bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation on the Influence Caused by Shield Tunneling: WSN Monitoring and Numerical Simulation
Authors: Liu Hao , Shi Jinjiang , Li Jiasen , Liu Chao
Published: February 2021

Traditional monitoring techniques are faced with the problems of low acquisition frequency and easy to be affected by the construction environment during the shield tunneling, which cannot meet the actual needs of timeliness monitoring of surrounding environmental impact on shield tunnel construction. Based on this actual demand, a wireless sensor network (WSN) system was used to monitor the response of shield tunnel segments and surrounding buildings during the shield tunneling in this study. According to the result of the signal transmission test, an optimization scheme of microelectromechanical system (MEMS) sensor layout is designed to improve the monitoring efficiency of the WSN system. Through the comparative analysis of WSN system monitoring data and traditional monitoring data, it is found that, with the increasing distance between the monitoring section and the tunnel face, the convergence value of tunnel lining clearance gradually tends to be stable, and the wireless monitoring results of transverse clearance convergence of the tunnel in this section are consistent with the overall deformation trend of the convergence gauge monitoring results. This study also simulated the shield tunneling adjacent buildings using a nonlinear finite element method. A parameter sensitivity analysis of the support pressure of the excavation face and the grouting pressure at the tail of the shield is carried out. The results show that the surface settlement can be reduced by properly increasing the grouting pressure and the support pressure of the excavation face. Moreover, increasing the support pressure of the excavation face has a better inhibition effect on the settlement of the surface soil than increasing the grouting pressure.
Semi-Supervised Ensemble Classifier with Improved Sparrow Search Algorithm and Its Application in Pulmonary Nodule Detection
Authors: Zhang Jiangnan , Xia Kewen , He Ziping , Yin Zhixian , Wang Sijie
Published: February 2021

The Adaptive Boosting (AdaBoost) classifier is a widely used ensemble learning framework, and it can get good classification results on general datasets. However, it is challenging to apply the AdaBoost classifier directly to pulmonary nodule detection of labeled and unlabeled lung CT images since there are still some drawbacks to ensemble learning method. Therefore, to solve the labeled and unlabeled data classification problem, the semi-supervised AdaBoost classifier using an improved sparrow search algorithm (AdaBoost-ISSA-S4VM) was established. Firstly, AdaBoost classifier is used to construct a strong semi-supervised classifier using several weak classifiers S4VM (AdaBoost-S4VM). Next, in order to solve the accuracy problem of AdaBoost-S4VM, sparrow search algorithm (SSA) is introduced in the AdaBoost classifier and S4VM. Then, sine cosine algorithm and new labor cooperation structure are adopted to increase the global optimal solution and convergence performance of sparrow search algorithm, respectively. Furthermore, based on the improved sparrow search algorithm and adaptive boosting classifier, the AdaBoost-S4VM classifier is improved. Finally, the effective improved AdaBoost-ISSA-S4VM classification model was developed for actual pulmonary nodule detection based on the publicly available LIDC-IDRI database. The experimental results have proved that the established AdaBoost-ISSA-S4VM classification model has good performance on labeled and unlabeled lung CT images.
Recognition and Prevention of Bed Separation Water: Based on Trapezoid Platform Model
Authors: Hu Ru , Wu Jiwen , Zhai Xiaorong , Liu Wei
Published: February 2021

In recent years, bed separation water inrush, as a new type of water disaster, has posed serious threat to mining safety in China’s many coal mines. This study focused on periodic water inrush accidents in the No. 7335 working face owned by Xuzhuang Coal Mine, Jiangsu Province, China. Based on the theory of key strata, the formation positions of the separation layer in the overlying strata were first identified; next, the trapezoid platform model of the fracture of the overlying strata was introduced for illustrating the evolutional process of the bed separation space and accurately calculating the position and the geometrical morphology of the bed separation space. On that basis, the relation between the fracture of the overlying stratum and the inrush of bed separation water was revealed with the use of the plate theory. Moreover, the prevention and control measures of the bed separation water were formulated. Research show that the arrangement of the diversion drilling holes can successfully eliminate the threat of the bed separation water to the lower working face.
Extracellular Vesicles: Novel Roles in Neurological Disorders
Authors: Jin Qian , Wu Peipei , Zhou Xinru , Qian Hui , Xu Wenrong
Published: February 2021

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.
An E‐Commerce Economic Dynamic Data Evaluation Model Based on Multiuser Demand Constraints
Authors: Wang Chenyuan
Published: February 2021

