bluuebunny/crossref_metadata_2025 huggingface dataset:
HOW THE SATELLITE CITY IS AFFECTING Co2 EMISSIONS
Authors: LIAO DANQI , GUO LISI , LIU GENGYUAN , WU FENG , CHEN CAOCAO , YIN XIN’AN , XUE JINGYAN , YANG QING , LI HUI , CASAZZA MARCO
Published: October 2021

To achieve the Paris Agreement’s goals, many cities are building satellite cities to relieve the population and environment pressure of the central city. However, past experiences showed that long-term effects of such a solution were partially limited, due to limited attention on the effects of energy consumption and carbon emissions, depending on the dynamics of population and industrial development. This paper overcomes the previous limitations, applying a Long-range Energy Alternatives Planning model to the area of Xiong’an New District, an area extending from Hebei province (China) and nearby Beijing, is planned to support the development of Beijing. The proposed model was based on three different population migration, industrial and transposition scenarios to test their impacts on urban greenhouse gas (GHG) emissions. Results show that: (1) Increased population and building area will markedly increase GHG emissions from residential consumption in Hebei province, while slightly decrease GHG emissions in Beijing. (2) Green planning, including industrial structure changes, industrial transformation, will markedly decrease the GHG emissions in Hebei provinces and it can take down for the emissions increase due to the population migration. This paper proved the effectiveness of a multi-scalar, multi-dimensional, and multi-actor modeling approach for a satellite city and new town development planning, implying that a similar approach could be applied in planning and managing the development of future satellite cities.
Computer Vision for Autonomous UAV Flight Safety: An Overview and a Vision-based Safe Landing Pipeline Example
Authors: Kakaletsis Efstratios , Symeonidis Charalampos , Tzelepi Maria , Mademlis Ioannis , Tefas Anastasios , Nikolaidis Nikos , Pitas Ioannis
Published: October 2021

Recent years have seen an unprecedented spread of Unmanned Aerial Vehicles (UAVs, or “drones”), which are highly useful for both civilian and military applications. Flight safety is a crucial issue in UAV navigation, having to ensure accurate compliance with recently legislated rules and regulations. The emerging use of autonomous drones and UAV swarms raises additional issues, making it necessary to transfuse safety- and regulations-awareness to relevant algorithms and architectures. Computer vision plays a pivotal role in such autonomous functionalities. Although the main aspects of autonomous UAV technologies (e.g., path planning, navigation control, landing control, mapping and localization, target detection/tracking) are already mature and well-covered, ensuring safe flying in the vicinity of crowds, avoidance of passing over persons, or guaranteed emergency landing capabilities in case of malfunctions, are generally treated as an afterthought when designing autonomous UAV platforms for unstructured environments. This fact is reflected in the fragmentary coverage of the above issues in current literature. This overview attempts to remedy this situation, from the point of view of computer vision. It examines the field from multiple aspects, including regulations across the world and relevant current technologies. Finally, since very few attempts have been made so far towards a complete UAV safety flight and landing pipeline, an example computer vision-based UAV flight safety pipeline is introduced, taking into account all issues present in current autonomous drones. The content is relevant to any kind of autonomous drone flight (e.g., for movie/TV production, news-gathering, search and rescue, surveillance, inspection, mapping, wildlife monitoring, crowd monitoring/management), making this a topic of broad interest.
Weight-Sharing Neural Architecture Search: A Battle to Shrink the Optimization Gap
Authors: Xie Lingxi , Chen Xin , Bi Kaifeng , Wei Longhui , Xu Yuhui , Wang Lanfei , Chen Zhengsu , Xiao An , Chang Jianlong , Zhang Xiaopeng , Tian Qi
Published: October 2021

Neural architecture search (NAS) has attracted increasing attention. In recent years,
individual
search methods have been replaced by
weight-sharing
search methods for higher search efficiency, but the latter methods often suffer lower instability. This article provides a literature review on these methods and owes this issue to the
optimization gap
. From this perspective, we summarize existing approaches into several categories according to their efforts in bridging the gap, and we analyze both advantages and disadvantages of these methodologies. Finally, we share our opinions on the future directions of NAS and AutoML. Due to the expertise of the authors, this article mainly focuses on the application of NAS to computer vision problems.
Ransomware Mitigation in the Modern Era: A Comprehensive Review, Research Challenges, and Future Directions
Authors: McIntosh Timothy , Kayes A. S. M. , Chen Yi-Ping Phoebe , Ng Alex , Watters Paul
Published: October 2021

Although ransomware has been around since the early days of personal computers, its sophistication and aggression have increased substantially over the years. Ransomware, as a type of malware to extort ransom payments from victims, has evolved to deliver payloads in different attack vectors and on multiple platforms, and creating repeated disruptions and financial loss to many victims. Many studies have performed ransomware analysis and/or presented detection, defense, or prevention techniques for ransomware. However, because the ransomware landscape has evolved aggressively, many of those studies have become less relevant or even outdated. Previous surveys on anti-ransomware studies have compared the methods and results of the studies they surveyed, but none of those surveys has attempted to critique on the internal or external validity of those studies. In this survey, we first examined the up-to-date concept of ransomware, and listed the inadequacies in current ransomware research. We then proposed a set of unified metrics to evaluate published studies on ransomware mitigation, and applied the metrics to 118 such studies to comprehensively compare and contrast their pros and cons, with the attempt to evaluate their relative strengths and weaknesses. Finally, we forecast the future trends of ransomware evolution, and propose future research directions.
Advances in the Evolution and Ecology of 13- and 17-Year Periodical Cicadas
Authors: Simon Chris , Cooley John R. , Karban Richard , Sota Teiji
Published: October 2021

