bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Butorphanol Use in Patient-Controlled Analgesia: A Meta-Analysis
Authors: Zhu Zhihua , Zhang Wenyu
Published: July 2021

Objective. This meta-analysis evaluates the efficacy and safety regarding usage of butorphanol in patient-controlled analgesia (PCA). Methods. Several databases such as PubMed, Cochrane Library, Embase, CNKI, and VIP were explored with the help of computer search and manual retrieval. Randomized controlled trial (RCT) was selected, and the meta-analysis was conducted using RevMan 5.1. The primary efficacy endpoint was the postoperative visual analog scale score, postoperative Ramsay sedation scale (RSS), and adverse events. Results. Nine RCTs met the inclusion criteria and were included in this meta-analysis. No significant differences were found between the butorphanol group and nonbutorphanol group at 12 h and 48 h. The postoperative RSS score at 12 h, 24 h, and 48 h was representative of the calming effect of butorphanol. No significant difference was found on the endpoint of the postoperative RSS score at 12 h, 48 h, and 24 h. The RSS score was lower in the butorphanol group in comparison to the nonbutorphanol group. The butorphanol group was also associated with lower rate of nausea, vomiting, itching, and dizziness compared to the nonbutorphanol group. Conclusion. Butorphanol may be used in PCA as a successful postoperative analgesia and is also associated with lower side effects. Further research is needed to verify the efficacy and safety of butorphanol.
Design of Longwall Coal Pillar for the Prevention of Water Inrush from the Seam Floor with Through Fault
Authors: Li Ang , Ji Bing nan , Ma Qiang , Liu Chaoyang , Wang Feng , Ma Li , Mu Pengfei , Mou Lin , Yang Yuxuan , Ding Xuesong
Published: July 2021

Setting up a waterproof coal pillar is an important measure to prevent water inrush from the Weibei mining through fault floor. Based on the plastic slip line field theory, a mechanical model of floor water inrush induced by confined water in the through fault zone was established. The mechanical expressions of confined water pressure and the width of the waterproof coal pillar under the state of limit equilibrium were derived. Combining the laws of floor deformation, failure and fault activation under two kinds of coal pillar width, the safety width of the waterproof coal pillar was determined. Furthermore, the safety threshold is better than the empirical value mentioned in the “coal mine safety regulations.” Following this, grouting transformation was carried out on the K2 sand layer of the cut roadway floor. This provided a theoretical basis and engineering practice for water disaster prevention and the control of the structural floor under similar conditions in the Weibei mining area for future benefit.
Case Studies of Comprehensive Gas Control Method during Fully Mechanized Caving of Low-Permeability Ultrathick Coal Seams
Authors: Jiang Bangyou , Gu Shitan , Li Wenshuai , Zhang Guangchao , Zhang Jihua
Published: July 2021

Slicing fully mechanized caving mining is a standard high-efficiency mining method for ultrathick coal seams. However, the effectiveness of gas control has accentuated the difficulty in fully mechanized top coal caving of low-permeability ultrathick coal seams. This study focused on mining the No. 9-15 coal in Liuhuanggou Coal Mine, Xinjiang Province, China. To this aim, the results of theoretical analyses and field tests were combined to explore a comprehensive gas control method for fully mechanized caving of low-permeability ultrathick coal seams. The No. (9-15)06 panel was a top-slicing panel of the No. 9-15 coal with a mining height of 9 m. Gas analysis results revealed that gas emissions in the No. (9-15)06 panel are mainly sourced from the coal wall, caving top coal, goaf, and neighboring coal seams. Based on gas source separation, a comprehensive gas control method was proposed. The proposed method was based on the combination of gas predrainage alongside the coal seam, high-position drilling on the top, preburial of pipes in the goaf, and pressure-balancing ventilation. The permeability and gas predrainage were enhanced by hydraulic fracturing in low-permeability coal seams. According to the characterizations of coal seam and crustal stress distribution, the arrangement of the boreholes and backward-segmented fracturing technology were designed. From the field results, the coal seam presented a remarkable prefracturing under hydraulic fracturing. Besides, the mean gas predrainage from the boreholes was enhanced by four times compared to the prehydraulic fracturing state. Finally, using the proposed comprehensive control method based on the gas sources, field tests were performed in the No. (9-15)06 panel. The measured results demonstrated that gas concentration in the return airflow is fluctuated within a range of 0.05% to 0.35%. The proposed gas control method can provide an insightful reference for other similar projects.
A Comparison on Numerical Simulation Models for Vibrational Performances of the Wood Truss Joist Floor System
Authors: Shen Yinlan , Zhou Haibin , Xue Shuo , Zhang Jinchuan
Published: July 2021

