Xiaokang Wang,3 Fang Wang,4 Zhongliang Li,5 Hui Wang,6 Jiahui Li,7 Jing Wang,8 Haiying He,9 Liping Deng,10 Yushu Feng,11 Xiufang Fan,12 Wen Li,13 Qinghua Lu,14 Yanying Ma,15 Guoying Zhao,16 Simmy Reddy,17 Yanqiu Wu,2,&ast; Yonghui Yu1,3,&ast; 1Department of Neonatology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China; 2Department of Pediatric, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, People’s Republic of China; 3Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Neonatology, Liaocheng People’s Hospital, Liaocheng, 252000, People’s Republic of China; 5Department of Neonatology, W.F. Maternal and Child Health Hospital, Weifang, 261011, People’s Republic of China; 6Department of Neonatology, Hebei PetroChina Central Hospital, Langfang, 065000, People’s Republic of China; 7Department of Neonatology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, People’s Republic of China; 8Department of Neonatology, Women and Children’s Healthcare Hospital of Linyi, Linyi, 276000, People’s Republic of China; 9Department of Neonatology, Baogang Third Hospital of Hongci Group, Baotou, 014010, People’s Republic of China; 10Department of Neonatology, Heze Municipal Hospital, Heze, 274031, People’s Republic of China; 11Department of Neonatology, Linyi People’s Hospital, Linyi, 276000, People’s Republic of China; 12Department of Neonatology, Jinan Maternity and Child Health Care Hospital, Jinan, 250001, People’s Republic of China; 13Department of Neonatology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 14Department of Neonatology, Shandong Maternal and Child Health Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, People’s Republic of China; 15Department of Neonatology, Jinan Second Maternal and Child Health Care Hospital, Jinan, 271100, People’s Republic of China; 16Department of Neonatology, Binzhou Medical University Hospital, Binzhou, 256603, People’s Republic of China; 17Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghui Yu, Department of Neonatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 234, Jingwu, Road, Huai Yin District, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-0531-66953201, Email alice20402@126.com; yuyonghui6888@126.com Yanqiu Wu, Department of Pediatric, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20, Yuhuangding East Road, Zhi fu District, Yantai, 264000, People’s Republic of China, Tel +86-0535-6691999, Email yqwu76@126.comPurpose: Significant antibiotic overuse due to prolonged antibiotic duration has not draw enough attention in developing countries with high antibiotic consumption. We aimed to describe the current status of prolonged early antibiotic duration in very-low-birth-weight (VLBW) infants in a large regional multicenter cohort in China.Patients and Methods: Institution-based prospective cohort study was conducted in all VLBW infants admitted to 16 Grade A tertiary hospitals between January 1, 2019 and December 31, 2020. Early antibiotic use was defined as antibiotic initiation within the first 3 days of life. Prolonged early antibiotic course was defined as early antibiotic initiation for more than 7 days in infants with early-onset sepsis (EOS) or more than 3 days in infants with unlikely EOS. Antibiotic use was described as days of therapy (DOT) per 1000 patient days (PD).Results: Among 1684 eligible VLBW infants, 1544 (91.7%) infants were prescribed with prolonged early antibiotic course, including 618 infants with EOS and 926 infants with unlikely EOS. The median duration of early antibiotic course was 13 (IQR 8;20) days, with 78.0% of courses > 7 days and 43.6% of courses > 14 days. Total early antibiotic use was 408.3DOT/1000Pd, of which prolonged antibiotic courses accounted for 98.2% of all antibiotic use days. More than three antibiotics used, escalation antibiotic therapy, antibiotics for special use and the use of third generation cephalosporins and carbapenems were significantly common in prolonged courses compared to short courses in both infants with EOS and unlikely EOS group (P< 0.05).Conclusion: A large proportion of VLBW infants had excessively prolonged early antibiotic durations in the regional multicenter in China. Timely discontinuation of antibiotics in VLBW infants according to standardized guidelines and limit on the use of third-generation cephalosporins and carbapenems may be key drivers in reducing the antibiotic overuse in developing countries like ours.Keywords: very-low-birth-weight infants, early antibiotic use, prolonged antibiotic course, days of therapy

