bluuebunny/crossref_metadata_2025 huggingface dataset:
Elastostatics of Bernoulli-Euler Beams Resting on Displacement-Driven Nonlocal Foundation
Authors: Vaccaro Marzia Sara , Pinnola Francesco Paolo , Marotti de Sciarra Francesco , Barretta Raffaele
Published: February 2021

The simplest elasticity model of foundation underlying a slender beam under flexure was conceived by Winkler, requiring local proportionality between soil reactions and beam deflection. Such an approach leads to well-posed elastostatic and elastodynamic problems, but, as highlighted by Wieghardt, it provides elastic responses which are not technically significant for a wide variety of engineering applications. Thus, Winkler's model was replaced by Wieghardt himself by assuming that the beam deflection is the convolution integral between soil reaction field and an averaging kernel. Due to conflict between constitutive and kinematic compatibility requirements, the corresponding elastic problem of an inflected beam resting on Wieghardt foundation results to be ill-posed. Modifications of the original Wieghardt model were proposed by introducing fictitious boundary concentrated forces of constitutive type, which are physically questionable, being significantly influenced on prescribed kinematic boundary conditions. Inherent difficulties and issues are overcome in the present research using a displacement-driven nonlocal integral strategy got by swapping input and output fields involved in Wieghardt's original formulation. That is, nonlocal soil reaction fields are output of integral convolutions of beam deflection fields with an averaging kernel. Equipping the displacement-driven nonlocal integral law with the bi-exponential averaging kernel, an equivalent nonlocal differential problem, supplemented with non-standard constitutive boundary conditions involving nonlocal soil reactions, is established. As a key implication, the integro-differential equations governing the elastostatic problem of an inflected elastic slender beam resting on displacement-driven nonlocal integral foundation are replaced with much simpler differential equations supplemented with kinematic, static and new constitutive boundary conditions. The proposed nonlocal approach is illustrated by examining and analytically solving exemplar problems of structural engineering. Benchmark solutions for numerical analyses are also detected.
Is There a Slope Discount?
Authors: Huang Yi , Hewings Geoffrey
Published: February 2021

This paper focuses on the physical attributes of land that intrinsically limit land use and possibly affect land values. In particular, we investigate if the slope of a land does decrease its price and investigate the role of land slope in forming more reliable constant-quality land price indices and aggregate house price indices. We find that, while land slopes do decrease the land price per unit, they have a small effect on the quality-adjusted land price indices in selected neighborhoods in Auckland, New Zealand, where sloped terrain is common.
CTLA-4 in Regulatory T Cells for Cancer Immunotherapy
Authors: Sobhani Navid , Tardiel-Cyril Dana Rae , Davtyan Aram , Generali Daniele , Roudi Raheleh , Li Yong
Published: February 2021

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.
A GIS-Based Framework for Optimizing Site Selection of New Cities in the State of Kuwait: A Study in Environmental Geomorphology
Authors: Hassan Ahmed , Alfaraj Maha , Fayad Mahmoud , Allen Casey D
Published: February 2021

The State of Kuwait seeks sustainable development through implementation of clear and specific urban plans, some of which suffer from a severe lack of geomorphological and spatially-based environmental planning, such as the use of geographic information systems (GIS). Choosing the optimal location for a city based on sound environmental planning is of the utmost importance to achieving environmental sustainability, as it can spare the State and other decision-making entities a great deal of stress in the long run. GIS, in particular, offers great potential for the environmental planner and decision-maker to choose the most appropriate places for the cities of the future, especially when coupled with geomorphological analyses. To achieve the Vision of Kuwait 2035, one of the State’s planning objectives focuses on Urban Planning for the Establishment of Environmental Cities that Achieve (UPEECA) environmental sustainability criteria. To gain a more holistic analysis related to the Vision, this study aims to: 1) Conduct suitability modelling for establishing new cities in Kuwait, 2) Assess the current 2005-2030 urban plan, and 3) Propose possible recommendations and solutions for potential urban problems. The study relies on integrating several methods to devise a framework that will aid researchers and decision-makers in selecting optimal locations for built structures based on analysis and modelling (e.g., digital elevation model, geologic mapping, geomorphology, natural hazards, heritage/archaeological sites, military areas, oil fields, soils)
Prevalence of Color Vision Deficiency among Medical Students
Authors: Aziz Muhammad Zunair , Uddin Muhammad Moeez , Farooque Umar , Farooque Rizwan , Karimi Sundas
Published: February 2021