Wood truss joist floors are increasingly used to replace traditional solid timber joist floors in low‐rise timber houses. An understanding of the vibration performance of wood truss joist floors is critical for the design and serviceability of the floors. It is difficult to model wood truss joist floors accurately because of the complicated boundary conditions and numerous sophisticated flexible connections. This paper discusses three simplified modeling methods for the wood truss joist floor system. The modeling results were validated by a series of static deflection tests and vibration modes and frequencies tests of a full‐size floor. And predictive analysis of human‐induced vibration of the floor was also conducted. The vibration characteristics of the wood truss joist floor were investigated. The examination of the applicability of these modeling methods was provided. The results indicate that the point loading deflection more easily affects the deflection of the adjacent joist. However, the deflection influence on other joists that are three spaces away is minimal. Walking on the wood truss joist floor produces steep vibration acceleration fluctuations at the floor center for a relatively long time period. The sheathing‐to‐joist connections and the metal plate connections of the joists have significant influences on the vibration response of the wood truss joist floor. The modeling method, which considers the flexible metal plate connections and flexible sheathing‐to‐joist connections, performs best for predicting the vibration performance of the floor.
Elevated Interarm Systolic Blood Pressure Difference Is Positively Associated with Increased Likelihood of Coronary Artery Disease
Authors: Li Min , Fan Fangfang , Zhang Yan , Ma Wei , Huo Yong
Published: July 2021

Background. Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We investigated the relationship between interarm systolic blood pressure difference and coronary artery disease. Methods. We retrospectively analyzed data for patients undergoing coronary angiography and brachial-ankle pulse wave velocity examination during hospitalization from 2013 to 2018. Patients underwent simultaneous upper arm blood pressure measurement. Interarm systolic blood pressure difference (IASBPD) was defined as the absolute value of the difference between the right and left upper limb systolic blood pressure. Patients with IASBPD ≥10 mmHg constituted the high group, and those with IASBPD <10 mmHg constituted the normal group. We also recorded data for cardiovascular risk factors. Coronary artery disease was defined as ≥50% vessel stenosis or having undergone interventional therapy according to coronary angiography results. Results. Compared with the normal group, the number of patients with coronary artery disease was higher in the high group (86.1% vs. 74.6%,

P
=
0.029

). Multiple logistic regression showed that IASBPD ≥10 mmHg were positively correlated with coronary artery disease (odds ratio, 2.313; 95% confidence interval, 1.086–4.509;

P
=
0.029

), and as the IASBPD value increased, the correlation also gradually increased. Conclusions. IASBPD ≥10 mmHg was positively related to coronary artery disease and increased IASBPD values were correlated with coronary artery disease severity.
Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis
Authors: Wang Ji-Gan , Zhong Zhi-Juan , Li Meng , Fu Jun , Su Yu-Heng , Ping You-Min , Xu Zi-Ji , Li Hao , Chen Yan-Hao , Huang Yu-Li
Published: July 2021

Background. This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. Methods. We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. Results. A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67–100%), 82.72% (95% CI: 78.19–86.81%), 53.02% (45.28–60.68%), and 14.16% (95% CI: 8.4–21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73–63.87%), 55.23% (95% CI: 50.22–60.19%), 27.07% (95% CI: 19.87–34.93%), 46.37% (95% CI: 39.97–52.83%), 28.87% (95% CI: 22.76–35.40%), 28.75% (95% CI: 21.46–36.64%), 17.32% (95% CI: 15.44–19.29%), and 36.19% (95% CI: 21.90–51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.
How Does Policy Perception Affect Green Entrepreneurship Behavior? An Empirical Analysis from China
Authors: Chu Fengdi , Zhang Wei , Jiang Yuan
Published: July 2021

As sustainable development has become a worldwide concern in dealing with tensions between economic development and resource sustainability, green entrepreneurship as a potential solution is gaining popularity. This paper investigates the perceptions of green policies and their impact on green entrepreneurial behavior. Furthermore, green self-efficacy is identified as a psychological mechanism linking green entrepreneurship policies and green entrepreneur behavior and moral reflectiveness as a boundary condition. Building on the policy acceptance model (PAM), the relationships between two policy perceptions and two green entrepreneurial behaviors, the mediating effect of green self-efficacy, and the moderating effect of moral reflectiveness are explored. Results support the mediation and moderation effects, implying that governmental institutions can strive to improve entrepreneurs’ perceived usefulness and ease of use in terms of public policies to strengthen their engagement in green entrepreneurial behaviors.
Credit Risk Management of Consumer Finance Based on Big Data
Authors: Wang Huibo
Published: July 2021

In recent years, China’s consumer finance has developed rapidly, but the foundation is unstable, and the industry has serious problems of violent competition, excessive credit, and fraud. Therefore, we should attach great importance to the healthy development of consumer finance, especially the management of its credit risk. The application of big data credit investigation can provide early warning of potential risks and prevent the risk of excessive credit investigation. This paper starts with the definition of basic core concepts, such as traditional credit investigation, big data credit investigation, and consumer finance, analyzes the performance and causes of consumer finance credit risk, and combs in detail the relevant theories of the application of big data credit investigation in consumer finance credit risk management. The application of big data credit investigation has optimized the risk management process of consumer financial institutions, deepened the concept of Internet consumer finance, improved the risk management system, created a diversified credit information system, and strengthened the innovation of Internet consumer finance products and services. For example, credit scores provide the most intuitive quantification of consumer credit risk. For consumers with different levels of credit scores, different credit approval processes can be matched. For customers with high scores, the work process can be simplified without affecting the work results. It can reduce the workload of employees by 20% and increase the accuracy of customer credit risk prediction by 16%.
Thyroid Nodule Classification in Ultrasound Images by Fusion of Conventional Features and Res-GAN Deep Features
Authors: Hang Yuan
Published: July 2021