Forecasting the future earnings of listed companies based on multiuser constraints is the focus of investors, securities dealers, creditors, and management. Some empirical studies at home and abroad indicate that the financial reports issued by listed companies regularly contain information about future changes in earnings. On this basis, this article uses the Bayesian dynamic regression model to predict the changes in the future earnings of listed companies and compares the results with traditional analysis models. Through case analysis, it can be seen that the prediction effect of the Bayesian dynamic regression model is generally better than that of the traditional regression model. The Bayesian model can better predict the results, and through the prediction results, it can also establish an evolutionary game model of the industrial innovation replication dynamic system, which can assist enterprises in making profit decisions.
A New Hybrid Fuzzy Model: Satisfaction of Residents in Touristic Areas toward Tourism Development
Authors: Mehdiabadi Amir , Wanke Peter Fernandes , Khorshid Seddigheh , Spulbar Cristi , Birau Ramona
Published: February 2021

This research brings a practical approach to the issue of the level of satisfaction from residents in tourist destinations by using three attractive methods together. After reviewing the theoretical foundations and the meta-synthesis method in identifying indicators, fuzzy Delphi was used for screening, fuzzy SWARA (stepwise weight assessment ratio analysis) for weighting, and fuzzy EDAS (evaluation based on distance from average solution) for 16 very important tourism areas in Iran. Six important factors (economic, cultural, environmental, perceptual, social, and health) along with 42 important criteria were identified in the meta-combination method, while also obtaining the total weight of the indicators. Finally, the sensitivity analysis of the model is performed and practical suggestions presented.
The Outer Retinal Membrane Protein 1 Could Inhibit Lung Cancer Progression as a Tumor Suppressor
Authors: Zhang Min , Jiang Jun , Ma Cui
Published: February 2021

Some related reports indicate that the outer retinal membrane protein 1 (ROM1) functions importantly in the regulation of the biological process of tumor. Nevertheless, studies towards the role of ROM1 in lung cancer are few. Here, our data demonstrated that ROM1 displayed a relation with lung cancer tumorigenesis and development. In the Tumor Genome Atlas (TCGA) cohort, reduced ROM1 level was observed in lung cancer tissues, instead of normal tissues. After bioinformatics analysis, the data revealed that ROM1 level was associated with the tumor stage. Additional results indicated that highly expressed ROM1 exhibited a positive correlation with the overall survival rate, and ROM1 was probably a promising prognostic biomarker of lung cancer. Additionally, our results indicated that knocking out ROM1 could promote cell proliferation, migration, and invasion. Our data conclusively demonstrated that ROM1 modulated lung cancer tumorigenesis and development, as a prognosis and treatment biomarker.
Nutrient Stimulation of Indigenous Microorganisms for Oil-in-Water Emulsion in a Medium Temperature Petroleum Reservoir with Ca2+-Rich Brine
Authors: Shi Guoxin , Jia Yuanyuan , Bai Lei , Li Guoqiang , Liu Xiaoli , Liu Meichen , Dai Xuecheng , Tian Xuefeng , Wang Hongbo , Ma Ting
Published: February 2021

One of the challenges indigenous microbial enhanced oil recovery (MEOR) is facing is the high percentage of divalent ions, which obstruct the growth and metabolism of microorganisms and destabilize the oil-in-water (o/w) emulsion. Six formulas were selected for the stimulation of indigenous microbes and to compare their performances on the oil emulsification and oil spreading in the Luliang oilfield containing Ca2+-rich brine. Illumina MiSeq sequencing of 16S rRNA genes was applied to investigate the structural response of microbial communities to various formulas. The results showed that the addition of proper organic phosphorus and the optimal P/N ratio (0.01) can facilitate production of biosurfactant and create stable o/w emulsion with specific reservoir condition containing Ca2+-rich brine, through direct stimulation of certain functional microbes. This study provides a promising path for direct enrichment of biosurfactant-producing and oil-degrading Dietzia genus and a potential instructional approach of indigenous MEOR in Luliang oilfield.
Cortical Representations of Transversus Abdominis and Multifidus Muscles Were Discrete in Patients with Chronic Low Back Pain: Evidence Elicited by TMS
Authors: Li Xin , Liu Howe , Ge Le , Yan Yifeng , Lo Wai Leung Ambrose , Li Le , Wang Chuhuai
Published: February 2021