Introduction Color vision deficiency (CVD) constitutes one of the frequently observed eye disorders in all human populations. Color is a prominent sign utilized in the medical profession to study and identify histopathological specimens, lab instruments, and patient examination. Color deficiency affects the medical skills of students resulting in poor clinical examination and color appreciation. There is no effective screening of CVD at any level of the medical profession. Hence, this study was aimed to determine the prevalence of CVD among medical students. Materials and methods This was a cross-sectional study conducted from September 2019 to February 2020 over a period of six months in Karachi, Pakistan. All medical students aged 18-21 years of either gender enrolled in the first and second years of medical college were included in this study. The examination was performed during daylight. Ishihara plates were placed at a distance of 75 cm from the subject and tilted so that the plane of the paper lies perpendicular to the line of vision. Students were given five seconds to read the plate and one examiner was instructed to mark the checklist. A score of less than 12 out of 14 red/green test plates (not including the demonstration plate) was considered as a CVD. All statistical analysis was performed using Statistical Package for Social Sciences version 20.0 (Armonk, NY: IBM Corp). Results The mean age of the medical students was 19.61± 1.22 years. There were (n=123) 53.0% females and (n=111) 47.0% males. Most of the medical students (n=131, 56.0%) belonged to the upper-middle-class socioeconomic group. CVD was observed in (n=13) 6.0%of medical students. Age (p=0.001) and socioeconomic status (p=0.001) were the only demographic factors significantly associated with color deficiency. Conclusions Color deficiency, although an unnoticed concern, is fairly common among medical students. Medical students must be screened for CVD as this will enable them to be aware of their limitations in their future observational skills as a doctor and devise ways of overcoming them in clinical practice.
Comparison of Typical Controllers for Direct Yaw Moment Control Applied on an Electric Race Car
Authors: Medina Andoni , Rubio Angel , Bistue Guillermo
Published: February 2021

Direct yaw moment control (DYC) is an effective way to alter the behaviour of electric cars with independent drives. Controlling the torque applied to each wheel can improve the handling performance of a vehicle making it safer andfaster on a race track. The state-of-the-art literature covers the comparison of various controllers (PID, LPV, LQR, SMC, etc.) using ISO manoeuvres. However, more advanced comparison on important characteristics of the controllers performance is missed, such as the robustness of the controllers under changes in the vehicle model, steering behaviour, use of the friction circle and, ultimately, lap time on a track. In this study, we have compared the controllers according to some of the aforementioned parameters on a modelled race car. Interestingly, best lap times are not provided by perfect neutral or close-to-neutral behaviour of the vehicle, but rather by allowing certain deviations from the target yaw rate. In addition, a modified PID controller showed that its performance is comparable to other more complex control techniques such as MPC.
An Critical Analysis of Speech Recognition of Tamil and Malay Language Through Artificial Neural Network
Authors: Pal Thamburaj Kingston , Ponniah Kartheges , Sivanathan Ilangkumaran , Kumar Muniisvaran
Published: February 2021

Human and Computer interaction has been a part of our day-to-day life. Speech is one of the essential and comfortable ways of interacting through devices as well as a human being. The device, particularly smartphones have multiple sensors in camera and microphone, etc. speech recognition is the process of converting the acoustic signal to a smartphone as a set of words. The efficient performance of the speech recognition system highly enhances the interaction between humans and machines by making the latter more receptive to user needs. The recognized words can be applied for many applications such as Commands & Control, Data entry, and Document preparation. This research paper highlights speech recognition through ANN (Artificial Neural Network). Also, a hybrid model is proposed for audio-visual speech recognition of the Tamil and Malay language through SOM (Self-organizing map0 and MLP (Multilayer Perceptron). The Effectiveness of the different models of NN (Neural Network) utilized in speech recognition will be examined.
The Effect of Employee Empowerment, Team Work and Employe Training on Job Satisfaction (Study on Employee PT. Kusumahadi Santosa and PT. Dan Liris)
Authors: Priyatama Nova Yudha Liandi , Fajariyanti Fajariyanti
Published: February 2021

The study purposes were 1) Examining the effect of Employee Empowerment on Job Satisfaction; Examining the effect of Team Work on Job Satisfaction; 3) Examining the effect of Employee Training on Job Satisfaction. This research was conducted on employees of PT. Kusumahadi Santosa and PT. Dan Liris. This research is a survey method. The sample used in this study were 148 respondents. Sampling technique used is convenience sampling as for the collection of data in this study using a questionnaire. Data were analyzed using SPSS 23. The results of this study can be concluded that: 1) Employee Empowerment has negative effect and not significant on Job Satisfaction; 2) Teamwork has positive and significant influence on Job Satisfaction; 3) Employee Training has positive and significant influence on Job Satisfaction. From the results of this study the authors suggest that companies increase the amount of training provided in order to increase employee job satisfaction. Employees should be more caring, respectful and also maintain relationships with coworkers / team members so that relationships with team members are better that will increase job satisfaction.
The Effect of Emotional Stability on Organizational Citizenship Behaviour (OCB) with Job Autonomy and Job Meaning as Moderations Variables (A Study on Employees Sahid Group Hotel Surakarta)
Authors: Rahayu Nia , Cholil Muhammad
Published: February 2021

