bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Urosepsis after Minimally Invasive Percutaneous Nephrolithotomy in Patients with Preoperative Urinary Tract Infection
Authors: Wang Shen , Yuan Peng , Peng Ejun , Xia Ding , Xu Hua , Wang Shaogang , Ye Zhangqun , Chen Zhiqiang
Published: January 2020

The purpose of this study was to assess risk factors of urosepsis after minimally invasive percutaneous nephrolithotomy (MPCNL) for the treatment of upper urinary tract stones in patients with preoperative urinary tract infection (UTI) and to explore preventive measures. Between 2008 and 2016, patients with preoperative UTI who underwent MPCNL for upper urinary tract stones were retrospectively collected. Patients were divided into nonurosepsis and urosepsis groups. Perioperative outcomes of all patients were evaluated and compared between the two groups. Risk factors for post‐MPCNL urosepsis were investigated using univariate and multivariate regression analysis. A total of 843 patients including 22 patients with postoperative urosepsis (urosepsis group) and 821 patients without urosepsis (nonurosepsis group) were finally included in this study. All patients with postoperative urosepsis were cured and discharged after treatment. In univariate analysis it was demonstrated that the incidence of urosepsis after MPCNL was significantly correlated with channel size (P = 0.001), surgical time (P = 0.003), as well as the tear of the collection system and percutaneous renal channel crossing the renal papilla (P = 0.004). Moreover, multivariate analysis showed that smaller channel size (OR = 11.192, 95% CI: 2.425–51.650, P = 0.002), longer surgical time (OR = 6.762, 95% CI: 1.712–17.844, P = 0.008), and tear of collection system and percutaneous renal channel crossing the renal papilla (OR = 5.531, 95% CI 1.228–14.469, P = 0.012) were independent risk factors for urosepsis following MPCNL in patients with preoperative UTI. In conclusion, in patients with preoperative UTI undergoing MPCNL for upper urinary tract stones, smaller channel size, prolonged operation time, as well as tear of the collection system and percutaneous renal channel crossing the renal papilla are independent risk factors for postoperative urosepsis. Therefore, it is indicated that, in clinical practice, it is of great significance to choose appropriate channel size and avoid renal injury and control surgical time to prevent the urosepsis after MPCNL in patients with preoperative UTI.
Association of Hyperhomocysteinemia with Increased Coronary Microcirculatory Resistance and Poor Short‐Term Prognosis of Patients with Acute Myocardial Infarction after Elective Percutaneous Coronary Intervention
Authors: Peng Yang-Pei , Huang Ming-Yuan , Xue Yang-Jing , Pan Jia-Lin , Lin Cong
Published: January 2020

Background. This study aims to investigate the coronary microcirculatory resistance and prognosis of patients with acute myocardial infarction (AMI) concomitant with hyperhomocysteinemia (HHcy) after an elective percutaneous coronary intervention (PCI). Methods. A total of 101 patients that underwent elective PCI between May 2015 and July 2018 due to AMI were consecutively enrolled in this study. Patients were divided into a HHcy group (53) and a normal Hcy group (control; 48) based on their plasma homocysteine concentration. The characteristics of coronary angiography, the index of microcirculatory resistance (IMR) of infarct‐related vessels (IRV), changes in left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) before and after PCI, and the incidence of major adverse cardiovascular events (MACE) three months after PCI were compared between these groups. Results. Compared to the results from the Hcy group, the HHcy group had a higher IMR. The HHcy group had significantly higher LVEDd and a lower LVEF than the Hcy group 3 months after PCI. Additionally, the incidence of MACE at three months after PCI was higher in the HHcy group than in the Hcy group. Pearson correlation analysis revealed a positive correlation with IMR in the HHcy group. Furthermore, there was a difference in the LVEDd measured at one day after PCI and at three months after PCI in the HHcy group. Conclusion. AMI patients concomitant with HHcy that undergo elective PCI are prone to coronary microcirculatory dysfunction and have a poor cardiac function and poor prognosis at three months after PCI.
Linguistic Interval-Valued Intuitionistic Fuzzy Archimedean Power Muirhead Mean Operators for Multiattribute Group Decision-Making
Authors: Qin Yuchu , Cui Xiaolan , Huang Meifa , Zhong Yanru , Tang Zhemin , Shi Peizhi
Published: January 2020

