bluuebunny/crossref_metadata_2025 huggingface dataset:
EFSUMB multidisciplinary guidelines and recommendations on the use of musculoskeletal ultrasound in clinical practice: what else?
Authors: Naredo Esperanza
Published: November 2021

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New views on ancient peoples
The Dawn of Everything: A New History of Humanity
David Graeber and David Wengrow
Farrar, Straus and Giroux, 2021. 704 pp.
Authors: Ellis Erle C.
Published: November 2021

A bold reappraisal of human history upends long-held theories about early societies
Capitalizing on the G7 Research Compact
Authors: Broadman Harry G. , Guile Bruce R. , Delpy David T. , Pisano Albert P.
Published: November 2021

Rules for S&T collaboration should be integrated with trade and investment agreements
In Science Journals
Authors: Vignieri Sacha , Zahn Laura M. , Suleymanov Yury , Yeston Jake , Stajic Jelena , Jiang Di , Sugden Andrew M. , Malo Courtney S. , Alderton Gemma , Vinson Valda , Purnell Beverly A. , Hines Pamela J. , Williams Ifor , Ferrarelli Leslie K.
Published: November 2021

Highlights from the
Science
family of journals
Prophet in purgatory
Authors: Cohen Jon
Published: November 2021

Peter Daszak is fighting accusations that his work on pandemic prevention helped spark COVID-19
Researchers probe climate as a cause of banner nut years
Authors: Pennisi Elizabeth
Published: November 2021

New database could help solve mystery of tree “masting”
Star ecologist put on leave after university probe ends
Authors: Pennisi Elizabeth
Published: November 2021

McMaster University, for now, hasn’t made findings on Jonathan Pruitt public
Berlin law upends postdoc hiring
Authors: Vogel Gretchen
Published: November 2021

Legislation to help early-career researchers sparks national debate over how to address job insecurity
Semantic segmentation of gonio-photographs via adaptive ROI localisation and uncertainty estimation
Authors: Peroni Andrea , Paviotti Anna , Campigotto Mauro , Abegão Pinto Luis , Cutolo Carlo Alberto , Gong Jacintha , Patel Sirjhun , Cobb Caroline , Gillan Stewart , Tatham Andrew , Trucco Emanuele
Published: November 2021

Objective

To develop and test a deep learning (DL) model for semantic segmentation of anatomical layers of the anterior chamber angle (ACA) in digital gonio-photographs.

Methods and analysis

We used a pilot dataset of 274 ACA sector images, annotated by expert ophthalmologists to delineate five anatomical layers: iris root, ciliary body band, scleral spur, trabecular meshwork and cornea. Narrow depth-of-field and peripheral vignetting prevented clinicians from annotating part of each image with sufficient confidence, introducing a degree of subjectivity and features correlation in the ground truth. To overcome these limitations, we present a DL model, designed and trained to perform two tasks simultaneously: (1) maximise the segmentation accuracy within the annotated region of each frame and (2) identify a region of interest (ROI) based on local image informativeness. Moreover, our calibrated model provides results interpretability returning pixel-wise classification uncertainty through Monte Carlo dropout.

Results

The model was trained and validated in a 5-fold cross-validation experiment on ~90% of available data, achieving ~91% average segmentation accuracy within the annotated part of each ground truth image of the hold-out test set. An appropriate ROI was successfully identified in all test frames. The uncertainty estimation module located correctly inaccuracies and errors of segmentation outputs.

Conclusion

The proposed model improves the only previously published work on gonio-photographs segmentation and may be a valid support for the automatic processing of these images to evaluate local tissue morphology. Uncertainty estimation is expected to facilitate acceptance of this system in clinical settings.
Intratumoral co-injection of the poly I:C-derivative BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy
Authors: Alvarez Maite , Molina Carmen , De Andrea Carlos E , Fernandez-Sendin Myriam , Villalba Maria , Gonzalez-Gomariz Jose , Ochoa Maria Carmen , Teijeira Alvaro , Glez-Vaz Javier , Aranda Fernando , Sanmamed Miguel F , Rodriguez-Ruiz Maria E , Fan Xinyi , Shen Wen H , Berraondo Pedro , Quintero Marisol , Melero Ignacio
Published: November 2021

Background

BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid that acting on toll-like receptor 3 (TLR3), melanoma differentiation-associated protein 5 (MDA5) and protein kinase RNA-activated (PKR) elicits rejection of directly injected transplanted tumors, but has only modest efficacy against distant untreated tumors. Its clinical activity has also been documented in early phase clinical trials. The 5,6-dimethylxanthenone-4-acetic acid (DMXAA) stimulator of interferon genes (STING) agonist shows a comparable pattern of efficacy when used via intratumoral injections.

