bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Regional Election Implementation as Determinant of Performance of Simultaneous Regional Election: Community Trust and Satisfaction as Mediation, and Regulatory Harmonization as Moderation
Authors: Mindarti Lely Indah , Malik Akmal , Supriyono Bambang , Hermawan
Published: March 2021

The objectives of this research are to analyze how to build the political and managerial balance of government in direct and simultaneous regional elections in Indonesia based on the managerial approach of government and the decentralization approach quantitatively. Data analysis uses the Social Network Analysis (SNA) or Social Network Theory (SNT) approach to map policies using the XL Node and first-order confirmatory factor analysis which is a form of measurement model in the Structural Equation Model (SEM). The population in this study is the Regency/City and Province Organizers of the 2018 elections, which are 88 pairs of Regional Heads/Deputy Regional Heads. The sample of this study was voters who assessed the quality of the elections and other variables, totaling 340 respondents. The results of the study indicate that community trust and community satisfaction can be mediation for the quality of the implementation of regional election to influence the performance of simultaneous regional election. In addition, harmonization of regulations is a moderating variable that can affect the quality of the implementation of regional elections, public trust, and public satisfaction with the performance of simultaneous regional elections. This study conducted a quantification study related to new approaches in building a balance with the managerial approach of governance (Rosenbloom, DH (2015). Public Administration: Understanding Management, Politics, and Law in the Public Sector, 8th ed. Boston, MA: McGraw-Hill; Frederickson, HG (1980). New Public Administration. University of Alabama Press; Frederickson, GN and NA Lynch (1984). The impact of synchronous communication on the problem of electing a leader in a ring. In Proc. 16th Annual ACM Symp. Theory of Computing, Washington, D.C., pp. 493–503. https://doi.org/10.1145/800057.808719 ) and the decentralization approach (Smith, BC (1985). Decentralization: The Territorial Dimension of the State. Taylor & Francis; Smith, BC (2012). Desentralisasi, Dimensi Teritorial Suatu Negara (diterjemahkan oleh Tim MIPI). Jakarta: MIPI).
Discussion of “The Quality of Mandatory Nonfinancial Risk Disclosures and the Moderating Effect of Audit Firm and Partner Characteristics”
Authors: Hay David C.
Published: March 2021

The paper on mandatory nonfinancial risk disclosures and the effect of auditor characteristics examines a topical issue and finds unexpected results. It finds that there is no overall Big 4 effect, but that some of the Big 4 audit firms are associated with a higher quality of risk disclosure. Audit partners with wider experience, and female auditors, are associated with better risk disclosure. I review the paper, applying a predictive validity model. I suggest areas where research on this issue could be further developed.
Blunted hyperemic response to mental stress in young, non-Hispanic black men is not impacted by acute dietary nitrate supplementation
Authors: Akins John D. , Curtis Bryon M. , Patik Jordan C. , Olvera Guillermo , Nasirian Aida , Campbell Jeremiah C. , Shiva Sruti , Brothers R. Matthew
Published: March 2021

This study tested the hypothesis that non-Hispanic black (BL) men have a blunted forearm hyperemic response to mental stress, which would be augmented following acute nitrate supplementation. The increase in forearm blood flow during mental stress was attenuated in BL men and was not impacted by nitrate supplementation. This supports findings of altered vascular function in this population. This is especially important as BL experience a higher prevalence of stress, which contributes to CVD risk.
Outer Membrane Vesicles (OMVs) Produced by Gram‐Negative Bacteria: Structure, Functions, Biogenesis, and Vaccine Application
Authors: Furuyama Noemi , Sircili Marcelo Palma
Published: March 2021

Gram‐negative bacteria produce outer membrane vesicles (OMVs) with 10 to 300 nm of diameter. The contribution of OMVs to bacterial pathogenesis is a topic of great interest, and their capacity to be combined with antigens impact in the future to the development of vaccines.
Distribution of Large‐Scale English Test Scores Based on Data Mining
Authors: Chu Na , Ma Wanzhi
Published: March 2021

Data mining technology is an effective knowledge mining and data relationship induction technology based on massive data, which is widely used in data analysis in many fields. In order to improve the utilization effect of students’ performance and meet the teaching needs of modern education, data mining technology can be applied to the existing performance database to mine the data information and treatment. Data mining technology is used to analyse and process the data stored in the student achievement management system, which provides the basis for improving the teaching quality and optimizing the teaching resources. Based on the analysis of the relevant data of large‐scale English test results, this paper finds out the relevant rules that affect college English test results, forms the corresponding performance prediction rules, uses data mining technology to more comprehensively analyse the factors that affect students’ performance, establishes a model, and uses data mining tools to mine and analyse students’ English test data. It is of great practical significance to select the model with high accuracy, further optimize the parameters, make good use of the data, and then take targeted measures to guide the teaching reform, help students make more efficient learning plans, and improve and perfect the existing problems in teaching.
The Efficiency of Fluoride Bioactive Glasses in Protecting Enamel Surrounding Orthodontic Bracket
Authors: Abbassy Mona Aly , Bakry Ahmed Samir , Hill Robert
Published: March 2021