In spite of the gargantuan number of patients affected by the thyroid nodule, the detection at an early stage is still a challenging task. Thyroid ultrasonography (US) is a noninvasive, inexpensive procedure widely used to detect and evaluate the thyroid nodules. The ultrasonography method for image classification is a computer-aided diagnostic technology based on image features. In this paper, we illustrate a method which involves the combination of the deep features with the conventional features together to form a hybrid feature space. Several image enhancement techniques, such as histogram equalization, Laplacian operator, logarithm transform, and Gamma correction, are undertaken to improve the quality and characteristics of the image before feature extraction. Among these methods, applying histogram equalization not only improves the brightness and contrast of the image but also achieves the highest classification accuracy at 69.8%. We extract features such as histograms of oriented gradients, local binary pattern, SIFT, and SURF and combine them with deep features of residual generative adversarial network. We compare the ResNet18, a residual convolutional neural network with 18 layers, with the Res-GAN, a residual generative adversarial network. The experimental result shows that Res-GAN outperforms the former model. Besides, we fuse SURF with deep features with a random forest model as a classifier, which achieves 95% accuracy.
A New Method for Research on Unsteady Pressure Dynamics and Productivity of Ultralow-Permeability Reservoirs
Authors: Wang Kun , Li Li , Chen Xiao , Liang Wei , Yang Yong , Yan Zhenghe , Dai Jianwen , Li Wei , Wang Yahui , Wang Weifang , Li Min , Wang Danling
Published: July 2021

In the numerous low-permeability reservoirs, knowing the real productivity of the reservoir became one of the most important steps in its exploitation. However, the value of permeability interpreted by a conventional well-test method is far lower than logging, which further leads to an inaccurate skin factor. This skin factor cannot match the real production situation and will mislead engineer to do an inappropriate development strategy of the oilfield. In order to solve this problem, key parameters affecting the skin factor need to be found. Based on the real core experiment and digital core experiment results, stress sensitivity and threshold pressure gradient are verified to be the most influential factors in the production of low-permeability reservoirs. On that basis, instead of a constant skin factor, a well-test interpretation mathematical model is established by defining and using a time-varying skin factor. The time-varying skin factor changes with the change of stress sensitivity and threshold pressure gradient. In this model, the Laplace transform is used to solve the Laplace space solution, and the Stehfest numerical inversion is used to calculate the real space solution. Then, the double logarithmic chart of dimensionless borehole wall pressure and pressure derivative changing with dimensionless time is drawn. The influences of parameters in expressions including stress sensitivity, threshold pressure, and variable skin factor on pressure and pressure derivative and productivity are analyzed, respectively. At last, the method is applied to the well-test interpretation of low-permeability oil fields in the eastern South China Sea. The interpretation results turn out to be reasonable and can truly reflect the situation of low-permeability reservoirs, which can give guidance to the rational development of low-permeability reservoirs.
Value of Perfusion CT in the Prediction of Intracerebral Hemorrhage after Endovascular Treatment
Authors: Austein Friederike , Fischer Antonia Carlotta , Fiehler Jens , Jansen Olav , Lindner Thomas , Gellißen Susanne
Published: July 2021

Background. Intracerebral hemorrhage (ICH) is a serious complication of endovascular treatment (EVT) in stroke patients with large vessel occlusion (LVO) and associated with increased morbidity and mortality. Aims. Identification of radiological predictors is highly relevant. We investigated the predictive power of computed tomography perfusion (CTP) parameters concerning ICH in patients receiving EVT. Methods. 392 patients with anterior circulation LVO with multimodal CT imaging who underwent EVT were analyzed. CTP parameters were visually evaluated for modified ASPECTS regions and compared between patients without ICH, those with hemorrhagic infarction (HI), and those with parenchymal hematoma (PH) according to the ECASS criteria at follow-up imaging and broken down by ASPECTS regions. Results. 168 received intravenous thrombolysis (IV-rtPA), and 115 developed subsequent ICH (29.3%), of which 74 were classified as HI and 41 as PH. Patients with HI and PH had lower ASPECTS than patients without ICH and worse functional outcome after 90 days (

p
<
0.05

). In 102 of the 115 patients with ICH, the deep middle cerebral artery (MCA) territory was affected with differences between patients without ICH, those with HI, and those with PH regarding cerebral blood volume (CBV) and blood-brain barrier permeability measured as flow extraction product (FED) relative to the contralateral hemisphere (

p
<
0.05

). Patients with PH showed larger perfusion CT infarct core than patients without ICH (

p
<
0.01

). Conclusion. None of the examined CTP parameters was found to be a strong predictor of subsequent ICH. ASPECTS and initial CTP core volume were more reliable and may be useful and even so more practicable to assess the risk of subsequent ICH after EVT.
New Evidence for Artemisia absinthium L. Application in Gastrointestinal Ailments: Ethnopharmacology, Antimicrobial Capacity, Cytotoxicity, and Phenolic Profile
Authors: Ivanov Marija , Gašić Uroš , Stojković Dejan , Kostić Marina , Mišić Danijela , Soković Marina
Published: July 2021