Methods

Mice subcutaneously engrafted with bilateral MC38 and B16.OVA-derived tumors were treated with proinflammatory immunotherapy agents known to be active when intratumorally delivered. The combination of BO-112 and DMXAA was chosen given its excellent efficacy and the requirements for antitumor effects were studied on selective depletion of immune cell types and in gene-modified mouse strains lacking basic leucine zipper ATF-like transcription factor 3 (BATF3), interferon-α/β receptor (IFNAR) or STING. Spatial requirements for the injections were studied in mice bearing three tumor lesions.

Results

BO-112 and DMXAA when co-injected in one of the lesions of mice bearing concomitant bilateral tumors frequently achieved complete local and distant antitumor efficacy. Synergistic effects were contingent on CD8 T cell lymphocytes and dependent on conventional type 1 dendritic cells, responsiveness to type I interferon (IFN) and STING function in the tumor-bearing host. Efficacy was preserved even if BO-112 and DMXAA were injected in separate lesions in a manner able to control another untreated third-party tumor. Efficacy could be further enhanced on concurrent PD-1 blockade.

Conclusion

Clinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.
Maximizing cancer therapy via complementary mechanisms of immune activation: PD-1 blockade, neoantigen vaccination, and Tregs depletion
Authors: D'Alise Anna Morena , Leoni Guido , De Lucia Maria , Langone Francesca , Nocchi Linda , Tucci Fabio Giovanni , Micarelli Elisa , Cotugno Gabriella , Troise Fulvia , Garzia Irene , Vitale Rosa , Bignone Veronica , Di Matteo Elena , Bartolomeo Rosa , Charych Deborah H , Lahm Armin , Zalevsky Jonathan , Nicosia Alfredo , Scarselli Elisa
Published: November 2021

Background

A number of different immune pathways are involved in the effective killing of cancer cells, collectively named as the ‘Cancer Immunity Cycle’. Anti-PD-1 checkpoint blockade (CPB) therapy is active on one of these pathways and reinvigorates anticancer T cell immunity, leading to long-term responses in a limited fraction of patients with cancer. We have previously shown that neoantigens-based adenovirus vectored vaccine in combination with anti-PD-1 further expands pre-existing anticancer immunity and elicits novel neoantigen-specific T cells thereby increasing efficacy to 50% of tumor clearance in mice. Here we added a third component to the CPB plus vaccine combination, which is able to modify the suppressive tumor microenvironment by reducing the number of tumor-infiltrating regulatory T cells (Tregs), as strategy for improving the therapeutic efficacy and overcoming resistance.

Methods

The antitumor efficacy of anti-PD-1, neoantigen vaccine and Treg modulating agents, either Bempegaldesleukin (BEMPEG: NKTR-214) or an anti-CTLA-4 mAb with Treg-depleting activity, was investigated in murine tumor models. We evaluated tumor growth in treated animals, neoantigen-specific T cells in tumors, tumor-infiltrating lymphocytes (TILs) and intratumoral Tregs.

Results

The addition of BEMPEG or anti-CTLA-4 to the combination of vaccine and anti-PD-1 led to complete eradication of large tumors in nearby 100% of treated animals, in association with expansion and activation of cancer neoantigen-specific T cells and reduction of tumor-infiltrating Tregs.

Conclusion

These data support the notion that the integrated regulation of three steps of the cancer immunity cycle, including expansion of neoantigen-specific T cells, reversal of the exhausted T cell phenotype together with the reduction of intratumoral Tregs may represent a novel rationally designed drug combination approach to achieve higher cure rates.
Lesion-symptom mapping with NIHSS sub-scores in ischemic stroke patients
Authors: Rajashekar Deepthi , Wilms Matthias , MacDonald M Ethan , Schimert Serena , Hill Michael D , Demchuk Andrew , Goyal Mayank , Dukelow Sean P , Forkert Nils Daniel
Published: November 2021

Background

Lesion-symptom mapping (LSM) is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome. In clinical practice, patients are commonly evaluated using the National Institutes of Health Stroke Scale (NIHSS), an 11-domain clinical score to quantitate neurological deficits due to stroke. So far, LSM studies have mostly used the total NIHSS score for analysis, which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation. Thus, the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.

Methods

Employing a multivariate technique, LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial. The NIHSS domains were grouped into six categories using two schemes. LSM was conducted for each category of the two groupings and the total NIHSS score.

Results

Sub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive, specialised assessments.

Conclusion

These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships, which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.

Trial registration number

NCT01778335.
The state of Canada’s biosecurity efforts to protect biodiversity from species invasions
Authors: Reid Connor H. , Hudgins Emma J. , Guay Jessika D. , Patterson Sean , Medd Alec M. , Cooke Steven J. , Bennett Joseph R.
Published: November 2021

