bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable Photoelectrochemical Hydrogen Evolution for 1000 h at 14% Efficiency in a Monolithic Vapor-fed Device
Authors: Kistler Tobias A. , Um Min Young , Agbo Peter
Published: March 2020

This report builds on our recent disclosure of a fully-integrated, photoelectrochemical (PEC) device for hydrogen evolution using a structure incorporating a III–V triple-junction photovoltaic (PV) embedded in a Nafion membrane. Catalyst integration is realized by compression of catalyst-modified, carbon electrodes against the front and back PV contacts, resulting in a wireless, monolithic PEC assembly. Using this device architecture, we demonstrate significant enhancements in device stability and longevity, by transitioning from a liquid-water to water-vapor anode. Our use of a gas-fed anode enables 1000 h of cumulative device operation at a peak solar-to-hydrogen efficiency of 14%, during simulated, solar illumination at 1 sun and outdoor, diurnal cycling. Vapor-fed water oxidation is shown to reduce drops in device performance by mitigating the corrosion effects that are commonly associated with full-aqueous immersion of the electrochemical and photovoltaic elements in PEC devices.
Challenges in the interpretation and therapeutic manipulation of human ingestive microstructure
Authors: Gero Daniel
Published: March 2020

This minireview focuses on the interpretative value of ingestive microstructure by summarizing observations from both rodent and human studies. Preliminary data on the therapeutic manipulation of distinct microstructural components of eating are also outlined. In rodents, the interpretative framework of ingestive microstructure mainly concentrates on deprivation state, palatability, satiation, and the role of learning from previous experiences. In humans, however, the control of eating is further influenced by genetic, psychosocial, cultural, and environmental factors, which add complexity and challenges to the interpretation of the microstructure of meal intake. Nevertheless, the presented findings stress the importance of microstructural analyses of ingestion, as a method to investigate specific behavioral variables that underlie the regulation of appetite control.
Lower limb massage in humans increases local perfusion and impacts systemic hemodynamics
Authors: Monteiro Rodrigues Luis , Rocha Clemente , Ferreira Hugo T. , Silva Henrique N.
Published: March 2020

The impact of effleurage, a well-known massage procedure used in human rehabilitation, in the lower limb hemodynamics, is demonstrated. When applied in a sole limb, massage increases skin microcirculatory flowmotion not only locally but also beyond, affecting systemic hemodynamics. This observation is an interesting example of the efficacy of cardiovascular integration mechanisms involving distal microcirculatory homeostasis. The proposed methodology allows a mechanistic view over skin flowmotion regulation, being applicable to further explore massage and its impact on microcirculatory physiology.
Emerging approaches for restoration of hearing and vision
Authors: Kleinlogel Sonja , Vogl Christian , Jeschke Marcus , Neef Jakob , Moser Tobias
Published: March 2020

Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For long, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye and ear has generated hope for a fundamental improvement of vision and hearing restoration. To date, one gene therapy for the restoration of vision has been approved and undergoing clinical trials will broaden its application including gene replacement, genome editing, and regenerative approaches. Moreover, optogenetics, i.e. controlling the activity of cells by light, offers a more general alternative strategy. Over little more than a decade, optogenetic approaches have been developed and applied to better understand the function of biological systems, while protein engineers have identified and designed new opsin variants with desired physiological features. Considering potential clinical applications of optogenetics, the spotlight is on the sensory systems. Multiple efforts have been undertaken to restore lost or hampered function in eye and ear. Optogenetic stimulation promises to overcome fundamental shortcomings of electrical stimulation, namely poor spatial resolution and cellular specificity, and accordingly to deliver more detailed sensory information. This review aims at providing a comprehensive reference on current gene therapeutic and optogenetic research relevant to the restoration of hearing and vision. We will introduce gene-therapeutic approaches and discuss the biotechnological and optoelectronic aspects of optogenetic hearing and vision restoration.
Impact of an Irrigation Dam on the Transmission and Diversity of Plasmodium falciparum in a Seasonal Malaria Transmission Area of Northern Ghana
Authors: Kyei-Baafour Eric , Tornyigah Bernard , Buade Benjamin , Bimi Langbong , Oduro Abraham R. , Koram Kwadwo A. , Gyan Ben A. , Kusi Kwadwo A.
Published: March 2020

