bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic efficiency of "ecological health" of the region
Authors: Merzlikina G. S.
Published: January 2020

The results of the study of the possibility of assessing the economic effectiveness of the "environmental health" of the region are presented. A new content of the concept of “ecological health” of the region is proposed, is a state in which all systems of the region perform their functions and allow achieving a balance, of dynamic equilibrium with the environment. The main functions (economic and environmental) are identified and the environmental health criteria of the region are identified: the implementation of environmental protection costs (adequacy, dynamics), the increase in financial results (possibly due to the operation of environmental facilities), the availability of specialists in the field of environmental and economic management, research and developments aimed at protecting the environment, the possibility of selling "clean" environmentally friendly products, the implementation of "clean" technologies and the use of “clean equipment ”, investing in fixed assets for environmental protection measures (treatment facilities), measuring and evaluating environmental and economic efficiency, measuring and assessing damage, pollution charges, tax planning; measurement of waste, emissions, effluents; assessment of the level and dynamics of their disposal, use, measurement and assessment of environmental parameters, the possibility of monitoring (technical means of monitoring and evaluation); measuring the "quantity" of environmental health. The results of an attempt to assess the economic efficiency of environmental health in three regions of the Southern Federal District: Astrakhan, Volgograd and Rostov regions on the basis of known statistical indicators are presented. It is determined that the indicators currently used are of a "symptomatic", not a "causal" nature, to assess the effectiveness of environmental current and capital costs, do not allow to determine the necessary level of environmental and economic efficiency. The analysis of scientific publications on the assessment of the ecological state (ecological health) of the region is carried out. It was revealed that in most scientific developments the same “symptomatic” indicators are used that do not allow an objective assessment of the economic efficiency of “environmental activities”. The necessity of forming an analytical platform of indicators of economic efficiency of the ecological health of the region is substantiated.
Comprehensive tools and methodologies quality improvement in the management competitiveness trade enterprises
Authors: Gurina M. A. , Rumyanceva J. V.
Published: January 2020

The paper substantiates the need for the use of integrated methods of research and quality management in the trading enterprise – the model of attractive quality N. Cano and QFD (Quality Function Deployment) analysis, which can be quite used as strategic approaches in the concept of TQC (Total Quality Management (technological)). The authors prove with the help of practical studies that in decision-making to improve competitiveness and improve the process of creating a product (service) requires a methodology that will not only form a matrix of customer preferences and determine the degree of sensitivity to different characteristics of quality, but also to translate the request into the language of technology. For testing these methods improve the quality of the selected company Servismaster LTD is employed in the service sector are technically complex equipment in Agro-Industrial Complex market. This area is a dynamically developing industry and the problems of quality and competitiveness in the market of agricultural machinery are very relevant. A deep understanding of customer needs is necessary to ensure a high level of service for technological products. The result of using model H. Kano has become the differentiation of different characteristics by types for regular customers, providing large orders to the trade organization on the terms of trust. Structuring of quality functions allowed to develop management solutions for quality management of service processes in the enterprise. The conducted research with the help of complex methods and methodology of improving the quality of customer service Servismaster LTD allowed to determine the requirements of consumers and correlate them with the parameters of the processes of the trading company, which in the future will allow to develop the necessary solutions to improve the competitiveness of the enterprise.
Lean production as a factor of competitiveness of a business entity
Authors: Armashova G. S.
Published: January 2020

The article describes the essence of lean manufacturing technology and the main tools for its implementation and implementation. Through the use of the simplest “lean manufacturing” toolkit, the management of enterprises forms a vision of a specific result for employees, a change in conscious thinking, which in turn, in the future, will allow integrating into the production and management process more complex elements of “lean manufacturing”. It should be noted that a separate tool "lean production is responsible for solving a specific task or part of it, while their integrated practice ensures the achievement of planned indicators. A high level of performance in various areas of business is determined by the introduction of lean technology into various fields of activity. The proposed management model the introduction of "lean production" takes into account the fundamental basis of the concept, taking into account the situational conditions, in which the subject of management operates. The key element of this model reflects the philosophical aspect of the essence of "lean production" strategic orientations, partnerships, improving the professional level of workers, continuous learning, identification and problem solving. Harmonization of the overall concept and goals in the proposed model specifies the applied technology tools “Lean production.” To assess the effectiveness of the introduction of technology in the activities of the enterprise, Xia formation visual graphic elements can compare the results of one subject as relatively different calendar periods, and in terms of comparing two or more business entities. By optimizing resource management through the integration of lean manufacturing technology, an enterprise significantly increases cost savings, improves production performance
Methodological approach to the terminological analysis of the key concepts of economic security
Authors: Salikov Y. A. , Mikhailiuk V. S.
Published: January 2020