Apart from model organisms, 13- and 17-year periodical cicadas (Hemiptera: Cicadidae: Magicicada) are among the most studied insects in evolution and ecology. They are attractive subjects because they predictably emerge in large numbers; have a complex biogeography shaped by both spatial and temporal isolation; and include three largely sympatric, parallel species groups that are, in a sense, evolutionary replicates. Magicicada are also relatively easy to capture and manipulate, and their spectacular, synchronized mass emergences facilitate outreach and citizen science opportunities. Since the last major review, studies of Magicicada have revealed insights into reproductive character displacement and the nature of species boundaries, provided additional examples of allochronic speciation, found evidence for repeated and parallel (but noncontemporaneous) evolution of 13- and 17-year life cycles, quantified the amount and direction of gene flow through time, revealed phylogeographic patterning resulting from paleoclimate change, examined the timing of juvenile development, and created hypotheses for the evolution of life-cycle control and the future effects of climate changeon Magicicada life cycles. New ecological studies have supported and questioned the role of prime numbers in Magicicada ecology and evolution, found bidirectional shifts in population size over generations, quantified the contribution of Magicicada to nutrient flow in forest ecosystems, and examined behavioral and biochemical interactions between Magicicada and their fungal parasites and bacterial endosymbionts.
When Do Children Lose the Language Instinct? A Critical Review of the Critical Periods Literature
Authors: Hartshorne Joshua K.
Published: October 2021

While it is clear that children are more successful at learning language than adults are—whether first language or second—there is no agreement as to why. Is it due to greater neural plasticity, greater motivation, more ample opportunity for learning, superior cognitive function, lack of interference from a first language, or something else? A difficulty in teasing apart these theories is that while they make different empirical predictions, there are few unambiguous facts against which to test the theories. This is particularly true when it comes to the most basic questions about the phenomenon: When does the childhood advantage dissipate, and how rapidly does it do so? I argue that a major reason for the lack of consensus is limitations in the research methods used to date. I conclude by discussing a recently emerging methodology and by making suggestions about the path forward.
Improved Adsorption Capacity of Nannochloropsis sp. through Modification with Cetyltrimethylammonium Bromide on the Removal of Methyl Orange in Solution
Authors: Buhani  , Suharso  , Miftahza Nurul , Permatasari Desy , Sumadi
Published: October 2021

In this research, biomass modification of Nannochloropsis sp. with surfactant cetyltrimethylammonium bromide (CTAB) through a cation exchange reaction to produce adsorbent Nannochloropsis sp.-cetyltrimethylammonium bromide (AlgN-CTAB) has been carried out. Biomass modification of Nannochloropsis sp. by CTAB has been successfully carried out through confirmation from the analysis data produced by Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM-EDX). AlgN-CTAB adsorbent has been tested for its adsorption ability against anionic dye of methyl orange (MO) in solution by way of a sequence of experiments by the batch method. The optimum conditions for MO removal from the solution occurred at an adsorbent quantity of 0.1 g, pH of 5, and an interaction time of 60 min. MO adsorption kinetic data by AlgN and AlgN-CTAB tended to take the kinetic model of pseudo-second-order (PSO) with PSO rate constant ([Formula: see text]) values of 0.56 and 2.17 g mg-1 min-1, serially. The MO adsorption isotherm pattern by AlgN tends to take the Freundlich adsorption isotherm, whereas in AlgN-CTAB it follows the Langmuir and Dubinin-Radushkevich adsorption isotherms. The results of the adsorption-desorption of MO by AlgN-CTAB with 4 repetition cycles resulted in % removal of [Formula: see text]. The AlgN-CTAB adsorbent can be used repeatedly and is very effective in absorbing MO in water.
A State‐Domain Robust Chi‐Square Test Method for GNSS/INS Integrated Navigation
Authors: Yu Zhangjun , Zhang Qiuzhao , Yu Ke , Zheng Nanshan
Published: October 2021

Aiming at abrupt faults in GNSS/INS integrated systems in complex environments, classical fault detection algorithms are mostly developed from the measurement domain. A robust chi‐square test method based on the state domain is proposed in this paper. The fault detection statistic is built based on the difference between the prior state estimation and the posterior state estimation in Kalman filtering. To improve the calculation stability, singular value decomposition (SVD) is used to factor the covariance matrix of the difference. The relevant formulas of the proposed method were theoretically derived, and the relationship between the proposed method and the existing innovation chi‐square test method was revealed. The proposed method was compared with state‐of‐the‐art chi‐square test methods and verified by GNSS/INS integrated navigation experiments using simulation data and real data. The experimental results show that the proposed method (a) directly works in the state domain, (b) does not require the known real system state, (c) has computational efficiency and good robustness, and (d) accurately detects abrupt faults.
Evaluation of Vegetable Circulation Efficiency and Analysis of Influencing Factors in Henan Province
Authors: Guo Xueqiang , Li Bingjun
Published: October 2021