Artemisia absinthium L. (Asteraceae) is traditionally used for gastrointestinal ailments and disorders linked to numerous risk factors including microbial infections. We aimed to provide contemporary evidence for its ethnopharmacological use and determine its antimicrobial capacity and mode of action, cytotoxicity, and phenolic constituents. Ethnopharmacological survey was conducted using semistructured interviews. Antimicrobial and antibiofilm capacities were determined by microdilution/crystal violet assay, respectively. Modes of action tested include estimation of exopolysaccharide production (congo red binding assay) and interference with membrane integrity (crystal violet uptake and nucleotide leakage assay). Cytotoxicity was determined using crystal violet assay. Polyphenolic profiling was done by advanced liquid chromatography/mass spectrometry (UHPLC-LTQ OrbiTrap MS). Artemisia absinthium in Serbia is traditionally used for gastrointestinal disorders, among others. Further study revealed high antifungal capacity of herb ethanolic extract towards range of Candida species (MIC 0.5–1 mg/mL) along with promising antibacterial activities (MIC 0.25–4 mg/mL). Interference with membrane integrity could be observed as a possible antimicrobial mechanism. Antibiofilm potential can be considered as high (towards C. krusei) to limited (towards P. aeruginosa) and moderate based on reduction in exopolysaccharide content. In concentrations up to 400 µg/mL, no cytotoxicity was observed towards HaCaT and HGF-1 cell lines. Polyphenolic analysis revealed twenty-one different constituents. A. absinthium usage as a gastrointestinal ailment remedy has been confirmed in vitro by its antimicrobial capacity towards microorganisms whose presence is linked to the diseases and associated complications and noncytotoxic nature of the natural product. The observed activities could be attributed to the present phenolic compounds.
Impact of Sino-US Trade Liberalization on China’s Carbon Emissions and Future Works on Fractional Phenomenon
Authors: Yi Yanchun , Li Yaqing , Qi Ji
Published: July 2021

This study estimates the effects of the Sino-US trade liberalization on CO2 emissions in China and its influencing mechanism. We used the exchange of CNY/USD as the instrumental variable to alleviate the endogeneity with the two-stage least squares method. Different from the existing literature focusing on implied carbon, we use panel data of 27 provinces in China from 1998 to 2018 to examine the relationship between the Sino-US trade liberalization and CO2 emissions. We found that the Sino-US trade liberalization had a positive effect on the environment and reduced CO2 emissions.
Quantitative Inversion of Water‐Inrush Incidents in Mountain Tunnel beneath a Karst Pit
Authors: Wan Fei , Xu Peiwen , Zhang Peng , Qu Hongfu , Wang Lihua , Zhang Xuan
Published: July 2021

Quantitative inversion of accidents is an important work of finding the cause of accidents and avoiding their recurrence. However, quantitative inversion of accidents is difficult due to the lack and limitation of accidents monitoring information. Focusing on water‐inrush incidents of Jiguan Mountain tunnel, this paper proposes a set of workflows to find out the missing conditions and quantitative inversion of accidents by flow analysis and structural safety analysis on the basis of investigating the rain capacity and water outflow in water‐inrush incidents. First, hydraulic boundary in water‐inrush incidents is acquired by analyzing the relationship of catchment, infiltration, and accumulation of rainwater in karst pit using the flooding algorithm of ArcGIS and the topographic mapping of UAV photogrammetry. Second, the permeability coefficients of karst infiltration zone and tunnel surrounding rock are acquired by two‐step decoupling and inverse analyzing the water inflow, flow rate, and interval time between rainfall and water inrush. Third, tunnel accidents of the overload of tunnel lining induced by the catchment and infiltration of karst pit under extreme rainfall conditions are numerically simulated by using FLAC. The results indicate that quantitative inversion of water‐inrush incidents reveals the process and cause of accidents and provides the safety index of tunnel structure. Not only is the water‐inrush incidents of karst tunnel controlled by hydrogeology conditions, but also the rainfall recharge should not be ignored.
Microbiological and Clinicoepidemiological Profile of a Series of Patients with Infective Endocarditis at a Center in Eastern Nepal
Authors: Bajracharya Sohani , Khanal Basudha , Siwakoti Shraddha , Singh Rupa Rajbhandari , Sharma Sanjib Kumar
Published: July 2021