The purpose of this research is to examine the emotional stability on Organizational Citizenship Behaviour (OCB) which is moderated by two variables, they are job autonomy and job meaning with the object of research conducted on employees of Hotel Sahid Group Surakarta. This research is expected to provide an explanation of the variables that affect emotional stability in Organizational Citizenship Behaviour (OCB). The data in this study were taken using simple random sampling. The sample used in this study were employees of Hotel Sahid Group Surakarta with totaling 120 respondents. Researchers used the SPSS for Windows 17.0 computer program software for data analysis process. The research showed that emotional stability had a positive and significant effect on Organizational Citizenship Behaviour (OCB). The result also show that the variables of job autonomy and job meaning moderate the positive and significant relationship between emotional stability in Organizational Citizenship Behaviour (OCB).
TIANXIA (ALL-UNDER-HEAVEN): AN ALTERNATIVE SYSTEM OR A ROSE BY ANOTHER NAME?
Authors: ŞAHİN Mehmet
Published: February 2021

Tianxia is considered as an alternative institutionalization to govern the international system. It refers to world governance that is regulated by a world institution. Accordingly, a world institution plays the harmonizer role under this system. States, on the other hand, choose their economic models and the leader organizes the relations among different units. This paper thus argues that Tianxia is an alternative framework to Western-oriented IR theories. In that sense, this article aims to explore the similarities between the philosophical idea of Tianxia and Western-oriented IR Theory. More specifically, the article explores the issue from the international system perspective. The epistemological gaps and ontological similarities between the two frameworks will be demonstrated.
Students’ acceptance of mobile-based assessment
Authors: Saputri Nur Adillawati Kosim , Abdullah Ade Gafar , Hakim Dadang Lukman
Published: February 2021

The effective development of a Mobile-Based Assessment (MBA) depends on students’ acceptance. The aim of this paper was to examine the determinant factor of students’ behavioral intention to use mobile-based assessment. Data were collected from 105 second grade students of a vocational high school through an online survey questionnaire. Partial Least Squares (PLS) was used to test the measurement and the structural model. Results showed Perceived Ease of Use as the strongest direct predictor of Behavioral Intention to Use, followed by Perceived Usefulness. Content and Mobile Self-Efficacy only has an indirect effect. These four variables explain 51.3 percent of the variance of Behavioral Intention to Use.
What is the Industrial Structure Changes of China?
Authors: Wang Yijie , Ke Yanyan , Ma Xianrui , Ren Yitian
Published: February 2021

Although China has made great achievements in economic scale, the model of high-quality economic developments is still in the exploratory stage. A series problems, such as unreasonable industrial structure and low production efficiency, need to be resolved urgently. The transformation and upgrading of industrial structure is the inevitable choice. The analysis of industrial relations is an important method to reveal the internal mechanism of industrial structure change. Therefore, based on the concepts of sensitivity and influence coefficient, this paper proposed the concepts of driven and driving coefficient, and constructed the industrial complex networks of China from 1999 to 2013 according to the EORA input-output table. From the perspectives of the interaction power, industrial linkages and community structure, this paper systematically analyzes the evolution of China’s industrial structure. Results show that China’s industrial structure is undergoing a transformation from industry-oriented to industry-service-oriented. The interaction linkages between industries has formed a robust association structure. The traditional sectors such as infrastructure construction and industries are still the largest consumer group driving the development of other industries. Besides, light industry, infrastructure construction and finance have become increasingly important hub industries in the industrial system. However, some unbalanced community structures are formed in the economic system, which has resulted in a waste of resources and low production efficiency to a certain extent. Effectively grasping the relationship between China’s industrial structure evolution and its association is conducive to formulating economic restructuring policies, promoting the upgrading of China’s economic and, realizing the leap from quantitative change to qualitative change.
Managing Two-Echelon Remanufacturing Under Patent Protection
Authors: Cao Xiaogang , Wen Hui
Published: February 2021

We propose a two-echelon remanufacturing model in the context of two periods in which the factor of patent protection of the original manufacturer is considered. Through the analysis of the Stackelberg game among the supplier, the original manufacturer and the remanufacturer we obtain the equilibrium solutions of the unit patent licensing fee of the original manufacturer, the recycling effort degree of the remanufacturer, the wholesale price of new and remanufactured core components and the retail price of new and remanufactured products in the second period which are all dependent on the retail price of new products in the first period in cases with patent protection and without patent protection. In the numerical study we analyze the impacts of the remanufacturing rate of used products and the retail price of new products in the first period on the equilibrium results of the second period, and make a comparison between the case with patent protection and the case without patent protection.
Load Balancing Algorithm of Controller Based on SDN Architecture Under Machine Learning
Authors: Liang Siyuan , Jiang Wenli , Zhao Fangli , Zhao Feng
Published: February 2021