Two important tasks in multiattribute group decision-making (MAGDM) are to describe the attribute values and to generate a ranking of all alternatives. A superior tool for the first task is linguistic interval-valued intuitionistic fuzzy number (LIVIFN), and an effective tool for the second task is aggregation operator (AO). To date, nearly ten AOs of LIVIFNs have been presented. Each AO has its own features and can work well in its specific context. But there is not yet an AO of LIVIFNs that can offer desirable generality and flexibility in aggregating attribute values and capturing attribute interrelationships and concurrently reduce the influence of unreasonable attribute values. To this end, a linguistic interval-valued intuitionistic fuzzy Archimedean power Muirhead mean operator and its weighted form, which have such capabilities, are presented in this paper. Firstly, the generalised expressions of the AOs are established by a combination of the Muirhead mean operator and the power average operator under the Archimedean T-norm and T-conorm operations of LIVIFNs. Then the properties of the AOs are explored and proved, their specific expressions are constructed, and the special cases of the specific expressions are discussed. After that, a new method for solving the MAGDM problems based on LIVIFNs is designed on the basis of the weighted AO. Finally, the designed method is illustrated via a practical example, and the presented AOs are evaluated via experiments and comparisons.
Astragalus Polysaccharide Attenuates Cisplatin‐Induced Acute Kidney Injury by Suppressing Oxidative Damage and Mitochondrial Dysfunction
Authors: Ma Qing , Xu Yao , Tang Lumin , Yang Xiaoqian , Chen Zhejun , Wei Yuehan , Shao Xinghua , Shao Xiaoguang , Xin Zhixiang , Cai Biao , Wang Qi , Mou Shan
Published: January 2020

Cisplatin is a widely used chemotherapeutic drug in the treatment of various solid tumors. However, the cisplatin‐induced acute kidney injury remains a disturbing complication, which still lacks effective prevention. Cisplatin‐induced oxidative damage and mitochondrial dysfunction are anticipated to be crucial in the occurrence of kidney injury. Astragalus polysaccharide (APS) has been reported to possess multiple biological activities including anti‐inflammatory, antioxidant, and mitochondria protection. In this study, we investigated the potentially protective effect of APS against cisplatin‐induced kidney injury both in vivo and in vitro. We found that APS pretreatment attenuated the cisplatin‐induced renal dysfunction and histopathological damage in mice; in addition, it also protected the viability of HK‐2 cells upon cisplatin exposure. APS attenuated the cisplatin‐induced oxidative damage by reducing reactive oxygen species (ROS) generation and recovering the activities of total superoxide dismutase and glutathione peroxidase in mice kidney. In addition, electron microscope analysis indicated that cisplatin induced extensive mitochondrial vacuolization in mice kidney. However, APS administration reversed these mitochondrial morphology changes. In HK‐2 cells, APS reduced the cisplatin‐induced mitochondrial and intracellular ROS generation. Furthermore, APS protected the normal morphology of mitochondria, blocked the cisplatin‐induced mitochondrial permeability transition pore opening, and reduced the cytochrome c leakage. Subsequently, APS reduced the cisplatin‐induced apoptosis in mice renal and HK‐2 cells. In conclusion, our data suggested that APS pretreatment might prevent cisplatin‐induced kidney injury through attenuating oxidative damage, protecting mitochondria, and ameliorating mitochondrial‐mediated apoptosis.
Genetic Polymorphisms and Forensic Efficiencies of a Set of Novel Autosomal InDel Markers in a Chinese Mongolian Group
Authors: Zhang Wenqing , Jin Xiaoye , Wang Yijie , Kong Tingting , Cui Wei , Chen Chong , Guo Yuxin , Zhu Bofeng
Published: January 2020

Insertion/deletion (InDel) markers have been treated as a prospective and helpful aid in the fields of forensic human identifications and biogeography origin researches for the past few years. In this study, we analyzed genetic polymorphisms and forensic efficiencies of 35 InDels in a novel multiplex PCR‐InDel panel in a Chinese Mongolian group. All these 35 InDel loci were observed to conform to Hardy–Weinberg equilibrium and linkage equilibrium. The mean values of expected heterozygosity and observed heterozygosity were 0.4788 and 0.4852, respectively. Besides, the interpopulation differentiations and genetic distributions based on 35 InDels found that the Chinese Mongolian group might have closer genetic relationships and similar population genetic structures with East Asian populations.
A Survey of Tactile‐Sensing Systems and Their Applications in Biomedical Engineering
Authors: Al-Handarish Yousef , Omisore Olatunji Mumini , Igbe Tobore , Han Shipeng , Li Hui , Du Wenjing , Zhang Jinjie , Wang Lei
Published: January 2020