Water bodies such as dams are known to alter the local transmission patterns of a number of infectious diseases, especially those transmitted by insects and other arthropod vectors. The impact of an irrigation dam on submicroscopic asexual parasite carriage in individuals living in a seasonal malaria transmission area of northern Ghana was investigated. A total of 288 archived DNA samples from two cross-sectional surveys in two communities in the Bongo District of Northern Ghana were analysed. Parasite density was determined by light microscopy and PCR, and parasite diversity was assessed by genotyping of the polymorphic Plasmodium falciparum msp2 block-3 region. Submicroscopic parasitaemia was estimated as the proportional difference between positive samples identified by PCR and microscopy. Dry season submicroscopic parasite prevalence was significantly higher (71.0%, p=0.013) at the dam site compared with the nondam site (49.2%). Similarly, wet season submicroscopic parasite prevalence was significantly higher at the dam site (54.5%, p=0.008) compared with the nondam site (33.0%). There was no difference in parasite density between sites in the dry season (p=0.90) and in the wet season (p=0.85). Multiplicity of infection (MOI) based on PCR data was significantly higher at the dam site compared with the nondam site during the dry season (p<0.0001) but similar between sites during the wet season. MOI at the nondam site was significantly higher in the wet season than in the dry season (2.49, 1.26, p<0.0001) but similar between seasons at the dam site. Multivariate analysis showed higher odds of carrying submicroscopic parasites at the dam site in both dry season (OR = 7.46, 95% CI = 3.07–18.15) and in wet season (OR = 1.73, 95% CI = 1.04–2.86). The study findings suggest that large water bodies impact year-round carriage of submicroscopic parasites and sustain Plasmodium transmission.
Synthesis of Mixed Ligand Ruthenium (II/III) Complexes and Their Antibacterial Evaluation on Drug-Resistant Bacterial Organisms
Authors: Matshwele James T. P. , Nareetsile Florence , Mapolelo Daphne , Matshameko Pearl , Leteane Melvin , Nkwe David O. , Odisitse Sebusi
Published: March 2020

The potential antimicrobial properties of a tridentate polypyridyl ligand 4-butoxy-N,N-bis(pyridin-2-ylmethyl)aniline (BUT) 1 and its corresponding mixed ligand ruthenium complexes were investigated on drug-resistant and non-drug-resistant bacterial species. The ligand and its complexes were synthesized and successfully characterized by1H NMR, UV/Vis, and FTIR spectra; ESI-MS; and magnetic susceptibility. Electronic spectra and magnetic susceptibility of these Ru(II)/(III) complexes suggest that they are of a low spin crystal field split, where the Ru(III) is ad5and Ru(II)d6low spin. These compounds were tested for antibacterial activity on two bacterial species:Staphylococcus aureus(S. aureus) andKlebsiella pneumoniae(K. pneumoniae), as well as their drug-resistant strains methicillin-resistantStaphylococcus aureus(MRSA) and multidrug resistantKlebsiella pneumoniae(MDRK. pneumoniae). All the compounds inhibited growth of the two non-drug-resistant bacteria and only one drug-resistant strain MRSA. However, only the ligands BUT and 2,2-dipyridylamine showed activity against MRSA, while all complexes did not show any antibacterial activity on MRSA. We observed large zones of inhibition for the Gram-positiveS. aureusand MRSA bacteria, compared to the Gram-negativeK. pneumoniaebacteria. DNA cleavage studies with gel electrophoresis showed denatured bacterial DNA on the gel from all the complexes, with the exception of the ligand, suggesting DNA nuclease activity of the complexes in the bacterial DNA.
Quantification of the Nucleophilicities of 3-X-Thiophenes: Highlighting the Hyperortho Correlation
Authors: Gabsi W. , Boubaker T. , Goumont R.
Published: March 2020

Kinetics studies for the coupling reactions of the 3-X-thiophene 1a-c (X = CH3, H and Br) with the electrophiles 2a and 3a-c have been investigated in acetonitrile at 20°C The second-order rate constants have been employed to determine the nucleophilicity parameters N and s of the thiophene 1 according the Mayr equation log k (20°C) = s (E + N). The nucleophilic-specific parameters N and s quantified in this work have been derived and compared with the reactivity of other C nucleophiles. Based on the linear correlations log k1 = f(E) and log k1 = f(σp+), we have shown that the mechanism of interactions occurs by a unique process: electrophilic heteroaromatic substitution of an α-carbon position of substituted 3-X-thiophenes 1 known hyperortho correlation.
Generation of Dynamical S-Boxes for Block Ciphers via Extended Logistic Map
Authors: Cassal-Quiroga B. B. , Campos-Cantón E.
Published: March 2020

In this work, we present a simple algorithm to design n × n-bits substitution boxes (S-boxes) based on chaotic time series of the logistic map for different carrying capacities. The use of different carrying capacities in the chaotic map leads to low computational complexity, which is desirable to get high-speed communication systems. We generate a main sequence by means of two auxiliary sequences with uniform distribution via the logistic map for different carrying capacities. The elements of the main sequence are useful for generating the elements of an S-box. The auxiliary sequences are generated by considering lag time chaotic series; this helps to hide the chaotic map used. The U-shape distribution of logistic chaotic map is also avoided, in contrast with common chaos-based schemes without considering lag time chaotic series, and uncorrelated S-box elements are obtained. The proposed algorithm guarantees the generation of strong S-boxes that fulfill the following criteria: bijection, nonlinearity, strict avalanche criterion, output bits independence criterion, criterion of equiprobable input/output XOR distribution, and maximum expected linear probability. Finally, an application premised on polyalphabetic ciphers principle is developed to obtain a uniform distribution of the plaintext via dynamical S-boxes.
Intention to Screen for Cervical Cancer in Debre Berhan Town, Amhara Regional State, Ethiopia: Application of Theory of Planned Behavior
Authors: Getahun Tomas , Kaba Mirgissa , Derseh Behailu Tariku
Published: March 2020