Background. The microbiological and clinicoepidemiological profile of infective endocarditis (IE) has undergone significant change over time. The pattern of IE studied at local level provides broader vision in understanding the current scenario of this disease. This study aimed to depict the overall picture of IE and its changing profile by evaluating the microbiological and clinicoepidemiological features in the context of a tertiary care center of eastern Nepal. Methods. The descriptive study was conducted from September 2017 to August 2018 among IE patients presenting to B. P. Koirala Institute of Health Sciences, Nepal. Detailed history and clinical manifestations of patients were noted. Microorganisms isolated from the blood culture were processed for identification by standard microbiological methods, and susceptibility testings were done. Each patient was assessed daily during hospital stay. Results. Ten definite and 7 possible endocarditis cases were studied. The mean age was 41.4 ± 15.85 (17–70) years with predominance of male (4.7 : 1). Rheumatic heart disease (41.1%) was the most common underlying heart disease observed followed by injection drug user endocarditis (23.5%). All the cases had native valve endocarditis. Aortic valve was the most common valve involved (35.3%) followed by mitral, tricuspid, and pulmonary valves. Blood culture positivity was 53%. Staphylococcus aureus was the major causative agent responsible for 23.5% of the cases followed by Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. Mortality of 2 cases (11.8%) was associated with S. aureus and P. aeruginosa. Majority of patients developed acute kidney injury (35.3%) and congestive cardiac failure (23.5%). Conclusion. IE patients in our center exhibited differences from the west in terms of age at presentation and predisposing factors but held similarity in terms of commonly isolated microorganisms. The changing patterns of IE, etiological agents, and their antimicrobial susceptibility observed in this study may be helpful for clinicians in formulating a new empirical antibiotic treatment protocol.
HIF-1α RNAi Combined with Asparagus Polysaccharide Exerts an Antiangiogenesis Effect on Hepatocellular Carcinoma In Vitro and In Vivo
Authors: Zhu Tingting , Cheng Ziwei , Peng Xiaolin , Xing Dongwei , Zhang Minguang
Published: July 2021

Background. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and life-threatening malignancies globally. Hypoxia activates hypoxia-inducible factor-1α (HIF-1α), which is the key factor in promoting angiogenesis in HCC. Currently, there are few studies on the effects of HIF-1α-targeted gene therapy combined with traditional Chinese herbal extracts. Objective. We investigated the effects of HIF-1α RNA interference (RNAi) combined with asparagus polysaccharide (ASP) on HCC in vitro and in vivo. Methods. CCK-8, wound-healing, transwell, and human umbilical vein endothelial cell tube formation assays were performed to evaluate the proliferation, migration, invasion, and angiogenesis of HCC cells in vitro. In addition, western blotting, qPCR, and immunohistochemistry were performed to detect the expression of HIF-1α, vascular endothelial growth factor, AKT, p-AKT, ERK, p-ERK, and CD34 in HCC cells. Results. The combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep1 and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. In addition, this combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways. These results were observed both in vitro and in vivo. Conclusion. Our study indicates that HIF-1α RNAi combined with ASP inhibits angiogenesis in HCC via the PI3K and MAPK signaling pathways. Thus, we suggest that this combination may be an effective method for the comprehensive treatment of HCC, which may provide new ideas for the treatment of other malignant tumors.
Modeling High-Grade Serous Ovarian Carcinoma Using a Combination ofIn VivoFallopian Tube Electroporation and CRISPR-Cas9–Mediated Genome Editing
Authors: Teng Katie , Ford Matthew J. , Harwalkar Keerthana , Li YuQi , Pacis Alain S. , Farnell David , Yamanaka Nobuko , Wang Yu-Chang , Badescu Dunarel , Ton Nu Tuyet Nhung , Ragoussis Jiannis , Huntsman David G. , Arseneau Jocelyne , Yamanaka Yojiro
Published: July 2021

Ovarian cancer is the most lethal gynecologic cancer to date. High-grade serous ovarian carcinoma (HGSOC) accounts for most ovarian cancer cases, and it is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination of in vivo electroporation and CRISPR-Cas9–mediated genome editing. Mutation of tumor suppressor genes associated with HGSOC in two different combinations (Brca1, Tp53, Pten with and without Lkb1) resulted in successfully generation of HGSOC, albeit with different latencies and pathophysiology. Implementing Cre lineage tracing in this system enabled visualization of peritoneal micrometastases in an immune-competent environment. In addition, these models displayed copy number alterations and phenotypes similar to human HGSOC. Because this strategy is flexible in selecting mutation combinations and targeting areas, it could prove highly useful for generating mouse models to advance the understanding and treatment of ovarian cancer.

Significance:

This study unveils a new strategy to generate genetic mouse models of ovarian cancer with high flexibility in selecting mutation combinations and targeting areas.
Macrophage-Derived Cholesterol Contributes to Therapeutic Resistance in Prostate Cancer
Authors: El-Kenawi Asmaa , Dominguez-Viqueira William , Liu Min , Awasthi Shivanshu , Abraham-Miranda Julieta , Keske Aysenur , Steiner KayLee K. , Noel Leenil , Serna Amparo N. , Dhillon Jasreman , Gillies Robert J. , Yu Xiaoqing , Koomen John M. , Yamoah Kosj , Gatenby Robert A. , Ruffell Brian
Published: July 2021

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted AR nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of liver X receptor (LXR)-β, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC.