Over the past few decades, tactile sensors have become an emerging field of research in both academia and industry. Recent advances have demonstrated application of tactile sensors in the area of biomedical engineering and opened up new opportunities for building multifunctional electronic skin (e‐skin) which is capable of imitating the human sense‐of‐touch for medical purposes. Analyses have shown that current smart tactile sensing technology has the advantages of high performance, low‐cost, time efficiency, and ease‐of‐fabrication. Tactile sensing systems have thus sufficiently matured for integration into several fields related to biomedical engineering. Furthermore, artificial intelligence has the potential for being applied in human‐machine interfacing, for instance, in medical robotic manipulation, especially during minimally invasive robotic surgery, where tactile sensing is usually a problem. In this survey, we present a comprehensive review of the state of the art of tactile sensors. We focus on the technical details of transduction mechanisms such as piezoresistivity, capacitance, piezoelectricity, and triboelectric and highlight the role of novel and commonly used materials in tactile sensing. In addition, we discuss contributions that have been reported in the field of biomedical engineering, which includes its present and future applications in building multifunctional e‐skins, human‐machine interfaces, and minimally invasive surgical robots. Finally, some challenges and notable improvements that have been made in the technical aspects of tactile sensing systems are reported.
Aronia melanocarpaPrevents Alcohol-Induced Chronic Liver Injury via Regulation of Nrf2 Signaling in C57BL/6 Mice
Authors: Wang Zhuqian , Liu Yange , Zhao Xuyu , Liu Shuyan , Liu Yang , Wang Di
Published: January 2020

Aronia melanocarpa(AM), which is rich in anthocyanins and procyanidins, has been reported to exert antioxidative and anti-inflammatory effects. This study aimed to systematically analyze the components of AM and explore its effects on alcohol-induced chronic liver injury in mice. A component analysis of AM revealed 17 types of fatty acids, 17 types of amino acids, 8 types of minerals, and 3 types of nucleotides. Chronic alcohol-induced liver injury was established in mice via gradient alcohol feeding over a period of 6 months, with test groups orally receiving AM in the last 6 weeks. AM administration yielded potential hepatoprotective effects by alleviating weight gain and changes in organ indexes, decreasing the ratio of alanine aminotransferase/aspartate aminotransferase, reducing lipid peroxidation, enhancing antioxidant activities, decreasing oxidation-related factor levels, and regulating inflammatory cytokine levels. Histological analyses suggest that AM treatment markedly prevented organ damage in alcohol-exposed mice. Furthermore, AM activated nuclear factor erythroid 2-like 2 (Nrf2) by downregulating the expression of Kelch-like ECH-associated protein 1, resulting in elevated downstream antioxidative enzyme levels. AM activated Nrf2 via modulation of the phosphatidylinositol-3-hydroxykinase/protein kinase B signaling pathway. Altogether, AM prevented alcohol-induced liver injury, potentially by suppressing oxidative stress via the Nrf2 signaling pathway.
Likelihood of Accomplishing an In‐Patient Hysteroscopic Myomectomy in a One‐Step Procedure: A Systematic Review and Meta‐Analysis
Authors: Indraccolo Ugo , Bini Vittorio , Favilli Alessandro
Published: January 2020

Purpose. To assess the feasibility rate of one‐step hysteroscopic myomectomy according to the technique adopted. Methods. In July 2016, PubMed, ClinicalTrials.gov, SCOPUS, Scielo, and AJOL databases were used for searching references. Series of in‐patient hysteroscopic myomectomies reporting success rate in only one‐step procedure, categorization of submucous fibroids, explanation of the surgical technique, and description of patients were considered eligible for meta‐analysis (retrospective, prospective randomized studies). Two authors extracted the data. Rate of myomectomies accomplished in only a surgical step and rate of intraoperative complications were extracted per protocol. A modified GRADE score was used for quality assessment. Random‐effect models were already assumed. Mean rates were compared among subgroups. Results. One thousand two hundred and fifty‐seven studies were screened and 241 of these were read for eligibility. Seventy‐eight series were included in qualitative synthesis and 24 series were included in quantitative synthesis. Wide heterogeneity was found. In series with <50% of G2 myomas treated, the slicing technique feasibility rate was 86.5% while techniques for enucleating the deep portion of the myomas showed a feasibility rate of 92.3% (p < 0.001). In series with ≥50% of G2 myomas treated, the slicing technique feasibility rate was 70.6% while techniques for enucleating the deep portion of myomas showed a feasibility rate of 88.4% (p < 0.001). Complications were significantly lower for alternative techniques to the classical slicing. Conclusion. In case of submucous myomas with intramural development, the slicing technique was correlated with a lower rate of in‐patient hysteroscopic myomectomies accomplished in a one‐step procedure and a higher complications rate.
Zeeman Effect in Phase Space
Authors: Paiva R. A. S. , Amorim R. G. G. , Ulhoa S. C. , Santana A. E. , Khanna F. C.
Published: January 2020