Background. Cervical cancer is a major public health problem in many developing countries. Despite the value of screening to prevent morbidity and mortality from cervical cancer, little available literature shows early detection and treatment to be limited in Ethiopia. The aim of this study was to determine the magnitude of and identify factors associated with women’s intention to screen for cervical cancer using the theory of planned behavior. Methods. A community-based cross-sectional study design supplemented with a qualitative approach was employed. Using multistage sampling, a total of 821 women were used in the study. An interviewer-administered survey questionnaire was used to collect quantitative data, whereas purposively selected 12 female health care providers were included in in-depth interviews. Descriptive statistics and simple and multiple binary logistic regression analysis were used to determine the magnitude of women’s intention, identify associated factors, and explore barriers for intention to cervical cancer screening among Debre Berhan women, Ethiopia. The statistical association was determined at a P value of less than 0.05. Moreover, thematic analysis was used to search the hindrances of women’s intention to screen for cervical cancer. Results. The median age of women who participated in this study was 39 years with IQR of 35 to 42 years. Three hundred sixty-one (361, 45.3%) of women had an intention to screen for cervical cancer within three months from the date of the interview. Positive attitude towards cervical cancer screening (AOR=6.164; 95% CI: 4.048, 9.387), positive subjective norm (AOR=2.001; 95% CI: 1.342, 2.982), and higher perceived behavioral control (AOR=7.105; 95% CI: 4.671, 10.807) were predictors of the women’s intention to screen for cervical cancer. The qualitative finding revealed that women did not like to be screened for cervical cancer because they thought that procedure pinch the cervix and it may result in perforating the uterus that would expose them for infertility. In addition, the qualitative findings supported quantitative results, where the constructs of the theory of planned behavior play an essential role in the betterment of women’s intention. Conclusion. This study showed that women’s intention to screen for cervical cancer was low. Positive attitudes towards cervical cancer screening (CCS), subjective norms, and perceived behavioral control were predictors of women’s intention to screen for cervical cancer. Thus, efforts should be exerted to improve the attitude of women involving influential people, which could improve women’s intention for cervical cancer screening. Moreover, behavioral change communication focusing on the constructs of the theory of planned behavior is crucial.
Distributions and Sources of Sedimentary Sterols as well as Their Indications of Sewage Contamination in the Guanting Reservoir, Beijing
Authors: Wen Xin , Bai Yijuan , Zhang Shurong , Ding Aizhong , Zheng Lei , Li Jian
Published: March 2020

In this study, domestic sewage contamination in the Guanting Reservoir, one of the major water source reservoirs of Beijing, was examined using sterols as tracing molecular markers. Nineteen sediment samples in seven cross-sections in the Guanting Reservoir were collected, extracted, and analyzed by gas chromatography-mass spectrometry (GC-MS). Seven different sterols were identified and quantified from the surface sediment samples in the Guanting Reservoir. The total sterols in sediments of the reservoir ranged from 2.78 μg g−1 to 40.31 μg g−1 with the average concentration of 13.53 μg g−1. Concentrations of fecal sterols, coprostanol and epicoprostanol in the Guishui River reservoir area were generally higher than in the Yongding River reservoir area. The average concentrations of coprostanol and epicoprostanol in the Yongding River reservoir area were 0.41 μg g−1 and 0.34 μg g−1, respectively. The average concentrations of coprostanol and epicoprostanol in the Guishui River reservoir area were 0.72 μg g−1 and 0.70 μg g−1, respectively. Ratios of sterols indicated higher sewage pollution in regions close to river mouths and reservoir banks. Principal component analysis (PCA) indicated three distinct sources of sterols from domestic sewage, phytoplankton, and terrestrial higher plants. This article identified the current situation of sewage contamination in sediments of the Guanting Reservoir, which could provide important references for further implementation of pollution control and basin management in the region.
Method of Coupling Metrics for Object-Oriented Software System Based on CSBG Approach
Authors: Gu Aihua , Li Lu , Li Shujun , Xun Qifeng , Dong Jian , Lin Jianhong
Published: March 2020

Context. Coupling between classes is an important metric for software complexity in software systems. Objective. In order to overcome the shortcomings of the existing coupling methods and fully investigate the weighted coupling of classes in different cases in large-scale software systems, this study analyzed the relationship between classes at package level, class level, and method level. Method. The software system is considered as a set of special bipartite graphs in complex networks, and an effective method for coupling measurement is proposed as well. Furthermore, this method is theoretically proved to satisfy the mathematical properties of coupling measurement, leading to overcome the disadvantages of the majority of existing methods. In addition, it was revealed that the proposed method was efficient according to the analyses of existing methods for coupling measurement. Eventually, an algorithm was designed and a program was developed to calculate coupling between classes in three open-source software systems. Results. The results indicated the scale-free characteristic of complex networks in the statistical data. Additionally, the calculated power-law value was used as a metric for coupling measurement, so as to calculate coupling of the three open-source software. It indicated that coupling degrees of the open-source software systems contained a certain impact on evaluation of software complexity. Conclusions. It indicated that coupling degrees of the open-source software systems contained a certain impact on evaluation of software complexity. Moreover, statistical characteristics of some complex networks provided a reliable reference for further in-depth study of coupling. The empirical evidence showed that within a certain range, reducing the coupling was helpful to attenuate the complexity of the software, while excessively blindly pursuit of low coupling increases the complexity of software systems.
A Classification and Novel Class Detection Algorithm for Concept Drift Data Stream Based on the Cohesiveness and Separation Index of Mahalanobis Distance
Authors: Li Xiangjun , Zhou Yong , Jin Ziyan , Yu Peng , Zhou Shun
Published: March 2020