Objectives. The aim of this study was to evaluate the protective effect of using four different fluoride bioactive enamel sealers against an acidic erosion challenge. Materials and Methods. A sample of 50 freshly extracted sound upper premolars had their buccal surface bonded to 50 orthodontic brackets using Transbond PLUS color change adhesive; the first four groups had four compositions of fluoride bioactive glasses based on 37 mol% SiO2, 43.9‐53.9 mol% CaO, 6.1 mol% P2O5 and CaF2, and 0‐10 mol% of Na2O applied to their surfaces and the fifth group served as control (which was not treated by any bioactive sealer). All specimens were challenged by 1% citric acid for 18 minutes which was stirred by a magnetic stirrer. The enamel surfaces next to the orthodontic brackets were examined by SEM. The Wilcoxon signed‐rank test was used to compare the area covered by the fluoride bioactive pastes before/after erosion (p < 0.05). Samples from the layer formed on top of the examined teeth were tested before/after erosion to be examined by the attenuated total reflectance Fourier‐transform infrared spectroscopy (FTIR/ATR). Results. The FTIR/ATR test showed that fluoride bioactive pastes’ applications resulted in the formation of a hydroxyapatite‐rich layer; the SEM analysis showed that the aforementioned layer significantly resisted erosion challenge when compared to the control group (p < 0.05). Conclusions. Fluoride bioactive pastes can efficiently protect the enamel surfaces next to orthodontic brackets from acidic erosion challenges.
Relationships of Rheumatoid Factor with Thickness of Retina and Choroid in Subjects without Ocular Symptoms Using Swept-Source Optical Coherence Tomography
Authors: Li Qingjian , Qian Yiwen , Xu Sennan , Zhang Minjie , Liang Xu , Che Xin , Jiang Jing , Liu Zuguo , Zhang Yu , Liu Yan , Wang Zhiliang
Published: March 2021

Purpose. Researches have confirmed that the retinal and choroidal thickness in patients with autoimmune disease-associated uveitis displays significant changes. However, the relationships between rheumatoid factor (RF) and thickness of the retina and choroid in individuals without ocular manifestations remain unclear. The aim of this study is to assess the associations of RF with retinal and choroidal thickness. Methods. The individuals enrolled in the cross-sectional research received full ocular examinations. The participants were classified as the RF (+) group (

RF
≥
15.0

 IU/ml) and the RF (−) group (

RF
<
15.0

 IU/ml) according to the serum RF titers. The thickness of the retina and choroid was measured by swept-source optical coherence tomography (SS-OCT). Results. The study covered 65 right eyes of 65 individuals that are RF-positive and 130 right eyes of 130 age- and sex-matched individuals that are RF-negative. The RF (+) group showed decreased choroidal thickness that achieved statistical significance only in the outer inferior and outer temporal sectors, as compared to the RF (−) group. There was no statistically significant difference regarding the retinal thickness between the two groups. Pearson’s correlation analysis revealed that the RF was significantly negatively related to the choroidal thickness in all areas. However, there was no significant correlation between the RF and the retinal thickness. Conclusions. Serum RF titers are closely linked with choroidal thickness before the emergence of ocular symptoms. Research into the relationships may improve our understanding of the role of serum RF in the pathogenesis of uveitis.
Hydrochemical Characteristics and Formation Mechanism of Strontium-Rich Groundwater in Shijiazhuang, North China Plain
Authors: Li Duo , Gan Shuang , Li Junfeng , Dong Zihan , Long Qi , Qiu Shuwei , Zhou Yahong , Lu Changyu
Published: March 2021

Strontium is a kind of trace element. Groundwater containing strontium is called mineral water when its content reaches a level that is beneficial for human physiology. Some groundwater resources in Shijiazhuang are rich in strontium. In this study, groundwater samples collected from 103 sites were studied for the hydrochemical characteristics of strontium and its formation mechanism in the groundwater system in Shijiazhuang City. The methods of source provenance analysis, factor correlation analysis, and runoff condition analysis were carried out in the study. The results showed that the content of strontium in eastern Shijiazhuang is higher than 0.229 mg/L, with a maximum content of 1.942 mg/L. The source of strontium is the dissolution of strontium-containing minerals in carbonate rock, sheet hemp rock, clastic rock, and granite in the Taihang Mountain area of the Hutuo River Basin. Strontium is positively correlated with total dissolved solids, bicarbonate, calcium magnesium, and free carbon dioxide. The erosion ability of groundwater strengthens the dissolution of strontium, and the geochemical action is mainly due to the dissolution. The enrichment and distribution of strontium are related to the conditions of groundwater runoff. Areas with good runoff conditions and strong mining are low in strontium, while areas with poor runoff conditions have high strontium content.
A Stochastic Switched Epidemic Model with Two Epidemic Diseases
Authors: El Koufi Amine , Bennar Abdelkrim , Yousfi Noura
Published: March 2021

In this paper, we study a stochastic epidemic model with double epidemics which includes white noise and telegraph noise modeled by Markovian switching. Sufficient conditions for the extinction and persistence of the diseases are established. In the end, some numerical simulations are presented to demonstrate our analytical results.
Sensitivity of Multistage Fill Slope Based on Finite Element Model
Authors: Yuan Bingxiang , Li Zihao , Su Zhilei , Luo Qingzi , Chen Minjie , Zhao Zuqing
Published: March 2021