The issue of defining concepts and developing terminology is fundamental in any science. Definitions and terms influence the final results of research. Currently, a large number of diverse approaches to the interpretation of the concept of “economic security” are presented in the scientific literature, while the content of each analyzed term reflects one or another approach of the author. Given the dynamic growth of objective interest in the requirements and practical aspects and issues of ensuring economic security, the systematization and development of the methodological apparatus for ensuring economic security, according to the authors, is a priority of scientific research. The results of a study on the substantiation of a methodological approach to conducting a terminological analysis of key concepts on the example of the maxim "economic security" are presented. This approach offers a five-step gradation of terminological constructions and allows you to highlight the key factors that most fully and accurately characterize the concept of economic security, as well as give an author's definition that meets the criteria of significance. The methodological approach is universal and can be used for terminological analysis of scientific categories both in the field of economic security and in other scientific fields.
Application of methods of mathematical modeling in the optimization design of technological processes of food production
Authors: Popov E. S. , Pozhidaeva E. A. , Pevtsova E. S. , Sokolova A. V. , Kolmakova A. S.
Published: January 2020

Optimization of thermochemical and biological transformations occurring during the heat treatment of food products can be carried out only taking into account the dynamics of the formation of temperature fields inside the processed products. A mathematical model of the Sous-Vide processing process has been developed, which provides the determination of the dynamics of changes in the temperature field of Sous-Vide processed functional food products based on animal and vegetable raw materials. To calculate the process of Sous-Vide processing of functional products, we used the differential equation of unsteady heat conduction taking into account the Bio criterion. When solving a system of partial differential equations, the mathematical package flexPDE is used. In calculations, a spatial grid with the number of nodes 20000 was used, the accuracy of calculations was 10E-4. Experimentally determined values of thermal conductivity, specific heat capacity, density and thermal diffusivity of each of the components of the food system are used in calculations. The results of the calculated experiment in mathematical modeling of the Sous-Vide processing process show the evolution of temperature fields in different sections of the food system and on its upper surface, having the shape of an ellipsoid of rotation. The dependences of the change in the thermophysical characteristics of the longitudinal and transverse flow of the food system coolant. The results of the computational experiment show a good convergence of the mathematical model and the results obtained, which is 94%, which indicates the adequacy of the developed mathematical model of the Sous-Vide processing process. The obtained mathematical model allows, by means of a computational experiment, to analyze and optimize the Sous-Vide processing modes of a wide range of food raw materials, of various geometric shapes and sizes, with different physicochemical and thermal properties, taking into account their non-stationarity under thermal influence.
Development of technology of raw smoked sausage “Salami Super” by thermal exposure
Authors: Kichko J. S. , Klychkova M. V. , Romanko M. D.
Published: January 2020

Smoked sausage has always been a tasty and expensive product. Despite the many advantages of this product, there is, from the point of view of practitioners, and a significant drawback is the complexity of production, high risk of the possibility of a marriage, the duration of the production. Therefore, the problem of accelerating the production process in order to reduce the time of maturation and drying of smoked sausages is relevant. Technology of speeded production involves issues of Svetovrachane, structural changes, processes of taste and agrometeorologia. For these purposes, a starter culture, glucono-Delta-lactone, protein supplements, and other components. On the basis of this, there is a need to develop new technologies to produce smoked sausages with an accelerated ripening process, while maintaining the organoleptic characteristics of the product and increase the profitability of production. The article presents the development of a new formulation of biologically complete product of sausage smoked “Salami Super” with a minimum maturity when making a complex food additive “Albumix 4010”. This product was manufactured using a new technology with the use of maturation accelerators and correction in heat treatment, which reduced the production time to 12–16 days, thereby increasing profitability. During the work, raw materials for the production of smoked sausage were selected, organoleptic, physico-chemical and microbiological studies were carried out. In the study, a smoked sausage "Braunschweig" was taken for trade comparison. The raw smoked sausage “Salami Super” made with use of accelerators of maturation in total with correction in heat treatment corresponds to all indicators of quality and safety, and also the term of development is reduced, thereby having increased profitability.
Determination of the Rheological Properties of Red and White Bread Wheat Flours with Different Methods
Authors: Dölek Ekinci Pelin , Gökbulut Incilay
Published: January 2020