Data stream mining has become a research hotspot in data mining and has attracted the attention of many scholars. However, the traditional data stream mining technology still has some problems to be solved in dealing with concept drift and concept evolution. In order to alleviate the influence of concept drift and concept evolution on novel class detection and classification, this paper proposes a classification and novel class detection algorithm based on the cohesiveness and separation index of Mahalanobis distance. Experimental results show that the algorithm can effectively mitigate the impact of concept drift on classification and novel class detection.
Acupuncture for the Treatment of Tension‐Type Headache: An Overview of Systematic Reviews
Authors: Huang Jinke , Shen Min , Qin Xiaohui , Guo Weichi , Li Hui
Published: March 2020

Objectives. Because current evidence regarding the effectiveness of acupuncture for a tension‐type headache (TTH) is controversial, we evaluated the reliability of the methodological quality and outcome measures of systematic reviews/meta‐analyses (SRs/MAs) on acupuncture for TTH. Methods. We conducted a comprehensive literature search for SRs/MAs in major databases from the database’s inception to September 2019. The Methodological Quality of Systematic Reviews 2 (AMSTAR‐2) and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were used to assess the methodological quality of the included reviews and the quality of evidence, respectively. Results. Eight reviews were included in the analysis. The AMSTAR‐2 assessment results showed that the methodological quality of all included reviews was critically low. Thirty‐six outcome measures were included in these reviews. The GRADE results showed that 25 (25/36, 69.4%) outcomes provided low‐ or very low‐quality evidence, four (4/36, 11.1%) provided moderate‐quality evidence, and seven (7/36, 19.4%) provided high‐quality evidence. Descriptive analysis results showed that acupuncture treatment for TTH reduced headache frequency and severity. Conclusions. Acupuncture appears to be an effective treatment modality for TTH, but the credibility of the results is limited owing to the generally low methodological quality and evidence quality in the included SRs/MAs.
A Stabilization Method Based on an Adaptive Feedforward Controller for the Underactuated Bipedal Walking with Variable Step-Length on Compliant Discontinuous Ground
Authors: Wang Yang , Yao Daojin , He Jie , Xiao Xiaohui
Published: March 2020

Both compliance and discontinuity are the common characteristics of the real ground surface. This paper proposes a stabilization method for the underactuated bipedal locomotion on the discontinuous compliant ground. Unlike a totally new control method, the method is actually a high-level control strategy developed based on an existing low-level controller meant for the continuous compliant ground. As a result, although the ground environment is more complex, the calculation cost for the robot walking control system is not increased. With the high-level control strategy, the robot is able to adjust its step-length and velocity simultaneously to stride over the discontinuous areas on the compliant ground surface. The effectiveness of the developed method is validated with a numerical simulation and a physical experiment.
Comparative Proteomic Investigation of Plasma Reveals Novel Potential Biomarker Groups for Acute Aortic Dissection
Authors: Cheng Na , Wang Hao , Zhang Weizong , Wang Heng , Jin Xiang , Ma Xiang , Ma Yitong
Published: March 2020

Acute aortic dissection (AAD) is a catastrophic cardiovascular disease with high disability and mortality due to multiple fatal complications. However, the molecular changes of the serum proteome after AAD are not very clear. Here, we performed isobaric tags for relative and absolute quantitation- (iTRAQ-) based comparative proteomic analysis to investigate the proteome profile changes after AAD by collecting plasma samples from 20 AAD patients and 20 controls. Out of the 345 identified proteins, 266 were considered as high-quality quantified proteins (95%confident peptides≥2), of which 25 proteins were accumulated and 12 were reduced in AAD samples. Gene ontology enrichment analysis showed that the 25 AAD-accumulated proteins were enriched in high-density lipoprotein particles for the cellular component category and protein homodimerization acidity for the molecular function category. Protein-protein interaction network analysis showed that serum amyloid A proteins (SAAs), complement component proteins, and carboxypeptidase N catalytic chain proteins (CPNs) possessed the key nodes of the network. The expression levels of six selected AAD-accumulated proteins, B2-GP1, CPN1, F9, LBP, SAA1, and SAA2, were validated by ELISA. Moreover, ROC analysis showed that the AUCs of B2-GP1 and CPN1 were 0.808 and 0.702, respectively. Our data provide insights into molecular change profiles in proteome levels after AAD and indicate that B2-GP1 and CPN1 are potential biomarkers for AAD.
Campus Sewage Treatment by Golenkinia SDEC-16 and Biofuel Production under Monochromic Light
Authors: Nie Changliang , Jiang Liqun , Yu Ze , Yang Zhigang , Hou Qingjie , Pei Haiyan
Published: March 2020