Introduction. The transversus abdominis (TVA) and multifidus (MF) muscles are the main segmental spinal stabilizers that are controlled by the primary motor cortex of the brain. However, relocations of the muscle representation in the motor cortex may occur after chronic lower back pain (cLBP); it still needs more evidence to be proven. The current study was aimed at applying transcranial magnetic stimulation (TMS) to investigate the changes of representation of TVA and MF muscles at the cortical network in individuals with cLBP. Methods. Twenty-four patients with cLBP and 12 age-matched healthy individuals were recruited. Responses of TVA and MF to TMS during muscle contraction were monitored and mapped over the contralateral cortex using a standardized grid cap. Maps of the center of gravity (CoG), area, volume, and latency were analyzed, and the asymmetry index was also computed and compared. Results. The locations of MF CoG in cLBP individuals were posterior and lateral to the CoG locations in healthy individuals. In the healthy group, the locations of TVA and MF CoG were closed to each other in both the left and right hemispheres. In the cLBP group, these two locations were next to each other in the right hemisphere but discrete in the left hemisphere. In the cLBP group, the cortical motor map of TVA and MF were mutually symmetric in five out of eleven (45.5%) subjects and leftward asymmetric in four out of ten (40.0%) subjects. Conclusions. Neural representations of TVA and MF muscles were closely organized in both the right and left motor cortices in the healthy group but were discretely organized in the left motor cortex in the cLBP group. This provides strong support for the neural basis of pathokinesiology and clinical treatment of cLBP.
Correlates of Long-Term Survival of Patients with pN+ Esophageal Squamous Cell Carcinoma after Esophagectomy
Authors: He Ming , Qi Zhan , Qiu Rong , Hu Yuanping , Li Juan , Li Yuekao , Wang Yuxiang
Published: February 2021

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. Patients with ESCC have poor long-term survival, especially those with lymphatic metastasis (pN + ESCC). In this retrospective study, we evaluated the correlates of long-term survival time of patients with pN + ESCC. A total of 453 patients with pN + ESCC who underwent surgical R0 resection between Jan 2008 and Sep 2011 were enrolled. The follow-up ended on December 2019. The clinical, pathological, inflammation-related factors and general survival data of these patients were analyzed using SPSS 22.0 software. The 1-, 3-, and 5-year overall survival (OS) rates were 73.7%, 34.6%, and 25.6%, respectively; the 1-, 3-, and 5-year disease-free survival (DFS) rates were 45.0%, 26.3%, and 20.4%, respectively. The median OS and DFS were 23 and 14 months, respectively. On multivariate analyses, gender, site of lesion, number of dissected lymph nodes, stage pTNM, adjuvant therapy, and neutrophil lymphocyte ratio were independent predictors of OS. Site of lesion, stage pTNM, and adjuvant therapy were independent predictors of DFS. Recursive partitioning analysis (RPA) scores of each patient were calculated based on the independent predictors of OS, and the patients were divided into 3 classes: low-risk, medium-risk, and high-risk. The OS, DFS, and local recurrence-free survival were significantly different among these three RPA classes

P
<
0.001

. Several factors showed an independent association with long-term postoperative survival of pN + ESCC patients after radical surgery. RPA scores can potentially be used to predict the prognosis of ESCC.
Experimental Study on the Effect of Brittleness on the Dynamic Mechanical Behaviors of the Coal Measures Sandstone
Authors: Xu Junce , Pu Hai , Sha Ziheng
Published: February 2021

As one of the most crucial mechanical parameters of the rock materials, the effect of brittleness on the deformation and failure is of great practical significance for geotechnical construction and disaster prevention and mitigation. In this paper, the deformation and failure behaviors of the different brittle samples under dynamic loading were investigated using a split Hopkinson pressure bar (SHPB) experimental system. Besides, scanning electron microscopy (SEM) was also employed to study the relationship between the microscopic failures and rock brittleness and strain rate effects. The results revealed that the brittleness indexes BI3 and BI5 of the samples under uniaxial compression follow a linearly decreasing trend affected by the temperature changes, while the brittleness of the sample shows an increasing trend with the increase of strain rate under the dynamic loading. Also, the decline in the brittleness leads to an increase in the prepeak yield deformation phase of the sample under dynamic loading; after the peak point, the sample failure mode transitions from type I to type II with self‐sustaining failure. Moreover, it was found that the dynamic strength increase factor presents a negative correlation with the sample brittleness. Finally, the macroscopic failure mode of the sample changes from split failure with multiple cracks to shear failure with few cracks due to the effect of decreasing brittleness. The failure surface of the sample gradually becomes smooth with the increase of brittleness, which manifests as a decrease in microcracks, and the gradual increase of the strain rate makes the failure surface rough, accompanied by an increase in microcracks.
Citral Delays Postharvest Senescence of Kiwifruit by Enhancing Antioxidant Capacity under Cold Storage
Authors: Wei Ling , Chen Chuying , Wan Chunpeng , Chen Ming , Chen Jinyin
Published: February 2021