Based on the strength reduction method, the laws of slope displacement and the changing positions of the sliding surface during the filling process are studied. The model of multistage fill slope is established by the finite element software PLAXIS. The difference is compared between the slope with no reinforcement and with reinforcement under the same working condition. Sensitivity analysis is carried out from two aspects which are internal factors and external factors. The finite element analysis shows that the settlement of the multistage fill slope with no reinforcement is mainly concentrated on the right side of the slope and gradually decreases with the increase of the filling height. The position of the sliding outlet is located at the joint of the first and the second grade of the slope. The effect of the reinforcement on the sliding surface is ideal. It is obvious that the reinforcement can supply the slope with a better position of the sliding surface, which is beneficial to the stability of the slope. The sensitivity analysis shows that unit weight, ratio of slope, and height of each grade are negatively correlated with the safety factor. At the same time, the platform width, cohesion, and internal friction angle are positively correlated with the safety factor. The internal friction angle has the greatest influence on the stability of the slope. Besides, the platform width and the height of each grade should be controlled at about 4 m. The sensitivity analysis provides a reference for the design of the multistage filling slope.
Dynamic Modeling and Active Vibration Isolation of a Noncontact 6‐DOF Lorentz Platform Based on the Exponential Convergence Disturbance Observer
Authors: Zhou Xubin , Chen Weidong , Zhao Fagang , Sui Dapeng , Xiao Qing , Liu Xingtian , Zhou Liping , Zhang Quan
Published: March 2021

In order to study the vibration isolation and positioning performance of the noncontact 6‐DOF platform in the space microgravity environment, this paper presented a cosimulation model of a virtual prototype. Based on the model driven by biaxial noncontact Lorentz force actuators (NLFAs), an equivalent dynamic model has been established. In the meanwhile, the 6‐DOF sliding mode robust controller with exponential convergence disturbance observer is developed. The mechanical system simulation model was designed using ADAMS, and the corresponding 6‐DOF decoupling control system and disturbance observer programs were developed using MATLAB/Simulink. According to the mechatronics simulation results, the system can enable the floating platform to achieve micron‐level posture positioning within 0.5 s. In vibration isolation simulation, the disturbance observer can predict the external disturbance input and compensate the control force more accurately so that the floating platform can effectively suppress low‐frequency disturbance and step disturbance under the control of the sliding mode controller. And the displacement of the floating platform under the disturbance of 1–100 Hz frequency sweep is less than 1 μm.
Recursive Algorithms of Maximum Entropy Thresholding on Circular Histogram
Authors: Yang Guifeng , Fan Jiulun , Wang Dong
Published: March 2021

Circular histogram thresholding is a novel color image segmentation method, which makes full use of the hue component color information of the image, so that the desired target can be better separated from the background. Maximum entropy thresholding on circular histogram is one of the exist circular histogram thresholding methods. However, this method needs to search for a pair of optimal thresholds on the circular histogram of two-class thresholding in an exhaustive way, and its running time is even longer than that of the existing circular histogram thresholding based on the Otsu criteria, so the segmentation efficiency is extremely low, and the real-time application cannot be realized. In order to solve this problem, a recursive algorithm of maximum entropy thresholding on circular histogram is proposed. Moreover, the recursive algorithm is extended to the case of multiclass thresholding. A large number of experimental results show that the proposed recursive algorithms are more efficient than brute force and the existing circular histogram thresholding based on the Otsu criteria.
A Quantum Approximate Optimization Algorithm with Metalearning for MaxCut Problem and Its Simulation via TensorFlow Quantum
Authors: Wang Haibin , Zhao Jiaojiao , Wang Bosi , Tong Lian
Published: March 2021

A quantum approximate optimization algorithm (QAOA) is a polynomial-time approximate optimization algorithm used to solve combinatorial optimization problems. However, the existing QAOA algorithms have poor generalization performance in finding an optimal solution from a feasible solution set of combinatorial problems. In order to solve this problem, a quantum approximate optimization algorithm with metalearning for the MaxCut problem (MetaQAOA) is proposed. Specifically, a quantum neural network (QNN) is constructed in the form of the parameterized quantum circuit to detect different topological phases of matter, and a classical long short-term memory (LSTM) neural network is used as a black-box optimizer, which can quickly assist QNN to find the approximate optimal QAOA parameters. The experiment simulation via TensorFlow Quantum (TFQ) shows that MetaQAOA requires fewer iterations to reach the threshold of the loss function, and the threshold of the loss value after training is smaller than comparison methods. In addition, our algorithm can learn parameter update heuristics which can generalize to larger system sizes and still outperform other initialization strategies of this scale.
[Retracted] Fatigue Performance of Reinforced Concrete T‐Girders under Cyclic Loading
Authors: Zhang Jinquan , Bai Bing , Zhang Kechao , Cheng Shoushan , Zhao Shangchuan , Wang Lei , Zhuang Chenxu
Published: March 2021

This paper examines the performance of reinforced concrete girders under cyclic loading. Seven T‐girders were casted and tested. All girders were loaded under different constant cyclic loading in the midspan with the load ratio of 0.14∼0.23 and frequency of 3∼4 Hz. The study shows that the longitudinal reinforcement fracture is the main cause of girder rupture. And during cyclic loading, the concrete cracks, strains, and deflections generally indicate a “three‐stage” law. The measured data were small but developed quickly in the initial stage. Thereafter, the degradation gradually stabilized and continued for a long time. In the final stage, the cracks, strains, and stiffness degradation developed sharply and the girders failed quickly. The duration of the stage is very short and may be difficult to be caught. For the life estimation, the longitudinal rebar S‐N curve is fitted using different collected data. The results show that the curve is in good agreement with the corresponding data, which may be an excellent candidate for the evaluation of fatigue life.
An Intelligent Offloading System Based on Multiagent Reinforcement Learning
Authors: Weng Yu , Chu Haozhen , Shi Zhaoyi
Published: March 2021