The integration of microalgal cultivation in wastewater can fulfill the dual roles of pollutant degradation and biomass output. Meanwhile, the LED lights with different wavelengths have a great effect on the growth and metabolism of microalgae. In this study, Golenkinia SDEC-16, a strain isolated for biofuel production, was evaluated to verify its potentials for campus sewage treatment and lipid accumulation under the red, green, and blue lights. The results indicated that the treated campus sewage met the first grade level in the Chinese pollutant discharge standards for municipal wastewater treatment plants within seven days under both red and blue light. The green light failed to exhibit excellent performance in nutrient removal, but facilitated the lipid synthesis as high as 42.99 ± 3.48%. The increased lipid content was achieved along with low biomass accumulation owing to low effective light utilization, indicating that the green light could be merely used as a stimulus strategy. The red light benefited the photosynthesis of Golenkinia SDEC-16, with the maximal biomass concentration of 0.80 ± 0.03 g/L and lipid content of 36.90 ± 3.62%, which can attain the optimal balance between biomass production and lipid synthesis.
Numerical Solution of Burgers’ Equation Based on Mixed Finite Volume Element Methods
Authors: Zhao Jie , Li Hong , Fang Zhichao , Bai Xue
Published: March 2020

In this article, mixed finite volume element (MFVE) methods are proposed for solving the numerical solution of Burgers’ equation. By introducing a transfer operator, semidiscrete and fully discrete MFVE schemes are constructed. The existence, uniqueness, and stability analyses for semidiscrete and fully discrete MFVE schemes are given in detail. The optimal a priori error estimates for the unknown and auxiliary variables in the L2Ω norm are derived by using the stability results. Finally, numerical results are given to verify the feasibility and effectiveness.
Fish Husbandry Practices and Water Quality in Central Kenya: Potential Risk Factors for Fish Mortality and Infectious Diseases
Authors: Wanja Daniel W. , Mbuthia Paul G. , Waruiru Robert M. , Mwadime Janet M. , Bebora Lilly C. , Nyaga Philip N. , Ngowi Helena A.
Published: March 2020

Fish mortality has an enormous impact on the aquaculture industry by reducing fish production and slowing industrial growth. A cross-sectional study was carried out in Kirinyaga County, Central Kenya, to evaluate potential risks of fish mortality and disease transmission and suitability of pond water for rearing fish. A semistructured questionnaire that focused on general information, management practices, and disease history was administered to 92 small-scale fish farmers. Parasitological examination of fish sampled from selected farms (farms that were reporting mortality at the time of sampling) was done by following the standard procedure. Water quality parameters for 33 ponds were evaluatedin situ(recorded on pond site) andex situ(analysed at the laboratory) following the standard methods. The risks were assessed by adjusted odds ratio based on univariate regression analysis. Prevalent fish husbandry practices that were found to be associated with fish mortality and acquisition of pathogens in the study area were the use of raw livestock manure (0R = 1.500), high fish stocking density (0R = 1.168), and feeding fish on homemade rations (0R = 1.128). Parasitological investigation found infestation withDiplostomumspp.,Dactylogyrusspp.,Clinostomumspp., andPiscicolaleeches. Water temperature and pH were found fit for rearing fish. Of the 33 fishpond water samples tested, 1 (3%) and 6 (18%) exceeded the recommended limits of <100 mg/L and <0.2 mg/L of nitrate and nitrite, respectively. Of the 29 fishpond water tested, 15 (59%) exceeded the recommended limits of <100 mg/L of total ammonia. The findings show that the use of raw livestock manure, high fish stocking density, high nitrates and nitrites, and high ammonia levels in fishponds are potential risk factors for fish mortality and acquisition of infectious pathogens in a pond environment in a rural setup, in Central Kenya. There is a need to address the above factors in small-scale farming practices to minimize fish loss and also to prevent the occurrence and spread of infectious pathogens.
Life-Span of Classical Solutions to Hyperbolic Inverse Mean Curvature Flow
Authors: Wang Zenggui
Published: March 2020

In this paper, we investigate the life-span of classical solutions to hyperbolic inverse mean curvature flow. Under the condition that the curve can be expressed in the form of a graph, we derive a hyperbolic Monge–Ampère equation which can be reduced to a quasilinear hyperbolic system in terms of Riemann invariants. By the theory on the local solution for the Cauchy problem of the quasilinear hyperbolic system, we discuss life-span of classical solutions to the Cauchy problem of hyperbolic inverse mean curvature.
Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet‐Induced Nonalcoholic Fatty Liver Disease Mice
Authors: Choi Doo Jin , Kim Seong Cheol , Park Gi Eun , Choi Bo-Ram , Lee Dae Young , Lee Young-Seob , Park Sung-Bum , Park Yong Il , Kim Geum Soog
Published: March 2020