The two-dimensional hydrogen atom in an external magnetic field is considered in the context of phase space. Using the solution of the Schrödinger equation in phase space, the Wigner function related to the Zeeman effect is calculated. For this purpose, the Bohlin mapping is used to transform the Coulomb potential into a harmonic oscillator problem. Then, it is possible to solve the Schrödinger equation easier by using the perturbation theory. The negativity parameter for this system is realised.
TiO2/Diazonium/Graphene Oxide Composites: Synthesis and Visible-Light-Driven Photocatalytic Degradation of Methylene Blue
Authors: Hoan Nguyen Thi Vuong , Minh Nguyen Ngoc , Nhi Thoi Thi Kim , Van Thang Nguyen , Tuan Vu Anh , Nguyen Vo Thang , Thanh Nguyen Mau , Van Hung Nguyen , Khieu Dinh Quang
Published: January 2020

In the present article, the synthesis of TiO2/diazonium/graphene oxide and its photocatalytic activity for methylene blue (MB) degradation have been demonstrated. The functionalization of graphene oxide (GO) with diazonium salt (diazonium-GO) was conducted for enhancing the dispersibility of GO in distilled water. TiO2 was highly dispersed in diazonium-GO to form TiO2/diazonium/graphene. The obtained specimens were characterized by X-ray diffraction, FT-IR spectroscopy, Raman spectroscopy, UV-Vis spectroscopy, scanning electron microscope, transmission electron microscopy, and X-ray photoelectron spectroscopy. It was found that the TiO2 phase in TiO2/diazonium/GO composites can be controlled by adjusting the amount of ethanol or titanium oxide in the reactant mixture. The obtained composites exhibited photocatalytic activities for methylene blue degradation (MB). The composite with ac. 70% anatase can provide the highest MB degradation efficiency. The studying of some intermediates for MB photocatalytic degradation using LC-MS showed that structure of MB by the cleavage and oxidation of one or more of the methyl group substituent on the amine groups lead to form compounds with low molecular masses. Total organic carbon studies confirmed a complete mineralization of MB. The present catalyst was stable and recyclable after three times with a negligible loss of catalytic activity. In addition, the TiO2/diazonium/GO can also photocatalyze for the degradation of some other dyes (phenol, methyl red, and Congo red).
LncRNA CAR10 Upregulates PDPK1 to Promote Cervical Cancer Development by Sponging miR‐125b‐5p
Authors: Hu Tingting , Zhang Qian , Gao Lingxue
Published: January 2020

Cervical cancer is one of the malignant tumors that seriously threaten women’s health. The mechanism of development needs to be deeply studied. In recent years, lncRNA has been identified as one of the important factors affecting the malignant progression of tumors. In this study, we illustrated the important mechanism of lncRNA CAR10 in the development of cervical cancer. We found that CAR10 is significantly increased in4 cervical cancer tissues and cells, which can promote the proliferation of cervical cancer cells in vitro and in vivo, indicating that CAR10 is involved in the progression of cervical cancer as an oncogene. Further studies showed that CAR10 is a target gene of miR‐125b‐5p, and miR‐125b‐5p can inhibit the effect of CAR10 on the proliferation of cervical cancer cells. In addition, we also found that 3‐phosphoinositide‐dependent protein kinase 1 (PDPK1) is also a target gene of miR‐125b‐5p, and CAR10 can upregulate the expression level of PDPK1. The results showed that CAR10 acts as a ceRNA to upregulate the expression of PDPK1 by sponging miR‐125b‐5p. Knockdown of PDPK1 can inhibit the effect of CAR10 on cervical cancer cells. Our study demonstrates that, based on ceRNA mechanism, CAR10/miR‐125b‐5p/PDPK1 network can regulate the proliferation of cervical cancer cells and play an important role in the development of cervical cancer. In addition, our study also suggests that intervention of CAR10/miR‐125b‐5p/PDPK1 network may be a new strategy for targeted therapy of cervical cancer.
Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis
Authors: Garcia Nadja Pinto , Júnior Alexander Leonardo S. , Soares Geyse Adriana S. , Costa Thainá Cristina C. , dos Santos Alicia Patrine C. , Costa Allyson Guimarães , Tarragô Andréa Monteiro , Martins Rejane Nina , do Carmo Leão Pontes Flávia , de Almeida Emerson Garcia , de Paula Erich Vinícius , Martins-Filho Olindo Assis , Malheiro Adriana
Published: January 2020

Background. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results. Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion. In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.
Walking Gait Phase Detection Based on Acceleration Signals Using Voting-Weighted Integrated Neural Network
Authors: Yan Lei , Zhen Tao , Kong Jian-Lei , Wang Lian-Ming , Zhou Xiao-Lei
Published: January 2020