Neuroblastoma is one of the most common pediatric solid tumors that threaten the health of children, accounting for about 15% of childhood cancer-related mortality in the United States. Currently, multiple therapies have been developed and applied in clinic to treat neuroblastoma including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, the resistance to therapies is inevitable following long-term treatment, leading to treatment failure and cancer relapse. Hence, to understand the mechanisms of therapy resistance and discover reversal strategies have become an urgent task. Recent studies have demonstrated numerous genetic alterations and dysfunctional pathways related to neuroblastoma resistance. These molecular signatures may be potential targets to combat refractory neuroblastoma. A number of novel interventions for neuroblastoma patients have been developed based on these targets. In this review, we focus on the complicated mechanisms of therapy resistance and the potential targets such as ATP-binding cassette transporters, long non-coding RNAs, microRNAs, autophagy, cancer stem cells, and extracellular vesicles. On this basis, we summarized recent studies on the reversal strategies to overcome therapy resistance of neuroblastoma such as targeting ATP-binding cassette transporters, MYCN gene, cancer stem cells, hypoxia, and autophagy. This review aims to provide novel insight in how to improve the therapy efficacy against resistant neuroblastoma, which may shed light on the future directions that would enhance the treatment outcomes and prolong the survival of patients with neuroblastoma.

This Dissertation aims at establishing an integrated framework of multimodal experiments and multiphysics theory to extend the understanding of the mechanics in electrochemically active materials using organic mixed ionic-electronic conductors (OMIECs) as a model system. OMIECs allow the transport of both ions and electrons, which is accompanied by the (electronic, micro-) structural reorganization. The electronic structural change in OMIECs induces transforms in the electrical conductivity and optical absorbance. The change in molecular packing invites the size change and evolution of mechanical properties. The multiphysics processes render OMIECs a fascinating platform for understanding the multi-physics coupling and advancing organic electrochemical devices. Despite significant progress, there are urgent needs in the experimental techniques and the subsequent mechanical characterization, theoretical understanding of the multiphysics processes, and mechanics-informed design principles for high-performance devices. Specifically, (i) an accurate and straightforward experimental method is in need to better understand the mechanical behaviors and kinetics such as swelling and softening of OMIECs upon electrochemical redox reactions; (ii) a theoretical framework is missing that describes the rich coupled multiphysics processes such as large deformation, charge and mass transport, electrostatics, and phase evolution in OMIECs; (iii) the rational design of the materials and structures based on mechanics principles are required for mechanically reliable, high-performance organic electrochemical devices. In this Dissertation, the mechanics of OMIECs are studied systematically. The basics of OMIECs, knowledge gaps, and the outline are introduced in Chapter 1. The in-situ environmental nanoindentation apparatus and the associating characterization techniques are presented in Chapter 2. In Chapter 3, a theoretical mechanics model is presented that elucidates the interfacial mechanical degradation of thin-film electrodes and outlines the design principles for mechanically reliable electrodes. In Chapter 4, the electrochemical doping kinetics and its stress dependency on conductive polymers are studied via a designed moving front device. Chapter 5 presents a thermodynamically consistent continuum theory of two-phase OMIECs undergoing large deformation, charge and mass transport, electrostatics, and phase separation, which forms the theoretical foundation for such conductive polymer systems. The conclusion and perspectives on future work are presented in Chapter 6.