In order to explore the deep-seated reasons affecting the development of vegetable circulation in Henan Province, combined with the panel data of Henan Province from 2014 to 2019, this paper first makes a static analysis on the vegetable circulation efficiency in Henan Province by using DEA method. Second, the Malmquist method is used to establish the total factor productivity evaluation model of vegetable circulation in Henan Province, and the dynamic analysis is carried out. The analysis results show that the main problem in the development of vegetable circulation in Henan Province is the low level of management and technology. Then, GM(1, N) model is established to further analyze the specific factors affecting the vegetable circulation efficiency in Henan Province. Finally, some reasonable suggestions are put forward for the development of vegetable circulation in Henan Province.
Automated Shape Analysis and DEM Study on Graded Crushed Stone
Authors: Bai Hao , Li Ruidong , Hu Xiangyu , Chen Fei , Liao Zhiyong
Published: October 2021

Graded crushed stone (GCS), as a cheap and essential component, is of great importance in road construction. The irregularity and variability of particle shape is known to affect the packing characteristics of GCS, such as compactness and void ratio. In this study, the realistic particle outline is first automatically extracted based on digital image processing and deep learning algorithms. Then, the elongation (EI), roundness (Rd), and roughness (Rg) of GCS are quantified by shape evaluation algorithms. Moreover, based on the establishment of the GCS shape library, the gravity deposition with various elongations is simulated using the discrete element method to study the packing features of GCS. The elongation effects on the macroscopic and microscopic quantities are explored. Finally, the shear behavior of GCS is studied. The results illustrate that elongation has a significant effect on the packing of GCS.
Blunt Traumatic Retropharyngeal Hematoma with Respiratory Symptoms: A Systematic Review of Reported Cases
Authors: Tsao Yu-Ling , Hsu Chien-Chin , Chen Kuo-Tai
Published: October 2021

Background. In patients with blunt trauma, particularly geriatric patients and those with minor trauma, an insidious retropharyngeal hematoma (RH) may deteriorate and have lethal consequences. We review the relevant literature to elucidate the clinical characteristics, treatment, complications, and outcomes of blunt traumatic RH with respiratory symptoms. Data Resources. We reviewed 57 case reports and added one case from our hospital for data analysis. A total of 68 cases were included in this review. Results. The ages of patients ranged from 13 to 94 years, and geriatric patients (age >66 years) constituted 61.2% of the reviewed patients. Falls (54.4%) and traffic accidents (35.3%) were the major trauma mechanisms. Most patients’ symptoms developed within 24 hours of blunt trauma (95.2%), and 73.5% of patients with RH had at least one associated injury. Many patients underwent conservative treatment for RH (63.2%). Surgical treatment (23.5%) and transarterial embolization (8.8%) were used to control retropharyngeal hemorrhage. Twelve patients died; RH and cervical spinal injury were the direct causes of death in 5 patients, whereas the other 7 patients died because of cardiac, pulmonary, or gastrointestinal causes or withdrawal of life support. Conclusions. Geriatric patients constituted the largest proportion of patients with RH, and minor trauma was adequate to result in RH in elderly people. The cornerstone of RH management is airway management. Surgery and transarterial embolization are commonly used to control active bleeding in patients with RH. The long-term outcome depends on patients’ associated injuries and in-hospital complications.
A Single-Center Retrospective Study of the Impact of Thyroid Cancer on the Malignant Risk of Contralateral TI-RADS 3 and 4 Nodules
Authors: Liu Huan , Jin Jun , Chen Qiao , Li Zhongmin
Published: October 2021

Background. The incidence of thyroid nodules increases in the general population. Similarly, we have also seen a dramatic increase in the number of thyroid surgeries. However, the mortality rate of thyroid cancer remained stable or even decreased. The purpose of our study was to investigate whether thyroid cancer affects the malignant risk of the contralateral TI-RADS 3 and 4 nodules. Methods. We conducted a retrospective cohort study in our institution for all thyroid procedures due to nodules from December 2018 to December 2019. All eligible patients were divided into the experimental group (bilateral nodules) and the control group (unilateral nodules) to assess whether the proportion of malignant nodules was different between the two groups. Multivariate logistic regression analysis was used to control potential confounding factors to investigate whether their differences were statistically significant. Results. A total of 330 patients underwent thyroid surgery, of whom 137 were eligible, including 84 in the experimental group and 53 in the control group. The proportion of malignant nodules was significantly different between the experimental group and the control group (29.8% versus 58.5%, unadjusted OR 0.30, 95% CI: 0.17–0.82,

p
=
0.001

). However, after controlling for potential confounding factors, including age (

p
=
0.004

), gender (

p
=
0.775

), and TI-RADS classification (

p
≤
0.001

), we found that the difference was not significant (adjusted OR 1.08, 95% CI: 0.39–3.01,

p
=
0.886

). Conclusion. There is no evidence that thyroid cancer affects the malignant risk of the contralateral TI-RADS 3 and 4 nodules. This study has been registered with the Chinese Clinical Trial Registry (clinical trial registration number: ChiCTR2000038611, registration time: September 26, 2020).
Effect of Retorting Temperature on the Pyrolysis Characteristic of Longkou Oil Shale
Authors: Wang Wei , Ma Yue , Li Shuyuan , Yue Changtao , Gao Jiancun
Published: October 2021