Human gait phase recognition is a significant technology for rehabilitation training robot, human disease diagnosis, artificial prosthesis, and so on. The efficient design of the recognition method for gait information is the key issue in the current gait phase division and eigenvalues extraction research. In this paper, a novel voting-weighted integrated neural network (VWI-DNN) is proposed to detect different gait phases from multidimensional acceleration signals. More specifically, it first employs a gait information acquisition system to collect different IMU sensors data fixed on the human lower limb. Then, with dimensionality reduction and four-phase division preprocessing, key features are selected and merged as unified vectors to learn common and domain knowledge in time domain. Next, multiple refined DNNs are transferred to design a multistream integrated neural network, which utilizes the mixture-granularity information to exploit high-dimensional feature representative. Finally, a voting-weighted function is developed to fuse different submodels as a unified representation for distinguishing small discrepancy among different gait phases. The end-to-end implementation of the VWI-DNN model is fine-tuned by the loss optimization of gradient back-propagation. Experimental results demonstrate the outperforming performance of the proposed method with higher classification accuracy compared with the other methods, of which classification accuracy and macro-F1 is up to 99.5%. More discussions are provided to indicate the potential applications in combination with other works.
Passivity and Synchronization of Coupled Different Dimensional Delayed Reaction-Diffusion Neural Networks with Dirichlet Boundary Conditions
Authors: Lin Shanrong , Huang Yanli , Yang Erfu
Published: January 2020

Two types of coupled different dimensional delayed reaction-diffusion neural network (CDDDRDNN) models without and with parametric uncertainties are analyzed in this paper. On the one hand, passivity and synchronization of the raised network model with certain parameters are studied through exploiting some inequality techniques and Lyapunov stability theory, and some adequate conditions are established. On the other hand, the problems of robust passivity and robust synchronization of CDDDRDNNs with parameter uncertainties are solved. Finally, two numerical examples are given to testify the effectiveness of the derived passivity and synchronization conditions.
A Mode Selected Mixed Logic Dynamic Model and Model Predictive Control of Buck Converter
Authors: Jiang Lei , Liu Enliang , Liu Ding
Published: January 2020

A Mixed Logic Dynamic (MLD) model and control method based on mode selection are proposed for the Buck convertor. In establishing the hybrid system model, the factors such as the inductor current are neglected, and the Model Predictive Control (MPC) is used to switch the most favorable working state of the control target. Since the modeling process ignores the inductance and current, it is necessary to convert the optimization prediction control resulting to avoid the problem that the model is inconsistent with the control object. The method proposed in this paper uses fewer auxiliary logic variables and mixed logic variables in the modeling process, simplifying the model and improving the solution speed. This method can not only make the Buck converter work in the Continuous Current Mode (CCM) but also work in the Discontinuous Current Mode (DCM), extending the adjustment range of the Buck converter. The simulation results show that the proposed method has a better control performance than the traditional MLD model.
Early‐Age Cracking Analysis of a HVFA Concrete Structure Based on Thermo‐Hygro‐Mechanical Modeling Combined with XFEM
Authors: Cui Wei , Luo Yanjun , Peng Shuang
Published: January 2020

Due to the low hydration rate of high‐volume fly ash (HVFA) concrete at early age, the temperature gradient between the concrete core and surfaces could be effectively reduced. However, the low hydration rate results in a lack of hydration degree for early‐age HVFA concrete. Thus, during curing, compared to the strength of ordinary Portland cement (OPC), a subsequent lower one of HVFA concrete leads to a more sensitive response to inner stresses induced by thermal and moisture loads. Based on ABAQUS, in this paper, user subroutines in the temperature and moisture fields were developed, with regard to the hydration degree, for simulation of the temperature and moisture influences on concrete. Additionally, the Double Power Law (DPL) model was used to depict early‐age deformations of concrete in the mechanical field. Combined with the extended finite element method (XFEM), another subroutine for early‐age cracking analysis in the mechanical field was then developed. Together with aforementioned subroutines, a thermo‐hygro‐mechanical model is derived. For evaluation of early‐age cracking initiation and propagation of a pier composed of HVFA concrete, the model was implemented with XFEM. The obtained results show that (1) temperature and restraints are the main causes of cracking; (2) moisture loss affects surface cracks on structures at early age; and (3) although the temperature difference between the core and surfaces is not much obvious due to the reduced rate of heat dissipation from hydration, cracking of early‐age HVFA concrete is still likely to happen for its low early strength. Thus, timely curing is critical to prevent early cracking.
Low‐Frequency Ultrasound Enhances Bactericidal Activity of Antimicrobial Agents against Klebsiella pneumoniae Biofilm
Authors: Liu Xu , Wang Jin , Weng Chun-xiao , Wang Rui , Cai Yun
Published: January 2020

