bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutional Pension Service: The Role, Dilemma and Way out of Social Workers-Taking H Pension Welfare Institution as an Example
Authors: Chen Xinying
Published: June 2021

With the intensification of the Chinese population aging trend, the demand for institutional pension is rising. As a delivery system of social welfare services, social work can promote the development of institutional pension services in China. In this respect, social workers should play the roles of service providers, demand and service evaluators, emotional and action supporters, resource linkers, resource and information managers in institutional pension, and promote the orderly progress of various services. However, through the case analysis of an H pension welfare institution, it is found that social workers and the H pension institution do not have a clear understanding of the role of social workers, and social work agency adopts “stocking” pattern for social workers, both of which lead to two dilemmas of role specialization and administrative tendency. In this regard, the following methods are proposed to solve the problem of role dilemma. The social work agency establishes long-term professional training mechanisms and incentive mechanisms. The H pension welfare institution needs to enhance its awareness of the role of social workers and give them more freedom to provide services. The government promotes the establishment of a sound incentive mechanism for the social work industry.
Techniques and materials used to optimize attached gingiva size: literature review
Authors: Khabadze Z. S. , Adzhieva A. B. , Nedashkovsky A. A. , Generalova Yu. A. , Sherozia M. G. , Shilyaeva E. S.
Published: June 2021

The aim of this review was to examine the techniques for performing keratinized gingival augmentation and grafts, as well as the materials used, which are often required to ensure proper wound closure. Tissue engineering of the oral mucosa represents an interesting alternative to obtain sufficient autologous tissue to repair oral soft tissue defects using biodegradable scaffolds and can improve vascularization and epithelialization, which are critical for successful outcomes.
Substantiation of application of pneumoexercise machine mouth gag in patients with chewing muscle hypertonus
Authors: Makedonova Iu. A. , Vorobyev A. A. , Osyko A. N. , Alexandrov A. V. , Pavlova-Adamovich A. V. , Stavskaya S. V.
Published: June 2021

The hypertone of chewing muscles is the leading reason of development of pain of non-odontogenic character in maxillofacial area. This pathology is rather widespread, at the same time has permanent character and is characterized average or heavy degree of expressiveness of clinical symptoms. Muscular pains considerably reduce working capacity and worsen quality of life of patients. Treatment of a hypertone of chewing muscles is relevant in stomatology. For clear understanding of genesis of development of muscular frustration in work the anatomy of a temporal and mandibular joint and chewing muscles is in detail presented systems. Modern methods of treatment of a hyper tone of chewing muscles include correction of occlusion that doesn’t eliminate a painful symptom; orthopedic and orthodontic treatment with application a cap. However, application of above-mentioned methods is rather effective, there is no exact understanding of the mechanism of their action. At some patients the temporary improvement of a state is noted, – gets the chronic sluggish long course of development of a disease which doesn’t give in by any known methods subsequently from others. Dentists perfectly understand this fact, at the same time the disappointment from the treatment comes in spite of the fact that all efforts were bent on improvement of knowledge in the field of factors predictors of development of pathology, modern methods of diagnostics and treatment of muscular frustration. In this work the use of the pneumoexercise machine mouth gag as the device relaxing muscles and separating device on the one hand, and possibilities of his use as a stimulator of process of the return development of the available already structural and functional changes of muscle tissue with another is proved. Accurate indications and contraindications to use of this device are submitted. It is recommended to use the device as the low-invasive method which isn’t leading to irreversible consequences. Further need of development of practical recommendations on uses of the pneumoexercise machine mouth gag as is obvious to patients and their parents, and to dentists in the medical and preventive purposes.
Dynamics of hematological parameters in patients with asymptomatic and mild course of COVID19 infection
Authors: Ismagilov R. R. , Bilalov F. S. , Ahmadullina Yu. A. , Sitdikova M. N. , Gilmanov A. Zh.
Published: June 2021

We studied changes in the parameters of the general (clinical) blood test in dynamics in outpatient patients with an asymptomatic course and a mild degree of severity of COVID-19. The study involved 67 patients. 30 men and 37 women were examined, their average age was 35 years. All the interviewed patients did not take specific antiviral drugs. Clinical manifestations were evaluated at the time of the survey on the 1st and 7th day from the day of receiving a positive PCR result. The parameters of the general (clinical) blood test were determined by flow cytometry in the CBC + 5Diff mode on a Unicel® DxH 800 hematological analyzer (Beckman Coulter, USA) in dynamics on the 1st and 7th days of observation. The features of clinical manifestations in patients with an asymptomatic course and mild severity coincided with the data of other authors. Hematological changes were mainly characterized by changes in the number of white blood cells and their subpopulations. On the 7th day of observation, there was a significant tendency to increase the number of white blood cells, lymphocytes, eosinophils, neutrophils and platelets within the reference intervals.
Discovery of the relativistic Schrödinger equation
Authors: Barley K , Vega-Guzmán J , Ruffing A , Suslov S K
Published: June 2021