With the rapid development of cloud computing and other related services, higher requirements are put forward for network transmission and delay. Due to the inherent distributed characteristics of traditional networks, machine learning technology is difficult to be applied and deployed in network control. The emergence of SDN technology provides new opportunities and challenges for the application of machine learning technology in network management. A load balancing algorithm of Internet of things controller based on data center SDN architecture is proposed. The Bayesian network is used to predict the degree of load congestion, combining reinforcement learning algorithm to make optimal action decision, self-adjusting parameter weight to adjust the controller load congestion, to achieve load balance, improve network security and stability.
Monolayer platform to generate and purify human primordial germ cells in vitro provides new insights into germline specification
Authors: Sebastiano Vittorio , Kang Gugene , Vijayakumar Sivakamasundari , Sala Roberta , Chen Angela , Adebayo Abidemi , Cipriano Andrea , Fowler Jonas , Ang Lay Teng , Loh Kyle
Published: February 2021

Generating primordial germ cells (PGCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but currently entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days. We used our simplified differentiation platform and single-cell RNA-sequencing to uncover new insights into PGC specification. Transient WNT activation for 12 hours followed by WNT inhibition specified PGCs; by contrast, sustained WNT instead induced primitive streak. Thus, somatic (primitive streak) and PGCs are related—yet distinct—lineages segregated by temporally-dynamic signaling. Pluripotency factors including NANOG are continuously expressed during the transition from pluripotency to posterior epiblast to PGCs, thus bridging pluripotent and germline states. Finally, hPSC-derived PGCs can be easily purified by virtue of their CXCR4+PDGFRA−GARP− surface-marker profile and single-cell RNA-sequencing reveals that they harbor strong transcriptional similarities with fetal PGCs.
One-pot production of butyl butyrate from glucose using a cognate “diamond-shaped” E. coli consortium
Authors: Sinumvayo Jean Paul , Zhao Chunhua , Liu Guoxia , Li Yin , Zhang Yanping
Published: February 2021

Esters are widely used in plastics, textile fibers, and general petrochemicals. Usually, esters are produced via chemical synthesis or enzymatic processes from the corresponding alcohols and acids. However, the fermentative production of esters from alcohols and/or acids has recently also become feasible. Here we report a cognate microbial consortium capable of producing butyl butyrate. This microbial consortium consists of two engineered butyrate- and butanol-producing E. coli strains with nearly identical genetic background. The pathways for the synthesis of butyrate and butanol from butyryl-CoA in the respective E. coli strains, together with a lipase-catalyzed esterification reaction, created a “diamond-shaped” consortium. The concentration of butyrate and butanol in the fermentation vessel could be altered by adjusting the inoculation ratios of each E. coli strain in the consortium. After optimization, the consortium produced 7.2 g/L butyl butyrate with a yield of 0.12 g/g glucose without the exogenous addition of butanol or butyrate. To our best knowledge, this is the highest titer and yield of butyl butyrate produced by E. coli reported to date. This study thus provides a new way for the biotechnological production of esters.
Steroids as the novel class of high-affinity allosteric modulators of muscarinic receptors
Authors: Dolejší Eva , Szánti-Pintér Eszter , Chetverikov Nikolai , Nelic Dominik , Randáková Alena , Doležal Vladimír , Kudová Eva , Jakubik Jan
Published: February 2021

The membrane cholesterol was found to bind and modulate the function of several G-protein coupled receptors including muscarinic acetylcholine receptors. We investigated the binding of 20 steroidal compounds including neurosteroids and steroid hormones to muscarinic receptors. Corticosterone, progesterone, and some neurosteroids bound to muscarinic receptors with an affinity of 100 nM or greater. We established a structure-activity relationship for steroid-based allosteric modulators of muscarinic receptors. Further, we show that corticosterone and progesterone allosterically modulate the functional response of muscarinic receptors to acetylcholine at physiologically relevant concentrations. It can play a role in stress control or in pregnancy, conditions where levels of these hormones dramatically oscillate. Allosteric modulation of muscarinic receptors via the cholesterol-binding site represents a new pharmacological approach at diseases associated with altered cholinergic signalling.
Increased Expression of eEF1A2 and PI3K-Akt Signaling Pathway Genes Promotes The Progression of Cervical Cancer
Authors: Xin Huizhen , Pan Huan , Zhe Xiangyi , Zhang Chunhe , Li Hongtao , Zheng Weinan , Shao Renfu , Li Dongmei , Pan Zemin
Published: February 2021