Intelligent vehicles have provided a variety of services; there is still a great challenge to execute some computing-intensive applications. Edge computing can provide plenty of computing resources for intelligent vehicles, because it offloads complex services from the base station (BS) to the edge computing nodes. Before the selection of the computing node for services, it is necessary to clarify the resource requirement of vehicles, the user mobility, and the situation of the mobile core network; they will affect the users’ quality of experience (QoE). To maximize the QoE, we use multiagent reinforcement learning to build an intelligent offloading system; we divide this goal into two suboptimization problems; they include global node scheduling and independent exploration of agents. We apply the improved Kuhn–Munkres (KM) algorithm to node scheduling and make full use of existing edge computing nodes; meanwhile, we guide intelligent vehicles to the potential areas of idle computing nodes; it can encourage their autonomous exploration. Finally, we make some performance evaluations to illustrate the effectiveness of our constructed system on the simulated dataset.
Comprehensive Quality Evaluation of American Ginseng for Different Parts and Abnormal Trait Based on the Major Ginsenoside Contents and Morphological Characteristics
Authors: Yu Jingping , Xu Tong , Lin Haiyan , Lin Ying , Zhou Jie , Zhang Yongqing
Published: March 2021

The demand for American ginseng, a famous traditional medicine and high‐grade healthy food, has increased dramatically over recent years. However, only the main root is popular among consumers, whereas other parts of American ginseng are rarely available in the market. In this study, the contents of 5 major ginsenosides (Re, Rc, Rg1, Rd, and Rb1) were determined through high‐performance liquid chromatography. Our study showed that all these 5 major ginsenosides are found in different parts of American ginseng plants, and the total content in different parts varied significantly in the following order: fibrous root > flower > branch root > main root > leaf > stem. Interestingly, the total content in the fibrous root was approximately 2.24 times higher than that in the main root. Further research indicated that the ginsenoside content in American ginseng with abnormal characteristics (physical deformity caused by disease and discolouration) is similar to that in the normal plant. Interestingly, a positive correlation was observed between the main root diameter and total ginsenoside content, whereas a negative correlation was observed between the main root length and total ginsenoside content. Our comprehensive study revealed that all parts of American ginseng, including the main root with abnormal characteristics, possess medicinal or economic value. Therefore, our results provide feasible evidence to further explore the potential application of American ginseng.
Human Posture Detection Method Based on Wearable Devices
Authors: Li Xiaoou , Zhou Zhiyong , Wu Jiajia , Xiong Yichao
Published: March 2021

The dynamic detection of human motion is important, which is widely applied in the fields of motion state capture and rehabilitation engineering. In this study, based on multimodal information of surface electromyography (sEMG) signals of upper limb and triaxial acceleration and plantar pressure signals of lower limb, the effective virtual driving control and gait recognition methods were proposed. The effective way of wearable human posture detection was also constructed. Firstly, the moving average window and threshold comparison were used to segment the sEMG signals of the upper limb. The standard deviation and singular values of wavelet coefficients were extracted as the features. After the training and classification by optimized support vector machine (SVM) algorithm, the real-time detection and analysis of three virtual driving actions were performed. The average identification accuracy was 90.90%. Secondly, the mean, standard deviation, variance, and wavelet energy spectrum of triaxial acceleration were extracted, and these parameters were combined with plantar pressure as the gait features. The optimized SVM was selected for the gait identification, and the average accuracy was 90.48%. The experimental results showed that, through different combinations of wearable sensors on the upper and lower limbs, the motion posture information could be dynamically detected, which could be used in the design of virtual rehabilitation system and walking auxiliary system.
Nuclear Receptor Coactivator NCOA3 Regulates UV Radiation–Induced DNA Damage and Melanoma Susceptibility
Authors: de Semir David , Bezrookove Vladimir , Nosrati Mehdi , Dar Altaf A. , Miller James R. , Leong Stanley P. , Kim Kevin B. , Liao Wilson , Soroceanu Liliana , McAllister Sean , Debs Robert J. , Schadendorf Dirk , Leachman Sancy A. , Cleaver James E. , Kashani-Sabet Mohammed
Published: March 2021

Melanoma occurs as a consequence of inherited susceptibility to the disease and exposure to UV radiation (UVR) and is characterized by uncontrolled cellular proliferation and a high mutational load. The precise mechanisms by which UVR contributes to the development of melanoma remain poorly understood. Here we show that activation of nuclear receptor coactivator 3 (NCOA3) promotes melanomagenesis through regulation of UVR sensitivity, cell-cycle progression, and circumvention of the DNA damage response (DDR). Downregulation of NCOA3 expression, either by genetic silencing or small-molecule inhibition, significantly suppressed melanoma proliferation in melanoma cell lines and patient-derived xenografts. NCOA3 silencing suppressed expression of xeroderma pigmentosum C and increased melanoma cell sensitivity to UVR. Suppression of NCOA3 expression led to activation of DDR effectors and reduced expression of cyclin B1, resulting in G2–M arrest and mitotic catastrophe. A SNP in NCOA3 (T960T) reduced NCOA3 protein expression and was associated with decreased melanoma risk, given a significantly lower prevalence in a familial melanoma cohort than in a control cohort without cancer. Overexpression of wild-type NCOA3 promoted melanocyte survival following UVR and was accompanied by increased levels of UVR-induced DNA damage, both of which were attenuated by overexpression of NCOA3 (T960T). These results describe NCOA3-regulated pathways by which melanoma can develop, with germline NCOA3 polymorphisms enabling enhanced melanocyte survival in the setting of UVR exposure, despite an increased mutational burden. They also identify NCOA3 as a novel therapeutic target for melanoma.