Citral is an aliphatic aldehyde extracted from citrus essential oil. The aim of the study was to examine how citral treatment affects the weight loss, firmness, respiration, and ripening index, as well as the antioxidant capacity of kiwifruit (Actinidia chinensis cv. ‘Jinkui’). The citral treatment was seen to reduce the weight loss, softening, and fruit respiration compared to control fruits. Citral treatment also had an inhibitory effect on ripening index, O2•− production rate, and malondialdehyde (MDA) accumulation. The degradations of ascorbic acid (AsA) content, total flavonoids content (TFC), and total phenolics content (TPC) were also suppressed by citral. In contrast, citral treatment induces the activation of antioxidant enzyme system such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Collectively, the results indicated that citral treatment delays postharvest senescence and prolongs storage life by enhancing antioxidant capacity in harvested kiwifruits. These findings suggest that citral has the potential to be used as a promising natural preservative for the extension of postharvest quality in harvested kiwifruit.
Fuzzy-Model-Based Control for Markov Switching Singularly Perturbed Systems with the Stochastic Communication Protocol
Authors: An Zhiguo , Chen Qijuan , Liu Junxiang , Luan Le , Wang Yong , Zhou Kai , Mo Wenxiong , Huang Huihong
Published: February 2021

This work is concerned with the

H

∞

control for Markov switching singularly perturbed systems with the stochastic communication protocol. To coordinate the data transmission and save the bandwidth usage, the stochastic communication protocol with a compensator is applied to schedule the information exchange. The goal of this work is to design a joint-Markov-process-based controller such that the resulting system is stochastically stable with prescribed performance. Based on the Lyapunov functional technique, a sufficient condition is derived to ensure the existence of the achieved controller. Finally, the effectiveness and correctness of the developed results are verified by the simulation example.
Robust Airport Gate Assignment Based on the Analysis of Flight Arrival Time
Authors: Tan Caimao , He Junliang
Published: February 2021

At present, hub airport is facing a lot of emergency situations, e.g., the management of irregular flight, which affects the sustainable development of the airport. Most of the methods for evaluating the robustness of airport gate assignment have been proposed by giving an independent evaluation function based on their experience, and thus, subjective factors are involved in varying degrees. Therefore, this paper puts forward an objective evaluation method based on the analysis of airport flight arrival, which gives a digital transformation strategy for the airport resource scheduling. A novel evaluation method based on data analysis of flight arrival time, and a mathematical model are formulated accordingly. In order to solve the proposed NP-hard problem, a new hybrid genetic algorithm combined with a heuristic algorithm is designed. In numerical experiments, the actual flight data of an international hub airport are used to analyze and verify the effectiveness of the proposed method. The results showed the advantages in scheme stability, operating cost savings, and risk reduction of the proposed method.
VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients
Authors: Chen Fangfang , Yin Shuai , Luo Bin , Wu Xiaoyan , Yan Honglin , Yan Dandan , Chen Chuang , Guan Feng , Yuan Jingping
Published: February 2021

Aim. The main objective of this article was to evaluate the association of voltage‐dependent anion channel 1 (VDAC1) with Cytochrome C (Cytc) expression, various clinicopathological features, and prognosis in breast cancer (BC) patients. Meanwhile, the correlation of Cytc expression with various clinical features and 5‐year disease‐free survival (5‐DFS) of BC was also investigated. Methods. In vivo, expression of VDAC1 and Cytc was examined in 219 BC tissues and 100 benign breast lesions by immunohistochemical (IHC) analysis. In vitro, MTT and wound healing migration assay were performed to detect the effect of VDAC1 on BC cells. Results. Expression of VDAC1 is conversely associated with Cytc in BC (P = 0.011), especially in triple‐negative breast cancer (TNBC) (P = 0.004). Knockdown of VDAC1 inhibited proliferation (P < 0.001) and migration (P < 0.05) of MCF‐7 cells. High expression of VDAC1 and low expression of Cytc had a significant association with multiple clinicopathological parameters (P < 0.05) and poor 5‐DFS (P < 0.001) in BC. Conclusion. VDAC1 was elevated in BC tissues and conversely associated with Cytc. Detection of VDAC1 may provide guidance for the poor prognosis of BC, especially TNBC.
Reliability of Lower Extremity Muscle Power and Functional Performance in Healthy, Older Women
Authors: Katsoulis Konstantina , Mathur Sunita , Amara Catherine E.
Published: February 2021