In this study, rheological properties of the bread wheat flour dough from 6 wheat genotypes were determined. For the pereparation of flour, 3 red bread (Pandas, Sagitorya, Pehlivan) and 3 white bread (Kaşifbey, Göktan, Ceyhan-99) were selected as wheat genotype. To determine the rheological properties of the wheat flour dough, farinograph, extensograph, mixolab and glutograph devices were used. According to the results of the Farinograph analysis, the average development time of wheat White and red genotypes were 1.95 minutes and 8.96 minutes, respectively. According to the extensograph results of the flour samples, the most extended stability value was determined with 7.47 min in Ceyhan-99 cultivar. As a result of the research, it was determined that flour yields of red bread varieties were higher other genotypes, gas retention capacities of white bread flours were showed high result in extensograph application and resistance of dough to elongation was higher. In the Mixolab analysis, it determined that white bread wheat varieties have higher values in terms of kneading properties and gluten properties, and red bread wheat varieties have higher values in values of viscosity, amylase value and starch retrogradation.
PRIMARY AND SECONDARY SOMATIC EMBRYOGENESIS OF CACAO: THE EFFECT OF EXPLANT TYPES AND PLANT GROWTH REGULATORS
Authors: Ajijah Nur , Hartati Rr Sri
Published: January 2020

The success of cacao somatic embryogenesis is affected by many factors, including the basal salt medium, the genotype, the explant type, and the concentration and composition of plant growth regulators (PGRs). The study aimed to evaluate the effects of PGRs composition on the primary somatic embryo (PSE) response and the effect of explant type and PGRs composition used in inducing PSE on the secondary somatic embryogenesis (SSE) response. PSEs were induced from basal petal and staminoid explants of MCC 01 and MCC 02 clones on DKW medium containing 2,4-D 2 mg l-1 + kinetin 0.5 mg l-1 or 2,4-D 2 mg l-1 + kinetin 0.125 – 0.250 mg l-1 + thidiazuron (TDZ) 2.5 – 5 µg l-1 or 2,4-D 2 mg l-1 + TDZ 10 µg l-1. Genotype, explant type, and PGR composition dependently affected PSE response. The best PSE response was obtained from staminoid explant of MCC 02 clone on medium containing 2,4-D 2 mg l-1 + kinetin 0.5 mg l-1 (20%, 9 embryos). The explant type and PGR composition used in inducing PSEs affect the SSE response. The highest  SSE response of MCC 01 clone was obtained from petal explant with medium containing 2,4-D 2 mg l-1 + kinetin 0.5 mg l-1. The formation of SSEs could increase the multiplication rate of MCC 01 clone by 7 times.
FLOWER BUD REMOVAL AND EARTHING UP TIME INCREASED GROWTH AND TUBER YIELD OF POTATO AT EASTERN TIGRAY, ETHIOPIA
Authors: Fitsum Gebregwergis , Gebremichael Mehari , Gebremedhin Hailay
Published: January 2020

In Ethiopia, potato is a staple food crop and source of cash income for smallholder farmers, but the national average yield in farmers’ field is lower than experimental yields due to poor agronomic activities. The study aimed to determine the effects of flower removal and earthing up time on growth and tuber yield of potato. The experiment comprised of three flower removal stage and five earthing up time treatments, which were laid out in a randomized complete block design of 3x5 factorial arrangements with three replications. Results indicated that plant height, stem number, tuber length and tuber diameter were shown significantly affected (p < 0.05) by the main effect of flower removal and earthing up time but not by their interaction. Fresh shoot biomass and physiological maturity were recorded significantly affected (p < 0.05) by earthing up time, but not by flower removal stage and its interaction with earthing up time. Total fresh biomass, marketable and unmarketable tuber yield, as well as total tuber yield were significantly affected (p < 0.05) by main factors and their interaction effects. The results clearly indicated that the highest total tuber yield (30.96 ton ha-1) was recorded from flower bud removed potato earthed up at 15 days after complete emergence. Therefore, flower bud removed potato earthed up at 15 days after full emergence was better in terms of all yield contributing characters and tuber yield.
Feto-Maternal Outcomes Of Hypertensive Disorders Of Pregnancy In Yekatit-12 Teaching Hospital, Addis Ababa, Ethiopia: A Retrospective Study
Authors: Mengistu Mekoya Dabulo , Kuma Tilahun
Published: January 2020