Auditory language comprehension recruits cortical regions that are both close to sensory-motor landmarks (supporting auditory and motor features) and far from these landmarks (supporting word meaning). We investigated whether the responsiveness of these regions in task-based functional MRI is related to individual differences in their physical distance to primary sensorimotor landmarks. Parcels in the auditory network, that were equally responsive across story and math tasks, showed stronger activation in individuals who had less distance between these parcels and transverse temporal sulcus, in line with the predictions of the “tethering hypothesis,” which suggests that greater proximity to input regions might increase the fidelity of sensory processing. Conversely, language and default mode parcels, which were more active for the story task, showed positive correlations between individual differences in activation and sensory-motor distance from primary sensory-motor landmarks, consistent with the view that physical separation from sensory-motor inputs supports aspects of cognition that draw on semantic memory. These results demonstrate that distance from sensorimotor regions provides an organizing principle of functional differentiation within the cortex. The relationship between activation and geodesic distance to sensory-motor landmarks is in opposite directions for cortical regions that are proximal to the heteromodal (DMN and language network) and unimodal ends of the principal gradient of intrinsic connectivity.

Supplementary information

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients.Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves.Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years.Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.

Many bacteria metabolize aromatic compounds via catechol as a catabolic intermediate, and possess multiple genes or clusters encoding catechol-cleavage enzymes. The presence of multiple isozyme-encoding genes is a widespread phenomenon that seems to give the carrying strains a selective advantage in the natural environment over those with only a single copy. In the naphthalene-degrading strain Pseudomonas putida ND6, catechol can be converted into intermediates of the tricarboxylic acid cycle via either the ortho- or meta-cleavage pathways. In this study, we demonstrated that the catechol ortho-cleavage pathway genes (catBICIAI and catBIICIIAII) on the chromosome play an important role. The catI and catII operons are co-transcribed, whereas catAI and catAII are under independent transcriptional regulation. We examined the binding of regulatory proteins to promoters. In the presence of cis-cis-muconate, a well-studied inducer of the cat gene cluster, CatRI and CatRII occupy an additional downstream site, designated as the activation binding site. Notably, CatRI binds to both the catI and catII promoters with high affinity, while CatRII binds weakly. This is likely caused by a T to G mutation in the G/T-N11-A motif. Specifically, we found that CatRI and CatRII regulate catBICIAI and catBIICIIAII in a cooperative manner, which provides new insights into naphthalene degradation.

Additional file 5. Coding Sequence of Irak1 and Traf6 Genes.

Additional file 4. miRNA sequences.

Additional file 2. Supplementary methods and materials.

Additional file 3. Primers of target genes.

Additional file 1. Animal protocol.

Additional file 1. Antimicrobial Resistance of Common EOS and HALOS Causing Pathogens at 25 NICUs, January 2017 - December 2019.

With the ever-increasing popularity of Service-oriented Architecture (SoA) and Internet of Things (IoT), a considerable number of enterprises or organizations are attempting to encapsulate their provided complex business services into various lightweight and accessible web APIs (application programming interfaces) with diverse functions. In this situation, a software developer can select a group of preferred web APIs from a massive number of candidates to create a complex mashup economically and quickly based on the keywords typed by the developer. However, traditional keyword-based web API search approaches often suffer from the following difficulties and challenges. First, they often focus more on the functional matching between the candidate web APIs and the mashup to be developed while neglecting the compatibility among different APIs, which probably returns a group of incompatible web APIs and further leads to a mashup development failure. Second, existing approaches often return a web API composition solution to the mashup developer for reference, which narrows the developer's API selection scope considerably and may reduce developer satisfaction heavily. In view of the above challenges and successful application of game theory in the IoT, based on the idea of game theory, we propose a compatible and diverse web APIs recommendation approach for mashup creations, named MCCOMP+DIV, to return multiple sets of diverse and compatible web APIs with higher success rate. Finally, we validate the effectiveness and efficiency of MCCOMP+DIV through a set of experiments based on a real-world web API dataset, i.e., the PW dataset crawled from ProgrammableWeb.com., Comment: 15 pages, 11 figures