Klebsiella pneumoniae biofilms on inserted devices have been proposed as one of the important factors for hospital‐acquired infections, which cause increased resistance to currently used antibiotics. Therefore, it is urgently necessary to develop new treatments with more efficient bacterial clearance. In the present study, we aimed at investigating whether low‐frequency ultrasound (LFU) could enhance the bactericidal activity of antimicrobial agents (meropenem (MEM), tigecycline (TGC), fosfomycin (FOM), amikacin (AMK), and colistin (COL)) against K. pneumoniae biofilm infection. K. pneumoniae biofilm was cultivated on the catheter in vitro. Synergistic effects were observed in groups of single ultrasound (S‐LFU, 5 min) or multiple ultrasound (M‐LFU, 5 min every 8 h (q8h)) in combination with MEM, TGC, and FOM. However, AMK and COL did not show the synergistic effect with either S‐LFU or M‐LFU. S‐LFU in combination with FOM only significantly decreased bacterial counts right after ultrasound, while M‐LFU could prolong the synergistic effect until 24 h. The results showed that LFU in combination with antimicrobial agents had a synergistic effect on K. pneumoniae biofilm, and M‐LFU might extend the time of synergistic effect compared with S‐LFU.
Analysis, Stabilization, and DSP-Based Implementation of a Chaotic System with Nonhyperbolic Equilibrium
Authors: Yang Xuan-Bing , He Yi-Gang , Li Chun-Lai , Liu Chang-Qing
Published: January 2020

This paper reports an autonomous dynamical system, and it finds that one nonhyperbolic zero equilibrium and two hyperbolic nonzero equilibria coexist in this system. Thus, it is difficult to demonstrate the existence of chaos by Šil’nikov theorem. Consequently, the topological horseshoe theory is adopted to rigorously prove the chaotic behaviors of the system in the phase space of Poincaré map. Then, a single control scheme is designed to stabilize the dynamical system to its zero-equilibrium point. Besides, to verify the theoretical analyses physically, the attractor and stabilization scheme are further realized via DSP-based technique.
Event-Triggered Average Consensus of Multiagent Systems with Switching Topologies
Authors: Dong Gaosen , Yang Chunde , Zhu Wei
Published: January 2020

Event-triggered average consensus of multiagent systems with switching topologies is studied in this paper. A distributed protocol based on event-triggered time sequences and switching time sequences is designed. Based on the inequality technique and stability theory of differential equations, a sufficient condition for achieving average consensus is obtained under the assumption that switching signal is ergodic and the total period over which connected topologies is sufficiently large. A numerical simulation is presented to show the effectiveness of the theoretical results.
Population Pharmacokinetics of Clozapine: A Systematic Review
Authors: Albitar Orwa , Harun Sabariah Noor , Zainal Hadzliana , Ibrahim Baharudin , Sheikh Ghadzi Siti Maisharah
Published: January 2020

Background and Objective. Clozapine is a second‐generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models. Methods. A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded. Results. Twelve studies were included in this review. Clozapine pharmacokinetics was described as one‐compartment with first‐order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models. Conclusions. Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug‐drug interactions in a well‐designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.
Selective Inhibition of HDAC3 Targets Synthetic Vulnerabilities and Activates Immune Surveillance in Lymphoma
Authors: Mondello Patrizia , Tadros Saber , Teater Matt , Fontan Lorena , Chang Aaron Y. , Jain Neeraj , Yang Haopeng , Singh Shailbala , Ying Hsia-Yuan , Chu Chi-Shuen , Ma Man Chun John , Toska Eneda , Alig Stefan , Durant Matthew , de Stanchina Elisa , Ghosh Sreejoyee , Mottok Anja , Nastoupil Loretta , Neelapu Sattva S. , Weigert Oliver , Inghirami Giorgio , Baselga José , Younes Anas , Yee Cassian , Dogan Ahmet , Scheinberg David A. , Roeder Robert G. , Melnick Ari M. , Green Michael R.
Published: January 2020

CREBBP mutations are highly recurrent in B-cell lymphomas and either inactivate its histone acetyltransferase (HAT) domain or truncate the protein. Herein, we show that these two classes of mutations yield different degrees of disruption of the epigenome, with HAT mutations being more severe and associated with inferior clinical outcome. Genes perturbed by CREBBP mutation are direct targets of the BCL6–HDAC3 onco-repressor complex. Accordingly, we show that HDAC3-selective inhibitors reverse CREBBP-mutant aberrant epigenetic programming, resulting in: (i) growth inhibition of lymphoma cells through induction of BCL6 target genes such as CDKN1A and (ii) restoration of immune surveillance due to induction of BCL6-repressed IFN pathway and antigen-presenting genes. By reactivating these genes, exposure to HDAC3 inhibitors restored the ability of tumor-infiltrating lymphocytes to kill DLBCL cells in an MHC class I and II–dependent manner, and synergized with PD-L1 blockade in a syngeneic model in vivo. Hence, HDAC3 inhibition represents a novel mechanism-based immune epigenetic therapy for CREBBP-mutant lymphomas.

Significance:

We have leveraged the molecular characterization of different types of CREBBP mutations to define a rational approach for targeting these mutations through selective inhibition of HDAC3. This represents an attractive therapeutic avenue for targeting synthetic vulnerabilities in CREBBP-mutant cells in tandem with promoting antitumor immunity.