Significance:

These results suggest that macrophage-targeted therapies can be combined with androgen deprivation therapy to treat patients with prostate cancer by limiting cholesterol bioavailability and the production of intratumoral androgens.

See related commentary by Al-Janabi and Lewis, p. 5399
M6A Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma
Authors: Qiu Xinyao , Yang Shuai , Wang Shan , Wu Jianmin , Zheng Bo , Wang Kaiting , Shen Siyun , Jeong Seogsong , Li Zhixuan , Zhu Yanjing , Wu Tong , Wu Xuan , Wu Rui , Liu Weiwei , Wang Hong-Yang , Chen Lei
Published: July 2021

N6-methyladenosine (m6A) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important m6A demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC). Regulation of PD-L1 expression by ALKBH5 was confirmed in human ICC cell lines. Sequencing of the m6A methylome identified PD-L1 mRNA as a direct target of m6A modification whose levels were regulated by ALKBH5. Furthermore, ALKBH5 and PD-L1 mRNA were shown to interact. ALKBH5 deficiency enriched m6A modification in the 3′UTR region of PD-L1 mRNA, thereby promoting its degradation in a YTHDF2-dependent manner. In vitro and in vivo, tumor-intrinsic ALKBH5 inhibited the expansion and cytotoxicity of T cells by sustaining tumor cell PD-L1 expression. The ALKBH5-PD-L1–regulating axis was further confirmed in human ICC specimens. Single-cell mass cytometry analysis unveiled a complex role of ALKBH5 in the tumor immune microenvironment by promoting the expression of PD-L1 on monocytes/macrophages and decreasing the infiltration of myeloid-derived suppressor-like cells. Analysis of specimens from patients receiving anti-PD1 immunotherapy suggested that tumors with strong nuclear expression patterns of ALKBH5 are more sensitive to anti-PD1 immunotherapy. Collectively, these results describe a new regulatory mechanism of PD-L1 by mRNA epigenetic modification by ALKBH5 and the potential role of ALKBH5 in immunotherapy response, which might provide insights for cancer immunotherapies.

Significance:

This study identifies PD-L1 mRNA as a target of ALKBH5 and reveals a role for ALKBH5 in regulating the tumor immune microenvironment and immunotherapy efficacy.
Hereditary and Inflammatory Bowel Disease-Related Early Onset Colorectal Cancer Have Unique Characteristics and Clinical Course Compared with Sporadic Disease
Authors: Arif Arif A. , Chahal Daljeet , Ladua Gale K. , Bhang Eric , Salh Bill , Rosenfeld Greg , Loree Jonathan M. , Donnellan Fergal
Published: July 2021

Background:

Early onset colorectal cancer (EoCRC), diagnosed in those <50 years old, is increasing in incidence. We sought to differentiate characteristics and outcomes of EoCRC in patients with sporadic disease or preexisting conditions.

Methods:

We evaluated 2,135 patients with EoCRC in a population-based cohort from the Canadian province of British Columbia. Patients were identified on the basis of presence of hereditary syndromes (n = 146) or inflammatory bowel disease (IBD; n = 87) and compared with patients with sporadic EoCRC (n = 1,902).

Results:

Proportions of patients with preexisting conditions were highest in the youngest decile of 18–29 (34.3%, P < 0.0001). Patients with sporadic EoCRC were older, more likely female, and had increased BMI (P < 0.05). IBD-related EoCRC had the highest rates of metastatic disease, poor differentiation, adverse histology, lymphovascular, and perineural invasion (P < 0.05). Survival was lower in patients with IBD (HR, 1.80; 95% CI, 1.54–3.13; P < 0.0001) and higher in hereditary EoCRC (HR, 0.47; 95% CI, 0.45–0.73; P < 0.0001) compared with sporadic. Prognosis did not differ between ulcerative colitis or Crohn's disease but was lower in those with undifferentiated-IBD (HR, 1.87; 95% CI, 1.01–4.05; P = 0.049). Lynch syndrome EoCRC had improved survival over familial adenomatous polyposis (HR, 0.31; 95% CI, 0.054–0.57; P = 0.0037) and other syndromes (HR, 0.43; 95% CI, 0.11–0.99; P = 0.049). In multivariate analysis controlling for prognostic factors, hereditary EoCRC was unchanged from sporadic; however, IBD-related EoCRC had worse overall survival (HR, 2.21; 95% CI, 1.55–3.16; P < 0.0001).

Conclusions:

EoCRC is heterogenous and patients with preexisting conditions have different characteristics and outcomes compared with sporadic disease.

Impact:

Prognostic differences identified here for young patients with colorectal cancer and predisposing conditions may help facilitate treatment planning and patient counseling.