Evaluation of the long-term reliability of muscle power and functional performance tests in older, healthy adults is warranted since determining whether performance is consistent over longer durations is more relevant for intervention studies. Objective. To assess the long-term test–retest reliability of measures of muscle power and lower body functional performance in healthy, nonexercising, older women. Methods. Data were derived from a nonexercising control group (n = 18; age = 73.3 (3.4) years; height = 159.6 (7.7) cm; body mass = 69.5 (12.7) kg; BMI = 27.3 (4.8)) of a randomized controlled trial of muscle power training in older women. Participants underwent lower extremity muscle power (Biodex) and functional testing (Short Physical Performance Battery, gait speed, 30-second chair stands, stair climbing, and 400-meter walk) at week 0 (baseline), 9, and 15. Results. For the upper leg, intraclass correlation coefficients (ICCs) were very high for knee extension power (0.90–0.97) and high to very high for knee flexion power (0.83–0.96). For lower-leg power, ICCs were high to very high for plantar flexion and dorsiflexion (0.83–0.96). ICCs for functional performance were moderate to very high (0.64–0.93). Coefficient of variation of the typical error (CVTE) was <10.5% for knee extension/flexion power, 9.9–20.0% for plantar flexion/dorsiflexion power, and 1.9–14.9% for functional performance. Knee extension power and stair climb power demonstrated the highest reliability for muscle power and function, respectively. Mean values did not change over time, with the exception of the chair stands (

p
<
0.05

); however, these changes were not considered clinically meaningful. Conclusions. The current study provides evidence supporting the long-term reliability of performance assessments of muscle power and lower body functional capacity over a period of up to 15 weeks in healthy, older women.
Peculiar Presentation of COVID-19: A Case Report of Concurrent Stroke and Guillain–Barré Syndrome
Authors: Ansari Behnaz , Hemasian Helia
Published: February 2021

Background. Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has turned into a pandemic. There are few studies reporting Guillain–Barré syndrome (GBS) and stroke separately associated with COVID-19. In this study, we report an unusual case of COVID-19 with stroke and GBS concurrently. Case Report. A 59-year-old woman presented with left-sided weakness of two weeks’ duration followed by right-sided weakness and foot paresthesia. She also complained of cough, myalgia, and respiratory distress of three weeks’ duration. On examination, the patient had respiratory distress. The limb examination revealed asymmetric weakness. All limb reflexes were absent. Pinprick sensation was impaired. The chest CT scan and PCR of nasopharyngeal swab confirmed the diagnosis of COVID-19. Further evaluation revealed acute cerebral infarction and GBS. Consequently, the patient was treated by plasmapheresis, and her symptoms partially improved. Conclusion. According to reports, 36.4% of COVID-19 cases display neurological complications. The neurological manifestations of the disease can involve both the central and peripheral nervous systems. Previously, a few cases of GBS and cerebrovascular disease have been reported in association with COVID-19 separately, while in the present case, CNS and PNS involvement occurred concurrently. It is hypothesized that this concurrence is related to the imbalance of the systemic inflammatory responses and blood vessel autonomous dysfunction.
Unilateral Hypoglossal Nerve Palsy in a Patient with a Difficult Airway Requiring Prolonged Intubation
Authors: Leuzinger Kahlin , Misra Lopa
Published: February 2021

Isolated cranial nerve injury is a very rare complication of anesthesia. Specifically, hypoglossal nerve palsy affects mobility of the tongue and basic functions of swallowing and speech, and injury can be associated with placement and/or positioning of the endotracheal tube. Many etiologies are described that are unrelated to anesthesia such as tumors, stroke, trauma, or surgical dissection. Identification of hypoglossal neuropraxic-type injury from compression or stretching during anesthetic procedures can be difficult and tends to be a diagnosis of exclusion. Here, we present a case of a unilateral isolated hypoglossal nerve palsy following prolonged intubation in a surgery that involved large fluid shifts resulting in tongue swelling, in which establishment of the airway was initially difficult requiring two attempts. We suggest it is equally as possible that stretch injury occurred during airway instrumentation versus prolonged compression of the nerve between the endotracheal tube and the hyoid bone, possibly relating to a swollen tongue. We outline some treatments that have been used in previous reports and analyze their relation to improvements in symptoms. We conclude that instrumentation of the airway and prolonged intubation are both potential risk factors for hypoglossal nerve palsy, and identification of these risk factors can improve patient care by prompting patient discussions, guiding intraoperative management, and initiating earlier therapies.
Systematic Review and Meta-Analysis of Randomized Controlled Trials of Fuke Qianjin Tablet
Authors: Jie Pan , Kai-Ni Zuo , Xiao-Mei Wang , Meng-Pei Zhang , Zhi-Heng Wang , Hao-Xiang Zhang , Wen-Tao Zhu
Published: February 2021