This article is highlighted in the In This Issue feature, p. 327
Biological Sex and IgE Sensitization Influence Severity of Depression and Cortisol Levels in Atopic Dermatitis
Authors: Vinnik Tatyana , Kreinin Anatoly , Abildinova Gulshara , Batpenova Gulnar , Kirby Michael , Pinhasov Albert
Published: January 2020

Background: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. Objective and Methods: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. Results: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. Conclusion: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.
A Guiding Nightlight Decreases Fear of Falling and Increases Sleep Quality of Community-Dwelling Older People: A Quantitative and Qualitative Evaluation
Authors: Thölking Thessa W. , Lamers Eef C.T. , Olde Rikkert Marcel G.M.
Published: January 2020

Background: Even though poor lighting at nighttime is an important risk factor for falls (and most falls occur during the night), lighting interventions to improve nightly lighting from bed to bathroom are rarely evaluated for fall prevention. Objective: We tested the hypothesis that an automated guiding light would reduce nightly fear of falling (FOF) and increase sleep quality of community-dwelling older people. Methods: This study had a pragmatic uncontrolled before-after design, including participants during a period of 8 months if they (i) were aged at least 65 years, (ii) ambulated independently at night, and (iii) had no cognitive or audiovisual impairments obstructing outcome measurement. Automated LED strips (GightTM) were installed in the participants’ homes. The primary outcome measure was overnight FOF on a scale of 0–10. Secondary outcome measures included sleep quality on a scale of 0–10 and fall rate. Additionally, a sample of participants was interviewed about their experiences with Gight. Results: Sixty-four participants were included (mean age: 80.8 ± 8.1 years; 89% living independently). Mean study length was 118 days (range: 30–231). In the intention-to-treat analysis, overnight FOF declined from 5.5 ± 3.0 to 3.8 ± 3.2 (p = 0.001), and sleep quality increased from 6.7 ± 2.4 to 7.4 ± 1.7 (p = 0.012). The fall rate during the study was too low to detect changes. Participants appreciated Gight (8.4 ± 0.8 on a scale of 10), and the majority (57%) reported a subjective decrease in FOF. Conclusion: Gight shows promising results for overnight FOF and sleep quality, but the effect of lighting interventions on fall rate should be evaluated further before widespread implementation.
High-Throughput Screening of Blood Donors for Twelve Human Platelet Antigen Systems Using Next-Generation Sequencing Reveals Detection of Rare Polymorphisms and Two Novel Protein-Changing Variants
Authors: Vorholt Stephanie Maria , Hamker Nele , Sparka Hagen , Enczmann Jürgen , Zeiler Thomas , Reimer Tanja , Fischer Johannes , Balz Vera
Published: January 2020

Background: Exposure to non-matching human platelet alloantigens (HPA) may result in alloimmunization. Antibodies to HPA can be responsible for post-transfusion purpura, refractoriness to donor platelets, and fetal and neonatal alloimmune thrombocytopenia. For the supply of compatible apheresis platelet concentrates, the HPA genotypes are determined in a routine manner. Methods: Here, we describe a novel method for genotyping twelve different HPA systems simultaneously, including HPA-1 to HPA-5, HPA-9w, HPA-10w, HPA-16w, HPA-19w, HPA-27w, and the novel HPA-34w by means of amplicon-based next-generation sequencing (NGS). Blood donor samples of 757 individuals with a migration background and 547 of Western European ancestry were genotyped in a mass-screening setup. An in-house software was developed for fast and automatic analysis. TaqMan assay and Sanger sequencing results served for validation of the NGS workflow. Finally, blood donors were divided in several groups based on their country of origin and the allele frequencies were compared. Results: For 1,299 of 1,304 samples (99.6%) NGS was successfully performed. The concordance with TaqMan assay and Sanger sequencing results was 99.8%. Allele-calling dropouts that were observed for two samples with the TaqMan assay caused by rare single nucleotide polymorphisms were resolved by NGS. Additionally, twenty rare and two novel variants in the coding regions of the genes ITGB3, GPB1A, ITGBA2, and CD109 were detected. The determined allele frequencies were similar to those published in the gnomAD database. Conclusions: No significant differences were observed in the distribution of allele frequencies of HPA-1 through HPA-5 and HPA-15 throughout the analyzed groups except for a lower allele frequency for the HPA-1b allele in the group of donors with Southern Asian ancestry. In contrast, other nucleotide variants that have not yet been phenotypically characterized occurred three times more often in blood donors with a migration background. High-throughput amplicon-based NGS is a reliable method for screening HPA genotypes in a large sample cohort simultaneously. It is easily upgradeable for genotyping additional targets without changing the setup or the analysis pipeline. Mass-screening methods will help building up blood donor registries to provide matched blood products.
Effects of Perennial Allergen Immunotherapy in Allergic Rhinitis in Patients with/without Asthma: A-Randomized Controlled Real-Life Study
Authors: Ünal Derya
Published: January 2020