Background In resource poor countries, hypertensive disorders of pregnancy are common and form one of the deadly triad, along with hemorrhage and infection, which contribute greatly to maternal and fetal jeopardy. Methods The aim of this study was to assess the prevalence of hypertensive disorders of pregnancy, and determine the effects of hypertensive disorders of pregnancy on the feto-maternal outcomes. It was a descriptive, cross-sectional, retrospective study on 615 women who attended delivery at Yekatit-12 Teaching Hospital from July 2017 - Jan 2018. Data was analyzed using SPSS version 20 software. Descriptive statistics were used to calculate rates. Chi-square statistics were used to estimate the associations among selected predictor variables. A p-value < 0.05 was taken as statistically significant. Results Out of the 615 study population, the prevalence of hypertensive disorders of pregnancy was found to be 25.4%, of which the majority (54.5%) was severe pre-eclampsia. Eclampsia accounted for 2.6%, and superimposed pre-eclampsia was 2.6%. The rate of severe pre-eclampsia with HELLP syndrome was 7.1% of all mothers with the hypertensive disorders. The majority of mothers with hypertensive disorders (59.6%) had age range of 25-34 years. About 46% of mothers required interventions to terminate the pregnancy either by cesarean section (42.3%) or instrumental deliveries (3.7%). The rate of preterm, low birth weight, and low Apgar at 1st and 5thminutes accounted for 30%, 25%, 24.4% and 16.7% of neonates born to mothers with hypertensive disorders, respectively. Over 19% of neonates required resuscitation and 11.5% NICU referral. The rate of still birth was 2.6%. Conclusion The prevalence of hypertensive disorders of pregnancy is high in the study area and complicates maternal and fetal outcomes of the pregnancy. To deter its detrimental effects both on fetal and maternal outcomes of pregnancy, antenatal surveillance should be expanded to enable early detection, stringent follow-up and timely intervention in severely affected pregnancies.
Primary or secondary wound healing of the Pin Sites After Removal of the External Fixator: Study Protocol for a Prospective, Randomized Controlled Mono-center Trial
Authors: Roth Franz , Cagienard Flavio , Link Björn-Christian , Hodel Sandro , Lehnig Drik , Babst Reto , Beeres Frank J.P.
Published: January 2020

Background: Temporary fixation with an external fixator is used for numerous indications in orthopedic trauma surgery. It is unclear whether primary wound healing or the secondary open wound healing after removal of the external fixator should be advocated for the pin site. This study compares primary wound closure with secondary wound healing for the pin sites. The primary aim is to compare the infections rates of the pin site. Secondary aim is to compare time to wound healing and esthetic outcome. The hypothesis was that primary wound closure does not lead to more infections than secondary wound healing. Methods: This is a prospective, randomized, controlled and blinded monocenter study based on a non-inferiority design. To obtain an equal patient population and groups, all pin entry sites of the patients are treated alternately at the time of removal of the external fixator with primary wound closure and secondary wound healing. Patients are randomized whether the proximal pin entry site is treated with wound closure or by secondary open wound healing, from which the further sequence develops. The pre- and postoperative protocol is standardized for all pin entry sites. A photo documentation of the pin entry sites takes place 2 and 52 weeks postoperatively during the routine clinically follow-up visits. Further controls take place after 6, 12 and 26 weeks after the removal. The primary outcome was to demonstrate the non-inferiority of primary wound closure compared to secondary wound healing in terms of postoperative wound infections according to center of disease control (CDC). The secondary outcomes are time to complete wound healing (days) and esthetical outcome (Subjective preference of patients and Vancouver scar scale). Discussion: This study aims in answering how to deal with the pin site after removal of the external fixator. To date, no routine and generally accepted protocol exists for the management of pin sites after removal of the external fixator. This prospective, randomized, blinded monocenter trial will answer if primary wound closure or secondary wound healing should be advocated after removal of the external fixator.
The effect of Xuanbai Chengqi decoction on patients with pneumonia-derived sepsis: study protocol for a randomized controlled trial
Authors: Jun Zhang , Yu Yi , Zheng Bojun , Jing Huang
Published: January 2020

Background: Sepsis and septic shock are major healthcare problems. pneumonia-derived is one of the important aspects of sepsis. The theory of traditional Chinese medicine (TCM) dictates that diseases of the lung and those of the large intestine react with each other. Methods/Design: A single-blind, randomised controlled clinical trial will be conducted involving 90 patients with pneumonia-derived sepsis. Participants will be randomised at a 1:1 ratio to receive Xuanbai Chengqi decoction (XCD) (experimental arm) or the same amount of saline treatment (control arm). The intervention will comprise one session/day for 1 week. The primary outcomes will be 28-day mortality, and levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid and serum and static lung compliance, dynamic lung compliance, plateau pressure, and peak airway pressure, 1, 3 and 7 days after treatment completion with respect to baseline levels. Secondary outcomes will be the symptom score of traditional Chinese medicine, duration of parenteral nutrition, prevalence of complications and the course of antibiotic use. Measurements will be taken at baseline, 1, 3 and 7 days during the intervention, after 28 days after completing the intervention. Adverse events between arms will be evaluated. Discussion: This is the first trial to evaluate the effects of XCD on management of pneumonia-derived sepsis. If the results are as expected, they will provide evidence of XCD in promoting the results in pneumonia-derived sepsis patients. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900024072. Registered on 24 June 2019.
Adjunctive Subgingival application of Chlorhexidine gel in nonsurgical periodontal treatment for chronic periodontitis: A systematic review and meta-analysis
Authors: Zhao Han , Hu Jingchao , Zhao Li
Published: January 2020