Oil shale samples from Longkou City, Shandong Province, China, were pyrolyzed in a fixed bed reactor at retorting temperature varied from 400 to 550°C under nitrogen atmosphere with heating rate of 15°C/min. The influence of retorting temperature on the yield and characteristics of shale oil and retorting gases were determined. It was observed that the oil yield increased to the maximum value, 15.68 wt%, as the retorting temperature increased from 440 to 550°C. And increasing retorting temperature improved also gas yields, but reduced the char yield. The contents of H2, CO2, and CH4 in the retorting gas increased with the rising of retorting temperature. The ratio of alkane/alkene hydrocarbon (C1-C5) decreased because of the secondary cracking reactions of gas phase in the high temperature. The carbon and nitrogen contents of shale oil increased with increasing retorting temperature, while those of hydrogen and oxygen decreased. The sulfur content was not significantly affected by the retorting temperature. In addition, the shale oil obtained from 550°C had the lowest aromatic content, 25.12 wt%, and the highest saturate content, 50.03 wt%, compared to the other retorting temperatures due to the cracking of aliphatic compounds. The alkanes with 8-34 carbons and alkenes with 8-27 carbons were detected in the shale oil. The concentration more than 20 mg/goil was C23-C30 in the range of 400-550°C. The total content of n-alkanes decreased to 369.25 mg g-1oil, and that of n-alkene reached the maximum value at 550°C, 181.62 mg/goil, with the rise of retorting temperature. It was demonstrated that the higher temperature was beneficial to promoting the reaction of aromatization, dehydrogenation, fraction, and other reactions in the pyrolysis process.
Systems Biology and Chemoinformatics‐Based Strategies to Explore the Biological Mechanism of Fugui Wenyang Decoction in Treating Vascular Dementia Rats
Authors: Yang Kailin , Zeng Liuting , Ge Anqi , Cao Chuandong , Zhang Haiyan , Bao Tingting , Yi Yaqiao , Ge Jinwen
Published: October 2021

Objective. To explore the biological mechanism of Fugui Wenyang Decoction (FGWYD) in treating vascular dementia (VD) rats based on systems pharmacology, proteomics, and a multidirectional pharmacology integration strategy. Methods. Chemoinformatics was utilized to construct and analyze the FGWYD‐VD protein‐protein interaction (PPI) network. Then, the total protein in the brain tissue of the infarcted side of the rat was extracted for protein identification, pattern identification, and protein quantitative analysis. The differentially expressed proteins are analyzed by bioinformatics. Finally, the important proteins in the oxidative stress‐related biological process proteins and indicators were detected through experimental pharmacology to verify the findings of systems biology and chemoinformatics. Results. There were a total of 73 FGWYD components with 245 FGWYD and 145 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate the inflammation module, oxidative stress, the synaptic plasticity regulation module, and the neuronal apoptosis section module. Compared with the sham operation group, there were 23 upregulated proteins and 17 downregulated proteins in the model group (P < 0.05). Compared with the model group, there were 16 upregulated proteins and 10 downregulated proteins in the FGWYD group (P < 0.05). Bioinformatics analysis shows that those proteins were closely related to processes such as inflammation, oxidative stress, neuronal apoptosis, neuronal growth and differentiation, signaling pathways, and transcriptional regulation. Multidirectional pharmacology further verified the neuroprotective mechanism of the Nrf2/HO‐1 pathway in FGWYD treatment of VD. Conclusion. The mechanism of FGWYD in the treatment of VD may be related to inflammation, oxidative stress, angiogenesis, and neuronal apoptosis.
Arteriovenous Malformation in the Auricle in a 59-Year-Old Woman
Authors: Jeong Junhui
Published: October 2021

Arteriovenous malformation (AVM) is a vascular lesion with a direct communication between an artery and a vein without a capillary system. AVM primarily occurs in the intracranial area, but can also occur in the extracranial area. If there is a tender mass with pulsation or recurrent bleeding in the auricle, AVM should be considered even though it rarely occurs in the auricle. AVM in the ear should be managed carefully because the skin is thin in the ear, the cartilage could be involved, and progressive growth or inappropriate management could cause bleeding, infection, and cosmetic problems such as deformity. I present a case of a 59-year-old woman with AVM in the auricle.
Chest Computerized Tomography Images under Iterative Model Reconstruction Algorithm in Patients with Lung Cancer
Authors: Li Jie , Wang Wei , Long Shizhi , Liu Xin , Huang Long , Li Yuanxun
Published: October 2021