We present a comprehensive analysis of the submissions to the first edition of the Endoscopy Artefact Detection challenge (EAD). Using crowd-sourcing, this initiative is a step towards understanding the limitations of existing state-of-the-art computer vision methods applied to endoscopy and promoting the development of new approaches suitable for clinical translation. Endoscopy is a routine imaging technique for the detection, diagnosis and treatment of diseases in hollow-organs; the esophagus, stomach, colon, uterus and the bladder. However the nature of these organs prevent imaged tissues to be free of imaging artefacts such as bubbles, pixel saturation, organ specularity and debris, all of which pose substantial challenges for any quantitative analysis. Consequently, the potential for improved clinical outcomes through quantitative assessment of abnormal mucosal surface observed in endoscopy videos is presently not realized accurately. The EAD challenge promotes awareness of and addresses this key bottleneck problem by investigating methods that can accurately classify, localize and segment artefacts in endoscopy frames as critical prerequisite tasks. Using a diverse curated multi-institutional, multi-modality, multi-organ dataset of video frames, the accuracy and performance of 23 algorithms were objectively ranked for artefact detection and segmentation. The ability of methods to generalize to unseen datasets was also evaluated. The best performing methods (top 15%) propose deep learning strategies to reconcile variabilities in artefact appearance with respect to size, modality, occurrence and organ type. However, no single method outperformed across all tasks. Detailed analyses reveal the shortcomings of current training strategies and highlight the need for developing new optimal metrics to accurately quantify the clinical applicability of methods.

Up till now, there have been numerous articles and papers concerning the issue of Point of View in Faulkner’s “A Rose for Emily”, most of which are focused on the analysis of narrator’s function in the construction of narrative structure or the presentation of thematic meanings. Despite some articles’ application of linguistic/stylistic research methods to the study of the story, few of them involves the analysis of point of view. Therefore, by clarifying and combining theories relevant to point of view proposed by both narratologists and stylists, the paper focuses on the analysis of point of view in Faulkner’s “A Rose for Emily” from both narratological and stylistic perspective through the exploration of three aspects: uniqueness of first-person point of view, transition and transgression of point of view, and omission of point of view, with the findings that the use of first-person plural narrator “we” serves the narrative function and involves community issues and racial problems deep in the south after the civil war, that the transition of teller-character to reflector-character influences narrative structure as well narrative distance of the story, which are closely related to the narrator’s authority and reliability, that the oscillation between third-person limited perspective and focal characters’ perspective helps to achieve the effect of omniscience within limitation, that the transgression of the narrator’s limited point of view into the realm of omniscient point of view creates double-layer effects of foreshadowing and self-exposure, and that the omitted point of view of Emily, Homer, and the negro servant are in close relation with the social, historical, and cultural background at the south in the first half of 20th century. Generally speaking, the paper verifies that the integrated theories of narratology and stylistics concerning point of view are of significance and innovativeness to the understanding of aesthetic effects and thematic meanings of fiction.

People's travel and traffic safety are affected by low visibility. With the development of transportation in recent years, the detection of license plate area under low visibility has become one of the hot topics of research. This article studies the license plate detection under low visibility based on video images. The research content is divided into two parts: defogging and license plate inspection. First of all, the collected image is processed in grayscale, the related defogging coefficient is set, and the dark channel algorithm is used to remove the fog component in the image, which greatly improves the clarity of the image. Second, using the top hat calculation related theory, combined with the image edge extraction, opening and closing operation steps to detect the license plate area. Finally with the help of MATLAB software for test verification, the results show that the algorithm has a good detection effect.

We present a new secret sharing-based revocation scheme, and apply it into key management for secure multicast communication. The group key is distributed via a broadcast/multicast channel. In our protocol, the member's storage cost is a little constant which is independent of the number of broadcast members. The broadcast size is only relative to the number of evicted members. And most important, the batched re-keying operation in our scheme is as same as the single re-keying operation. Our protocol provides complete forward and backwards security, and can be easily proved an unconditionally secure session key distribution scheme with t-revocation capability.