Significance:

This study explores NCOA3 as a regulator of the DDR and a therapeutic target in melanoma, where activation of NCOA3 contributes to melanoma development following exposure to ultraviolet light.
Biomarker Technologies to Support Early Clinical Immuno-oncology Development: Advances and Interpretation
Authors: Cannarile Michael A. , Gomes Bruno , Canamero Marta , Reis Bernhard , Byrd Allyson , Charo Jehad , Yadav Mahesh , Karanikas Vaios
Published: March 2021

Today, there is a huge effort to develop cancer immunotherapeutics capable of combating cancer cells as well as the biological environment in which they can grow, adapt, and survive. For such treatments to benefit more patients, there is a great need to dissect the complex interplays between tumor cells and the host's immune system. Monitoring mechanisms of resistance to immunotherapeutics can delineate the evolution of key players capable of driving an efficacious antitumor immune response. In doing so, simultaneous and systematic interrogation of multiple biomarkers beyond single biomarker approaches needs to be undertaken. Zooming into cell-to-cell interactions using technological advancements with unprecedented cellular resolution such as single-cell spatial transcriptomics, advanced tissue histology approaches, and new molecular immune profiling tools promises to provide a unique level of molecular granularity of the tumor environment and may support better decision-making during drug development. This review will focus on how such technological tools are applied in clinical settings, to inform the underlying tumor–immune biology of patients and offer a deeper understanding of cancer immune responsiveness to immuno-oncology treatments.
Heterogeneity of IFN-Mediated Responses and Tumor Immunogenicity in Patients with Cervical Cancer Receiving Concurrent Chemoradiotherapy
Authors: Chen Jianzhou , Chen Chuangzhen , Zhan Yizhou , Zhou Li , Chen Jie , Cai Qingxin , Wu Yanxuan , Sui Zhihan , Zeng Chengbing , Wei Xiaolong , Muschel Ruth
Published: March 2021

Purpose:

To ask whether the expression of immune markers and IFN signaling in tumor biopsies changes during concurrent chemoradiotherapy (CCRT).

Experimental Design:

Tumor biopsies and peripheral mononuclear blood cells (PMBC) before and immediately after 20 Gy/10 fractions (F) of radiation treatment (RT) from 30 patients with cervical cancer receiving CCRT were evaluated by IHC and qRT-PCR for immune markers and correlated with the short-term response.

Results:

Tumor immune response to radiation before and after 10F RT as reflected by CD8+ T-cell infiltration had substantial heterogeneity with increases, decreases, and no change all evident. Increases in CD8+ T cells during CCRT correlated with the presence of nuclear IRF1 in tumor cells (r = 0.68, P < 0.0001) and the patient short-term response (P < 0.01). Similarly, in a subset of patients (∼40%) PD-L1 positivity in tumor cells increased, which also correlated with nuclear IRF1 staining (r = 0.48, P < 0.01). Patients with augmented PMBC IFN signature expression after 10F had a significantly higher probability of PD-L1 induction (83% vs. 7%, P < 0.0001). Most patients exhibited abundant expression of SERPINB9 and CD47 in tumor cells, and tumor infiltration by CD68+ cells. SERPINB9 expression correlated with STAT1 signaling in tumor cells.

Conclusions:

CCRT leads to differential tumor immunogenicity and IFN signaling in patients with cervical cancer, suggesting radiation induction of immunity is limited to a subset of patients and may reflect the heterogeneity of intratumoral induction of IFNs.

See related commentary by Mondini and Deutsch, p. 3815
A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response
Authors: Duska Linda R. , Filiaci Virginia L. , Walker Joan L. , Holman Laura L. , Hill Emily K. , Moore Richard G. , Ring Kari L. , Pearl Michael L. , Muller Carolyn Y. , Kushnir Christina L. , Lankes Heather A. , Samuelson Megan I. , Carrick Kelley S. , Rajan Anand , Rodgers William H. , Kohn Elise C. , Piekarz Richard , Leslie Kimberly K.
Published: March 2021

Purpose:

This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma.

Patients and Methods:

This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21–24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response.

Results:

Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008).

Conclusions:

This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.
Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Peng Zhi , Wei Jia , Wang Feng , Ying Jieer , Deng Yanhong , Gu Kangsheng , Cheng Ying , Yuan Xianglin , Xiao Juxiang , Tai Yanfei , Wang Linna , Zou Jianjun , Zhang Yanqiao , Shen Lin
Published: March 2021

Purpose:

Capecitabine plus oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, advanced, or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Camrelizumab shows promising antitumor activity in advanced or metastatic G/GEJ adenocarcinoma in a phase I study. We reported the outcomes of cohort 1 in a multicenter, open-label, phase II trial, which assessed camrelizumab in combination with CAPOX followed by camrelizumab plus apatinib as a first-line combination regimen for advanced or metastatic G/GEJ adenocarcinoma.