To explore the effect of the full iterative model reconstruction algorithm (IMR) on chest CT image processing and its adoption value in the clinical diagnosis of lung cancer patients, multislice spiral CT (MSCT) scans were performed on 96 patients with pulmonary nodules. Reconstruction was performed by hybrid iterative reconstruction (iDose4) and IMR2 algorithms. Then, the image contrast, spatial resolution, density resolution, image uniformity, and noise of the CT reconstructed image were recorded. The benign and malignant pulmonary nodules of patients were collected and classified into malignant pulmonary nodule group and benign pulmonary nodule group, and the differences in chest CT imaging characteristics between the two groups were compared. The subject’s receiver operating characteristic (ROC) curve was used to analyze the diagnostic sensitivity, specificity, and area under the curve (AUC) of CT for benign and malignant pulmonary nodules. It was found that the spatial resolution, density resolution, image uniformity, and contrast of the CT image reconstructed by the IMR2 algorithm were remarkably greater than those of the iDose4 algorithm, and the noise was considerably less than that of the iDose4 algorithm (

P
<
0.05

). Among 96 patients with pulmonary nodules, 65 were malignant nodules, including 15 squamous cell carcinoma, 31 adenocarcinoma, and 19 small cell carcinomas. There were 31 cases of benign nodules, including 14 cases of hamartoma, 10 cases of tuberculous granuloma, 2 cases of sclerosing hemangioma, and 5 cases of diffuse lymphocyte proliferation. The pulmonary nodule malignant group and the pulmonary nodule benign group had statistical differences in pulmonary nodule size, nodule morphology, burr sign, lobular sign, vascular sign, bronchial sign, and pleural depression sign (

P
<
0.05

). The sensitivity, specificity, and area under the curve (AUC) of IMR2 algorithm processing chest CT images for liver cancer diagnosis were 85.7%, 82.3%, and 0.815, respectively, which were significantly higher than the original CT images (

P
<
0.05

). In short, chest MSCT based on the IMR2 algorithm can greatly improve the diagnosis efficiency of lung cancer and had practical significance for the timely detection of early lung cancer.
Radar Working State Recognition Based on the Unsupervised and Incremental Method
Authors: Li Huiqin , Li Yanling , He Chuan , Zhang Hui , Zhan Jianwei
Published: October 2021

Radar working state recognition is the basis of cognitive electronic countermeasures. Aiming at the problem that the traditional supervised recognition technology is difficult to obtain prior information and process the incremental signal data stream, an unsupervised and incremental recognition method is proposed. This method is based on a backpropagation (BP) neural network to construct a recognition model. Firstly, the particle swarm optimization (PSO) algorithm is used to optimize the preference parameter and damping factor of affinity propagation (AP) clustering. Then, the PSO‐AP algorithm is used to cluster unlabeled samples to obtain the best initial clustering results. The clustering results are input as training samples into the BP neural network to train the recognition model, which realizes the unsupervised recognition. Secondly, the incremental AP (IAP) algorithm based on theK‐nearest neighbor (KNN) idea is used to divide the incremental samples by calculating the closeness between samples. The incremental samples are added to the BP recognition model as a new known state to complete the model update, which realizes incremental recognition. The simulation experiments on three types of radar data sets show that the recognition accuracy of the proposed model can reach more than 83%, which verifies the feasibility and effectiveness of the method. In addition, compared with the AP algorithm andK‐means algorithm, the improved AP method improves 59.4%, 17.6%, and 53.5% in purity, rand index (RI), andF‐measure indexes, respectively, and the running time is at least 34.8% shorter than the AP algorithm. The time of processing incremental data is greatly reduced, and the clustering efficiency is improved. Experimental results show that this method can quickly and accurately identify radar working state and play an important role in giving full play to the adaptability and timeliness of the cognitive electronic countermeasures.
Degrees of Freedom in Functional Principal Components Analysis
Authors: Lin Zixin
Published: October 2021

This paper develops the analytical form of the degrees of freedom in functional principal components analysis. Under the framework of unbiased risk estimation, we derive an unbiased estimator with a clear analytical formula for the degrees of freedom in the one-way penalized functional principal components analysis paradigm. Specifically, a new analytical formula incorporating binary smoothing parameters is also derived based on the singular value decomposition and half-smoothed method regarding the two-way penalized functional principal components analysis framework. The performance of our procedures is demonstrated by simulation studies.
A Novel Systematic Oxidative Stress Score Predicts the Prognosis of Patients with Operable Breast Cancer
Authors: Zhang Kaiming , Ping Liqin , Du Tian , Wang Yan , Sun Ya , Liang Gehao , Wang Xi , Xie Xiaoming , Wei Weidong , Xiao Xiangsheng , Tang Jun
Published: October 2021