Invasive alien species (IAS) pose threats to native biodiversity globally and are linked to numerous negative biodiversity impacts throughout Canada. Considering the Canadian federal government’s commitments to environmental stewardship (e.g., the Convention on Biological Diversity), the successful management of IAS requires an understanding of how federal infrastructure, strategies, and decisions have contributed to previous outcomes. Here, we present an analysis of current efforts by the federal government to prevent IAS establishment in Canadian ecosystems and the unique challenges associated with Canadian IAS management. We then examine historical and current case studies of IAS in Canada with variable outcomes. By drawing comparisons with IAS management in the United States, Australia, and New Zealand, we discuss how the Canadian government may refine its policies and practices to enable more effective responses to IAS threats. We conclude by considering how future interacting stressors (e.g., climate change) will shape how we address IAS threats, and list six lessons for successful management. Most importantly, Canada must regard biodiversity impacts from IAS with as much urgency as direct economic impacts that have historically garnered more attention. Although we focus on Canada, our findings may also be useful in other jurisdictions facing similar challenges with IAS management.
Emerging issues for protected and conserved areas in Canada
Authors: Dietz Sabine , Beazley Karen F. , Lemieux Christopher J. , St. Clair Colleen , Coristine Laura , Higgs Eric , Smith Risa , Pellatt Marlow , Beaty Carolynn , Cheskey Edward , Cooke Steven J. , Crawford Lindsay , Davis Rob , Forbes Graham , Gadallah Fawziah (ZuZu) , Kendall Peter , Mandrak Nick , Moola Faisal , Parker Scott , Quayle James , Ray Justina C. , Richardson Karen , Smith Kevin , Snider James , Smol John P. , Sutherland William J , Vallillee Andre , White Lori , Woodley Alison
Published: November 2021

Horizon scanning is increasingly used in conservation to systematically explore emerging policy and management issues. We present the results of a horizon scan of issues likely to impact management of Canadian protected and conserved areas over the next 5–10 years. Eighty-eight individuals participated, representing a broad community of academics, government and nongovernment organizations, and foundations, including policymakers and managers of protected and conserved areas. This community initially identified 187 issues, which were subsequently triaged to 15 horizon issues by a group of 33 experts using a modified Delphi technique. Results were organized under four broad categories: ( i) emerging effects of climate change in protected and conserved areas design, planning, and management (i.e., large-scale ecosystem changes, species translocation, fire regimes, ecological integrity, and snow patterns); ( ii) Indigenous governance and knowledge systems (i.e., Indigenous governance and Indigenous knowledge and Western science); ( iii) integrated conservation approaches across landscapes and seascapes (i.e., connectivity conservation, integrating ecosystem values and services, freshwater planning); and ( iv) early responses to emerging cumulative, underestimated, and novel threats (i.e., management of cumulative impacts, declining insect biomass, increasing anthropogenic noise, synthetic biology). Overall, the scan identified several emerging issues that require immediate attention to effectively reduce threats, respond to opportunities, and enhance preparedness and capacity to react.
A mean-field approach to self-interacting networks, convergence and regularity
Authors: Catellier Rémi , D’Angelo Yves , Ricci Cristiano
Published: November 2021

The propagation of chaos property for a system of interacting particles, describing the spatial evolution of a network of interacting filaments is studied. The creation of a network of mycelium is analyzed as representative case, and the generality of the modeling choices are discussed. Convergence of the empirical density for the particle system to its mean-field limit is proved, and a result of regularity for the solution is presented.
Development of a poly(arylene sulfide sulfone) antibacterial electrospun film as a skin wound dressing application
Authors: Lang Xuzhi , Tang Zhurong , Wei Zhimei , Wang Xiaojun , Long Shengru , Zhang Gang , Yang Jie , Lin Qingyu
Published: November 2021

Tissue engineering has become a hot issue for skin wound healing because it can be used as an alternative treatment to traditional grafts. Nanofibrous films have been widely used due to their excellent properties. In this work, an organic/inorganic composite poly(arylene sulfide sulfone)/ZnO/graphene oxide (PASS/ZnO/GO) nanofibrous film was fabricated with the ZnO nanoparticles blending in an electrospun solution and post-treated with the GO deposition. The optimal PASS/ZnO/GO nanofibrous film was prepared by 2% ZnO nanoparticles, 3.0[Formula: see text]g/mL PASS electrospun solution, and 1% GO dispersion solution. The morphology, hydrophilicity, mechanical property, and cytotoxicity of the PASS/ZnO/GO nanofibrous film were characterized by using scanning electron microscopy, transmission electron microscope, water contact angle, tensile testing, and a Live/Dead cell staining kit. It is founded that the PASS/ZnO/GO nanofibrous film has outstanding mechanical properties and no cytotoxicity. Furthermore, the PASS/ZnO/GO nanofibrous film exhibits excellent antibacterial activity to both Escherichia coli and Staphylococcus aureus. Above all, this high mechanical property in the non-toxic and antibacterial nanofibrous film will have excellent application prospects in skin wound dressing.
A novel user review-based contextual recommender system
Authors: Khan N. Zafar Ali , Mahalakshmi R.
Published: November 2021