The present study aimed to evaluate the potential synergistic and protective effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extract in a ratio of 7 : 3, against hepatic steatosis in high fat diet (HFD)‐induced nonalcoholic fatty liver disease (NAFLD) mice. Forty‐eight mice were randomly divided into eight groups and orally administered daily for 6 weeks with a normal diet (ND) or high fat diet alone (HFD), HFD with AM (HFD + 100 mg/kg AM extract), HFD with LE (HFD + 100 mg/kg LE extract), HFD with ALM16 (HFD + 50, 100, and 200 mg/kg ALM16), or HFD with MT (HFD + 100 mg/kg Milk thistle extract) as a positive control. ALM16 significantly decreased the body and liver weight, serum and hepatic lipid profiles, including triglyceride (TG), total cholesterol (TC), high‐density lipoprotein‐cholesterol (HDL), and low‐density lipoprotein‐cholesterol (LDL), and serum glucose levels, compared to the HFD group. Moreover, ALM16 significantly ameliorated the HFD‐induced increased hepatic injury markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma‐glutamyltransferase (GGT)‐1. Furthermore, as compared to the mice fed HFD alone, ALM16 increased the levels of phosphorylated AMP‐activated protein kinase (p‐AMPK) and acetyl‐CoA carboxylase (p‐ACC), thereby upregulating the expression of carnitine palmitoyltransferase (CPT)‐1 and downregulating the expression of sterol regulatory element‐binding protein (SREBP)‐1c and fatty acid synthase (FAS). These results demonstrated that ALM16 markedly inhibited HFD‐induced hepatic steatosis in NAFLD mice by modulating AMPK and ACC signaling pathways, and may be more effective than the single extracts of AM or LE.
Synthesis and Characterization of Mesoporous Silica SBA-15 and ZnO/SBA-15 Photocatalytic Materials from the Ash of Brickyards
Authors: Khanh Nguyen Quach Nguyen , Yen Nguyen Thi , Hau Nguyen Duc , Tran Hoai Lam
Published: March 2020

SBA-15 has been successfully synthesized from ash of brickyard with the surface area of 700.100 m2/g, pore volume of 0.813 cm3·g−1, and pore size of 7.5 nm. SBA-15 material has been modified by a simple impregnation method, and the ZnO/SBA-15 obtained material retains the hexagonal structure of SBA-15, but the hexagonal capillary tube size is reduced, in which the surface area, volume of pores, and pore size is 212.851 m2·g−1, 0.244 cm3·g−1, and 3.7 nm, respectively. The ZnO/SBA-15 materials were investigated by the photodegradation of methylene blue under ultraviolet light and exhibited significant photocatalytic activity with the reached MB removal efficiency about 96.69%.
Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis
Authors: Zhao Zhiqiang , Gong Chunmei , Gao Yanfang , Liu Xiaoli , Wu Sai , Zhao Heping , Wang Xiaohui , Liu Huaixiang , Xiao Chen , Liu Jieyi , Li Jiong , He Yun
Published: March 2020

Cardiovascular development critical genes are key determinants in cardiovascular diseases. We hypothesize that SNPs in these genes may play critical roles in the development of hypertension. Therefore, we enrolled 516 paired hypertension patients and controls in a total of 2,742 subjects in a cross-sectional population study by the propensity score matching (PSM) method. Twenty-one SNPs from 5 cardiovascular developmental related genes were detected by the improved multiplex ligase detection reaction (iMLDR) method. Conditioned logistic regression under three different genetic models, namely, additive model, dominant model, and recessive model, was performed. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations of SNPs with hypertension. We found that the distribution of genotypes at rs833061, rs3025010, and rs699947 within the VEGFA gene and the distribution of alleles at rs3025010 in hypertension subjects were different from those in controls. Both rs833061 and rs3025010 were associated with hypertension in crude models, but only rs3025010 remains associated with hypertension after adjusting with confounding factors in the additive model and the dominant model. We also found that hypertension subjects with C/T and C/C genotypes at rs3025010 had lower SBP and DBP levels. In addition, rs3025010 could interact with rs6784267 within the CCM3 gene in the association. In conclusion, our findings suggest that rs3025010 may play a role in the pathogenesis of hypertension, which may be a potential target for individualized prevention and treatment of hypertension.
Overview of “Systematic Reviews” of the Built Environment’s Effects on Mental Health
Authors: Núñez-González Solange , Delgado-Ron J. Andrés , Gault Christopher , Lara-Vinueza Adriana , Calle-Celi Denisse , Porreca Riccardo , Simancas-Racines Daniel
Published: March 2020