We discuss the discovery of the relativistic wave equation for a spin-zero charged particle in the Coulomb field by Erwin Schrödinger (presumably during the Christmas holidays of 1925–1926). However, in this new approach, an essential discrepancy was found with the fine structure formula for energy levels already obtained by Sommerfeld in the framework of the ‘old’ quantum mechanics. As a result, Schrödinger had to withdraw the original ‘relativistically framed’ article, a draft of which has never been found, from a journal and start all over with his centennial article on the nonrelativistic stationary Schrödinger equation. Our goal here is to follow the original ‘relativistic idea’ from a modern mathematical viewpoint and elaborate on why Schrödinger did not publish it. We hope that this consideration will encourage readers to study quantum physics starting from one of the crucial moments of its creation.
Espacios de estancia prolongada para la población migrante centroamericana en tránsito por México
Authors: Jasso Vargas Rosalba
Published: June 2021

The objective of this article is to identify the main areas where Central American migrants spend most of their time during their transit through Mexico. The theoretical framework reviews the mobility-immobility and aspiration/ability approaches that focus on mobility restrictions and waiting times. The definition of waiting territories and the inclusion of the length of stay variable contribute to the study of transit migration from the perspective of immobility. Using the Migration Survey in the Northern Border (Emif Sur), the magnitude of displacements through the reported areas by migrants is estimated as having the longest length of stay in their migratory displacement. Long-term transit spaces correspond to different border regions and locations close to migratory routes. The provided empirical evidence indirectly suggests obstacles to mobility manifested in long- term transit spaces.
Learning English Vocabulary via Computer Gaming
Authors: Ng Lee-Luan  , Rino Shafierul Azizie Shahrir Raghbir
Published: June 2021

Due to the COVID-19 pandemic, educators have opted for online discussions and classes in which the teaching and learning sessions occur beyond the classroom environment. As various forms of technology such as gaming can be potentially used as platforms for online teaching and learning, the study aims to investigate the use of vocabulary learning strategies (VLS) in a massively multiplayer online role-playing game (MMORPG) among Malaysian English as a second language (ESL) players. Data were obtained via a 12-hour online game-play recorded sessions of Guild Wars 2 involving four Malaysian ESL players. The participants consisted of experienced online gamers aged between 24 and 25 years. The game-play sessions were also observed to provide supporting details on how the players utilised strategies when learning English vocabulary. The outcome of the study revealed that the ESL players employed different VLS during their game-play sessions. Gu and Johnson’s (1996) categorisation of VLS, which are metacognitive, cognitive, memory, and activation strategies, was subsequently modified to accommodate the MMORPG context. The results showed that the top five strategies used by the players were meaning-making, consultation, using online dictionary, word comparison, and incorporating words with real-world contexts.
The Relationship of Stress and Sleep Quality amongst Cognitive Science Students
Authors: CHEONG CAR LYN , TAN KOCK WAH
Published: June 2021

Stress is a common problem in modern life. Most Malaysian students suffer from high stress levels and poor sleep quality without realising their harmfulness to health and well-being. The major focus of the paper is to examine the relationship between stress and sleep quality among Cognitive Science undergraduate students. This paper also investigates if demographic attributes (gender differences and year of study) affect stress level and sleep quality. The participants of this study comprised 90 Cognitive Science undergraduate students studying at the Universiti Malaysia Sarawak.  Data was collected by using the Perceived Stress Questionnaire (Perceived Stress Scale) and Sleep Quality Questionnaire (Pittsburgh Sleep Quality Index). The results of the study showed that there was a weak relationship between stress and sleep quality. Those in the poor sleep category reported higher levels of perceived stress. Moreover, the findings showed that female students had higher stress levels than male students. First year students appeared to experience poorer sleep quality compared to final year students. The study also found no interaction effects between gender and year of study on sleep quality and stress. Further research could be conducted with a bigger population size and in other study programs. Future research could also assess non-demographic factors which might influence stress and sleep quality.
Predicting the Entrepreneurship Intention of Undergraduate University Students in Malaysia: A Comparison Study
Authors: MOHD NOOR NURUL HIDAYANA , MALEK EQMAL NAQIB , YAACOB MAHAZRIL ‘AINI , OMAR NORALINA
Published: June 2021

Entrepreneurship allows students to learn beyond their chosen field of study and provides an interdisciplinary work and development environment. This study aims to examine the influence of attitude towards behavior, subjective norm, and perceived behavioral control on entrepreneurship intention among Malaysian undergraduates. In addition, this study intends to compare the influence of attitude towards behavior, subjective norm, and perceived behavioral control on entrepreneurship intention between diploma and bachelor’s degree students. Based on a quantitative approach, primary survey data were collected from 400 undergraduate students at a public university using convenience sampling to limit bias. The findings in this study indicate that attitude towards behavior, subjective norm, and perceived behavioral control are significantly positively related to entrepreneurship intention for diploma and bachelor’s degree students. Notwithstanding this, the multiple regression results reveal that the strongest predictor of entrepreneurship intention for diploma students is the subjective norm while perceived behavioral control is the main predictor that affects entrepreneurship intention for bachelor’s degree students. These findings contribute to the entrepreneurial intention literature by applying the theory of planned behavior in Malaysia with valuable practical implications for the management of universities and the government.
Perceptions of Students Learning French as a Foreign Language in Malaysia
Authors: POINT RODOLPHE GILLES , NG CHIA-CHUN , TING SU HIE
Published: June 2021