Recommendation systems are shrewd applications for knowledge mining that profoundly handle the problem of data overload. Various literature explores different philosophies to create ideas and recommends different strategies according to the needs of customers. Most of the work in the suggested structure space focuses on extending the accuracy of the recommendation by using a few possible methods where the principle purpose remains to improve the accuracy of suggestions while avoiding other plan objectives, such as the particular situation of a client. By using appropriate customer rating data, the biggest test for a suggested system is to generate substantial proposals. A setting is an enormous concept that can think of numerous points of view: for example, the community of friends of a client, time, mindset, environment, organization, type of day, classification of an item, description of the object, place, and language. The rating behavior of customers typically varies in different environments. We have proposed a new review-based contextual recommender (RBCR) system application from this line of analysis, in particular a novel recommender system, which is an adaptable, quick, and accurate piece planning framework that perceives the significance of setting and fuses the logical data using piece stunt while making expectations. We have contrasted our suggested calculation with pre- and post-sifting methods as they have been the most common methodologies in writing to illuminate the issue of setting conscious suggestion. Our studies show that considering the logical data, the display of a system will increase and provide better, appropriate and important results on various evaluation measurements.
Effect of Combining Immersion Therapy with Shengji Ointment on Wound Healing Rate and Adverse Reaction Rate in Patients with Second-Degree Burn
Authors: Guo Yun , Yu Junjie
Published: November 2021

Objective. To explore the effect of combining immersion therapy with Shengji ointment on wound healing rate and adverse reaction rate (ARR) in patients with second-degree burn. Methods. The data of 80 patients with second-degree burn treated in our hospital from February 2019 to February 2020 were retrospectively analyzed by the means of retrospective study, and the patients were equally divided into the treatment group and the control group according to their admission order, with 40 cases each. Immersion therapy was performed to all patients (7 d); after that, patients in the control group received routine medication (7 d), and those in the treatment group were treated with Shengji ointment until the wounds were healed, so as to compare their wound healing condition, ARRs, levels of inflammatory factors, and infection incidence. Results. Compared with the control group after treatment, the treatment group presented significantly shorter wound healing time (12.14 ± 1.26 vs. 15.98 ± 1.20,

P

 < 0.001), better wound healing rate and quality (

P

 < 0.05), and lower levels of inflammatory factors (

P

 < 0.001); no significant between-group difference in ARRs was shown (

P

 > 0.05); 34 patients in the treatment group (85.0%) and 26 patients in the control group (65.0%) had no infections, so the incidence rate of infections was significantly lower in the treatment group than in the control group (P < 0.05). Conclusion. Combining immersion therapy with Shengji ointment can reduce the levels of inflammatory factors in patients with second-degree burn, lower the incidence rate of infections, provide the conditions for wound healing, and increase the wound healing rate, which shall be promoted and applied in practice.
Hypoxia Upregulates NOTCH3 Signaling Pathway to Promote Endothelial-Mesenchymal Transition in Pulmonary Artery Endothelial Cells
Authors: Wang Li-Le , Zhu Xiao-Li , Han Shu-Hua , Xu Lu
Published: November 2021

Background. To investigate the effect of hypoxia on pulmonary artery endothelial cells and the role of NOTCH3 in endothelial-mesenchymal transition (EnMT) and to provide a research model for pulmonary disease and explain the pathogenesis of the pulmonary disease. Methods. Pulmonary artery endothelial cells were divided into two groups and cultured in normoxic and hypoxic environments, respectively. QPCR, western blot, and immunofluorescence were used to detect endothelial cell-specific marker protein and mRNA expression in each group, and the ability of endothelial cells migration was evaluated by scratch and transwell experiment. Results. The pulmonary artery endothelial cells in the normoxic group presented a typical pebble-like arrangement, and the endothelial cells in hypoxic culture showed a long spindle appearance. Hypoxia induced high expression of NOTCH3, Jagged-1, Hes1, c-Src, and CSL. Immunofluorescence showed that endothelial cells in hypoxic culture began to express the α-SMA, and the expression of vWF increased with hypoxia. Cell viability, scratch, and transwell results showed that endothelial cells in the hypoxic group were more capable of viability and migration than those in the normoxic group. The induction of EnMT by hypoxia can be inhibited by using notch3-specific inhibitor DAPT and Jagged-1. This study also found that miR-7-5p can regulate endothelial NOTCH3, indicating that miRNA is also involved in the process of endothelial-mesenchymal transformation. Conclusion. Hypoxia promotes the transformation of endothelial cells into mesenchymal cells by opening the NOTCH3 pathway, which lays the foundation for disease progression or clinical prognosis, and is of great significance in the treatment of diseases.
A Prognostic Three-Axis Coordination Model for Supply Chain Regulation Using Machine Learning Algorithm
Authors: Manoharan Hariprasath , Teekaraman Yuvaraja , Kuppusamy Ramya , Radhakrishnan Arun , Jabarulla Mohamed Yaseen
Published: November 2021