Good mental health is related to mental and psychological well-being, and there is growing interest in the potential role of the built environment on mental health, yet the evidence base underpinning the direct or indirect effects of the built environment is not fully clear. The aim of this overview is to assess the effect of the built environment on mental health-related outcomes. Methods. This study provides an overview of published systematic reviews (SRs) that assess the effect of the built environment on mental health. We reported the overview according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched until November 2019 included the Cochrane Database of Systematic Reviews, EMBASE, MEDLINE (OVID 1946 to present), LILACS, and PsycINFO. Two authors independently selected reviews, extracted data, and assessed the methodological quality of included reviews using the Assessing Methodological Quality of Systematic Reviews-2 (AMSTAR-2). Results. In total, 357 records were identified from a structured search of five databases combined with the references of the included studies, and eleven SRs were included in the narrative synthesis. Outcomes included mental health and well-being, depression and stress, and psychological distress. According to AMSTAR-2 scores, the quality assessment of the included SRs was categorized as “high” in two SRs and as “critically low” in nine SRs. According to the conclusions of the SRs reported by the authors, only one SR reported a “beneficial” effect on mental health and well-being outcomes. Conclusion. There was insufficient evidence to make firm conclusions on the effects of built environment interventions on mental health outcomes (well-being, depression and stress, and psychological distress). The evidence collected reported high heterogeneity (outcomes and measures) and a moderate- to low-quality assessment among the included SRs.
The Many Difficulties and Subtleties in the Cognitive Assessment of Chronic Hepatitis C Infection
Authors: Abrantes Jefferson , Torres Daniel Simplicio , Brandão – Mello Carlos Eduardo
Published: March 2020

Since the discovery of HCV in 1989, several diseases have been related to chronic infection by this virus. Often, patients with hepatitis C virus (HCV) complain of cognitive impairment even before the development of hepatic cirrhosis, which they described as “brain fog.” Several studies have proposed a link between chronic HCV infection and the development of cognitive alterations, but the inclusion of confounding factors in their samples significantly limits the analysis of the results. In this article, we will give an overview about cognitive dysfunction in patients with HCV.
A High-Precision Spectrum-Detection Algorithm Based on the Normalized Variance of Nonreconstruction Compression Sensing
Authors: Shen Zhiyuan , Wang Qianqian
Published: March 2020

The traditional energy detection algorithm has been widely used in the field of signal detection, and a variety of improved algorithms have been derived. In the case of low signal-to-noise ratio, existing methods have shortcomings on achieving fast and accurate spectrum sensing that need to be resolved. This work proposes a normalized-variance-detection method based on compression sensing measurements of received signal. The discrete cosine transform sensing matrix is used to compress the signal, whose normalized variance is then calculated before being used as the testing variable for detecting the primary user signal. Taking the detection results as historical data into consideration, the classification model is obtained after training by applying a support vector machine for classifying and predicting test signals. Simulation results show that the proposed method outperforms the current state-of-the-art approaches by achieving faster and more accurate spectrum occupancy decisions.
Targeting of CD38 by the Tumor Suppressor miR-26a Serves as a Novel Potential Therapeutic Agent in Multiple Myeloma
Authors: Hu Yi , Liu Huimin , Fang Chuanfeng , Li Chen , Xhyliu Fjorela , Dysert Hayley , Bodo Juraj , Habermehl Gabriel , Russell Benjamin E. , Li Wenjun , Chappell Marcia , Jiang Xiaofeng , Ondrejka Sarah L. , Hsi Eric D. , Maciejewski Jaroslaw P. , Yi Qing , Anderson Kenneth C. , Munshi Nikhil C. , Ao Geyou , Valent Jason N. , Lin Jianhong , Zhao Jianjun
Published: March 2020

Multiple myeloma is an incurable refractory hematologic malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in multiple myeloma and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo. miR-26a was downregulated in patients with multiple myeloma cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and induced apoptosis in multiple myeloma cell lines. To identify the targets of miR-26a, RPMI8226-V-miR-26-GFP and RPMI8226-V-GFP cells were cultured using stable isotope labeling by amino acids in cell culture (SILAC) medium, followed by mass spectrometry analysis. In multiple myeloma cells overexpressing miR-26a, CD38 protein was downregulated and subsequently confirmed to be a direct target of miR-26a. Depletion of CD38 in multiple myeloma cells duplicated the multiple myeloma inhibition observed with exogenous expression of miR-26a, whereas restoration of CD38 overcame the inhibition of miR-26a in multiple myeloma cells. In a human multiple myeloma xenograft mouse model, overexpression of miR-26a inhibited CD38 expression, provoked cell apoptosis, and inhibited cell proliferation. Daratumumab is the first CD38 antibody drug for monotherapy and combination therapy for patients with multiple myeloma, but eventually resistance develops. In multiple myeloma cells, CD38 remained at low level during daratumumab treatment, but a high-quality response is sustained. In daratumumab-resistant multiple myeloma cells, CD38 expression was completely restored but failed to correlate with daratumumab-induced cell death. Therefore, a therapeutic strategy to confer selection pressure to maintain low CD38 expression in multiple myeloma cells may have clinical benefit.

Significance:

These results highlight the tumor suppressor function of miR-26a via its targeting of CD38 and suggest the therapeutic potential of miR-26a in patients with multiple myeloma.
B Cells Improve Overall Survival in HPV-Associated Squamous Cell Carcinomas and Are Activated by Radiation and PD-1 Blockade
Authors: Kim Sangwoo S. , Shen Sarek , Miyauchi Sayuri , Sanders P. Dominick , Franiak-Pietryga Ida , Mell Loren , Gutkind J. Silvio , Cohen Ezra E.W. , Califano Joseph A. , Sharabi Andrew B.
Published: March 2020

Purpose:

To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.