Patients and Methods:

Systemic treatment-naïve patients with EGFR2-negative advanced or metastatic G/GEJ adenocarcinoma received initial camrelizumab plus CAPOX for 4–6 cycles, and patients without progressive disease were administrated subsequent camrelizumab plus apatinib. Primary endpoint was objective response rate (ORR).

Results:

All 48 enrolled patients comprised the efficacy and safety analysis population. The ORR was 58.3% [95% confidence interval (CI), 43.2–72.4] with this combination regimen. Median duration of response was 5.7 months (95% CI, 4.4–8.3). Median overall survival was 14.9 months (95% CI, 13.0–18.6), and median progression-free survival was 6.8 months (95% CI, 5.6–9.5), respectively. The most common grade ≥3 treatment-related adverse events (>10%) were decreased platelet count (20.8%), decreased neutrophil count (18.8%), and hypertension (14.6%). Treatment-related death occurred in 1 patient (2.1%) due to abnormal hepatic function and interstitial lung disease.

Conclusions:

Camrelizumab combined with CAPOX followed by camrelizumab plus apatinib demonstrated encouraging antitumor activity and manageable toxicity as first-line therapy for patients with advanced or metastatic G/GEJ adenocarcinoma.
Effect of Supervised Training Therapy on Pulmonary Arterial Compliance and Stroke Volume in Severe Pulmonary Arterial Hypertension and Inoperable or Persistent Chronic Thromboembolic Pulmonary Hypertension
Authors: Nagel Christian , Benjamin Nicola , Egenlauf Benjamin , Eichstaedt Christina A. , Fischer Christine , Palevičiūtė Eglė , Čelutkienė Jelena , Harutyunova Satenik , Mayer Eckhard , Nasereddin Mohammed , Marra Alberto M. , Grünig Ekkehard , Guth Stefan
Published: March 2021

Background: Pulmonary arterial compliance (PAC) is a prognostic parameter in pulmonary arterial hypertension (PAH) reflecting the elasticity of the pulmonary vessels. Objectives: The objective of this post hoc analysis of a prospective randomized controlled trial (RCT) was to assess the effect of exercise training on PAC and stroke volume (SV) in patients with PAH and persistent/inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method: From the previous RCT, 43 out of 87 patients with severe PAH (n = 29) and CTEPH (n = 14) had complete haemodynamic examinations at baseline and after 15 weeks by right heart catheterization and were analysed (53% female, 79% World Health Organization functional class III/IV, 58% combination therapy, 42% on supplemental oxygen therapy, training group n = 24, and control group n = 19). Medication remained unchanged for all patients. Results: Low-dose exercise training at 4–7 days/week significantly improved PAC (training group 0.33 ± 0.65 mL/mm Hg vs. control group −0.06 ± 1.10 mL/mm Hg; mean difference 0.39 mL/mm Hg, 95% confidence interval [CI] 0.15–0.94 mL/mm Hg; p = 0.004) and SV (training group 9.9 ± 13.4 mL/min vs. control group −4.2 ± 11.0 mL/min; mean difference 14.2 mL, 95% CI 6.5–21.8 mL; p < 0.001) in the training versus control group. Furthermore, exercise training significantly improved cardiac output and pulmonary vascular resistance at rest, peak oxygen consumption, and oxygen pulse. Conclusions: Our findings suggest that supervised exercise training may improve right ventricular function and PAC at the same time. Further prospective studies are needed to evaluate these findings.
Association between Procalcitonin and Acute Kidney Injury in Patients with Bacterial Septic Shock
Authors: Fu Guang , Zhan Hai-chao , Li Hao-li , Lu Jun-fu , Chen Yan-hong , Wu Le-feng , Yang Zi-Long , Huang Jia-jia , Feng Yong-wen , Luan Ying-yi , Wu Ming
Published: March 2021

Objective: The objective of this study was to assess the relationship between serum procalcitonin (PCT) and acute kidney injury (AKI) induced by bacterial septic shock. Methods: A retrospective study was designed which included patients who were admitted to the ICU from January 2015 to October 2018. Multiple logistic regression and receiver operating characteristic (ROC) as well as smooth curve fitting analysis were used to assess the relationship between the PCT level and AKI. Results: Of the 1,631 patients screened, 157 patients were included in the primary analysis in which 84 (53.5%) patients were with AKI. Multiple logistic regression results showed that PCT (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.009–1.025, p < 0.001) was associated with AKI induced by septic shock. The ROC analysis showed that the cutoff point for PCT to predict AKI development was 14 ng/mL, with a sensitivity of 63% and specificity 67%. Specifically, in multivariate piecewise linear regression, the occurrence of AKI decreased with the elevation of PCT when PCT was between 25 ng/mL and 120 ng/mL (OR 0.963, 95% CI 0.929–0.999; p = 0.042). The AKI increased with the elevation of PCT when PCT was either <25 ng/mL (OR 1.077, 95% CI 1.022–1.136; p = 0.006) or >120 ng/mL (OR 1.042, 95% CI 1.009–1.076; p = 0.013). Moreover, the PCT level was significantly higher in the AKI group only in female patients aged ≤75 years (p = 0.001). Conclusions: Our data revealed a nonlinear relationship between PCT and AKI in septic shock patients, and PCT could be used as a potential biomarker of AKI in female patients younger than 75 years with bacterial septic shock.
Pustulosis palmoplantaris: Langfriste Kontrolle im Blick
Authors: Sondermann Wiebke
Published: March 2021