In this article, data processing of a supply chain management system has been monitored using the Internet of Space (IoS) which can be able to create possessions for managing the business process. In modern circumstances, many business inventiveness are trading and exporting products on their possession, but in many cases, information on such manufactured products is not monitored in an effective manner. To overcome the abovementioned issue, a precise model of monitoring several distributed products in supply chain management has been introduced with high sustainability error reduction. The framed model in the management process has been integrated with the boosting algorithm, a type of machine learning algorithm where training dataset has been introduced appropriately. This variation in the incorporation of the boosting optimization process not only increases the efficiency of the proposed model but also attempts to prove the success strategy under five different scenarios, where after sequential tests IoS model delivers high improvement in the distribution process for an average percentile of 67% than the existing methods.
Static Load Test on Trapezoidal Filling Structure of Crushed Concrete Particles Reinforced with Waste Tire Slices
Authors: Tong Fang , Ma Qiang , Hu Bin , Zheng Zhenyi
Published: November 2021

In this paper, a series of model tests about the trapezoidal filling structures filled with tire reinforced concrete particles has been conducted to study their stability and the ultimate bearing capacity. The effects of the reinforcing tire slices on the global stability and ultimate bearing capacity of the model were investigated, the results show that the tire slices reinforcement can reduce the total settlement of the trapezoidal filling structure, and the ultimate bearing capacity of the reinforced trapezoidal filling structure with tire slices is obviously improved. Among them, the settlements of crushed concrete particles reinforced with bottom layer, top layer, and two layers (both bottom layer and top layer) waste tire slices are 11.5%, 37.7%, and 46.2% less than that of unreinforcement, respectively. Compared with unreinforcement, when the top layer of the model is reinforced with tire slices, the Earth pressure values at the top layer and the bottom layer are reduced by 21.1% and 22.7%, respectively; the Earth pressure values at the top layer and the bottom layer are reduced 6.3% and 14.3%, respectively, when the bottom layer of the model is reinforced with tire slices, and the Earth pressure values at the top layer and the bottom layer are reduced 23.4% and 32.9%, respectively, when the two layers of the model are reinforced with tire slices. The sliding surface of the pure concrete particles filled trapezoidal structure is continuous and runs through the whole trapezoidal filling structure slope; the sliding zone of reinforced trapezoidal filling structure with tire slices decreases with the laying of tire slices.
Storage Assignment Optimization in Robotic Mobile Fulfillment Systems
Authors: Yuan Ruiping , Li Juntao , Wang Wei , Dou Jiangtao , Pan Luke
Published: November 2021

Robotic mobile fulfillment system (RMFS) is a new type of parts‐to‐picker order picking system, where robots carry inventory pods to stationary pickers. Because of the difference in working mode, traditional storage assignment methods are not suitable for this new kind of picking system. This paper studies the storage assignment optimization of RMFS, which is divided into products assignment stage and pods assignment stage. In the products assignment stage, a mathematical model maximizing the total correlation of products in the same pods is established to reduce the times of pod visits, and a scattered storage policy is adopted to reduce system congestion. A heuristic algorithm is designed to solve the model. In the pods assignment stage, a model is established minimizing the total picking distance of the mobile robots considering the turnover rate and the correlation of pods as well as the workload balance among picking corridors. A two‐stage hybrid algorithm combining greedy algorithm and improved simulated annealing is designed to solve the model. Finally, a simulation experiment is carried out based on the historical order data of an e‐commerce company. Results show that the storage assignment method proposed in the paper significantly improves the efficiency of order picking.
Identification of a Novel Ferroptosis-Related Gene Prediction Model for Clinical Prognosis and Immunotherapy of Colorectal Cancer
Authors: Yang Ya-bing , Zhou Jia-xin , Qiu Sheng-hui , He Jia-shuai , Pan Jing-hua , Pan Yun-long
Published: November 2021

Background. Colorectal cancer (CRC) is the third most common malignancies worldwide. Ferroptosis is a programmed, iron-dependent cell death observed in cancer cells. However, the prognostic potential and immunotherapy biomarker potential of ferroptosis-related genes (FRGs) in CRC patients remains to be clarified. Methods. At first, we comprehensively analysed the different expression and prognosis of related FRGs in CRC patients based on TCGA cohort. The relationship between functional enrichment of these genes and immune microenvironment in CRC was investigated using the TCGA database. Prognostic model was constructed to determine the association between FRGs and the prognosis of CRC. Relative verification was done based on the GEO database. Meanwhile, the ceRNA network of FRGs in the model was also performed to explore the regulatory mechanisms. Results. Eight differentially expressed FRGs were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the A, B, and C FRG clusters with different features. And FRG scores were constructed to quantify the FRG pattern of individual patients with colorectal cancer. The CRC patients with higher FRG score showed worse survival outcomes, higher immune dysfunction, and lower response to immunotherapy. The prognostic model showed a high accuracy for predicting the OS of CRC. Finally, a ceRNA network was analysed to show the concrete regulation mechanisms of critical FRGs in CRC. Conclusions. The FRG risk score prognostic model based on 8 FRGs exhibit superior predictive performance, providing a novel prognostic model with a high accuracy for CRC patients. Moreover, FRG score can be the potential biomarker of the response of immunotherapy for CRC.
Performance Degradation of Subsea Shield Tunnel Segment Accounting for Concrete Strength Loss and Steel Bar Corrosion
Authors: Guo Jiaqi , Yang Weiling , Xu Chong , Peng Bo , Lin Jinhai , Qian Yuan
Published: November 2021