See related commentary by Hayes, p. 1775
BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression
Authors: Xing Lijie , Wang Su , Liu Jiye , Yu Tengteng , Chen Hailin , Wen Kenneth , Li Yuyin , Lin Liang , Hsieh Phillip A. , Cho Shih-Feng , An Gang , Qiu Lugui , Kinneer Krista , Munshi Nikhil , Anderson Kenneth C. , Tai Yu-Tzu
Published: July 2021

Purpose:

Efforts are required to improve the potency and durability of CD38- and BCMA-based immunotherapies in human multiple myeloma. We here delineated the molecular and cellular mechanisms underlying novel immunomodulatory effects triggered by BCMA pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) MEDI2228 which can augment efficacy of these immunotherapies.

Experimental Design:

MEDI2228-induced transcriptional and protein changes were investigated to define significantly impacted genes and signaling cascades in multiple myeloma cells. Mechanisms whereby MEDI2228 combination therapies can enhance cytotoxicity or overcome drug resistance in multiple myeloma cell lines and patient multiple myeloma cells were defined using in vitro models of tumor in the bone marrow (BM) microenvironment, as well as in human natural killer (NK)-reconstituted NOD/SCID gamma (NSG) mice bearing MM1S tumors.

Results:

MEDI2228 enriched IFN I signaling and enhanced expression of IFN-stimulated genes in multiple myeloma cell lines following the induction of DNA damage–ATM/ATR-CHK1/2 pathways. It activated cGAS-STING-TBK1-IRF3 and STAT1-IRF1–signaling cascades and increased CD38 expression in multiple myeloma cells but did not increase CD38 expression in BCMA-negative NK effector cells. It overcame CD38 downregulation on multiple myeloma cells triggered by IL6 and patient BM stromal cell-culture supernatant via activation of STAT1-IRF1, even in immunomodulatory drug (IMiD)- and bortezomib-resistant multiple myeloma cells. In vitro and in vivo upregulation of NKG2D ligands and CD38 in MEDI2228-treated multiple myeloma cells was further associated with synergistic daratumumab (Dara) CD38 MoAb-triggered NK-mediated cytotoxicity of both cell lines and autologous drug-resistant patient multiple myeloma cells.

Conclusions:

These results provide the basis for clinical evaluation of combination MEDI2228 with Dara to further improve patient outcome in multiple myeloma.
Patrimônio em pedra
Authors:   Universidade de São Paulo. Instituto de Geociências, Lama Eliane Aparecida Del
Published: July 2021

O patrimônio pétreo brasileiro é muito rico e diversificado, como atestam os capítulos dessa obra. Pedras locais ou exóticas, com suas características intrínsecas garantem a perpetuação de edifícios e monumentos, mesmo que, às vezes, a conservação não faça jus à sua grandiosidade. O objetivo do livro é apresentar o patrimônio em pedra nas regiões brasileiras. A Unesco já reconheceu em nossos territórios vários sítios patrimoniais, tanto do início da colonização do país, como as cidades de Salvador, Belém, São Luís e outras, como de construções mais recentes, como é o caso da cidade de Brasília e do Conjunto Moderno da Pampulha. Dessa maneira, a publicação apresenta descrições de diversos patrimônios brasileiros, especialmente em pedra, com o intuito de divulgar nossa geodiversidade. Como contraponto serão apresentados alguns dos patrimônios mundiais da Unesco no capítulo 2 e, na sequência, o patrimônio construído nacional. Ressalta-se que a obra foi concebida e realizada durante a pandemia da Covid-19, com a perda de mais de 540.000 de brasileiras (os), dentre eles pessoas que se dedicavam ao patrimônio.
‘You would not want to be the murderer of our dreams and options, right?’
Authors: Rodríguez Velasco David , Ainciburu María Cecilia , Liu Xiaoxu Katia
Published: July 2021

Studies of how adult Chinese speakers express disagreement at work or in business have a well-established tradition; whereas, studies on young students and university lecturers are scarcer. In general, the description of relationships with authority figures has been characterised by evidence of greater distance and a greater rituality than equivalent Western uses. The objective of this work is to verify whether, in a mutated communicative situation, students express their opposition to lecturer via email using predominantly indirect and attenuated linguistic forms—as might be expected—or whether linguistics changes are evident. For this purpose, 149 university students wrote a letter to their language lecturer in which they express their disagreement with the grade received. The results of the analysis reveal that, contrary to what was predicted, acts of direct speech are prevalent.
The enigmatic Nearctic genus Ceramphis Casey revisited (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: July 2021