Background Subgingival applications of chlorhexidine (CHX) gel are commonly used as an adjunct in nonsurgical periodontal treatment (NSPT) for chronic periodontitis (CP). However, there is lack of data supporting the effects of adjunctive CHX gel on clinical outcomes. The objective of this meta-analysis was to evaluate the efficacy of adjunctive subgingival administration of CHX gel in NSPT compared to NSPT alone for CP. Methods An electronic search of four databases and a manual search of four journals were conducted up to August 2019. Only randomized controlled trials reporting on the clinical outcomes of subgingival use of CHX gel adjunct to scaling and root planing (SRP), as compared to SRP alone or with placebo, for at least 3 months were included. Primary outcomes were probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain at 3 and 6 months, when data on at least three studies were obtained. Results 17 studies were included for qualitative analysis and seven studies for quantitative analysis (four studies for the application of CHX gel adjunct to SRP at selected sites with at least pocket depth≥4mm and three studies for comparison of full-mouth disinfection (FMD) with subgingival use of CHX gel and full-mouth scaling and root planing (FMSRP). For subgroups, the clinical outcomes between adjunctive use of Xanthan-based CHX gel (XAN-CHX gel) and CHX gel were analyzed. Results indicated a significant improvement of PPD reduction following local adjunctive administration of XAN-CHX gel for SRP at selected sites (MD: 0.15mm). However, no difference was found in CAL gain. Moreover, no significant difference was observed in PPD and CAL at both 3 and 6 months post-treatment between FMD and FMSRP. Conclusion Adjunctive subgingival administration of XAN-CHX gel at individual selected sites appears to provide slight benefits in PPD reduction. Due to the lack of high-quality studies, further studies with larger sample sizes and strict standards are needed to confirm the conclusions.
Geographical rang evolution of whipping frogs based on a phylogeny of genus Polypedates (Anura: Rhacophoridae)
Authors: Deng Xiling , Yuan Limei , Yang Kong , Klaus Sebastian , Orlov Nikolai L. , Jiang Dechun , Li Jia-Tang
Published: January 2020

The authors have withdrawn this preprint from Research Square
Site suitability analysis of Solar PV Power generation in South Gonder, Amhara Region
Authors: Nebey Abraham , Zemene Biniyam , Gera Tewodros
Published: January 2020

The authors have withdrawn this preprint from Research Square
The peanut pods-associated microbiota and their effects on aflatoxin contamination
Authors: Yao Yanpo , Zhang Qi , Mwakinyali Silivano Edson , Gao Suyan , Ding Xiaoxia , Liang Shuqing , Xia Zhongkui , Li Peiwu
Published: January 2020

Background: Aflatoxin, which is highly carcinogenic and toxic, can seriously threaten the quality and safety of agricultural products, is mainly produced by Aspergillus flavus, which mainly exists in the soil of farmland. However, the correlation between aflatoxin, the microflora and environmental factors that survive in the roots of the plant is currently unknown. In this study, we used peanut-associated microbial populations as a model to address these issues.Results: We illustrated here that peanut pods significantly enriched with fungi and bacteria phyla. In the aflatoxin low pollution area, fungal and bacterial were more abundant than the high-pollution area, and the proportion of bacterial populations negatively correlated with aflatoxin was higher. However, some functions related to microbial-microbial and plant-microbial interactions were significantly enriched in areas with low levels of aflatoxin. Besides, we found that pH, Fe, Zn, P of the soil and temperature and humidity were the main factors that caused the differential composition and functional characteristics of microorganism. They can significantly affect the relationship between microbial flora and Aspergillus flavus and positively regulate aflatoxin production and microbial metabolism pathways, while OM, K, and other elements negatively regulated aflatoxin production and microbial metabolism pathways.Conclusions: The abundance of Aspergillus flavus and aflatoxin are significantly regulated by the population structure and function of microbiota, and this regulation is primarily affected by soil physical and chemical properties. Our results provide novel insights for understanding the contributions of the community enrichment process of the peanut pod-associated microbiome to the peanut hosts.
Age- and sex-related differences in vertebral bone marrow fat content in healthy adults from east China
Authors: Li qingping , Chen shaoqing , Zhou panpan , Guo anna , Ye peipei , Huang yingying , Yan zhihan , He jiawei
Published: January 2020