Subsea shield tunnels usually serve in a typical corrosive marine environment. Under the action of chloride penetration and carbonization, tunnel lining segments are often damaged because of concrete strength loss and steel bar corrosion induced concrete cracking during their service life, which seriously degrades the service performance of the tunnels. A systematical experimental and numerical investigation into the performance degradation of subsea shield tunnel segments accounting for concrete strength loss and steel bar corrosion is presented in this paper. The study demonstrates that chloride penetration decreases the peak strength and elastic modulus of the segment concrete by 42% and 46.1%, respectively. The average of the ratio of dissipated energy to the total energy of dry concrete is much smaller than that of water saturated concrete and chlorine solution saturated concrete, and chloride penetration reduces the energy storage capacity of concrete, and the ability to resist damage is weakened. When steel bars corrode for 120 days, the outer cracks continue to extend, and the concrete around the inner steel bars just begin to crack initiation; when corrode for 20 years, the length of the inner cracks gradually exceeds that of the outer cracks, and the inner cracks initiating from different steel bars coalesce with each other and form a continuous failure surface, causing great serious damage to the segment. Due to the difference in concrete strength, for the outer layer, the evolution processes of steel bar corrosion‐induced cracks show the characteristics of early initiation, slow propagation, and late coalescence, and those for the inner layer have the characteristics of late initiation, rapid propagation, and early coalescence. During the whole process the propagation speed of the inner and outer cracks appears to be fast first and then slow. Moreover, the study also illustrates that the final state of segment performance degradation after crack coalescence presents the characteristics of whole lamellar exfoliation of the concrete cover.
Grid‐Based Whole Trajectory Clustering in Road Networks Environment
Authors: Wang Fangshu , Wang Shuai , Niu Xinzheng , Zhu Jiahui , Chen Ting
Published: November 2021

In the data mining of road networks, trajectory clustering of moving objects plays an important role in many applications. Most existing algorithms for this problem are based on every position point in a trajectory and face a significant challenge in dealing with complex and length‐varying trajectories. This paper proposes a grid‐based whole trajectory clustering model (GBWTC) in road networks, which regards the trajectory as a whole. In this model, we first propose a trajectory mapping algorithm based on grid estimation, which transforms the trajectories in road network space into grid sequences in grid space and forms grid trajectories by recognizing and eliminating redundant, abnormal, and stranded information of grid sequences. We then design an algorithm to extract initial clustering centers based on density weight and improve a shape similarity measuring algorithm to measure the distance between two grid trajectories. Finally, we dynamically allocate every grid trajectory to the best clusters by the nearest neighbor principle and an outlier function. For the evaluation of clustering performance, we establish a clustering criterion based on the classical Silhouette Coefficient to maximize intercluster separation and intracluster homogeneity. The clustering accuracy and performance superiority of the proposed algorithm are illustrated on a real‐world dataset in comparison with existing algorithms.
Error Estimation of Euler Method for the Instationary Stokes–Biot Coupled Problem
Authors: Houédanou Koffi Wilfrid , Adetola Jamal
Published: November 2021

In this paper, we study a finite element computational model for solving the interaction between a fluid and a poroelastic structure that couples the Stokes equations with the Biot system. Equilibrium and kinematic conditions are imposed on the interface. A mixed Darcy formulation is employed, resulting in continuity of flux condition of essential type. A Lagrange multiplier method is used to impose weakly this condition. With the obtained finite element solutions, the error estimators are performed for the fully discrete formulations.
Multivariate Statistical Analysis Uncovers Spectrum–Effect Relationship between HPLC Fingerprints and Antioxidant Activity of Saffron
Authors: You Ya , Xu Zijin , Zhong Qingrou , Zhu Lin , Lin Susu , Li Qiaoqiao , Cao Yifeng , Tao Yi , Chen Suhong , Wang Ping
Published: November 2021

Crocus sativus L. is commonly used as functional food and medicinal herb in traditional Chinese medicine. In this study, the spectrum–effect relationship was established between HPLC fingerprints and in vitro antioxidant activity of saffron to improve the quality evaluation method of saffron. The fingerprints of 21 batches of saffron collected from different regions were assessed, and the data were further analyzed by chemometric methods, including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. The spectrum–effect relationship between fingerprints and antioxidant effect of saffron was analyzed by grey relational analysis and partial least square methods to figure out the antioxidant component of saffron. Thirteen common peaks of 21 batches of saffron were included in the analysis, and peak 3 (picrocrocin), peak 7 (crocin I), and peak 10 (crocin II) were identified as the main active components responsible for antioxidant efficacy. Besides, a multi-index quality control method was developed for simultaneous determination of these three antioxidant components in saffron. Taken together, this study provided new strategies for the quality control and the development of new bioactive products of saffron in the future.
Combination of GLP-1 Receptor Activation and Glucagon Blockage Promotes Pancreatic β-Cell Regeneration In Situ in Type 1 Diabetic Mice
Authors: Gu Liangbiao , Wang Dandan , Cui Xiaona , Wei Tianjiao , Yang Kun , Yang Jin , Wei Rui , Hong Tianpei
Published: November 2021