Background: There have been very few studiesin real-life settingscomparing the treatment effects of allergen immunotherapy (AIT) and pharmacotherapy for perennial allergic rhinitis (AR). Objective: This study was performed to compare AIT and pharmacotherapy in terms of their effects on the symptom control and quality of life (QOL) of AR patients with/without asthma. Methods: A total of 250 patients diagnosed with AR with/without asthma were included and assigned to the immunotherapy (AIT plus pharmacological treatment) or control (pharmacological treatment only) group. Clinical and medication scores, QOL scores, and lung function (forced expiratory volume in one second as a percentage; FEV1%) were measured at baseline and 3 years after the start of treatment. Results: This study showed that there was clinical improvement in AR symptoms in the AIT group, whereas standard pharmacotherapy alone had no significant effect on nasal symptoms. The QOL and satisfaction scores, as evaluated with a visual analogue scale (VAS), were further improved compared to the pharmacotherapy group. There was a significant improvement in medication scores in both AIT groups. According to our results, while total asthma scores and asthma control test scores were significantly improved in the HDM AIT group, they did not change in the Parietaria pollen AIT group. In our study FEV1% was increased compared to the baseline value in the AIT group, but it was not statistically significant. On the other hand, FEV1% remained without any improvement in patients on standard pharmacotherapy. Conclusion: Perennial AIT was found to be superior to pharmacotherapy in decreasing symptoms as well as in improving QOL scores in AR patients with/without asthma. HDM AIT was more effective for asthma symptoms than Parietaria pollen AIT.
Effectiveness and Safety of Vonoprazan versus Proton Pump Inhibitors for Second-Line Helicobacter pylori Eradication Therapy: Systematic Review and Meta-Analysis
Authors: Shinozaki Satoshi , Kobayashi Yasutoshi , Osawa Hiroyuki , Sakamoto Hirotsugu , Hayashi Yoshikazu , Lefor Alan Kawarai , Yamamoto Hironori
Published: January 2020

Background: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. Methods: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. Results: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27–1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71–5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16–1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58–1.32, p = 0.53). Conclusions: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.
The Accountability Deficit in the Philippines: Implications and Prospects for Democratic Consolidation
Authors: Arugay Aries A.
Published: January 2020

One of the major challenges that consolidating democracies such as the Philippines needs to address is how to combat and control the problems of corruption, abuse of power, and other forms of particularism. The absence of effective institutions and mechanisms to counter them would result in one major democratic deficit — the lack or weakness of accountability. This article attempts to expose the manifestations of the “accountability deficit” in the Philippines by looking at the problems, limitations, and inadequacies of elections and horizontal state agencies of restraint as institutions of accountability. It also probes into the emergence of an alternative means known as “societal accountability”, using the resignation, impeachment, and ouster (RIO) campaign against then President Joseph Estrada as a case study. This article concludes with some thoughts on the implications of the accountability deficit to the prospects for democratic consolidation in the Philippines.
Exceeding (Low) Expectations: Autonomy, Bureaucratic Integrity, and Capacity in the 2010 Elections
Authors: Calimbahin Cleo
Published: January 2020

Building quality democracy takes time. It requires a constant review of the performance of institutions that are tasked to deliver in concrete ways the democratic ideal. Improving democratic institutions requires sustained reform efforts. Election administration and election commissions need to be examined against this backdrop of broader democratization issues. Given the importance of election administration in the study of democratic processes, there are very few studies that focus on election administration. By focusing on a specific institution tasked to replicate the ideals of democracy such as the COMELEC, this study offers insights into a deeper understanding of autonomy, bureaucratic integrity and capacity. Though mostly overlooked, election administration plays a vital role in the study of broader democratization questions. Elections promise continuity and stability. But if election administration is done poorly due to the lack of autonomy, integrity, and capacity then it becomes an unsettling and destabilizing exercise.

With democratic structures in place for years, the Philippines continues to have problems with the most basic elements of election administration: accuracy in maintaining voter lists, counting votes and adjudicating disputes. The COMELEC oversees election administration, serving as referee and gatekeeper in the Philippines’ electoral arena. The COMELEC is a constitutional commission with ostensible autonomy and power, yet it is also a bureaucracy. The May 2010 election was the first automated election in the Philippines. Widely regarded as a success, there were many issues and incidents that show it was also business as usual for COMELEC. The speed of the canvass count astounded the voting populace, and perhaps operators, but the May 2010 election continues to show embedded problems within the commission that needs to be addressed in order to strengthen the COMELEC as an institution that can provide election administration efficiently and accurately in subsequent elections.