Objective: This study sought to explore the mRNA and protein expression levels of eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) and members of the PI3K-Akt signaling pathway in the context of cervical cancer. We sought to clarify the expression of eEF1A2, PI3K, Akt during cervical cancer tumorigenesis and development.Methods: Samples from 72 cases of cervical cancer were collected, as well as 46 cases of cervical intraepithelial neoplasia (CIN), which reflects the continuous process of cervical cancer development, divided into CIN I, CIN II, CIN III, and 40 cases of chronic cervicitis. qRT-PCR was to detect the mRNA levels of eEF1A2, PI3K, and Akt, with β-actin used as an internal control. eEF1A2, PI3K, p-Akt protein levels in cervical cancer, CIN, and chronic cervicitis tissues were detected by immunohistochemical. eEF1A2, PI3K and p-Akt protein expression levels in HeLa, SiHa, and human umbilical vein endothelial cells were detected by western blot.Results: qRT-PCR results showed that the level of mRNA expression of eEF1A2, PI3K, and Akt was higher in cervical cancer tissues than that in normal cervical tissues. Immunohistochemistry results showed that the eEF1A2, PI3K, and p-Akt protein levels were higher in cervical cancer tissues than in cervical chronic cervicitis tissues. The differences were statistically significant (P < 0.05). The expression of eEF1A2, PI3K, and p-Akt protein was higher in HeLa and SiHa cervical cell lines than that in normal epithelial cells.Conclusion: Together, these results suggest that the aberrant expression of eEF1A2, PI3K, and Akt may play a role in cervical cancer development and tumorigenesis.
Direct ink writing of 3D thermoelectric architectures for fabrication of micro power generators
Authors: Kim Fredrick , Yang Seong Eun , Ju Hyejin , Choo Seungjun , Lee Jungsoo , Kim Gyeonghun , Jung Soo-Ho , Kim Suntae , Cha Chaenyung , Kim Kyung Tae , Ahn Sangjoon , Chae Han Gi , Son Jae Sung
Published: February 2021

Micro-thermoelectric modules can be used to develop unique components such as energy harvesters, active coolers, and thermal sensors in various integrated systems. However, the manufacturing of these modules still relies on costly traditional micro-fabrication processes, producing only two-dimensional (2D) thermoelectric films. This limitation severely constrains temperature gradient formation across thermoelectric films, and hence, the sufficient amount of power required to run integrated systems is not generated. Herein, we present the direct ink writing of micro-scale three-dimensional (3D) thermoelectric architectures for fabricating high-performance micro-thermoelectric generators. The characteristics of (Bi, Sb)2(Te, Se)3-based particles were precisely engineered such that the colloidal inks achieved outstanding viscoelasticity, thereby facilitating the creation of complex 3D architectures having high thermoelectric figure-of-merits of 1.1 (p-type) and 0.5 (n-type). Micro-thermoelectric generators made of 3D-written vertical filaments exhibited large temperature gradients and a good resulting power density, opening an avenue for the cost-effective and rapid manufacturing of integrated micro-thermoelectric modules.
Role of Insulin/Glucagon Ratio and Cell Redox State in the Hyperglycaemia Induced by Exposure to Electromagnetic Fields in Rats.
Authors: Martiñón-Gutiérrez Gabriel , Luna-Castro María , Hernández-Muñoz Rolando
Published: February 2021

The exposure to extremely low-frequency electromagnetic fields (EMFs) with a might adversely affect the endocrine system and reproductive functions. Nonetheless, the use of EMFs in the form of magneto-therapy exerts beneficial actions in human medicine, but also affecting glucose and lipids metabolism, inducing hyperglycaemia and a “diabetic” response. Therefore, we used fed or fasted male rats for a single exposure to 60-Hz EMFs, determining serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to EMFs induced hyperglycaemia in both, fed and fasted rats, accompanied by an attenuated second serum insulin peak. In addition, EMFs also decreased serum levels of free fatty acids and lactate, while they increased those of pyruvate and acetoacetate. Changes in blood glucose level were related with a more oxidized cellular redox state and with the insulin/glucagon ratio. Moreover, rat’s glucose metabolism also coincided with variations in insulin and glucagon secretion, probably depending on cell redox state. The EMFs effects were not modified in animals previously subjected to a chronic exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by EMFs exposure were closely related with the cellular redox state and with the insulin/glucagon ratio.
Association Between Phosphate Disturbances and Mortality Among Critically Ill Patients With Sepsis or Septic Shock
Authors: Harbi Shmeylan Al , Al-Dorzi Hasan , Meshari Albatool Al , Tamim Hani , Abdukahil Sheryl Ann , Sadat Musharaf , Arabi Yaseen
Published: February 2021