Pancreatic β-cell neogenesis in vivo holds great promise for cell replacement therapy in diabetic patients, and discovering the relevant clinical therapeutic strategies would push it forward to clinical application. Liraglutide, a widely used antidiabetic glucagon-like peptide-1 (GLP-1) analog, has displayed diverse β-cell-protective effects in type 2 diabetic animals. Glucagon receptor (GCGR) monoclonal antibody (mAb), a preclinical agent that blocks glucagon pathway, can promote the recovery of functional β-cell mass in type 1 diabetic mice. Here, we conducted a 4-week treatment of the two drugs alone or in combination in type 1 diabetic mice. Although liraglutide neither lowered the blood glucose level nor increased the plasma insulin level, the immunostaining showed that liraglutide expanded β-cell mass through self-replication, differentiation from precursor cells, and transdifferentiation from pancreatic α cells to β-cells. The pancreatic β-cell mass increased more significantly after GCGR mAb treatment, while the combination group did not further increase the pancreatic β-cell area. However, compared with the GCGR mAb group, the combined treatment reduced the plasma glucagon level and increased the proportion of β-cells/α-cells. Our study evaluated the effects of liraglutide, GCGR mAb monotherapy, and combined strategy in glucose control and islet β-cell regeneration and provided useful clues for the future clinical application in type 1 diabetes.
Resource Allocation Scheme for Fog-Enabled Wireless Access Networks under the QoS of Users
Authors: Jiang Huilin , Chen Lili , Song Xiang , Liu Xueming
Published: November 2021

With the complexity of the network architecture, the diversity of network slicing, and the introduction of advanced techniques such as device to device (D2D), it is difficult for the next-generation (5G+ or 6G) networks to comprehensively consider the requirements of users from different slices and jointly allocate wireless resources to improve network energy efficiency. This paper studies the energy efficiency optimization problem for D2D-enabled fog radio access networks (FRANs). A resource allocation algorithm is proposed to maximize the network energy efficiency by jointly optimizing the beamforming vector, resource block allocation, and transmission power of the remote radio heads (RRHs), fog access point (FAP), and D2D users. The developed algorithm is based on nonlinear programming, convex optimization, and Lagrangian duality. Simulation results show that, by applying the proposed algorithm, the system throughput is significantly improved, and the network energy consumption is greatly reduced, which can ultimately improve the network energy efficiency obviously.
Children’s Neurological Status Epilepticus and Poor Prognostic Factors through Electroencephalogram Image under Composite Domain Analysis Algorithm
Authors: Zhang Runhan , Gao Chao , Liu Junting , Zhao Manting , Wu Yongli
Published: November 2021

This study aimed to analyze the application of composite domain analysis algorithm for electroencephalogram (EEG) images of children with epilepsy and to investigate the risk factors related to poor prognosis. 70 children with neurological epilepsy admitted to the hospital were selected as the research objects. Besides, the EEG of the children during the intermittent and seizure phases of epilepsy were collected, so as to establish a composite domain analysis algorithm model. Then, the model was applied in EEG analysis. The clinical disease type and prognosis of children were statistically analyzed, and the risk factors that affected the prognosis of children were investigated. The results showed that the EEG signal values of the detail coefficients (d51 and d52) and the approximate coefficient (c5) during the epileptic seizure period were higher markedly than the signal values of the epileptic intermittent period; the EEG signal of the epileptic intermittent period was a transient waveform, which appeared as sharp waves or spikes. The EEG signal of epileptic seizures was continuous, with a composite waveform of sharp waves and spikes, and the change amplitude of the wavelet envelope spectrum during epileptic seizures was also higher hugely than that of intermittent epilepsy. The accurate identification rate, specificity, and sensitivity of EEG analysis with the composite domain algorithm were higher than those without the algorithm. Among the five types of epileptic seizures in children, the proportion of systemic tonic-clonic status was the largest, and the proportion of myoclonic status was equal to that of complex partial epileptic status, both of which were relatively small. The proportion of children with a better prognosis was 75.71% (53/70), which was higher than those with a poor prognosis 24.29% (17/70). Abnormal imaging examination (odds ratio (OR) = 3.823 and 95% confidence interval (CI) = 1.643–8.897); seizure duration greater than 1 hour (OR = 1.855 and 95% CI = 1.076–3.199); C-reactive protein (CRP) (OR = 5.089 and 95% CI = 1.507–17.187); and abnormal blood glucose (OR = 3.077, 95%CI = 1.640–5.773) were all independent risk factors for poor prognosis (all