Ceramphis Casey is the only genus of Scydmaenini restricted to North America. Despite previous redescriptions of the only included species, C. deformata (Horn), not all taxonomically important structures have been illustrated, and consequently morphological affinities with other Scydmaenini genera remain unclear. Ceramphis deformata is redescribed with exoskeletal features documented by scanning electron microscopy. Similarities and differences in relation to all remaining Scydmaenini (preliminarily subdivided into three groups of genera) are discussed. Differences between Ceramphis and Scydmaenus seem rather minor and Ceramphis, apart from its unusual body shape, closely resembles a group of several subgenera of Scydmaenus characterized by the metanepisterna fused with the metaventrite. However, unclear taxonomy of Scydmaenus with its 30 ill-defined subgenera makes it impossible to decide whether Ceramphis should be maintained as a genus or reduced to a subgenus of Scydmaenus. For this reason, status of Ceramphis remains unchanged, until a comprehensive revision and phylogenetic analysis of the Adrastia-Ceramphis-Scydmaenus group of genera has been carried out.
The essential role of early-spring westerly wind burst in generating the centennial extreme 1997/98 El Niño
Authors: Lian Tao , Chen Dake
Published: July 2021

While both intrinsic low-frequency atmosphere–ocean interaction and multiplicative burst-like event affect the development of the El Niño–Southern Oscillation (ENSO), the strong nonlinearity in ENSO dynamics has prevented us from separating their relative contributions. Here we propose an online filtering scheme to estimate the role of the westerly wind bursts (WWBs), a type of aperiodic burst-like atmospheric perturbation over the western-central tropical Pacific, in the genesis of the centennial extreme 1997/98 El Niño using the CESM coupled model. This scheme highlights the deterministic part of ENSO dynamics during model integration, and clearly demonstrates that the strong and long-lasting WWB in March 1997 was essential for generating the 1997/98 El Niño. Without this WWB, the intrinsic low-frequency coupling would have only produced a weak warm event in late 1997 similar to the 2014/15 El Niño.
Statistical Calibrations of Surface Air Temperature Forecasts over East Asia using Pattern Projection Methods
Authors: Lyu Yang , Zhi Xiefei , Zhu Shoupeng , Fan Yi , Pan Mengting
Published: July 2021

In this study, two pattern projection methods, i.e., the Stepwise Pattern Projection Method (SPPM) and the newly proposed Neighborhood Pattern Projection Method (NPPM), are investigated to improve forecast skills of daily maximum and minimum temperatures (Tmax and Tmin) over East Asia with lead times of 1–7 days. Meanwhile, the decaying averaging method (DAM) is conducted in parallel for comparison. These post-processing methods are found to effectively calibrate the temperature forecasts on the basis of the raw ECMWF output. Generally, the SPPM is slightly inferior to the DAM, while its insufficiency decreases with increasing lead times. The NPPM shows manifest superiority for all lead times, with the mean absolute errors of Tmax and Tmin decreased by ~0.7°C and ~0.9°C, respectively. Advantages of the two pattern projection methods are both mainly concentrated on the high-altitude areas such as the Tibetan Plateau, where the raw ECMWF forecasts show most conspicuous biases. In addition, aiming at further assessments of these methods on extreme event forecasts, two case experiments are carried out towards a heat wave and a cold surge, respectively. The NPPM is retained as the optimal with the highest forecast skills, which reduces most of the biases to < 2°.C for both Tmax and Tmin over all the lead days. In general, the statistical pattern projection methods are capable of effectively eliminating spatial biases in forecasts of surface air temperature. Compared with the initial SPPM, the NPPM not only produces more powerful forecast calibrations, but also provides more pragmatic calculations and greater potential economic benefits in practical applications.
Millennials as the Future of Corrections: A Generational Analysis of Public Policy Opinions
Authors: Lee Heejin , Cullen Francis T. , Burton Alexander L. , Burton Velmer S.
Published: July 2021

This study presents a comprehensive assessment of what Millennials think about U.S. correctional policy. Using a 2017 national-level sample ( N = 1,000), Millennials’ correctional policy opinions across 13 outcomes are assessed and compared to the views of other generations. The main findings are twofold. First, Millennials are only modestly punitive but clearly supportive of progressive policies. Thus, Millennials favor a rehabilitative correctional orientation, believe in offender redeemability, and prefer policies to protect ex-felons’ civil rights and to expunge criminal records for minor offenses. Second, generational differences in public support for correctional policies are mostly limited. Americans of all generations tend to endorse inclusionary policies—a finding indicating that the future of American corrections might see a lengthy era of progressive reform.
Predicting Israeli Public Support for Capital Punishment: Crime Type and Severity, Offender, Observer, and Victim Characteristics
Authors: Cohen-Louck Keren , Levy Inna , Herzog Sergio
Published: July 2021

This study investigates whether crime type and severity, as well as offender, observer, and victim characteristics predict public attitudes towards capital punishment in Israel. We surveyed Israeli citizens by phone. A random and representative sample of 594 participants, ages 20 to 74, read scenarios illustrating crimes and were asked about their perception of capital punishment as an appropriate punishment. The results indicate that most participants did not support capital punishment. Perceived high-crime severity, a crime that constitutes terrorism, and male observer (participant) status predicted 34% in an increased likelihood of supporting capital punishment. The discussion attributes the stronger support of capital punishment in cases of terrorism to the Israeli experience of chronic terrorism and explains gender differences by gender-role socialization.