Background Bone-marrow water–fat composition is a useful imaging biomarker. However, the vertebral bone-marrow fat composition in healthy adults of east China is unknown. The aim of this study was to investigate differences in lumbar vertebral bone-marrow fat content between the sexes with age, using iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ). Methods Three-hundred-and-twenty-one healthy volunteers (age range 20–29 years: 32/33 men/women; 30–39 years: 40/37; 40–49 years: 21/45; 50–59 years: 26/37; ≥ 60 years: 15/26) were included in the present study. All subjects underwent IDEAL-IQ sequence imaging on a 3.0-T MR scanner. Bone-marrow fat-fraction ratio (FF%) was calculated for each vertebral body from sagittal lumbar images. Men and women were compared within age-groups by independent-samples t -tests, and different age-groups and vertebral segments were compared by Bonferroni post-hoc test. FF% correlations with age and body mass index (BMI) were analyzed with Spearman’s correlation coefficient. FF% and vertebral segment correlations were assessed by partial correlation analysis, after adjustment for sex and age. Results FF% averaged over L1–L5 was significantly higher in men than in women for the < 40-year age-groups ( P = 0.000). Bone-marrow fatty conversion was accelerated in women compared to men aged 40–49 years, but was similar in women and men aged > 60 years ( P > 0.05). FF% correlation with age was weakly positive in men ( r = 0.253, P = 0.003), and moderately positive in women ( r = 0.581, P < 0.001), but was non-significantly correlated with BMI and vertebral segments ( r = 0.218; r = 0.187, respectively). FF% was higher in the lower than in the upper lumbar segments ( P < 0.05). Conclusion IDEAL-IQ can accurately quantify lumbar bone-marrow fat infiltration. This increases with age, and differs between men and women and between lower and upper lumbar segments.
Multiple immune-related adverse events and anti-tumor efficacy: real-world data on various solid tumors
Authors: Shimozaki Keitaro , Sukawa Yasutaka , Beppu Noriko , Kurihara Isao , Suzuki Shigeaki , Mizuno Ryuichi , Funakoshi Takeru , Ikemura Shinnosuke , Tsugaru Kai , Togasaki Kazuhiro , Kawasaki Kenta , Hirata Kenro , Hayashi Hideyuki , Hamamoto Yasuo , Takaishi Hiromasa , Kanai Takanori
Published: January 2020

Background Immune checkpoint inhibitors have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in the real-world practice. Methods We conducted a retrospective study on patients with recurrent or metastatic non-small cell lung cancer, melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model. Results Among 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. OS in patients with multiple irAEs was significantly longer than that in patients with single irAE (42.3 months vs. 18.8 months; hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25–0.93; P = 0.03). Moreover, OS from the development of a second irAE in those with multiple irAEs was longer than that from the development of the first irAE in patients with single irAEs (median OS, 26.9 months vs. 17.7 months, respectively; HR, 0.59; 95% CI, 0.30–1.14; P = 0.11). Conclusions Our single-center retrospective study revealed a remarkable tendency associating the development of multiple irAEs with favorable prognoses.
Alternative splicing events implicated in carcinogenesis and prognosis of thyroid gland cancer
Authors: wu zenghong , Zhong Yi , Cai Fu-Cheng
Published: January 2020

Background: Alternative splicing events (ASEs), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, resulting in increased protein diversity and more than 95% of human genes experience AS and encode splice variants in the regular physiological processes. While the role of AS in the thyroid cancer as yet missing, therefore, it was necessary to carry out this study to provide more information about the combination of splicing and clinical parameters, as well as potential mechanism of the survival-related splicing events in thyroid cancer. Materials and methods: Here, we draw all-around AS profiles of thyroid cancer by analyzing RNA-seq data. We also constructed prognostic models via combining splicing signatures and clinicopathological parameters. Splicing network was constructed as a way to offer functional insight into the full practical knowledge of AS in the initiation and development of thyroid cancer. Results: There were 10446 genes, and 45150 AS events in 506 TC patients, which indicates that ASEs are universal in TC. Moreover, 1819 AS signatures were identified to be significantly related to OS of TC patients and among the seven types of ASES, ES was the most common, followed by AP and AT. Kaplan-Meier survival curves results suggested that seven types of ASEs were related to bad prognosis in TC patients (P<0.05). In TC, AA (AUC: 0.937), AD (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), ME (AUC: 0.999), RI (AUC: 0.837) all demonstrated an AUC over 0.6, of which ES and ME best predict the incidence of TC. We found that age and risk score (All) were risk factors for TC patients. As for ASEs is regulated by SFs, we study if the TC-ASEs were regulated by various SFs and the results demonstrated that the expression of 90 SFs was related to 469 ASEs OS in the TC cohort. Conclusions: In sum, the findings in the current study may provide a basis for spliceosomes in TC, and the methods used in this study could provide novel perspectives in other fields of tumor study to help shed light on future oncology research.
Prognostic value of Ki-67 in patients with hypertension and prostate cancer: A real-world study in a Chinese population
Authors: Cao Zhijun , Xiang Mengqi , Zhang Zhiyu , Zhang Jianglei , Jiang Minjun , Shen Gang , Zhou Yongqiang , Ouyang Jun , Chen Jianjun
Published: January 2020