P
<
0.05

). The composite domain analysis algorithm was helpful for clinicians to find the difference in the EEG signals between the epileptic seizure period and the epileptic intermittent period in a short time, thereby improving the doctor’s analysis of the results, which could reflect its marked superiority. In addition, abnormal imaging examinations, convulsion duration greater than 1 hour, CRP, and abnormal blood glucose were independent risk factors for poor prognosis in children. Therefore, the invasion of related risk factors could be reduced clinically by prognostic review with medical advice, attention to food safety and hygiene, and improvement of children’s immunity.
Estimating the Basal Heave Stability of Narrow Braced Excavations
Authors: Xiao Taoli , Yang Yanlu , Cai Hua , Yan Shaoxin , Cao Fang
Published: November 2021

Engineering practices indicate that narrow braced excavation exhibits a clear size effect. However, the slip circle method in the design codes fails to consider the effect of excavation width on basal heave stability, causing waste for narrow excavation. In this paper, numerical simulation for basal heave failure of excavation with different widths was performed by FEM with SSRT (shear strength reduction technique). The results revealed that the failure mechanism of narrow excavation is different from the complete slip circle mode. In addition, the safety factor decreases increasingly slowly as the excavation widens and stabilizes when approaching the critical width. Subsequently, the corresponding computation model was presented, and an improved SCM (slip circle method) was further developed. Finally, the engineering case illustrated that it can effectively optimize the design, which exhibits clear superiority.
Spatiotemporal Evolution of Earthquakes in Longmenshan Fault and Adjacent Area, before and after the 2008 Wenchuan Earthquake
Authors: Fan Gang , Wang Jun , Qi Shunchao , Lu Gongda , Yang Xingguo , Zhou Jiawen
Published: November 2021

Seismicity sequence following a main earthquake usually contains much meaningful information for unveiling the focal mechanism and predicting the reoccurrence interval of large earthquakes. The spatiotemporal evolution of earthquakes before and after the 2008 Wenchuan earthquake (Ms 8.0) is analysed comprehensively in this study. The frequency‐magnitude relation of the 3493 earthquake events retrieved from the database of the International Seismological Centre indicates that the adopted catalogue is complete for magnitudes ≥Ms 3.4. The seismicity during the 10 years before the Wenchuan earthquake remained stable, including the magnitudes and focal depths. However, seismicity attenuated sharply in the year following the Wenchuan earthquake, and the magnitude of earthquakes before the Wenchuan earthquake decreased gradually. The area of the seismogenic zone of the 2008 Wenchuan earthquake was smaller than the earthquake stricken area. The earthquakes that occurred in the Longmenshan fault area and adjacent area in the study period were mainly shallow earthquakes. The focal depths of earthquakes in the study area became stable gradually after the Wenchuan earthquake, mainly within the range from 10 to 16 km. The earthquakes in the study area were mainly distributed with an along‐dip distance of 0–20 km, and the seismicity was distributed uniformly along the fault strike.
Metabolomics Identifies Biomarker Signatures to Differentiate Pancreatic Cancer from Type 2 Diabetes Mellitus in Early Diagnosis
Authors: Xu Hongmin , Zhang Lei , Kang Hua , Liu Jie , Zhang Jiandong , Zhao Jie , Liu Shuye
Published: November 2021

Background and Purpose. Carbohydrate antigen 19-9 (CA19-9) based approaches differentiate less than 60% of cases of pancreatic cancer (PC) from those of pancreatic tissue damage caused by chronic pancreatitis and type 2 diabetes mellitus (DM). This study aims to identify potential blood-derived candidate biomarkers for improved diagnosis sensitivity. Methods. Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. Results. We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. Conclusion. We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.
Rapidly Progressive Lung Sarcomatoid Carcinoma Managed with Doxorubicin Plus Ifosfamide and Pemetrexed
Authors: Paredes Mogica Jan Alberto , Reyes Sanchez Eduardo , Zaragoza Morales Daniela Arantza , Pierre-Louis Guillen Nathalie , Magallanes Maciel Manuel Ernesto
Published: November 2021

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of nonsmall-cell lung cancer (NSCLC). It carries a poor prognosis, even among other subtypes of NSCLC. Currently, most treatment strategies for PSC are derived from regimens aimed at managing soft tissue sarcomas or NSCLC. The use of doxorubicin plus ifosfamide and pemetrexed has been well established in the management of soft tissue carcinoma and other nonsmall-cell lung cancers, respectively. We report the case of a 69-year-old male diagnosed with PSC who was managed with doxorubicin plus ifosfamide and pemetrexed therapy. Our patient initially responded to the therapy but had rapid progression and died 8 months after the initiation of treatment. Upon genetic analysis, it was revealed the patient had overexpression of the MDM2 protein, which has been associated with poor response to therapy. This case highlights the need for a personalized treatment approach, as well as the need for a standardized treatment regimen for managing PSC.