Objective: The aim of this study is to examine the association of hypophosphatemia and hyperphosphatemia on the first day of ICU admission with mortality in septic critically ill patients. Methods: In this retrospective cohort study, all adult patients who were admitted to medical-surgical ICUs between 2014 and 2017 with sepsis or septic shock were categorized as having hypophosphatemia, hyperphosphatemia or based on day 1 serum phosphate values. We compared the clinical characteristics and outcomes between the three groups. We used multivariate analysis to examine the association of hypophosphatemia and hyperphosphatemia with these outcomes.Results: Of the 1422 patients enrolled in the study, 188 (13%) had hypophosphatemia, 865 (61%) normophosphatemia and 369 (26%) had hyperphosphatemia. Among the three groups, the patients in the hyperphosphatemia group had significantly lower GCS, higher APACHE II scores, higher serum creatinine, increased use of vasopressors, and required mechanical ventilation with lower PaO2/FiO2 ratio compared with the other two groups. In addition, hyperphosphatemia group also showed significantly higher ICU mortality and hospital mortality in comparison to the other two groups. Conclusion: Hyperphosphatemia and not hypophosphatemia on the first ICU admission day was associated with an increase in the ICU and hospital mortality in septic critically ill patients.
FABP3 deficiency exacerbates metabolic derangement in cardiac hypertrophy via PPARα pathway
Authors: Zhuang Lingfang , Liu Zizhu , Li Chenni , Jin Qi , Lu Lin , Tao Rong , Yan Xiaoxiang , Chen Kang
Published: February 2021

Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic effects of fatty acid binding protein 3 (FABP3), on transverse aortic constriction (TAC)-induced cardiac hypertrophy. TAC or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARa, which stabilized and regulated its transcriptional activity on Mlycd, Gck. Finally, treatment with the PPARa agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency. Collectively, these findings indicate that the FABP3-PPARa axis contributes to metabolic homeostasis and participates in the development of hypertrophy and heart failure.
End-of-life Care Preferences among Cancer Patients in Southern Thailand: A University Hospital-based Cross-Sectional Survey
Authors: Pitanupong Jarurin , Janmanee Sahawit
Published: February 2021

Background: End-of-life care preferences may be highly individual, heterogenic, and variable according to culture and belief. This study aimed to explore preferences and factors associated with end-of-life care among Thai cancer patients with the goal of helping optimize their quality of life.Methods: A cross-sectional study surveyed cancer outpatients at Songklanagarind Hospital from August to November 2020. The questionnaires inquired about: 1) personal and demographic information, 2) experiences with end-of-life care received by relatives, and 3) end-of-life care preferences. To determine end-of life preferences, the data were analyzed using descriptive statistics. The data concerning patient demographics and end-of-life care preferences were compared using Fisher’s exact test. Results: The majority of the 96 cancer outpatients were female (65.6%), and the overall mean age was 55.8 ±11.6 years. More than half of them had an experience of observing someone die (68.8%), and they were predominantly satisfied with the care received by their relatives in passing away at home surrounded by family (47.0%) and being conscious until the time of death (68.2%). Most participants preferred receiving the full truth regarding their illness (99.0%), being free of uncomfortable symptoms (96.9%), having their loved ones around (93.8%), being mentally aware at the last hour (93.8%), and having the sense of being meaningful in life (92.7%). Their 3 most important end-of-life care wishes were receiving the full truth regarding their illness, disclosing the full truth regarding their illness to family members, and passing away at home. Conclusion: In order to optimize the quality of life of terminal patients, end-of-life care should ensure they receive the full truth regarding their illness, experience no distress symptoms, remain mentally aware at the last hour of life, feel meaningful in life, and pass away comfortably with loved ones around.
P2X7 Receptors and TMEM16 Channels Form a Hub with Implications for Macropore Formation and Current Facilitation
Authors: Dunning Kate , Martz Adeline , Peralta Francisco , Cevoli Federico , Boué-Grabot Eric , Taly Antoine , Compan Vincent , Gautherat Fanny , Wolf Patrick , Chataigneau Thierry , Grutter Thomas
Published: February 2021

P2X7 receptors (P2X7) are cationic channels involved in many diseases. They exhibit unique behaviors, such as “macropore” formation, which corresponds to enhanced large molecule cell membrane permeability, and current facilitation, which is caused by prolonged activation. These two phenomena have often been confounded, but thus far no clear mechanisms have been resolved. Here we provide evidence that current facilitation and macropore formation involve functional complexes comprised of P2X7 and TMEM16, a family of Ca2+-activated ion channel/scramblases. We found that current facilitation results in an increase of complex-embedded P2X7 open channel probability, a result mimicked by plasma membrane cholesterol depletion. We further show that macropore formation entails two distinct large molecule permeation components, one of which requires protein complexes featuring TMEM16F subtype, the other likely being direct permeation through the P2X7 pore itself. Such protein complexes can be considered to represent a regulatory hub intimately involved in distinct P2X7 functionalities.
Integrated Bioinformatics Analysis of Differentially-Expressed Genes and Immune Cell Infiltration Characteristics in Esophageal Squamous Cell Carcinoma
Authors: Feng Zitong , Qu Jingge , Liu Xiao , Liang Jinghui , Li Yongmeng , Jiang Jin , Zhang Huiying , Tian Hui
Published: February 2021

Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a significant challenge. The present study aimed to elucidate key candidate genes and immune cell infiltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identified by the “limma” R package, and a total of 152 robust DEGs were identified by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were significantly associated with extracellular matrix related process. Immune cell infiltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC.
Characteristics of 1270 Chinese Sibling Pairs with Cancer
Authors: Liu Ju , Yin Jian , Liu Yiwei , Xu Zhijian , Zhang Kai
Published: February 2021

Background: Previous research found that the cancer history of an individual’s sibling may be a better indicator than that of the parents. We aim to provide recommendations for early screening for individuals whose sibling had been diagnosed with cancer. Methods: During the physical examination in Cancer Hospital, Chinese Academy of Medical Sciences, 43,300 people were asked if they have at least two siblings who developed cancer. Eligible participants were asked to fill out a survey and participate in interviews. Results: A total of 1270 sibling-pairs from 766 families developed cancer, including 367 pairs of brothers (Bro-pairs), 368 pairs of sisters (Sis-pairs), and 535 pairs of brother-and-sister (BroSis-pairs). The mean ages at diagnosis of cancer for the three groups were from 58 to 62 years. More than half of Bro-pairs (55.3%) or Sis-pairs (51.1%) had cancer from the same systemic origin, and more than a quarter of Bro-pairs (28.1%) and Sis-pairs (37.2%) developed the same type of cancer. However, only 36.0% of BroSis-pairs developed cancers from the same systemic origin, and 18.9% developed the same type of cancer. In Bro-pairs and BroSis-pairs, lung cancer and digestive system cancer were the most common cancers, while in Sis-pairs, breast cancer, lung cancer, cervical cancer, liver cancer and thyroid cancer the most common ones. Conclusions: If an individual’s sibling is diagnosed with cancer, the individual should be screened as soon as possible, especially for lung cancer and digestive system cancers for both sexes. For sisters, breast cancer, cervical cancer and thyroid cancer should be screened early. Additionally, genetic services are essential for individuals who have siblings with cancer.
Knowledge and Perceptions of Alzheimer’s Disease in the United Kingdom
Authors: Kafadar Aysegul Humeyra , Cheung Kei Long
Published: February 2021

Background: Alzheimer’s disease (AD) is a global public health problem with an ageing population. Knowledge is essential to avoid AD's risk factors and promote early awareness, diagnosis and treatment of AD symptoms. AD knowledge is influenced by many cultural factors including cultural beliefs, attitudes and language barriers. This study aims: (1) to define AD knowledge level and perceptions amongst the general UK population; (2) to compare knowledge and perceptions of AD among three main ethnic groups (Asian, Blacks, and Whites); and (3) to assess potential associations of age, gender, education level, affinity with older people (65 or over), family history and caregiving history on AD knowledge.Methods: Data was collected from 190 participants who were living in the UK from three different ethnicities, which were Asian (15.8%), Black (16.3%), and White (67.9%). Demographic characteristics of participants and AD knowledge correlation were assessed by the 30-item Alzheimer’s Disease Knowledge Scale (ADKS), comprising 7 content domains. Data analysis included bivariate correlations to show associations between demographic characteristics of participants and their ADKS score, and multivariate analysis using ANOVA to illustrate potential correlations between ethnicity groups and ADKS score.Results: The general knowledge was found to be less than half, with 45.3% answering correctly out of all respondents. No significant differences were found for the total ADKS score between White, Black, and Asian participants. However, there were significant knowledge differences for ADKS domain scores. While Black participants had significantly more information about AD assessment and diagnosis (p=0.038), White respondents more likely to know about AD symptoms than their counterparts (p=0.009).Conclusion: The study's findings suggest that the AD knowledge level is not adequate for all ethnic groups. Moreover, ethnic groups differ in their AD knowledge and perceptions, and therefore, differ in their needs regards health communication. The study contributes to an understanding of ethnicity differences in AD knowledge in the UK population, and may also provide input into an intervention plan for different ethnicities’ information needs.
Dynamic modulation of inequality aversion in human interpersonal negotiations
Authors: Murphy Daniel , Harmer Catherine , Browning Michael , Pulcu Erdem
Published: February 2021