Background Prostate cancer is the second most common malignancy in males worldwide, with high mortality, especially when combined with hypertension. Ki-67 is one of the most reliable markers of growth for neoplastic human cell populations. However, the prognostic value of Ki-67 in patients with hypertension and prostate cancer remains unclear.Methods We retrospectively analyzed 296 patients with hypertension and prostate cancer from May 1, 2012, to October 1, 2015. The overall survival was evaluated by Cox regression models and Kaplan-Meier analysis. In addition, a nomogram was established, and the accuracy of the model was assessed by a calibration curve.Results A total of 101 (34.1%) patients died. In the multivariate analysis, being Ki-67(+) was associated with a >5-fold increase in the risk of death (hazard ratio [HR] 5.83, 95% confidence interval [CI] 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions The presence of Ki-67 predicts worsened outcomes for overall mortality. A cross-validated multivariate score including Ki-67 had excellent concordance and efficacy for predicting prostate cancer.
From tobacco smoking to mutational signature: the role of epigenetic changes in human cancers
Authors: Chen Zhishan , Wen Wanqing , Cai Qiuyin , Long Jirong , Wang Ying , Lin Weiqiang , Shu Xiao-ou , Zheng Wei , Guo Xingyi
Published: January 2020

Background Tobacco smoking is associated with a unique mutational signature in the human cancer genome. It is unclear whether tobacco smoking -altered DNA methylations and gene expressions affect smoking-related mutational signature.Methods We evaluated the smoking-related DNA methylation sites reported from five previous studies using peripheral blood cells to identify possible target genes. Using the mediation analysis approach, we evaluated whether the association of tobacco smoking with mutational signature was mediated through altered DNA methylation and expression of these target genes.Results Based on data obtained from 21,108 blood samples, we identified 374 smoking-related DNA methylation sites, annotated to 248 target genes. Using data from DNA methylations, gene expressions and smoking-related mutational signature generated from ~7,700 tumor tissue samples across 26 cancer types from The Cancer Genome Atlas (TCGA), we found 11 of the 248 target genes whose expressions were associated with smoking-related mutational signature at a Bonferroni-correction P < 0.001. This included four for head and neck cancer, and seven for lung adenocarcinoma. In lung adenocarcinoma, our results showed that smoking increased the expression of three genes, AHRR , GPR15 , and HDGF, and decreased the expression of two genes, CAPN8 , and RPS6KA1 , which were consequently associated with increased smoking-related mutational signature. Additional evidence showed that the elevated expression of AHRR (cg14817490) and GPR15 (cg19859270), were associated with smoking-altered hypomethylations. Lastly, we showed that the elevated expression of HDGF and decreases expression of RPS6KA1, were associated with poor survival of lung cancer patients.Conclusions Our findings provide novel insights into the contributions of tobacco smoking to carcinogenesis through complex molecular mechanisms of the elevated mutational signature by altered DNA methylations and gene expressions.
Hospitalization and Definitive Radiotherapy in Lung Cancer: Incidence, Risk Factors and Survival Impact
Authors: Hazell Sarah Z. , Mai Nicholas , Fu Wei , Hu Chen , Friedes Cole , Negron Alex , Voong Khinh Ranh , Feliciano Josephine L. , Han Peijin , Myers Samantha , McNutt Todd R. , Hales Russell K.
Published: January 2020

Background Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized.Methods Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and hospitalization and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively.Results Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n=136), 62% were Caucasian (n=168). Cancer-related hospitalization incidence was 17% (n=47), of which 21% of patients hospitalized (n=10/47) had >1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of hospitalization (95% confidence interval (CI) 1.2-5.0, P =0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin >10 (95% CI 1.3-5.4, P =0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.0-3.1, P =0.04).Conclusions Hospitalization during lung cancer radiotherapy was independently associated with increased mortality. Our data show baseline factors can predict those who may be at increased risk for hospitalization.
Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice through inducing apoptosis of CD4+ T cells
Authors: An Ke , Xue Mengjiao , Zhong Jiaying , Yu Shengnan , Qi Zhongquan , Xia Junjie
Published: January 2020