Purpose. The aim of the research was to evaluate the efficacy and safety associated with Fuke Qianjin tablet combined with conventional therapy in the treatment of pelvic inflammatory diseases and associated complications (endometritis) using a meta-analysis approach. Patients and Methods. We searched 8 electronic databases up to December 31, 2019, including PubMed, the Cochrane Library, Embase, Web of Science, CNKI, WanFang, VIP, and SinoMed. Eligible studies were clinical trials of Fuke Qianjin tablet combined with conventional therapy used in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. The meta-analysis was performed using STATA15 software. Results. A total of 125 RCTs (n = 14,494) were shortlisted for the meta-analysis, which included 23 trials for acute pelvic inflammatory disease, 69 trials for chronic pelvic inflammatory disease, and 33 trials for endometritis. The overall analysis illustrated Fuke Qianjin tablet combined with conventional therapy was significantly more efficacious than conventional therapy alone across all types of antibiotics treatment for acute pelvic inflammatory disease (OR = 5.57, 95% CI 4.09–7.58, Z = 10.90,

p
=
0.001

), chronic pelvic inflammatory disease (OR = 4.70, 95% CI 4.07–5.42, Z = 21.21,

p
=
0.001

) and endometritis (OR = 5.09, 95% CI 4.03–6.43; Z = 13.63,

p
=
0.001

) in both primary endpoints and secondary endpoints. There is also a trend that Fuke Qianjin tablet combined with conventional therapy has lower adverse reaction rates than conventional therapy alone. Conclusion. Fuke Qianjin tablet combined with conventional therapy showed better clinical efficacy in the treatment of acute pelvic inflammatory disease, chronic pelvic inflammatory disease, and endometritis. There were no obvious drug-related adverse reactions. Fuke Qianjin tablet presented advantages in shortening the remission time of clinical symptoms, reducing the concentration of serum inflammatory factors, improving endometrial thickness, menstruation, and reducing relapse rate.
Recent Advances on Nanotechnology-Based Strategies for Prevention, Diagnosis, and Treatment of Coronavirus Infections
Authors: Alimardani Vahid , Abolmaali Samira Sadat , Tamaddon Ali Mohammad
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is exponentially spreading across the world, leading to an outbreak of serious viral pneumonia. Antiviral therapies using chloroquine, hydroxychloroquine, and favipiravir have been approved by several countries to increase the quality of life of SARS-CoV-2-infected patients. Currently, several companies are intensively working on the production of coronavirus (CoV) vaccines, resulting in some specific vaccines that have been approved for CoV infections in humans. Nevertheless, efficient and specific prevention, treatment, and diagnosis are urgently required to combat the biological diversity and rapid mutation in CoV infections. Recently, significant attention has devoted to nanoformulation or nanoparticles (NPs) due to their specific features like high surface-to-volume ratio, drug encapsulation abilities, and specific optical properties to remove the complications of applied conventional therapeutic and diagnosis options. In this regard, NPs are increasingly used as new anti-CoV agents, vaccine carriers or adjuvants, and nanoscale biorecognition elements. The present review article provides a comprehensive discussion on the recent updates regarding the prevention, diagnosis, and treatment of different CoV infections with an emphasis on the application of NPs in vaccination, treatment, and diagnosis of CoV infections.
SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic PTP4A3 through Chromatin Remodeling in t(4;14) Multiple Myeloma
Authors: Chong Phyllis S.Y. , Chooi Jing Yuan , Lim Julia S.L. , Toh Sabrina Hui Min , Tan Tuan Zea , Chng Wee-Joo
Published: February 2021