Background. Breast cancer was associated with imbalance between oxidation and antioxidation. Local oxidative stress in tumors is closely related to the occurrence and development of breast cancer. However, the relationship between systematic oxidative stress and breast cancer remains unclear. This study is aimed at exploring the prognostic value of systematic oxidative stress in patients with operable breast cancer. Methods. A total of 1583 operable female breast cancer patients were randomly assigned into the training set and validation set. The relationship between systematic oxidative stress biomarkers and prognosis were analyzed in the training and validation sets. Results. The systematic oxidative stress score (SOS) was established based on five systematic oxidative stress biomarkers including serum creatinine (CRE), serum albumin (ALB), total bilirubin (TBIL), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN). SOS was an independent prognostic factor for operable breast cancer patients. A nomogram based on SOS and clinical characteristics could accurately predict the prognosis of operable breast cancer patients, and the area under the curve (AUC) of the nomogram was 0.823 in the training set and 0.872 in the validation set, which was much higher than the traditional prognostic indicators. Conclusions. SOS is an independent prognostic indicator for operable breast cancer patients. A prediction model based on SOS could accurately predict the outcome of operable breast cancer patients.
Clinical Features and Prognosis of Patients with Carcinoid Syndrome and Carcinoid Heart Disease: A Retrospective Multicentric Study of 276 Patients
Authors: Fijalkowski Robert , Reher Dominik , Rinke Anja , Gress Thomas M. , Schrader Jörg , Baum Richard P. , Kaemmerer Daniel , Hörsch Dieter
Published: October 2021

Introduction: Carcinoid syndrome is the most frequent functional syndrome of neuroendocrine neoplasia. It is characterized by flushing, diarrhea, wheezing, hypotension, and exanthema and may cause carcinoid heart disease. Methods: We assessed clinical characteristics and prognosis of patients with carcinoid syndrome and carcinoid heart disease in 276 patients from 3 referral centers. Results: Carcinoid syndrome patients had a mean age of 57 years (range 21–84) and a normal BMI of 24.9 (SD 4.5; range 13.8–39.6). Most primaries were of small bowel or unknown primaries with distant metastasis in 94.6%. Flushing was the most frequent symptom in 74.3% of patients, followed by diarrhea in 68.8%, and wheezing in 40.9%. Pain was described by 45.3%, weakness by 23.5%, and weight loss of >10% in 6 months by 30.1% of patients. Carcinoid heart disease was diagnosed in 37.3% of patients (n = 104) by echocardiography and involved predominantly in the tricuspid valve. Combinations with other valve defects were common. Somatostatin analogs were taken by 80.4% of patients and 17% needed additional loperamide/opium tincture. Surgery and peptide receptor radiotherapy were most frequent treatments. The median survival of patients with carcinoid syndrome after diagnosis was 9 years. Prognosis was significantly impaired by male sex and diagnosis of carcinoid heart disease but surprisingly significantly increased by the presence of symptoms flushing and weakness. Discussion/Conclusion: Carcinoid syndrome is associated with extensive disease and primaries in small bowels or of unknown primary. Weight loss, weakness, and pain are frequent, and carcinoid heart disease is diagnosed in more than one-third of patients.
The Value of a Systematic Protocol Using Endobronchial Ultrasound and Endoscopic Ultrasound in Staging of Lung Cancer for Patients with Imaging iN0–N1 Disease
Authors: Cordovilla Rosa , López-Zubizarreta Marco , Velasco Antonio , Álvarez Alberto , Rodríguez Marta , Gómez Asunción , Hernández-Mezquita Miguel Ángel , Iglesias Miguel
Published: October 2021

Introduction: We hypothesize that systematic, combined, and multidisciplinary study of the mediastinum (endobronchial ultrasound [EBUS] and endoscopic ultrasound [EUS]) in patients with NSCLC with radiologically normal mediastinum improves the results of mediastinal staging obtained with EBUS alone. Material and Methods: A retrospective study of the prospective database collected on the patients with NSCLC with a radiologically normal mediastinum and an indication for systematic staging with EBUS and EUS. EBUS staging was followed by EUS in patients in which the results from the pathological analysis of EBUS were negative. Results: Forty-five patients were included in the analysis. The combination of EBUS followed by EUS provided better results than EBUS alone: sensitivity (S) 95% versus 80%, negative predictive value (NPV) 96.15% versus 86.21%, negative likelihood ratio 0.05 versus 0.20, and post-test probability 3.8% versus 13.8%. This represents an increase in S (15%), the validity index (6.6%), and NPV (9.9%) compared to EBUS alone. There were 4 false negatives (FNs) (8.8%) with the EBUS test alone. After adding EUS, 3 more cases were positive (6.6%) and only 1 FN (2.2%). Conclusions: In patients with NSCLC and a radiographically normal mediastinum, a systematic and combined staging with EBUS and EUS show higher sensitivity in the detection of mediastinal metastasis than with the use of EBUS alone. The high accuracy of the test means that the use of mediastinoscopy is not necessary to confirm the results in these patients. Since the availability of EUS is low, it may be advisable for the interventional pulmonologist to receive training in EUS-b.
Pembrolizumab-Induced Lichen Planus on the Scalp of a Patient with Non-Small-Cell Lung Carcinoma
Authors: Yamashita Aya , Akasaka Eijiro , Nakano Hajime , Sawamura Daisuke
Published: October 2021