Negotiating with others about how finite resources should be distributed is an important aspect of human social life. However, little is known about mechanisms underlying human social-interactive decision-making in gradually evolving environments. Here, we report results from a novel iterative Ultimatum Game (UG) task, in which the proposer’s facial emotions and offer amounts were sampled probabilistically based on the participant’s decisions. Our model-free results confirm the prediction that both the proposer’s facial emotions and the offer amount should influence human choice behaviour. Model-based analyses extend these findings, indicating that participants’ decisions in the UG are guided by aversion to inequality. We highlight that the proposer’s facial affective reactions to participant decisions dynamically modulate how human decision-makers perceive self–other inequality, relaxing its otherwise negative influence on decision values. In iterative games, this cognitive model underlies how offers initially rejected can gradually become more acceptable under increasing affective load, and accurately predicts ~ 86% of participant decisions. Furthermore, modelling human choice behaviour isolated the role of the central arousal systems, assessed by measuring pupil size, during interpersonal negotiations. We demonstrate that pupil-linked central arousal systems selectively encode a key component of subjective decision values that relate to the magnitude of self–other inequality. Taken together, our results demonstrate that, under affective influence, aversion to inequality is a malleable cognitive process.
Local Content Implementation and Development in the Upstream Oil and Gas Sector in Ghana: Contemporary Issues on Policy Management
Authors: Suleman Shafic , Zaato Joshua Jebuntie
Published: February 2021

Upstream oil and gas activities dominates the debate on local content policies in Ghana. If well implemented, upstream activities have a trickledown effect on the local content policy linkages. However, local content policies alone do not assure success. In this paper narrative analysis and stakeholder consultations lead to in-depth discussions of how Ghana can use local content policy in upstream oil and gas operations to maximum benefit. The paper argues that, as is not the case for the Multinational Oil Companies (MOCs), the high risks and the huge financial commitments are a major challenge to the participation of indigenous Ghanaian companies. Balancing the needs of indigenous companies, local communities, and MOCs is critical; without it, efforts of policymakers to benefit from the oil sector will be futile.
Deregulation of Protein Phosphatase 2A inhibitor SET is Associated with Malignant Progression in Breast Cancer
Authors: Tozuka Katsunori , Wongsirisin Pattama , Nagai Shigenori E , Kobayashi Yasuhito , Kanno Miki , Kubo Kazuyuki , Takai Ken , Inoue Kenichi , Matsumoto Hiroshi , Shimizu Yoshihito , Suganuma Masami
Published: February 2021

To understand the mechanism underlying metastasis, identification of a mechanism-based and common biomarker for circulating tumour cells (CTCs) in heterogenous breast cancer is needed. SET, an endogenous inhibitor of protein phosphatase 2A, was overexpressed in all subtypes of invasive breast carcinoma tissues. Treatment with SET-targeted siRNAs reduced the motility of MCF-7 and MDA-MB-231 cells in transwell assay. SET knockdown reduced the number of mammospheres by 60-70% in MCF-7 and MDA-MB-231 cells, which was associated with the downregulation of OCT4 and SLUG. Hence, we analysed the presence of SET-expressing CTCs (SET-CTCs) in 24 breast cancer patients. CTCs were enriched using a size-based method and then immunocytochemically analysed using an anti-SET antibody. SET-CTCs were detected in 6/6 (100%) patients with recurrent breast cancer with a median value of 12 (12 cells/3 mL blood), and in 13/18 (72.2%) patients with stage I–III breast cancer with a median value of 2.5, while the median value of healthy controls was 0. Importantly, high numbers of SET-CTCs were correlated with lymph node metastasis in patients with stage I–III disease. Our results indicate that SET contributes to breast cancer progression and can act as a potential biomarker of CTCs for the detection of metastasis.
Searching for Success Factors in Deprescribing Proposals from Community Pharmacists
Authors: Osada Shin
Published: February 2021

BackgroundPolypharmacy is one of the most critical issues worldwide, especially in elderly people. In Japan, fees to support deprescription were established in 2018 which are calculated as the community pharmacists propose deprescribing in patients prescribed 6 or more medications regularly by submitting documents to the prescribing doctor, who may withdraw 2 or more medications. However, these are hardly calculated though many deprescribing proposals submitted.ObjectiveThe objective in this study, success factors in deprescribing proposals from the community pharmacists to prescribing doctors were searched for.MethodsTracing reports submitted from Aug 2017 to Mar 2020 were investigated retrospectively and factors that influenced the success of deprescribing were searched for.ResultsOne hundred and twenty-three tracing reports (67 reports of successful deprescribing and 56 reports of failure, success rate was 54.5%) were submitted to the prescribing doctors. Deprescribing proposals with existing unused medications or an assessment of possible adverse events significantly increased the deprescribing success rate. Whether the pharmacist experienced face-to-face communication with the prescribing doctors was not significant.ConclusionTracing reports with deprescribing proposals submitted by the community pharmacists may resolve polypharmacy. Mentioning unused medications or possible adverse events could increase the deprescribing success rate.