Im Rahmen der sog. 2PRECISE-Studie, einer multizentrischen, randomisierten, doppelblinden Phase 3b Parallel-Studie, wurden Patienten mit mittelschwerer bis schwerer PPP (palmoplantarer Psoriasis Area and Severity Index (PPPASI) ≥12 und Dermatology Life Quality Index (DLQI) ≥10) über 52 Wochen mit Secukinumab bzw. Placebo behandelt. Der primäre Endpunkt der Studie war die Bestimmung der Rate der Patienten mit einem ppPASI75 unter Therapie mit Secukinumab in Woche 16 gegenüber Placebo. Es wurde ein Signifikanzlevel von 2,5% zugrunde gelegt. 79 Patienten erhielten Secukinumab in einer Dosierung von 300mg und 80 Patienten wurden mittels Secukinumab 150mg behandelt. 78 Patienten wurden der Placebo-Gruppe zugeordnet. Ab Woche 16 erhielten 27 Patienten aus der Placebo-Gruppe 150mg Secukinumab und 28 Patienten 300mg Secukinumab. 10 Patienten hatten auf Placebo angesprochen. In Woche 16 erreichten 26,6% der mit 300mg Secukinumab behandelten Patienten und 17,5% der Patienten unter 150mg Secukinumab einen ppPASI75 im Vergleich zu 14,1% der mit Placebo behandelten Patienten (P = 0,0411). Der primäre Endpunkt wurde nicht erreicht, jedoch ergab sich eine Odds Ratio (OR) von 2,62 (95% Konfidenzintervall, 1,04–6,60) zugunsten von 300mg Secukinumab gegenüber Placebo. In Woche 52 wiesen 41,8% der mit 300mg Secukinumab behandelten Patienten und 35,0% der Patienten unter Secukinumab 150mg einen ppPASI75 auf. Das klinische Ansprechen der Patienten, die auch unter einer Plaque Psoriasis litten, war besser als das der Patienten mit einer reinen PPP. Die Lebensqualitätsverbesserung gemessen mit dem DLQI war unter 300mg Secukinumab deutlich besser als unter Placebo. In Woche 16 erreichten 13% der Patienten unter Secukinumab 300mg einen DLQI von 0 oder 1, während es unter Placebo nur 4,3% der Patienten waren. Es wurden in der Studie keine unerwarteten unerwünschten Ereignisse beobachtet.
Coronary Microvascular Dysfunction
Authors: Godo Shigeo , Suda Akira , Takahashi Jun , Yasuda Satoshi , Shimokawa Hiroaki
Published: March 2021

Over the past couple of decades, accumulating evidence has shown that structural and functional abnormalities of coronary microvasculature are highly prevalent, associated with adverse clinical outcomes in patients with various cardiovascular diseases. The term coronary microvascular dysfunction (CMD) has been coined to refer to this clinical condition and is increasingly recognized as an important clinical entity in many clinical settings. The potential mechanisms of CMD appear to be heterogenous, including enhanced coronary vasoconstrictive reactivity at microvascular level, impaired endothelium-dependent and independent coronary vasodilator capacities, and increased coronary microvascular resistance secondary to structural factors. Recent experimental and clinical studies have highlighted emerging modulators of vascular functions, vital insight into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will briefly review the current progress on pathophysiology, molecular mechanisms, and clinical management of CMD from bench to bedside.
Estimated Impact of Achieving Optimal Cardiovascular Health Among US Adults on Cardiovascular Disease Events
Authors: Bundy Joshua D. , Zhu Zhengbao , Ning Hongyan , Zhong Victor W. , Paluch Amanda E. , Wilkins John T. , Lloyd‐Jones Donald M. , Whelton Paul K. , He Jiang , Allen Norrina B.
Published: March 2021

Background

Better cardiovascular health (CVH) scores are associated with lower risk of cardiovascular disease (CVD). However, estimates of the potential population‐level impact of improving CVH on US CVD event rates are not currently available.

Methods and Results

Using data from the National Health and Nutrition Examination Survey 2011 to 2016 (n=11 696), we estimated the proportions of US adults in CVH groups. Levels of 7 American Heart Association CVH metrics were scored as ideal (2 points), intermediate (1 point), or poor (0 points), and summed to define overall CVH (low, 0–8 points; moderate, 9–11 points; or high, 12–14 points). Using individual‐level data from 7 US community‐based cohort studies (n=30 447), we estimated annual incidence rates of major CVD events by levels of CVH. Using the combined data sources, we estimated population attributable fractions of CVD and the number of CVD events that could be prevented annually if all US adults achieved high CVH. High CVH was identified in 7.3% (95% CI, 6.3%–8.3%) of US adults. We estimated that 70.0% (95% CI, 56.5%–79.9%) of CVD events were attributable to low and moderate CVH. If all US adults attained high CVH, we estimated that 2.0 (95% CI, 1.6–2.3) million CVD events could be prevented annually. If all US adults with low CVH attained moderate CVH, we estimated that 1.2 (95% CI, 1.0–1.4) million CVD events could be prevented annually.