A 67-year-old man with non-small-cell lung carcinoma was referred to our department because of a pruritic rash on his head and upper extremities. Prior to the development of the rash, he had received 4 cycles of combination therapy with pemetrexed, carboplatin, and pembrolizumab, followed by 2 cycles of pembrolizumab monotherapy. On physical examination, violaceous scaly erythema grouped on his scalp and upper extremities. Histologically, the scalp lesions demonstrated irregular acanthosis that formed a characteristic saw-tooth appearance with hypergranulosis and typical lichenoid tissue reaction. These findings suggested that the scalp lesions were lichen planus. Two-week administration of topical corticosteroid dramatically improved the rash. Immunotherapy with pembrolizumab, an anti-PD-1 antibody, can induce T-cell activation that results in various immune-related adverse effects such as lichenoid tissue reaction. However, lichen planus is generally found on the extremities and/or oral mucosa, and unlike in this case, the scalp is rarely affected. Although the exact mechanism underlying predominant scalp involvement is unknown, the present case indicates that anti-PD-1 therapy-induced lichen planus can develop not only on the extremities and oral mucosa but also on the scalp. Interestingly, the lesions were not induced by the combination of chemotherapy and pembrolizumab; rather, they occurred soon after initiation of pembrolizumab monotherapy. In the present case, pembrolizumab-induced T-cell activation which triggered lichenoid tissue reaction may have been suppressed by chemotherapy-induced immunosuppression. Dermatologists should have a thorough knowledge of the cutaneous lesions that manifest as irAEs of anti-PD-1 therapy.
Novel Mechanisms of Exosome-Mediated Phagocytosis of Dead Cells in Injured Heart
Authors: Patil Mallikarjun , Saheera Sherin , Dubey Praveen K. , Kahn-Krell Asher , Kumar Govindappa Prem , Singh Sarojini , Tousif Sultan , Zhang Qinkun , Lal Hind , Zhang Jianyi , Qin Gangjian , Krishnamurthy Prasanna
Published: October 2021

Rationale:

After myocardial ischemic injury, improper phagocytic clearance of dying cardiac cells and the ensuing lack of inflammation resolution results in adverse cardiac remodeling and dysfunction that might lead to heart failure. Therefore, therapeutic strategies to ameliorate immune cell phagocytic function are critical for augmenting cardiac repair after injury.

Objective:

To determine whether mesenchymal stem cell–derived exosomes (MSC-Exos) act as opsonin for apoptotic cells or trigger eat-me phagocytic signaling in resident/recruited phagocytes after myocardial ischemic injury.

Methods and Results:

We evaluated MSC-Exo–mediated opsonization of apoptotic cardiomyocytes and in vitro and in vivo effects of MFGE8 (milk fat globule epidermal growth factor-factor VIII)-deficient mouse MSC-Exo on macrophage engulfment of apoptotic cardiomyocytes and its implications on cardiac remodeling, repair, and function. Microscopy and FACS analyses show that opsonization of apoptotic cardiomyocytes with MSC-Exo enhances their engulfment by macrophages. Furthermore, preincubation of macrophages with MSC-Exo reprogrammed the signaling pathways involved in phagocytosis and expression of proreparative cytokines. Protein analysis of MSC-Exo reveals expression of MFGE8—a glycoprotein that bridges externalized phosphatidylserine on the apoptotic cell surface to αVβ3 or αVβ5 integrins on the phagocyte. Most intriguingly, siRNA inhibition of MFGE8 significantly reduced the MSC-Exo–mediated augmentation of dead cell engulfment, associated signaling, and proreparative phenotype. After myocardial ischemic injury, intramyocardial administration of MSC-Exo increases macrophage uptake of apoptotic bodies in the border zone of infarct and is associated with reduced proinflammatory response, increase in neovascularization, lower infarct size, and an improvement in cardiac function and MFGE8-deficient MSC-Exo administration failed to protect mice against myocardial infarction.

Conclusions:

Our data demonstrate that exosome-associated MFGE8 on one hand enhances opsonization of dead cells and on the other activates phagocytic signaling, thus augmenting removal of apoptotic cells, resolution of inflammation, and, therefore, efficient cardiac recovery after injury.
Drug‐Eluting or Bare‐Metal Stents for Left Anterior Descending or Left Main Coronary Artery Revascularization
Authors: Piccolo Raffaele , Bonaa Kaare H. , Efthimiou Orestis , Varenne Olivier , Urban Philip , Kaiser Christoph , Räber Lorenz , de Belder Adam , Remkes Wouter , van’t Hof Arnoud W. J. , Stankovic Goran , Lemos Pedro A. , Wilsgaard Tom , Reifart Jörg , Rodriguez Alfredo E. , Ribeiro Expedito E. , Serruys Patrick W. J. C. , Abizaid Alex , Sabaté Manel , Byrne Robert A. , de la Torre Hernandez Jose M. , Wijns William , Esposito Giovanni , Jüni Peter , Windecker Stephan , Valgimigli Marco ,   the Coronary Stent Trialists’ (CST) Collaboration
Published: October 2021

Background

New‐generation drug‐eluting stents (DES) reduce target‐vessel revascularization compared with bare‐metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no‐LAD/LM]).

Methods and Results

The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1‐stage individual patient data meta‐analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no‐LAD/LM group. At 6‐year follow‐up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (
P
‐interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68–0.85) than in the no‐LAD/LM territories (HR, 0.93; 95% CI, 0.83–1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70–0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65–0.85) in patients with LAD/LM disease randomized to DES. An interaction (
P
=0.004) was also found for all‐cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76–0.97).