Experimental Design:

Tumor RNA-sequencing data from over 800 patients with head and neck squamous cell carcinoma (HNSCC) and cervical cancer, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival (OS). A novel murine model of HPV+ HNSCC was used to study the effects of PD-1 blockade and radiotherapy on B-cell activation, differentiation, and clonality including analysis by single-cell RNA-sequencing and B-cell receptor (BCR)-sequencing. Human protein microarray was then used to quantify B-cell–mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade.

Results:

RNA-sequencing identified CD19 and IGJ as novel B-cell prognostic biomarkers for 3-year OS (HR, 0.545; P < 0.001). PD-1 blockade and radiotherapy enhance development of memory B cells, plasma cells, and antigen-specific B cells. BCR-sequencing found that radiotherapy enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA-sequencing identified dramatic increases in B-cell germinal center formation after PD-1 blockade and radiotherapy. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade.

Conclusions:

These findings establish a key role for B cells in patient outcomes and responses to PD-1 blockade in HPV-associated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B cells.
A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non–Small Cell Lung Cancer
Authors: Cascone Tina , Sepesi Boris , Lin Heather Y. , Kalhor Neda , Parra Edwin R. , Jiang Mei , Godoy Myrna C.B. , Zhang Jianjun , Fossella Frank V. , Tsao Anne S. , Lam Vincent K. , Lu Charles , Mott Frank E. , Simon George R. , Antonoff Mara B. , Mehran Reza J. , Rice David C. , Behrens Carmen , Weissferdt Annikka , Moran Cesar , Vaporciyan Ara A. , Lee J. Jack , Swisher Stephen G. , Gibbons Don L. , Wistuba Ignacio I. , William William N. , Heymach John V.
Published: March 2020

Purpose:

Nintedanib enhances the activity of chemotherapy in metastatic non–small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint.

Patients and Methods:

Eligible patients had stage IB (≥4 cm)–IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycles of cisplatin (75 mg/m2), docetaxel (75 mg/m2) every 21 days plus nintedanib, followed by surgery. With 33 planned patients, the study had 90% power to detect an MPR increase from 15% to 35%.

Results:

Twenty-one patients (stages I/II/III, N = 1/8/12) were treated. One of 15 patients treated with nintedanib 200 mg achieved MPR [7%, 95% confidence interval (CI), 0.2%–32%]. Best ORR in 20 evaluable patients was 30% (6/20, 95% CI, 12%–54%). Twelve-month recurrence-free survival and overall survival were 66% (95% CI, 47%–93%) and 91% (95% CI, 79%–100%), respectively. Most frequent treatment-related grade 3–4 toxicities were transaminitis and electrolyte abnormalities. On the basis of an interim analysis the study was discontinued for futility. Higher levels of CD3+ and cytotoxic CD3+CD8+ T cells were found in treated tumors of patients who were alive than in those who died (652.8 vs. 213.4 cells/mm2, P = 0.048; 142.3 vs. 35.6 cells/mm2, P = 0.018).

Conclusions:

Although tolerated, neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared with chemotherapy historical controls. Additional studies of the combination in this setting are not recommended. Posttreatment levels of tumor-infiltrating T cells were associated with patient survival. Use of MPR facilitates the rapid evaluation of neoadjuvant therapies.

See related commentary by Blakely and McCoach, p. 3499
Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis
Authors: Shi Lai , Yao Huanling , Liu Zheng , Xu Ming , Tsung Allan , Wang Yanming
Published: March 2020

Peptidyl arginine deiminase 4 (PAD4/PADI4) is a posttranslational modification enzyme that converts protein arginine or mono-methylarginine to citrulline. The PAD4-mediated hypercitrullination reaction in neutrophils causes the release of nuclear chromatin to form a chromatin network termed neutrophil extracellular traps (NET). NETs were first described as antimicrobial fibers that bind and kill bacteria. However, it is not known whether PAD4 can mediate the release of chromatin DNA into the extracellular space of cancer cells. Here, we report that murine breast cancer 4T1 cells expressing high levels of PADI4 can release cancer extracellular chromatin networks (CECN) in vitro and in vivo. Deletion of Padi4 using CRISPR/Cas9 abolished CECN formation in 4T1 cells. Padi4 deletion from 4T1 cells also reduced the rate of tumor growth in an allograft model, and decreased lung metastasis by 4T1 breast cancers. DNase I treatment, which degrades extracellular DNA including CECNs, also reduced breast to lung metastasis of Padi4 wild-type 4T1 cells in allograft experiments in the Padi4-knockout mice. We further demonstrated that DNase I treatment in this mouse model did not alter circulating tumor cells but decreased metastasis through steps after intravasation. Taken together, our genetic studies show that PAD4 plays a cell autonomous role in cancer metastasis, thus revealing a novel strategy for preventing cancer metastasis by inhibiting cancer cell endogenous PAD4.

Implications:

This study shows that PADI4 can mediate the formation of CECNs in 4T1 cells, and that endogenous PADI4 plays an essential role in breast cancer lung metastasis.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/18/5/735/F1.large.jpg.