Conclusions

The potential benefits of achieving high CVH in all US adults are considerable, and even a partial improvement in CVH scores would be highly beneficial.
Pluralism versus Separation: Tension in the Australian Church-State Relationship
Authors: Barker Renae
Published: March 2021

The relationship between the state and religion in Australia exists in a state of tension. On the one hand the “non-establishment” clause in section 116 of the Australian Constitution points to the separation of religion and state. On the other hand there is a high level of cooperation between the state and religion in the public sphere, most visible in the funding of religious schools by the federal government. These two visions of the Australian state-religion relationship are in tension. One requiring the removal of religion from the public sphere while the other calls for a plurality of religions to be accommodated in public spaces. This article seeks to resolve this tension by proposing a new way to understand the Australian state-religion relationship as non-establishment pluralism. Non-establishment in the sense that the Australian Constitution prohibits the establishment of any religion—be that a single state church, multiple state religions, or religion generally. Pluralism in that the state via ordinary legislation, public policy, and government action cooperates with religion in numerous areas of state and religious interest in the public sphere.
Thaqīl (Insufferable) vs. Ẓarīf (Refined)
Authors: Zakeri Mohsen
Published: March 2021

Ẓarf is a well-known concept in classical Arabic adab-literature — it stands for refinement, courtesy, elegance, and wit, among other things. Less known is its counterpart, thiqal, denoting all things heavy. A thaqīl (pl. thuqalāʾ) is a bore whose often boorish conduct is deemed insufferable by anyone whose company he seeks. The oldest extant text on the subject of the insufferable, Ibn al-Marzbān’s Dhamm al-thuqalāʾ, “Censure of the Insufferable,” is studied to shed more light on the characteristics of the thaqīl and on everything a ẓarīf is not.
Aspidosperma dardanoanum (Apocynaceae), a new species spanning from the Atlantic Forest into the Caatinga (Northeast Region, Brazil)

Authors: ALVES-SILVA JARINA WALÉRIA , DE SOUZA PEREIRA ANDREZA STEPHANIE , COUTINHO THALES SILVA , DEVIDES CASTELLO ANA CAROLINA
Published: March 2021

Aspidosperma dardanoanum, a new species occurring both in the Atlantic Forest and Caatinga (Northeast Region, Brazil) biomes is described and illustrated here. A distribution map and a comparative table with the diagnostic characters of Aspidosperma dardanoanum and species that occur in sympatry or resemble it are also provided.
Dianthus muglensis nom. nov. and notes on D. goerkii, the correct name for D. leucophaeus var. patens (Caryophyllaceae)

Authors: HAMZAOĞLU ERGİN , KOÇ MURAT
Published: March 2021

Dianthus muglensis are proposed as replacement name for D. elegans var. gramineus non D. gramineus by Schur, based on morphological data and according to the Art. 53.1 of ICN. Tha name D. leucophaeus var. patens was also investigated from both nomenclatural and taxonomical points of views reaching to the conclusioon that it deserves the species rank (the correct name is D. goerkii). Expanded descriptions, as well as data about distribution, habitat, and phenology are also provided for both the studied taxa.
2. Society and the Self in Early Piyyut
Authors: Swartz Michael D.
Published: March 2021

Michael Swartz, in ‘Society and the Self in Early Piyyut’, takes us on a textual journey in the company of some early liturgical authors from the Byzantine period whose work was probably recited in the synagogues of Palestine and other places before audiences that were not exclusively rabbinic. Through the analysis of selected piyyutim, Swartz shows that these liturgical poems help us better understand ideological frameworks and social structures of the Late Antique Jewish Palestinian society. These piyyutim, whose authors are generally known (unlike most other Jewish literary production from the period), complicate our vision of the Jewish society and the structures that held it together.
3. Some Remarks about Non-Rabbinic Judaism, Rabbinization, and Synagogal Judaism
Authors: Costa José
Published: March 2021

In ‘Some Remarks about Non-Rabbinic Judaism, Rabbinization, and Synagogal Judaism’, José Costa proposes the tripartite division of Late Antique Judaism into rabbinic Judaism, Christian Judaism (i.e., Jewish Christianity), and “synagogal Judaism”, a term coined by Simon Claude Mimouni (Le judaïsme ancien du VIe siècle avant notre ère au IIIe siècle de notre ère, 2012). Costa particularly engages with and criticizes Ra‘anan Boustan’s article ‘Rabbinization and the Making of Early Jewish Mysticism’ (2011). Costa suggests that the rabbinization process meant mainly the rabbinization of the synagogues and the religious activity within, a conclusion that can be shared also by those who do not adhere to the model of “synagogal Judaism”.
5. Varieties of Non-Rabbinic Judaism in Geonic and Contemporaneous Sources
Authors: Brody Robert
Published: March 2021

In ‘Varieties of Non-Rabbinic Judaism in Geonic and Contemporaneous Sources’, Robert Brody shows that, based on his analysis of several responsa attributed to Natronai Gaon and the letter of Pirqoy ben Baboy, rabbinic authorities were aware of the existence of several non-rabbinic Jewish groups in the eighth century. However, over the course of a little more than a century, rabbinic discourse shifted from knowledge of several such groups to the assumption that all non-rabbinic teachings derived from Anan ben David and his followers. Finally, Brody pinpoints several differences between the earlier non-rabbinic groups (on the one hand) and the Ananites and Karaites (on the other), who seem to have posed a greater threat to the rabbis.