Conclusions

As compared with BMS, new‐generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses.

Registration

URL:
https://www.crd.york.ac.uk/PROSPERO
; Unique identifier: CRD42017060520.
Bilirubin Nanoparticles Protect Against Cardiac Ischemia/Reperfusion Injury in Mice
Authors: Ai Wen , Bae Soochan , Ke Qingen , Su Shi , Li Ruijian , Chen Yanwei , Yoo Dohyun , Lee Eesac , Jon Sangyong , Kang Peter M.
Published: October 2021

Background

Ischemia/reperfusion (I/R) injury causes overproduction of reactive oxygen species, which are the major culprits of oxidative stress that leads to inflammation, apoptosis, myocardial damage, and dysfunction. Bilirubin acts as a potent endogenous antioxidant that is capable of scavenging various reactive oxygen species. We have previously generated bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol–conjugated bilirubin. In this study, we examined the therapeutic effects of BRNPs on myocardial I/R injury in mice.

Methods and Results

In vivo imaging using fluorophore encapsulated BRNPs showed BRNPs preferentially targeted to the site of I/R injury in the heart. Cardiac I/R surgery was performed by first ligating the left anterior descending coronary artery. After 45 minutes, reperfusion was achieved by releasing the ligation. BRNPs were administered intraperitoneally at 5 minutes before and 24 hours after reperfusion. Mice that received BRNPs showed significant improvements in their cardiac output, assessed by echocardiogram and pressure volume loop measurements, compared with the ones that received vehicle treatment. BRNPs treatment also significantly reduced the myocardial infarct size in mice that underwent cardiac I/R, compared with the vehicle‐treatment group. In addition, BRNPs effectively suppressed reactive oxygen species and proinflammatory factor levels, as well as the amount of cardiac apoptosis.

Conclusions

Taken together, BRNPs could exert their therapeutic effects on cardiac I/R injury through attenuation of oxidative stress, apoptosis, and inflammation, providing a novel therapeutic modality for myocardial I/R injury.
Inhibition of Aryl Hydrocarbon Receptor Attenuates Hyperglycemia‐Induced Hematoma Expansion in an Intracerebral Hemorrhage Mouse Model
Authors: Ren Reng , Lu Qin , Sherchan Prativa , Fang Yuanjian , Lenahan Cameron , Tang Lihui , Huang Yi , Liu Rui , Zhang John H. , Zhang Jianmin , Tang Jiping
Published: October 2021

Background

Hyperglycemia is associated with greater hematoma expansion (HE) and worse clinical prognosis after intracerebral hemorrhage (ICH). However, the clinical benefits of intensive glucose normalization remain controversial, and there are no approved therapies for reducing HE. The aryl hydrocarbon receptor (AHR) has been shown to participate in hyperglycemia‐induced blood–brain barrier (BBB) dysfunction and brain injury after stroke. Herein, we investigated the role of AHR in hyperglycemia‐induced HE in a male mouse model of ICH.

Methods and Results

CD1 mice (n=387) were used in this study. Mice were subjected to ICH by collagenase injection. Fifty percent dextrose was injected intraperitoneally 3 hours after ICH. AHR knockout clustered regularly interspaced short palindromic repeat was administered intracerebroventricularly to evaluate the role of AHR after ICH. A selective AHR inhibitor, 6,2′,4′‐trimethoxyflavone, was administered intraperitoneally 2 hours or 6 hours after ICH for outcome study. To evaluate the effect of AHR on HE, 3‐methylcholanthrene, an AHR agonist, was injected intraperitoneally 2 hours after ICH. The results showed hyperglycemic ICH upregulated AHR accompanied by greater HE. AHR inhibition provided neurological benefits by restricting HE and preserving BBB function after hyperglycemic ICH. In vivo knockdown of AHR further limited HE and enhanced the BBB integrity. Hyperglycemia directly activated AHR as a physiological stimulus in vivo. The thrombospondin‐1/transforming growth factor‐β/vascular endothelial growth factor axis partly participated in AHR signaling after ICH, which inhibited the expressions of BBB‐related proteins, ZO‐1 and Claudin‐5.

Conclusions

AHR may serve as a potential therapeutic target to attenuate hyperglycemia‐induced hematoma expansion and to preserve the BBB in patients with ICH.
Stochastic Downscaling to Chaotic Weather Regimes using Spatially Conditioned Gaussian Random Fields with Adaptive Covariance
Authors: Prudden Rachel , Robinson Niall , Challenor Peter , Everson Richard
Published: October 2021

Downscaling aims to link the behaviour of the atmosphere at fine scales to properties measurable at coarser scales, and has the potential to provide high resolution information at a lower computational and storage cost than numerical simulation alone. This is especially appealing for targeting convective scales, which are at the edge of what is possible to simulate operationally. Since convective scale weather has a high degree of independence from larger scales, a generative approach is essential. We here propose a statistical method for downscaling moist variables to convective scales using conditional Gaussian random fields, with an application to wet bulb potential temperature (WBPT) data over the UK. Our model uses an adaptive covariance estimation to capture the variable spatial properties at convective scales. We further propose a method for the validation, which has historically been a challenge for generative models.