NSD2 is the primary oncogenic driver in t(4;14) multiple myeloma. Using SILAC-based mass spectrometry, we demonstrate a novel role of NSD2 in chromatin remodeling through its interaction with the SWI/SNF ATPase subunit SMARCA2. SMARCA2 was primarily expressed in t(4;14) myeloma cells, and its interaction with NSD2 was noncanonical and independent of the SWI/SNF complex. RNA sequencing identified PTP4A3 as a downstream target of NSD2 and mapped NSD2–SMARCA2 complex on PTP4A3 promoter. This led to a focal increase in the permissive H3K36me2 mark and transcriptional activation of PTP4A3. High levels of PTP4A3 maintained MYC expression and correlated with a 54-gene MYC signature in t(4;14) multiple myeloma. Importantly, this mechanism was druggable by targeting the bromodomain of SMARCA2 using the specific BET inhibitor PFI-3, leading to the displacement of NSD2 from PTP4A3 promoter and inhibiting t(4;14) myeloma cell viability. In vivo, treatment with PFI-3 reduced the growth of t(4;14) xenograft tumors. Together, our study reveals an interplay between histone-modifying enzymes and chromatin remodelers in the regulation of myeloma-specific genes that can be clinically intervened.

Significance:

This study uncovers a novel, SWI/SNF–independent interaction between SMARCA2 and NSD2 that facilitates chromatin remodeling and transcriptional regulation of oncogenes in t(4;14) multiple myeloma, revealing a therapeutic vulnerability targetable by BET inhibition.
Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
Authors: Datar Ila J. , Hauc Sacha C. , Desai Shruti , Gianino Nicole , Henick Brian , Liu Yuting , Syrigos Kostas , Rimm David L. , Kavathas Paula , Ferrone Soldano , Schalper Kurt A.
Published: February 2021

Purpose:

To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC).

Experimental Design:

Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in >700 immunotherapy-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts.

Results:

Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in <5% of lung malignancies. Tumors with cancer cell–specific β2M downregulation displayed reduced T cells and increased natural killer (NK)–cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8+ T cells and NK-cell infiltration. Samples with cancer cell–selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell–selective downregulation of the HLA subunits was associated with shorter overall survival.

Conclusions:

Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.
Eligibility in Cancer Clinical Research: The Intersection of Discovery, Generalizability, Beneficence, and Justice
Authors: Giantonio Bruce J.
Published: February 2021

Eligibility criteria in clinical trials limit the study population for safety and scientific purposes. The American Society of Clinical Oncology and The Friends of Cancer Research collaboration reconsidered common eligibility criteria in cancer trials and found many to be unnecessarily restrictive. The current recommendations further their efforts to facilitate accrual and improve the generalizability of research results to practice.

See related articles, p. 2394, 2400, 2408, 2416, 2424, and 2430
Modified Hypoxia-Inducible Factor Expression in CD8+ T Cells Increases Antitumor Efficacy
Authors: Veliça Pedro , Cunha Pedro P. , Vojnovic Nikola , Foskolou Iosifina Petrina , Bargiela David , Gojkovic Milos , Rundqvist Helene , Johnson Randall S.
Published: February 2021

Adoptive transfer of antitumor cytotoxic T cells is an emerging form of cancer immunotherapy. A key challenge to expanding the utility of adoptive cell therapies is how to enhance the survival and function of the transferred T cells. Immune-cell survival requires adaptation to different microenvironments and particularly to the hypoxic milieu of solid tumors. The hypoxia-inducible factor (HIF) transcription factors are an essential aspect of this adaptation. In this study, we undertook experiments to define structural determinants of HIF that potentiate antitumor efficacy in cytotoxic T cells. We first created retroviral vectors to deliver ectopic expression of HIF1α and HIF2α in mouse CD8+ T cells, together or individually and with or without sensitivity to the oxygen-dependent HIFα inhibitors Von Hippel–Lindau and factor-inhibiting HIF (FIH). HIF2α, but not HIF1α, drove broad transcriptional changes in CD8+ T cells, resulting in increased cytotoxic differentiation and cytolytic function against tumor targets. A specific mutation replacing the hydroxyl group–acceptor site for FIH in HIF2α gave rise to the most effective antitumor T cells after adoptive transfer in vivo. In addition, codelivering an FIH-insensitive form of HIF2α with an anti-CD19 chimeric antigen receptor greatly enhanced cytolytic function of human CD8+ T cells against lymphoma cells both in vitro and in a xenograft adoptive transfer model. These experiments point to a means to increase the antitumor efficacy of therapeutic CD8+ T cells via ectopic expression of the HIF transcription factor.

See related Spotlight on p. 364
Ceramide Scores Predict Cardiovascular Risk in the Community
Authors: Vasile Vlad C. , Meeusen Jeffrey W. , Medina Inojosa Jose R. , Donato Leslie J. , Scott Christopher G. , Hyun Meredith S. , Vinciguerra Manlio , Rodeheffer Richard R. , Lopez-Jimenez Francisco , Jaffe Allan S.
Published: February 2021

Objective:

Cardiovascular disease remains a leading cause of mortality worldwide. Ceramide scores have been associated with adverse outcomes in patients with established coronary artery disease. The prognostic value of ceramide score has not been assessed in the general population. We tested the hypothesis that ceramide scores are associated with major adverse cardiac events (MACE) in a community-based cohort with average coronary artery disease burden at enrollment.