The study investigated the perceptions of students learning French as a foreign language in a Malaysian public university. The specific objectives were to examine: (1) the self-reported French language proficiency level; and (2) their perceptions of their listening, speaking, reading and writing skills in French. Questionnaire data were collected from 80 undergraduates enrolled in French Levels 1 and 2 courses. The analysis showed that language learners from Level 1 and Level 2 rated themselves as having fair proficiency level when they made their rating without comparing themselves to a French native speaker. However, when they compared themselves with a native French speaker, more of them rated their proficiency as poor. The results showed that the relative difficulty of mastering language skills in French, from the most difficult to the easiest, are writing, speaking, reading and listening. Similar results were found for Level 1 and Level 2 French but the undergraduates struggled with writing and speaking at Level 2 more than at Level 1 because of an increased vocabulary range, greater grammatical complexity and longer texts. The results suggest that the difficulties are not much in comprehension of the language but more towards expressing themselves whether in speaking or writing.
The political development in Sri Lanka after civil war ended: a critical review for after Zarb-e-Azb operation in Pakistan
Authors: Shabbir Taha , Naz Kehkashan
Published: June 2021

The Sri Lankan civil war began in 1983 and lasted until 2009. The tension stems from Sri Lanka's colonial period and subsequent post-colonial policies that harmed the Tamil people. Without viable alternatives, a part of the Tamil population resorted to the degree of brutality that precipitated a second civil war. Regional, domestic, and global attempts to bring the war to a halt have been futile, though some more local measures have been active. A ruthless military campaign brought the conflict to an end. However, nothing has been done in the aftermath of the war to try to resolve the civil war, including its roots. Sri Lanka's civil war exemplifies the uncertain existence of civil war resolution. With this in mind, the war's conclusion was unquestionably the product of a strategic triumph. However, the civil war should have ended; a unique constellation of structural, state, and national forces collaborated to allow for unrestricted military aggression. As long as the dominant forces, including the United States and significant European countries, understood that enough bloodshed had happened, the country's aggression could be brought to a stop. China and India, with India abstaining, voted to support the Sri Lankan government in its major offensive against insurgents. Internationally, the newly restored government used the full might of the forces against the rebels. As a consequence, those variables are deemed unusable in other situations.

Tamil-Sinhala rivalry stretches all the way back to Sri Lanka's colonial period. The Tamil community took advantage of numerous market opportunities under British rule, which lasted from 1815 to 1948. Additionally, many group members attended school in colonial countries owing to a shortage of educational facilities in their home countries. With the exception of a few, the Sinhalese culture, on the other side, maintained its isolation from the British. As could be anticipated, the proportion of Tamils employing in the civil service, academia, and law increased dramatically following Sri Lanka's independence in 1948. Historically, the Sinhalese population has been hesitant to accept pluralism, having collaborated with the British to effect a shift of domination since the 1930s. When Sri Lanka's compulsory adult franchise was expanded to all citizens in 1931, there were no arrangements for minority rights. Tamil and Muslim community members shared discontent in the inconsistency with which their desires are pursued. T was dissatisfied with current political developments, and a large number of Tamils boycotted the elections conducted in compliance with this document. Also immediate liberty was abolished in 1947 by the Soulbury Constitution. The argument that no individual should be discriminated against on the grounds of racial origin or faith, though, proved to be a procedural impediment. Finally, in effect, it established a unitary and majoritarian state.
Analisis Pengaruh Partisipasi Anggaran Dan Informasi Asimetri Terhadap Senjangan Anggaran (Budgetary Slack) Pada Perguruan Tinggi Swasta Di Kabupaten Pamekasan
Authors: Oktaviana Dewi Ika
Published: June 2021

Abstract: Someone's involvement in budgeting will create a budgetary slack. This article aims to analyze the effect of budgetary participation and information asymmetry on budgetary slack. This type of research includes quantitative research, the focus of which will be directed at budgetary participation and information asymmetry in private universities in Pamekasan. Furthermore, the data were analyzed using statistical tests such as data quality tests, classical assumption tests and hypothesis testing. The results showed that the first hypothesis was accepted, which means that there was a significant influence between budgetary participation and budgetary slack. For the second hypothesis it is also accepted that there is a significant influence between information asymmetry on budgetary slack. The third hypothesis is tested simultaneously, the results are budgetary participation and information asymmetry together can create a larger budgetary slack.
Nilai-Nilai Etika Bisnis Islam Sebagai Pondasi Pengembangan PT. Bank Syariah Indonesia (Perspektif Hukum Islam dan Global Compact)
Authors: El Muna Naily
Published: June 2021

Abstract: This study portrays the efforts of Islamic banking to motivate employees in familiarizing the values â€‹â€‹of Islamic business ethics. The development of Islamic banking has experienced significant growth. A survey by the financial services authority (OJK) stated that the assets of the Islamic banking industry increased 14 times from Rp. 21.5 trillion in 2005 to Rp. 296, 2 trillion in 2015. Islamic Banking I should implement the values â€‹â€‹of Islamic Business Ethics (EBI) in accordance with Islamic law. These values â€‹â€‹are divine values, balance (justice), freedom and responsibility. Researchers used a qualitative approach to normative juridical case studies. The findings and theories were built using snowball sampling, which is the process of searching for data from and according to needs. Data collection was carried out by: interviews, observation, and documentation. Data analysis used: data reduction, data presentation, drawing conclusions. The results of this study include: (1) EBI habituation process: (a) As a spirit, (b) There is an emotional bond, the equality of managers, and users of customer funds, (c) The principle of the object is halal, mutual acceptance, needs, habits, and existential, (d) Being accounted for in a balanced manner in the form of scope of work, (2) The process of familiarizing EBI with employees in accordance with Islamic law.
Mobility Assistants to Support Multi-Modal Routes in Smart Cities: A Scoping Review
Authors: Rocha Nelson Pacheco , Santinha Gonçalo , Rodrigues Mário , Rodrigues Carlos , Queirós Alexandra , Dias Ana
Published: June 2021

Objectives - This study aimed to identify: (i) the current research trends related to mobility assistants to support multi-modal routes in smart cities; (ii) the types of smart cities’ data being used; (iii) the methods applied to assess the proposed solutions; and iv) the major barriers for their dissemination. Methods - An electronic search was conducted in several databases, combining relevant keywords. Then titles and abstracts were screened against inclusion and exclusion criteria. Finally, the full texts of the eligible articles were retrieved and screened for inclusion. Results - A total of 19 articles were included. These articles either propose algorithms to optimize routes planning or presenting specific applications that make use of a broad range of smart cities’ data. Conclusion - The number of included articles is very reduced when compared with the total number of articles related to smart cities, which means that the mobility assistants to support multi-modal routes are still not significant within the smart cities’ research. Moreover, most of the included articles report applications in an early stage of development, which is a major barrier for the respective dissemination.
Integrating a New Generation of Interoperability Agents into the AIDA Platform
Authors: Nogueira Francisca , Ferreira Diana , Sousa Regina , Abelha António , Machado José
Published: June 2021

Health is an information rich and complex environment, which makes it essential to implement interoperability in different health organizations and the consequent homogeneity among Health Information Systems (HIS). The Agency for the Integration, Dissemination and Archiving of Medical and Clinical Information (AIDA) is a consistent agent monitoring platform capable of guaranteeing the automation of information as well as the interoperability and integration of HIS. This platform was designed as a solution to the information islands that are commonly found in hospital systems, and it is currently being used in several hospitals throughout Portugal. However, like any technological innovation, the solution requires a constant health technology assessment (HTA) to ensure the absence of obsolescence and a continued efficiency and security of the platform. Hence, this article focuses on the relevance and the need for vigilance, culminating in the restructuring of certain intelligent agents that make up the AIDA platform.
The Association of Metabolic Syndrome Components with Anthropometric Measurements
Authors: Ozdemir Cagla , Aypak Cenk , Gorpelioglu Suleyman
Published: June 2021

Aim: This study aims to research the association of metabolic syndrome components with anthropometric measurements like arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio, which are applied rarely.

Methods: This cross-sectional study was conducted with 292 patients in November-December 2019. The arm circumference, neck circumference, waist circumference, hip circumference, waist-hip ratio, waist-to-height ratio, and body mass index measurements of the patients were made. Glucose, high-density lipoprotein, low-density lipoprotein, systolic, and diastolic blood pressure measurements were also recorded. The association between metabolic syndrome components and anthropometric measurements was analyzed.

Results: Metabolic syndrome is diagnosed in 32.8% of the participants. According to body mass index, 18.6% of the patients were normal, 34.2% were overweight, and 47.2% were obese. There was a significant difference between the patients with and without metabolic syndrome in terms of laboratory parameters, blood pressure values, and anthropometric measurements. In the diagnosis of metabolic syndrome, optimal cut-off values for arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio were determined as 31.75 (AUC=0.703), 34.85 (AUC=0.763), 113.75 (AUC=0.757), 0.90 (AUC=0.701), 0.61 (AUC=0.769) for females while they were 35.75 (AUC=0.573), 39.75 (AUC=0.795), 111.5 (AUC=0.607), 0.96 (AUC=0.888), 0.61 (AUC=0.888) for males respectively.

Conclusion: A significant correlation was detected between arm circumference, neck circumference, hip circumference, waist-hip ratio, and waist-to-height ratio, and metabolic syndrome components. However, low-density lipoprotein was not correlated with neck circumference and high-density lipoprotein with waist-to-height ratio.

Keywords: metabolic syndrome, anthropometric measurement, body mass index, obesity, lipid profile
The Reliability and Validity Analysis of The Turkish Version of the Test to Assess the Psychological Dependence on Smoking
Authors: Bardakci Mert , Oztora Serdar , Dagdeviren Hamdi Nezih
Published: June 2021

Aim: Psychological component of cigarette dependence is as important as its physical component. In addition to psychoactive material in the cigarette, factors such as happiness, joy, accompaniment with another activity, feeling self-confident confidence and social status play an effective role in smoking dependence. This signifies the fact that smoking dependence has to be dealt with in a multidimensional way. Test to Assess the Psychological Dependence on Smoking (TAPDS) published by Ponciano-Rodríguez et al, is developed to assess the psychological dependence on tobacco. The aim of this study iis study aims to test the reliability and validity of the Turkish version of the Test to Assess the Psychological Dependence on Smoking in the Turkish population.

Methods: The Test to Assess the Psychological Dependence on Smoking (TAPDS) Turkish Version with 25 questions along with a sociodemographic form was handed out to volunteer participants. Data was were collected from a total number of 420 voluntary participants, who were randomly selected and current smokers. Confirmatory Factor Analysis was performed and Cronbach's α and McDonald's ω coefficients were used to determine the reliability of the scores of the scale.

Results: The participants consisted of 263 males and 157 females, with an average age of 31.07 years, ranging from 20 to 85. The factor loadings of the scale for all items are observed to be more than 0.30 and all the items are statistically significant. Cronbach's α and McDonald's ω values calculated for the total score are 0.93.

 Conclusion: The Turkish version of TAPDS appears to be effective for assessing psychological dependence of smoking and it can be recommended as a sufficient and highly reliable and valid scale to be used.

 Keywords: smoking, validity, reliability, psychological dependence
Plasma & Microwaves as Greener Options for Nanodiamond Purification: Insight Into Cytocompatibility
Authors: Mitev Dimitar P. , Alsharabasy Amir M. , Morrison Liam , Wittig Sebastian , Diener Christof , Pandit Abhay
Published: June 2021

The potential biomedical applications of nanodiamond have been considered over the last few decades. However, there is still uncertainty regarding the extent to which the surface characteristics of this material can influence potential applications. The present study investigated the effects of surface characteristics alongside the prospective of improving nanodiamond production using cold plasma and microwave technologies for the surface tailoring of the nanocarbons. Numerous approaches were applied to purify, refine and modify a group of nanosized diamonds at each step of their production cycle: from the detonation soot as the initial raw material to already certified samples. The degree of surface changes were deliberately performed slowly and kept at different non-diamond carbon presence stages, non-carbon elemental content, and amount converted superficial moieties. In total, 21 treatment procedures and 35 types of nanosize diamond products were investigated. In addition cultures of human fibroblast cells showed enhanced viability in the presence of many of the processed nanodiamonds, indicating the potential for dermal applications of these remarkable nanomaterials.
The Roles of circMTO1 in Cancer
Authors: Liu Wei , Xiong Yuanyuan , Wan Renhua , Shan Renfeng , Li Jianfeng , Wen Wu
Published: June 2021

Circular RNAs (circRNAs) are a recently discovered type of covalently-closed circular non-coding RNAs, mainly formed by non-sequential back-splicing of precursor mRNAs (pre-mRNAs). Recent studies have demonstrated that circRNAs can have either oncogenic or tumor-suppressor roles depending on the cellular context. CircRNA mitochondrial tRNA translation optimization 1 (circMTO1), a recently reported circular RNA originating from exons of MTO1 located on chromosome 6q13, was proved to be abnormally expressed in many malignant tumors, such as hepatocellular carcinoma, gastric carcinoma and colorectal cancer, resulting in tumor initiation and progression. However, there are no reviews focusing on the roles of circMTO1 in cancer. Here, we first summarize the main biological characteristics of circMTO1, and then focus on its biological functions and the possible underlying molecular mechanisms. Finally, we summarize the roles of circMTO1 in cancer and discuss future prospects in this area of research.
Alterations of Growth and Focal Adhesion Molecules in Human Breast Cancer Cells Exposed to the Random Positioning Machine
Authors: Sahana Jayashree , Corydon Thomas J. , Wehland Markus , Krüger Marcus , Kopp Sascha , Melnik Daniela , Kahlert Stefan , Relja Borna , Infanger Manfred , Grimm Daniela
Published: June 2021

In this study, we evaluated changes in focal adhesions (FAs) in two types of breast cancer cell (BCC) lines (differentiated MCF-7 and the triple-negative MDA-MB-231 cell line) exposed to simulated microgravity (s-μg) created by a random positioning machine (RPM) for 24 h. After exposure, the BCC changed their growth behavior and exhibited two phenotypes in RPM samples: one portion of the cells grew as a normal two-dimensional monolayer [adherent (AD) BCC], while the other portion formed three-dimensional (3D) multicellular spheroids (MCS). After 1 h and 30 min (MDA-MB-231) and 1 h 40 min (MCF-7), the MCS adhered completely to the slide flask bottom. After 2 h, MDA-MB-231 MCS cells started to migrate, and after 6 h, a large number of the cells had left the MCS and continued to grow in a scattered pattern, whereas MCF-7 cells were growing as a confluent monolayer after 6 h and 24 h. We investigated the genes associated with the cytoskeleton, the extracellular matrix and FAs. ACTB, TUBB, FN1, FAK1, and PXN gene expression patterns were not significantly changed in MDA-MB-231 cells, but we observed a down-regulation of LAMA3, ITGB1 mRNAs in AD cells and of ITGB1, TLN1 and VCL mRNAs in MDA-MB-231 MCS. RPM-exposed MCF-7 cells revealed a down-regulation in the gene expression of FAK1, PXN, TLN1, VCL and CDH1 in AD cells and PXN, TLN and CDH1 in MCS. An interaction analysis of the examined genes involved in 3D growth and adhesion indicated a central role of fibronectin, vinculin, and E-cadherin. Live cell imaging of eGFP-vinculin in MCF-7 cells confirmed these findings. β-catenin-transfected MCF-7 cells revealed a nuclear expression in 1g and RPM-AD cells. The target genes BCL9, MYC and JUN of the Wnt/β-catenin signaling pathway were differentially expressed in RPM-exposed MCF-7 cells. These findings suggest that vinculin and β-catenin are key mediators of BCC to form MCS during 24 h of RPM-exposure.
Deciphering the in vivo Dynamic Proteomics of Mesenchymal Stem Cells in Critical Limb Ischemia
Authors: Du Yipeng , Li Xiaoting , Yan Wenying , Zeng Zhaohua , Han Dunzheng , Ouyang Hong , Pan Xiudi , Luo Bihui , Zhou Bohua , Fu Qiang , Lu Dongfeng , Huang Zheng , Li Zhiliang
Published: June 2021

Objective

Regenerative therapy using mesenchymal stem cells (MSC) is a promising therapeutic method for critical limb ischemia (CLI). To understand how the cells are involved in the regenerative process of limb ischemia locally, we proposed a metabolic protein labeling method to label cell proteomes in situ and then decipher the proteome dynamics of MSCs in ischemic hind limb.

Methods and Results

In this study, we overexpressed mutant methionyl-tRNA synthetase (MetRS), which could utilize azidonorleucine (ANL) instead of methionine (Met) during protein synthesis in MSCs. Fluorescent non-canonical amino-acid tagging (FUNCAT) was performed to detect the utilization of ANL in mutant MSCs. Mice with hindlimb ischemia (HLI) or Sham surgery were treated with MetRSmut MSCs or PBS, followed by i.p. administration of ANL at days 0, 2 6, and 13 after surgery. FUNCAT was also performed in hindlimb tissue sections to demonstrate the incorporation of ANL in transplanted cells in situ. At days 1, 3, 7, and 14 after the surgery, laser doppler imaging were performed to detect the blood reperfusion of ischemic limbs. Ischemic tissues were also collected at these four time points for histological analysis including HE staining and vessel staining, and processed for click reaction based protein enrichment followed by mass spectrometry and bioinformatics analysis. The MetRSmut MSCs showed strong green signal in cell culture and in HLI muscles as well, indicating efficient incorporation of ANL in nascent protein synthesis. By 14 days post-treatment, MSCs significantly increased blood reperfusion and vessel density, while reducing inflammation in HLI model compared to PBS. Proteins enriched by click reaction were distinctive in the HLI group vs. the Sham group. 34, 31, 49, and 26 proteins were significantly up-regulated whereas 28, 32, 62, and 27 proteins were significantly down-regulated in HLI vs. Sham at days 1, 3, 7, and 14, respectively. The differentially expressed proteins were more pronounced in the pathways of apoptosis and energy metabolism.

Conclusion

In conclusion, mutant MetRS allows efficient and specific identification of dynamic cell proteomics in situ, which reflect the functions and adaptive changes of MSCs that may be leveraged to understand and improve stem cell therapy in critical limb ischemia.
Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors
Authors: Mascarelli Daniele E. , Rosa Rhubia S. M. , Toscaro Jessica M. , Semionatto Isadora F. , Ruas Luciana P. , Fogagnolo Carolinne T. , Lima Gabriel C. , Bajgelman Marcio C.
Published: June 2021

Immunotherapy explores several strategies to enhance the host immune system’s ability to detect and eliminate cancer cells. The use of antibodies that block immunological checkpoints, such as anti–programed death 1/programed death 1 ligand and cytotoxic T-lymphocyte–associated protein 4, is widely recognized to generate a long-lasting antitumor immune response in several types of cancer. Evidence indicates that the elimination of tumors by T cells is the key for tumor control. It is well known that costimulatory and coinhibitory pathways are critical regulators in the activation of T cells. Besides blocking checkpoints inhibitors, the agonistic signaling on costimulatory molecules also plays an important role in T-cell activation and antitumor response. Therefore, molecules driven to costimulatory pathways constitute promising targets in cancer therapy. The costimulation of tumor necrosis factor superfamily receptors on lymphocytes surface may transduce signals that control the survival, proliferation, differentiation, and effector functions of these immune cells. Among the members of the tumor necrosis factor receptor superfamily, there are 4-1BB and OX40. Several clinical studies have been carried out targeting these molecules, with agonist monoclonal antibodies, and preclinical studies exploring their ligands and other experimental approaches. In this review, we discuss functional aspects of 4-1BB and OX40 costimulation, as well as the progress of its application in immunotherapies.
Ground-State Structures of Hydrated Calcium Ion Clusters From Comprehensive Genetic Algorithm Search
Authors: Shi Ruili , Zhao Zhi , Huang Xiaoming , Wang Pengju , Su Yan , Sai Linwei , Liang Xiaoqing , Han Haiyan , Zhao Jijun
Published: June 2021

We searched the lowest-energy structures of hydrated calcium ion clusters Ca2+(H2O)n (n = 10–18) in the whole potential energy surface by the comprehensive genetic algorithm (CGA). The lowest-energy structures of Ca2+(H2O)10–12 clusters show that Ca2+ is always surrounded by six H2O molecules in the first shell. The number of first-shell water molecules changes from six to eight at n = 12. In the range of n = 12–18, the number of first-shell water molecules fluctuates between seven and eight, meaning that the cluster could pack the water molecules in the outer shell even though the inner shell is not full. Meanwhile, the number of water molecules in the second shell and the total hydrogen bonds increase with an increase in the cluster size. The distance between Ca2+ and the adjacent water molecules increases, while the average adjacent O-O distance decreases as the cluster size increases, indicating that the interaction between Ca2+ and the adjacent water molecules becomes weaker and the interaction between water molecules becomes stronger. The interaction energy and natural bond orbital results show that the interaction between Ca2+ and the water molecules is mainly derived from the interaction between Ca2+ and the adjacent water molecules. The charge transfer from the lone pair electron orbital of adjacent oxygen atoms to the empty orbital of Ca2+ plays a leading role in the interaction between Ca2+ and water molecules.
Stimuli Responsive, Programmable DNA Nanodevices for Biomedical Applications
Authors: Singh Udisha , Morya Vinod , Datta Bhaskar , Ghoroi Chinmay , Bhatia Dhiraj
Published: June 2021

Of the multiple areas of applications of DNA nanotechnology, stimuli-responsive nanodevices have emerged as an elite branch of research owing to the advantages of molecular programmability of DNA structures and stimuli-responsiveness of motifs and DNA itself. These classes of devices present multiples areas to explore for basic and applied science using dynamic DNA nanotechnology. Herein, we take the stake in the recent progress of this fast-growing sub-area of DNA nanotechnology. We discuss different stimuli, motifs, scaffolds, and mechanisms of stimuli-responsive behaviours of DNA nanodevices with appropriate examples. Similarly, we present a multitude of biological applications that have been explored using DNA nanodevices, such as biosensing, in vivo pH-mapping, drug delivery, and therapy. We conclude by discussing the challenges and opportunities as well as future prospects of this emerging research area within DNA nanotechnology.
Inferring Hypogene Karst at Depth from the Patterns of Non-Tectonic Syncline Networks in Eocene Limestones, Western Desert, Egypt
Authors: Tewksbury Barbara J. , Tarabees Elhamy A. , Welch Robert M. , Mehrtens Charlotte J.
Published: June 2021

Indirect indicators are critically important for recognizing hypogene karst that is too deep-seated to have explorable hypogene caves. We have suggested in previous publications that an extensive network of non-tectonic synclines in otherwise flat-lying Eocene limestone in Egypt might be such an indirect indicator. We proposed that synclines formed by sag of limestone layers overlying a zone of hypogene karst that today remains deep below the surface and suggested that hypogene speleogenesis resulted from ascending aggressive fluids associated with crustal extension and magmatism in Egypt during Red Sea Rift initiation. Without hypogene caves to explore, however, we were unable to provide compelling evidence for hypogene karst processes. By doubling our mapping area from 4,000 to 8,000 km2, a clear picture has emerged of patterns in the syncline network that provide compelling evidence for hypogene speleogenesis. Over this larger area, the network displays two distinct patterns: 1) synclines and ridges that outline polygons 700–2,000 m across, and 2) narrow N–S zones of synclines spaced 5–10 km apart, with WNW–ESE to NW–SE trending shallow synclines and ridges traversing the panels between N–S zones. The geometries suggest that the syncline network is controlled by two structural patterns in rocks underlying the limestones: 1) polygonal faults in underlying shales and 2) reactivated N–S, left-lateral basement faults that are largely blind at the current level of erosion. These structures served as conduits that conveyed fluids upward into the overlying Eocene limestones, triggering dissolution at depth and a pattern of sag above that was inherited from the nature and pattern of faults and fractures in rocks underlying the limestones. The unique patterns and characteristics of this network of synclines are applicable elsewhere as an indirect indicator of deep-seated hypogene karst. Our new data also strongly suggest that syncline formation spanned the time of crustal extension in Egypt associated with onset of Red Sea rifting ∼23–22 Ma. Endogenic CO2 associated with mantle-derived basaltic magmas was likely a significant component of fluids, perhaps involving highly aggressive supercritical CO2. Mantle-derived C and He in modern Egyptian oasis water suggest that hypogene speleogenesis may still be locally active.
Potential Therapeutic Targets and Vaccine Development for SARS-CoV-2/COVID-19 Pandemic Management: A Review on the Recent Update
Authors: Anand Uttpal , Jakhmola Shweta , Indari Omkar , Jha Hem Chandra , Chen Zhe-Sheng , Tripathi Vijay , Pérez de la Lastra José M.
Published: June 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.
Granulocyte-Macrophage Colony Stimulating Factor in Single Blastocyst Conditioned Medium as a Biomarker for Predicting Implantation Outcome of Embryo
Authors: Chen Peilin , Huang Chunyu , Sun Qing , Zhong Huixian , Xiong Feng , Liu Su , Yao Zhihong , Liu Zhiqiang , Wan Caiyun , Zeng Yong , Diao Lianghui
Published: June 2021

Background

It is highly desirable to develop new strategies based on secretomics to more accurately selection of embryos with the highest developmental potential for transfer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to promote embryo development and pregnancy establishment. However, the predictive value of GM-CSF in single blastocyst selection remains unclear. This study is to determine the concentration of GM-CSF in human single-blastocyst conditioned medium (SBCM) and to evaluate its association with embryo quality and pregnancy outcome.

Methods

The patients with ≤38 years of age receiving the first cycle of assisted reproductive therapy were included in this study. The patients who had <4 top-quality embryos formed by the fertilized two pronuclear zygotes on day 3 were excluded. A total of 126 SBCM samples (SBCMs) were included, of which blastocysts from 77 SBCMs were later transferred in subsequent frozen-thawed embryo transfer. The concentrations of GM-CSF were detected by single-molecule array (SIMOA) and analyzed for their possible association with embryo quality and pregnancy outcomes. The top-quality embryo (TQ), positive HCG (HP), clinical pregnancy (CP), and ongoing pregnancy (OP) rates were determined and compared between groups divided based on GM-CSF concentrations.

Results

The detection rate of GM-CSF was found to be 50% in all SBCMs. There were significant differences in TQ rate, HP rate, CP rate and OP rate among high concentration group, medium concentration group and low concentration group. Both GM-CSF alone or GM-CSF combined with the morphological score (MS) had a greater AUC of ROC curve than that of MS alone to predict the pregnancy outcome, and GM-CSF combined with MS had the highest AUC.

Conclusions

The concentration of GM-CSF in SBCM was detected at fg/ml levels, which was associated with embryo quality and pregnancy outcome. Collectively, GM-CSF may be used as a biomarker for prediction of pregnancy outcome and selection of embryos with high developmental potential for transfer in assisted reproductive technology (ART).
Memory B Cells in Pregnancy Sensitization
Authors: Nellore Anoma , Killian John T. , Porrett Paige M.
Published: June 2021

Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen re-encounter. Memory B cells also develop over the course of HLA-sensitization during pregnancy and transplantation. In this review, we discuss the potential contribution of memory B cells to pregnancy sensitization as well as the impact of these cells on transplant candidacy and outcomes. We start by summarizing how B cell subsets are altered in pregnancy and discuss what is known about HLA-specific B cell responses given our current understanding of fetal antigen availability in maternal secondary lymphoid tissues. We then review the molecular mechanisms governing the generation and maintenance of memory B cells during infection – including the role of T follicular helper cells - and discuss the experimental evidence for the development of these cells during pregnancy. Finally, we discuss how memory B cells impact access to transplantation and transplant outcomes for a range of transplant recipients.
Specialized Pro-Resolving Mediators Mitigate Cancer-Related Inflammation: Role of Tumor-Associated Macrophages and Therapeutic Opportunities
Authors: Lavy Margot , Gauttier Vanessa , Poirier Nicolas , Barillé-Nion Sophie , Blanquart Christophe
Published: June 2021

Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.