Background: Multiple sclerosis (MS) is an autoimmune disease of central nervous system characterized by severe demyelination of white matter. There is still no definite cure for MS because of its complex pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine that is used as a therapeutic application for many autoimmune diseases. It is also used to inhibit acute immune rejection because of its anti-inflammatory and immunosuppressive properties. However, it is unclear if ATO has a curative effect on EAE, and the underlying mechanisms have not been clearly elucidated. In this study, we attempted to explore the possibility of using ATO to ameliorate EAE in mice. Methods: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and proportion of CD4 + T cells. In vitro , to further investigate the mechanism that underly the ameliorating effects of ATO in EAE mice, CD4 + T cells were traeted with ATO and then used for apoptosis assay, JC-1 staining, transmission electron microscope, and western bloting. Results: We found that ATO alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation and decreased the expression of IL-2, IFN-γ, IL-1β, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4 + T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4 + T cells apoptosis through the mitochondrial pathway both in vitro and in vivo . Additionally, the administration of ATO had no adverse effect on liver and kidney function and did not induce apoptosis in the spinal cord. Conclusions: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.
Clinic managers’ perspectives on the sustainable implementation of a decommissioning programme in Sweden: a qualitative study
Authors: Fredriksson Mio , Gustafsson Inga-Britt , Winblad Ulrika
Published: January 2020

Background The sustainability of programmes and interventions is more rarely studied than initial implementation. The aim of this study was to investigate, from a sustainability perspective, the implementation of an extensive decommissioning programme in one of the local health systems in Sweden (a so-called region). Decommissioning may become increasingly relevant because health systems today face many challenges that increase the pressure on existing resources.Methods Interviews were performed with 26 clinic managers 3 years after initial implementation of a decommissioning programme. The analysis was based on a model of potential influences on sustainability by Wiltsey Stirman et al.Results Initial adoption was possible due to the involvement of the clinic managers in developing the programme, which comprised everything from closed and merged units to formalised admission criteria, altered prescription patterns and changed patient pathways. Conditions for sustainability were created by changed and intensified meeting structures that resulted in learning networks and through the clinic managers’ central role balancing the staff’s claims while trying to execute the region leadership’s demands. Factors working against sustainability were, among others, fragmented support from the health system’s central functions for HR and economy, altered local conditions with an escalating staffing crisis, too few follow-ups and a decline in the strategic leadership over the years.Conclusions We conclude that the programme was partly sustained and that the most important influences were intervention fit and modifications (i. innovation characteristics), clinic and health system leadership (ii. context), workforce and champions (iii. capacity) and shared decision-making and relationship building (iv. processes and interactions). Perhaps most important for sustainability was the continuous attention to the health system’s poor economy, visible via a great effort by the clinics to keep their budgets—a change in the culture at the clinics. Furthermore, the study shows that, although unpopular, there are also positive effects of decommissioning from the perspective of the primary implementers, e.g., opportunities to make difficult but necessary changes and increased collegial support when centralising services.
The magnitude and Associated Factors of Pneumonia Among Under-Five Children in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Merkeb Yoseph , Adane Fentahun
Published: January 2020

Background Currently, Pneumonia is the leading cause of morbidity and mortality among under-five children in developing countries including Ethiopia. Despite, these problems are easily preventable and treatable it contributes to more than 18% of deaths of under-five children every year in Ethiopia. Regardless of these facts, there is a paucity of information regarding the magnitude and its predictors of pneumonia in Ethiopia. Thus, assessing the pooled magnitude of pneumonia and its predictors among under-five children in Ethiopia is the main objective of this review. Methods The international databases such as MEDLINE/PubMed, EMBASE, Google Scholar, Science Direct were scientifically explored. We considered all primary studies reporting the magnitude of pneumonia among under-five children and its predictors in Ethiopia. We retrieved all necessary data by using a standardized data extraction format spreadsheet. STATA 14 statistical software was used to analyze the data and Cochrane Q test statistics and I 2 test was used to assess the heterogeneity between the studies. There was significant heterogeneity between the studies so that a random effect model was employed. Result The pooled magnitude of Pneumonia Among Under Five Children was 20.68%, (I 2 = 97.9%%; P ≤ 0.001) from 12 included studies in Ethiopia. Children who unvaccinated [OR = 2.45], food cooking in the main house [OR = 2.46], Vitamin A supplementation status [OR = 2.85], malnutrition [OR = 2.98], mixed breast feeding [OR = 2.46], child history of respiratory tract infection [OR = 4.11] were a potential determinates of pneumonia. Conclusion and Recommendations This review showed that the magnitude of pneumonia was relatively high. Hence, appropriate intervention on potential determinates such as health education on exclusive breastfeeding and nutrition, place of food cooking, increase immunization and Vitamin A supplementation and early control of respiratory tract infection was recommended to prevent those risk factors.