Approach and results:

In a prospective community-based cohort, we performed passive follow-up using a record linkage system to ascertain the composite outcome of MACE, defined as acute myocardial infarction, coronary revascularization (bypass grafting or percutaneous intervention), stroke, or death. Ceramides were analyzed as log-transformed continuous variables, ratios or scores, and quartiles with adjustment for confounders. We analyzed 1131 subjects, 52% females, mean age±(SD) 64±9 years. After a median follow-up of 13.3 years (Q1, 12.7; Q3, 14.4), 486 patients experienced a MACE: myocardial infarction (80), coronary artery bypass surgery (34), percutaneous coronary intervention (62), stroke (94), and all-cause death (362). Ceramide ratios were significantly associated with MACE independently of LDL-c (low-density lipoprotein cholesterol) and conventional coronary artery disease risk factors. Those in the highest quartile of ceramide score had nearly 1.5-fold risk of MACE, hazard ratio, 1.47 (95% CI, 1.12–1.92). There was a dose-response association across quartiles of ceramide ratios and MACE.

Conclusions:

Elevated ceramide score is a robust predictor of cardiovascular disease and MACE in the community. The risk conferred by the ceramide score has a dose-response behavior and is independent of conventional risk factors.
Platelet Quiescence in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Bypass Graft Surgery
Authors: Sarathy Kiran , Wells George A. , Singh Kuljit , Couture Etienne , Chong Aun Yeong , Rubens Fraser , Lordkipanidzé Marie , Tanguay Jean‐François , So Derek
Published: February 2021

Background

The optimal antiplatelet strategy for patients with acute coronary syndromes who require coronary artery bypass surgery remains unclear. While a more potent antiplatelet regimen will predispose to perioperative bleeding, it is hypothesized that through “platelet quiescence,” ischemic protection conferred by such therapy may provide a net clinical benefit.

Methods and Results

We compared patients undergoing coronary artery bypass surgery who were treated with a more potent antiplatelet inhibition strategy with those with a less potent inhibition through a meta‐analysis. The primary outcome was all‐cause mortality after bypass surgery. The analysis identified 4 studies in which the antiplatelet regimen was randomized and 6 studies that were nonrandomized. Combining all studies, there was an overall higher mortality with weaker strategies compared with more potent strategies (odds ratio, 1.38; 95% CI, 1.03–1.85;
P
=0.03).

Conclusions

Our findings support the concept of platelet quiescence, in reducing mortality for patients with acute coronary syndrome requiring coronary artery bypass surgery. This suggests the routine up‐front use of potent antiplatelet regimens in acute coronary syndrome, irrespective of likelihood of coronary artery bypass graft.
Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer
Authors: Hasegawa Kanae , Ito Hideaki , Kaseno Kenichi , Miyazaki Shinsuke , Shiomi Yuichiro , Tama Naoto , Ikeda Hiroyuki , Ishida Kentaro , Uzui Hiroyasu , Ohno Seiko , Horie Minoru , Yokoyama Osamu , Tada Hiroshi
Published: February 2021

Background

Medical castration, gonadotropin‐releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration.

Methods and Results

This study included 149 patients who underwent medical castration using gonadotropin‐releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [
P
<0.001]; QTc, 416±27 to 439±31 ms [
P
<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients.

Conclusions

Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.
Heart Failure, Atrioventricular Block, and Ventricular Tachycardia in Sarcoidosis
Authors: Rosenthal David G. , Fang Christina D. , Groh Christopher A. , Nah Gregory , Vittinghoff Eric , Dewland Thomas A. , Vedantham Vasanth , Marcus Gregory M.
Published: February 2021

Background

Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis.

Methods and Results

We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7–11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3–134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2–28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%–26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes.

Conclusions

The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.
Outcomes of Surgical Mitral and Aortic Valve Replacements Among Kidney Transplant Candidates: Implications for Valve Selection
Authors: Ngendahimana David K. , Deo Salil V. , Sundaram Varun , Lentine Krista L. , Herzog Charles A. , Al Dahabreh Laith , Srinivas Titte R. , Chavin Kenneth D. , Sarabu Nagaraju
Published: February 2021

Background

Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis.

Methods and Results

We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR.

Conclusions

For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis.