bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilização da toxina botulínica tipo a para fins terapêuticos
Authors: Silva Maressa Lima da , Ferreira Leticia Ramos , Peixoto Ana Carla , Neres Liberta Lamarta Favoritto Garcia , Cabral Mara Régina Lucena
Published: November 2021

O trabalho tem por objetivo demonstrar a importância da toxina botulínica no tratamento da dor apresentando a necessidade de uma análise descritiva para a importância da aplicação e seus respectivos mecanismos de ação, buscando um levantamento em artigos acadêmicos da ANVISA, CDL e SCIELO nos anos entre 1980 a 2014, sendo a mais procurada para uso na estética poucas pessoas tem o conhecimento que ela pode trazer benefícios também para aplicações nas dores. A aplicação da TBA é um tratamento na qual varia de acordo com a extensão e a força no musculo a ser tratado, quanto maior for a força do musculo ou mais extenso, maior será a dose, sendo assim o tratamento com a TBA além de ter um elevado grau de satisfação também tem um índice baixo em relação as complicações ou efeitos colaterais.
Marijuana use among adolescents: a cross-sectional study with Brazilian students from a remote area of the Amazon region
Authors: Souza Samara Borges de , Costa Franciane Ferreira , Queiroz Jocilena Pamela Quadros de , Silva-Oliveira Gláucia Caroline , Pinheiro Luiz Marcelo Lima , Oliveira-Filho Aldemir Branco de
Published: November 2021

Marijuana is the most used illicit drug worldwide. The frequent use of marijuana in adolescence is very worrying, as it is associated with health problems. In Brazil, surveys on the use of psychotropic drugs with adolescent students were conducted in large cities. This study determined the prevalence and factors associated with marijuana use among adolescent students in the Brazilian city of Soure, Pará, in the Amazon region. In this cross-sectional study, 736 high school adolescent students provided information through a structured form at the three schools in Soure in November 2019. Marijuana use, in life and frequent (last 30 days), was calculated. Logistic regression models identified factors associated with different marijuana use. The rates of marijuana use in life and frequent were 17.7% and 7.1%, respectively. The behavioral pattern of the adolescents' coexistence nucleus (parents, relatives, and friends) was fundamental for marijuana use in life. Also, the lack of interference or reduced participation of the family in the adolescent's life, the inadequate family structure, and the continuous example of friends were associated with the frequent use of marijuana. Measures to control and prevent marijuana use are necessary and should be available to adolescents, their families, and friends in this remote area of the Amazon region.
Dimensions of the 2020 wildfire catastrophe in the Pantanal wetland: the case of the municipality of Poconé, Mato Grosso, Brazil
Authors: Silgueiro Vinícius de Freitas , Souza Carolina Ortiz Costa Franco de , Muller Eriberto Oliveira , Silva Carolina Joana da
Published: November 2021

In 2020, a total of 3.9 million hectares were burned in the Pantanal biome, which represents approximately 30% of its total area. Of the three existing biomes in the state of Mato Grosso, the Pantanal was the most impacted and, among all the municipalities in Mato Grosso, Poconé had the largest burned area. We aimed to characterize the areas affected by fires in the municipality of Poconé in 2020 to support prevention and adaptation actions in future scenarios. For this, we used the mapping of areas affected by fires made from the detections of active fire collected by the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor and available by the Global Fire Emissions Database (GFED). The results showed that a total of 869,170 hectares were burned in Poconé in 2020. Of this total, 97.3% were in natural areas, viz. forest formations (37%), savanna (2.8%), grassland formations (23.4%), wetlands (29.7%), and vegetation in dried-up rivers and lakes (4.4%). Concerning land categories, almost half of the fires occurred in private rural properties registered in the Rural Environmental Registry (CAR). In this scenario, we highlighted the importance of monitoring fires and holding those responsible for them accountable. It is also important to implement preventive actions in synergy with managers and local communities as a way of adapting to the climate crisis, intense drought, and less water surface available in the region, which increases the risk and damage of fires.
Projeto cuidadores em saúde: um relato de experiência
Authors: Rocha Sebastião , Coutinho Vânia Lúcia , Monteiro Claudia Barbastefano , Loyola Cristina Maria Douat
Published: November 2021

Objetivo: Este estudo tem como objetivo relatar a experiência do desenvolvimento do Projeto Cuidadores em Saúde em comunidades quilombolas, na formação de cuidadoras leigas no Projeto Cuidadores em Saúde, no estado do Maranhão. Metodologia: Trata-se de um relato de experiência acerca do desenvolvimento e avaliação do projeto para a formação de cuidadores leigos. Resultado: os casos de hipertensão e diabetes foram detectados e acompanhados na comunidade pelos cuidadores, semanalmente, e encaminhados à Estratégia de Saúde da Família   para intervenção medicamentosa. Conclusão: Através desta experiencia constatamos que é possível que formar cuidadores leigos com esta carga horária e conteúdos desenvolvidos, para manter em cuidado e monitoramento comunidades quilombolas, quanto à hipertensão, ao diabetes melitos e à síndrome metabólica.
The effect of exposure to liquid air freshener on histological of the bronchial mice (Mus musculus)
Authors: Warobi Warobi , Maretha Delima Engga , Asnilawati Asnilawati , Masri Mashuri
Published: November 2021

Air fresheners are products that contain chemicals aimed at reducing unpleasant odours in confined spaces. The use of synthetic air fresheners turns out to harm health because some of their leased Volatile Organic Compounds are classified as toxic compounds and are carcinogens. Air freshener enters the body through the inhalation process in the respiratory system. Modern air fresheners are available in liquid (aerosol) and gel forms. Air fresheners contain addictive substances and solvents such as 1,4-dichlorobenzene which can affect pulmonary function. The purpose of this study is to know the effect of exposure to liquid air freshener on the histology of bronchi of mice (Mus musculus). This study used 20 male mice (Mus musculus) consisting of 4 treatments with 5 replications. The research design is true experimental in the form of a post-test only control group with Completely Randomized Design (CRD). The post-test was done by observing the histological picture of the mice's bronchi after exposure to liquid air freshener given 3x/day for a period of P1 = 2 weeks, P2 = 4 weeks and P3 = 6 weeks. Quantitative data on bronchial histology was tested using the One Way ANOVA statistical test followed by the Post Hoc Tukey test. The results of the study found changes in the histology of the bronchi, thickening of the epithelial tissue of mice. Analysis of comparative data between the control and treatment groups statistically obtained p = 0.010 <0.05, meaning that there was a significant effect and change in the bronchial tubes exposed to liquid air freshener. Histologically there were differences in histology between the control and treatment groups. It was concluded that liquid air freshener had a significant effect on the histological picture of the mice's bronchi.
Daylength influences reproductive success and sporophyte growth in the Arctic kelp species Alaria esculenta
Authors: Martins N , Barreto L , Bartsch I , Bernard J , Serrão EA , Pearson GA
Published: November 2021

Many organisms have endogenous clocks that synchronize biological processes with environmental changes, leading to optimized development and reproduction. However, certain environments, like the Arctic, pose a special challenge to circadian clocks, particularly due to extreme seasonal changes in daylength, ranging from permanent sunlight to complete darkness. Kelps seem to be well adapted to the variable environmental conditions characteristic of this region. However, daylength might affect kelp species that use circadian rhythms to control the timing of daily egg release from female gametophytes. We aimed to investigate how daylength and light intensity affect gametogenesis and reproductive success of summer-reproducing kelp species (using Alaria esculenta as a model). As daylength and temperature co-vary most of the year, we also investigated the thermal resilience of the sporophytes developed under different daylengths to understand if there is a cross-tolerance between light doses and temperature tolerance. Although continuous daylight, characteristic of Arctic summers, enhanced gametogenesis and increased gametophyte vegetative growth, and thereby the number of potential reproductive gametophyte cells, sporophyte production was higher under long (16 h light:8 h dark) and intermediate (12:12 h) days. Sporophyte growth was triggered by changing daylength from short to long days, suggesting a synchronization with annual daylength variation. High daily light doses during reproduction and early development improved subsequent sporophyte survival at high (sub)lethal temperatures, indicating cross-tolerance between light and temperature. Reproductive success in Arctic A. esculenta was hampered under continuous light, and we hypothesize that this might result from disturbance of synchronized egg release and subsequent fertilization.
SOFT SKILLS IN HIGHER EDUCATION: ENRICHING EMPLOYABILITY OF TECHNICAL STUDENTS
Authors: Kumari Sweta
Published: November 2021

The present paper attempts to intensify
capacity and inculcate employability among Technical
Students of Jharkhand in respect of globalization.
Demands of present business world or work place are
higher, and learning attitude, critical thinking, decision
making skills along with other employable skills seems
crucial in its employees. The technical students must be
trained during their technical course in accordance to the
industry-demands; and this is a real challenge of the
technical institutions in Jharkhand, especially for the
private one. Triangular role of the ‘Institution-FacultyStudents’ needs proper execution to fulfill the dynamic
objective of higher education that is ‘reaching of the unreached’ in knowledge, skills and values. Learning is a lifelong process and students need to learn from their day to
day activities. This paper deals with the process which
enables the technical students to develop a thought
process. Students need to learn appropriate reasons and
logics behind their every acceptance or rejections. In this
respect, a constructive environment is required to facilitate
students where they don’t hesitate to do mistakes and
solely focus on ‘Learning’.
A REVIEW ON SMART CITIES BASED ON IOTTECHNOLOGY
Authors: Kumar Prajapat Dinesh , Chopra Rahul
Published: November 2021

In an IOT based smart city various
component like smart water supply management,
traffic light control, street lightning system and
many more systems are make a city to a smart
city. In a smart city allthe necessary facilities such
as transportation, water, energy and security etc.
related issue can be solving in easy way and the
community and people provide a healthy and
safety environment.
The world is moving forward at a fast with
increasing technology in recent time. Thus, a lot
of safety issues in all parts of world. So, in this
paper mainly focus to provide a well deserved life
of all the persons living in the cities. Generally the
smart cities definition depends on geographical,
environmental andeconomical.
Islamic Education of Kyrgyzstan on the Way of Development
Authors: Sherov Sh. , Tairov K. , Zhumashova G.
Published: November 2021

The article examines the development of Islamic religious education in the history of the Kyrgyz Republic over the past 30 years. According to the study, religious Islamic education is divided into 3 stages: the first stage — 1991–2000, the second stage — 2000–2006, the third stage — 2006–2010, and the fourth — 2011–2020. The features of the development of Islamic education at each stage are analyzed. In addition, the process of implementation of the concept of “Reform of religious education and religious studies” adopted by the Government of Kyrgyzstan was analyzed. The attempts of the Commission on Religious Affairs of the Kyrgyz Republic and the Spiritual Directorate of Muslims of Kyrgyzstan to include secular subjects in the curricula of madrasahs and institutes were highlighted. For 30 years, the subject “History of Religious Culture” has been introduced in secondary schools on a pilot basis.
A Brief Review of the Study of Central Asian Agriculture
Authors: Khatamova M.
Published: November 2021

The article examines archaeobotanical and agricultural research conducted in Central Asia. Based on this research, the author divided the study of irrigational and agricultural culture in Central Asia into three groups. These have been studied in groups such as the issue of irrigation facilities and irrigation systems, the issue of tools of labor, and the issue of farming and economics in the restoration of the agricultural past, and the essence of the issue has been clarified.
Application of Imperative Paremias
Authors: Maatkalykova G.
Published: November 2021

Research relevance: imperative pairs were divided into subgroups, and attempts were made to their illustration. Research objectives: this article describes the ways in which imperative paremias are used in society. Research materials and methods: paremias determining the imperative paremias were analyzed, a comparison was made of its use in the consciousness and religion of various ethnic groups, and it was found that it was given in the same context. Research results: the main functions of imperatives were identified and their application as a norm of morality and behavior was studied. Conclusions: an imperative is a command of the mind, a rule of behavior.
Critical infrastructure and its functions
Authors:   SESE “The Academy of Financial Management”, KUDRJASHOV Vasyl
Published: November 2021

The analysis of definitions on the content and significance of critical infrastructure, contained in national and foreign scientific publications, as well as in regulatory documents, is carried out. Attention is drawn to the fact that the adopted approaches do not take into account the place of critical infrastructure in its totality, as well as in the use of critical infrastructure in production processes to provide critical services. New conceptual provisions for determining the content of critical infrastructure, its components, use in production processes, achievement of final results (provision of critical services) are substantiated and recommended for application in state regulation. The concept of critical functions, as well as their importance in the provision of critical services is revealed. Emphasis is placed on the need to take into account institutional aspects, which provides for the formation of characteristics of entities involved in the provision of critical services. It is noted that critical functions are divided into different types, and their classification is taken as a basis for classifying sectors of the economy as critical. There is a reasonable provision that such a division should be regulated by the legislation of the country in order to carry out state regulation of the formation and development of critical infrastructure. It is determined that in Ukraine the regulatory framework for the regulation of critical infrastructure is in its infancy and needs significant improvement. This applies both to the adoption of new (conceptual) approaches to the content and components of critical infrastructure, and to the regulation of the list of critical sectors. Equally important are regulation issues of the list of services, as well as the effectiveness of their use to ensure the development of the country in terms of preventing the deterioration of financial stability.
Gross domestic product and critical infrastructure
Authors:   SESE “The Academy of Financial Management”, KULYK Volodymy
Published: November 2021

GDP is considered as a critical infrastructure that characterizes the global interaction of consumers and manufacturers of the final product in the national economy. For the analysis and modelling of GDP, the Leontiev model is used to analyze and to model GDP as a critical infrastructure, where costs are interpreted in two ways - as consumer spending and as producer costs. This allows you to determine the degree of their influence on each other through the established production structure. Based on Leontiev's aggregated three-sector model, two scenarios were modelled: a) the impact of final consumer spending on output and the formation of added value and b) the impact of changes in added value on output and final consumer spending. The model includes three sectors – the agricultural sector, industry and service sectors. In the first scenario, the increase in the final consumed product in the agricultural sector by 1000 yen causes an increase in output in the agricultural sector by 1153.5 yen, in industry by 594.4 yen and in the service sector by 358.1 yen. At the same time, total production costs will increase by 1106.0 yen; added value will increase in the agricultural sector by 549.8 yen, in industry – 216.8 yen, in the service sector – 233.4 yen. The volume of production growth can be determined only through the Leontiev model. In the second scenario, an increase in added value in the agricultural sector by 1000 yen brings about an increase in output in the agricultural sector by 1153.5 yen, in industry by 1470.4 yen and in the service sector by 480.7 yen. For both scenarios, the assessment and verification of calculations of GDP growth and output are carried out by the balance method – output and GDP growth is described within the Leontiev model. The three-sectoral model is useful for educational purposes, scientific research; to reach the method in a specific example. The approach can be extended to models of greater dimension and large size.
The role of commercial banks in sustainable finance
Authors:   SESE “The Academy of Financial Management”, BORTNIKOV Gennadiy
Published: November 2021

The market for financial instruments for sustainable finance has enormous growth potential. So far, Ukrainian banks adhere to a passive strategy in sustainable financing, which, in contrast to the active strategy, assigns banks the role of an agent in the implementation of national or international programs. Moreover, ‘green’ financing at the state level is seen as synonymous with sustainable finance. Lending to energy efficiency projects for businesses and households dominates among all areas of sustainable financing. Banks with local capital and especially state-owned banks are losing access to wholesale borrowing markets. The dependence of many Ukrainian banks on the target funds of international lenders for the development of sustainable financing weakens national financial security in the absence of large-scale national programs. It is expedient at the level of the Government of Ukraine to develop a program to intensify sustainable financing, with an emphasis on green and social impact and implementation through state banks. Sustainable financing should not exacerbate structural imbalances due to the curtailment of lending to sectors that have accumulated problems with adherence to environmental standards, social norms and corporate governance. The National Bank as a regulator and supervisor is able to act as a catalyst for the development of sustainable finance in Ukraine, with adoption of relevant standards harmonised with EU taxonomy.
Accounting theory verbalism
Authors:   Ternopil Ivan Puluj National Technical University, KHOMУN Petro
Published: November 2021

Based on the deductive understanding of current publications in the area of accounting theory, it is determined that it is increasingly acquiring signs of verbalism. It is caused by an excessive enthusiasm for foreign terminology, and without a balanced application in the context of accounting, since it is based on arbitrary interpretations of foreign words, as a result of which the authors fall into a semantic trap. The author emphasizes the importance of focusing not on false verbose scholastic exercises in an attempt to pretend to be the discoverers of certain ephemeris terminologies, but on the real problems of accounting, which negatively affects the state of the domestic economy. It is noted that this happened due to the growing remoteness of accounting theory from pragmatism and the predominance of utopian ideas in it, which have nothing to do with accounting, but is only an adjustment to it in order to sell books that attract buyers by the incomprehensibility of names and ignoring the fundamentals of accounting theory. After all, even such a basic financial and economic category as capital, in many cases began to affect negative numbers, and the “tax shield of an enterprise” – depreciation is considered synonymous with its antipode – depreciation of fixed assets. And instead of at least solving the problem of the targeted use of accumulated financial resources for the simple reproduction of non-current assets, in many cases not only depreciation of fixed assets, but even the capital of the enterprise is directed to the payment of dividends. In addition, the current fashion for foreign-language terms distracts scientists from unsolved problems of methodological support of accounting, obscuring them with verbalism of ephemerality, which never end with at least some pragmatic methodological developments, but only verbose attempts to convince them of their pseudo-relevance, as a result of which the accounting theory goes astray. The possibility of solving the current paradoxes regarding the main accounting categories by using the achievements of predecessors, which are recognized by the classics of accounting theory, is substantiated.
The Limits of Annotation in Machine Learning a Documents Hohfeldian Legal Entities
Authors: Izzidien Ahmed
Published: November 2021

Natural language processing (NLP) summarisers aim to capture the essential elements of a document. Yet, the ontological character of a summary can be domain specific. In legal analysis, the Hohfeldian matrix is used to summarise principle legal relations between agents, such as individuals and organisations. We test a limit of using machine learning (ML) to detect such agents. Based on training with our 2400 hand labelled annotations, an F1= 80.1 is found. Extrapolating this suggests that over one million annotations are required to capture all the agents mentioned in a document. This questions the feasibility of such an approach, one that is unable to be inclusive of all agents who are party to a legal relation. Such complete capture is an essential criteria of fair ML and accurate legal summaries. An alternative approach based on hypernymy is suggested.
Pattern of Aeroallergen Sensitization and Quality of Life in Adult Thai Patients With Allergic Rhinitis
Authors: Katel Puspalal , Pinkaew Bannapuch , Talek Kanokporn , Tantilipikorn Pongsakorn
Published: November 2021

The prevalence of allergic rhinitis (AR) is steadily rising in the Thai population, causing a major impact on the quality of life (QoL). Enhancing knowledge on common aeroallergens in the local setting helps in the appropriate prevention and management of AR. In this study, the demographic characteristics, clinical data, aeroallergen sensitization pattern, allergic symptoms, visual analog scale (VAS) score, and QoL are described. We evaluated the association between VAS, QoL, and severity of symptoms, except the aeroallergen sensitization pattern. We retrospectively reviewed the medical records of adult AR patients with a positive skin prick test (SPT) for at least one aeroallergen from January 2018 to May 2020. Standard descriptive and inferential statistics were used for analysis. A total of 366 patients were enrolled. Indoor aeroallergen sensitization and outdoor aeroallergen sensitization were observed in 32% and 7.9% of patients, respectively. Mono-sensitization was noted in 16.9% of patients, while poly-sensitization was noted in 83.1% of patients. Mites (65%) and sedge (39.3%) were the most common indoor and outdoor allergens. Nasal obstruction (74.6%), runny nose (63.7%), and nasal itchiness (61.5%) were the primary symptoms affecting the QoL. The association between VAS and symptom scores showed a trend of association with AR severity (Allergic Rhinitis and its Impact on Asthma [ARIA] classification) and VAS. AR has a significant effect on QoL in all domains of the validated generic (short-form-36, SF-36) and specific (rhino-conjunctivitis QoL questionnaire, Rcq-36) questionnaires. Mite and sedge remain the most common indoor and outdoor aeroallergens. The pattern of sensitization and number of aeroallergens were not associated with AR based on the ARIA guidelines. Meanwhile, symptoms of patients affected the QoL and VAS scores, which can be used as a quick and reliable tool for monitoring and stepping up or stepping down the treatment according to the next-generation guidelines. AR has a significant impact on the QoL of adult Thai patients.
Development and Validation of a Pyroptosis-Related Long Non-coding RNA Signature for Hepatocellular Carcinoma
Authors: Wu Zeng-Hong , Li Zi-Wei , Yang Dong-Liang , Liu Jia
Published: November 2021

Background: Hepatocellular carcinoma (HCC) is a highly aggressive malignant disease, and numerous studies have demonstrated that an inflammatory environment can induce normal cells to transform into cancerous.

Methods: We integrated genomic data to comprehensively assess the association between pyroptosis and tumor microenvironment (TME) cell-infiltrating characteristics in HCC, as well as the potential molecular function and clinical significance of lncRNA.

Results: The analysis of CNV alteration frequency displayed that CNV changes were common in 33 PRGs, and most were focused on copy number amplification. As a result of lasso regression analysis, nine differentially expressed lncRNAs (AL031985.3, NRAV, OSMR-AS1, AC073611.1, MKLN1-AS, AL137186.2, AL049840.4, MIR4435-2HG, and AL118511.1) were selected as independent prognosis factors of HCC patients. Patients at high risk have poorer survival than those in the low-risk group in training and testing cohorts. A low-risk score was significantly associated with an IC50 of chemotherapeutics such as bortezomib (p < 0.001), but a high-risk score was significantly linked to docetaxel (p < 0.001), implying that signature served as a prospective predictor for chemosensitivity.

Conclusion: This work suggests pyroptosis-related lncRNAs features and their potential mechanisms on tumor microenvironment. The exploration may assist in identifying novel biomarkers and assist patients in predicting their prognosis, clinical diagnosis, and management.
A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer
Authors: Chen Xianwu , Zhang Yan , Wang Feifan , Zhou Xuejian , Fu Qinghe , Yang Xintao , Lin Juntao , Jin Xiaodong
Published: November 2021

Hypoxia is a common feature in various tumors that regulates aggressiveness. Previous studies have demonstrated that some dysregulated long non-coding RNAs (lncRNAs) are correlated with tumor progression, including bladder cancer (BCa). However, the prognostic effect of hypoxia-related lncRNAs (HRLs) and their clinical relevance, as well as their regulatory effect on the tumor immune microenvironment, are largely unknown in BCa. A co-expression analysis between hypoxia genes and lncRNA expression, which was downloaded from the TCGA database, was performed to identify HRLs. Univariate Cox regression analysis was performed to select the most desirable lncRNAs for molecular subtype, and further LASSO analysis was performed to develop a prognostic model. This molecular subtype based on four HRLs (AC104653, AL136084, AL139393, and LINC00892) showed good performance in the tumor microenvironment and tumor mutation burden. The prognostic risk model suggested better performance in predicting BCa patients’ prognosis and obtained a close correlation with clinicopathologic features. Furthermore, four of five first-line clinical chemotherapies showed different sensitivities to this model, and nine immune checkpoints showed different expression in the molecular subtypes or the risk model. In conclusion, this study indicates that this molecular subtype and risk model based on HRLs may be useful in improving the prognostic prediction of BCa patients with different clinical situations and may help to find a useful target for tumor therapy.
Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion
Authors: Wang Shizhi , Ding Bo , Cui Mengjing , Yan Wenjing , Xia Qianqian , Meng Dan , Shen Siyuan , Xie Shuqian , Jin Hua , Zhang Xing
Published: November 2021

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.
Autophagy Regulates VDAC3 Ubiquitination by FBXW7 to Promote Erastin-Induced Ferroptosis in Acute Lymphoblastic Leukemia
Authors: Zhu Ting , Liu Bo , Wu Di , Xu Gang , Fan Yang
Published: November 2021

Background: The discovery of ferroptosis is a major breakthrough in the development of cancer treatments. However, the mechanism by which ferroptosis contributes to acute lymphoblastic leukemia (ALL) is to be clarified. Here, we explored erastin-induced ferroptosis in ALL cells and the impact of autophagic activity on this process.

Materials and Methods: Cell viability was evaluated in various ALL cell lines following erastin treatment by the MTS assay, while cell death was evaluated via a trypan blue assay. Immunoblotting and quantitative real-time PCR were used to detect protein and mRNA expression, respectively. The UbiBrowser database was used to predict the E3 ligase of VDAC3, which was confirmed by immunoprecipitation. The role of FBXW7 in erastin-induced ferroptosis in vitro was evaluated via lentiviral-mediated silencing and overexpression. ALL xenograft mice were used to observe the impact of autophagy on erastin-induced ferroptosis.

Results: Resistance to erastin-induced ferroptosis was higher in Jurkat and CCRF-CEM cells than in Reh cells. The sensitivity could be modified by the autophagy activator rapamycin (Rapa) and the autophagy inhibitor chloroquine (CQ). Rapa sensitized ALL cells to erastin-induced ferroptosis. In ALL xenograft mice, the combination treatment of Rapa and erastin resulted in longer survival time than those observed with erastin or Rapa treatment alone. VDAC3 was regulated by autophagy post-transcriptionally, mainly via the ubiquitin-proteasome system (UPS). FBXW7 was verified as a specific E3 ligase of VDAC3. FBXW7 knockdown attenuated VDAC3 degradation by suppressing its ubiquitination, thereby increasing the sensitivity of ALL cells to erastin.

Conclusion: Autophagy regulated erastin-induced ferroptosis via the FBXW7-VDAC3 axis. Rapa sensitized ALL cells to erastin-induced ferroptosis both in vitro and in vivo. Our findings provide potential therapeutic targets for ALL.
The Half-Life-Extended IL21 can Be Combined With Multiple Checkpoint Inhibitors for Tumor Immunotherapy
Authors: Wu Shaoxian , Sun Runzi , Tan Bo , Chen Bendong , Zhou Wenyan , Gao David Shihong , Zhong Joshua , Huang Hao , Jiang Jingting , Lu Binfeng
Published: November 2021

In the era of immune checkpoint blockade cancer therapy, cytokines have become an attractive immune therapeutics to increase response rates. Interleukin 21 (IL21) as a single agent has been evaluated for cancer treatment with good clinical efficacy. However, the clinical application of IL21 is limited by a short half-life and concern about potential immune suppressive effect on dendritic cells. Here, we examined the antitumor function of a half-life extended IL21 alone and in combination with PD-1 blockade using preclinical mouse tumor models. We also determined the immune mechanisms of combination therapy. We found that combination therapy additively inhibited the growth of mouse tumors by increasing the effector function of type 1 lymphocytes. Combination therapy also increased the fraction of type 1 dendritic cells (DC1s) and M1 macrophages in the tumor microenvironment (TME). However, combination therapy also induced immune regulatory mechanisms, including the checkpoint molecules Tim-3, Lag-3, and CD39, as well as myeloid derived suppressor cells (MDSC). This study reveals the mechanisms of IL21/PD-1 cooperation and shed light on rational design of novel combination cancer immunotherapy.
HSBP1 Is a Novel Interactor of FIP200 and ATG13 That Promotes Autophagy Initiation and Picornavirus Replication
Authors: Mauthe Mario , Dinesh Kumar Nilima , Verlhac Pauline , van de Beek Nicole , Reggiori Fulvio
Published: November 2021

ATG13 and FIP200 are two subunits of the ULK kinase complex, a key regulatory component of the autophagy machinery. We have previously found that the FIP200-ATG13 subcomplex controls picornavirus replication outside its role in the ULK kinase complex and autophagy. Here, we characterized HSBP1, a very small cytoplasmic coiled-coil protein, as a novel interactor of FIP200 and ATG13 that binds these two proteins via FIP200. HSBP1 is a novel pro-picornaviral host factor since its knockdown or knockout, inhibits the replication of various picornaviruses. The anti-picornaviral function of the FIP200-ATG13 subcomplex was abolished when HSBP1 was depleted, inferring that this subcomplex negatively regulates HSBP1’s pro-picornaviral function during infections. HSBP1depletion also reduces the stability of ULK kinase complex subunits, resulting in an impairment in autophagy induction. Altogether, our data show that HSBP1 interaction with FIP200-ATG13-containing complexes is involved in the regulation of different cellular pathways.
Association Between the Circulating Level of 25-Hydroxyvitamin D and Clinical Results After Cardiac Surgery: A Meta-Analysis and Systematic Review
Authors: Zhang Yulin , Li Jiawen , Qiu Yu , Gong Xue , He Yunru , Yue Peng , Zheng Xiaolan , Liu Lei , Liao Hongyu , Zhou Kaiyu , Hua Yimin , Li Yifei
Published: November 2021

Background: Vitamin D (VitD) is an important pleiotropic hormone for organ systems. Studies have focused on the level of VitD, especially that of 25-hydroxyvitamin D (25-(OH)-VitD), in patients after cardiac surgery and the relationship between VitD deficiency and adverse outcomes, but the results have been inconsistent. We carried out a meta-analysis to evaluate differences in the 25-(OH)-VitD level before and after cardiac surgery, and evaluated the predictive value of 25-(OH)-VitD level in the clinical outcomes of patients undergoing cardiac surgery.

Methods: Studies related to VitD level and cardiac surgery were searched from PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from inception to October 2020. We applied the Newcastle–Ottawa Scale to assess the risk of a bias in individual studies. We examined the heterogeneity and publication bias and performed subgroup analyses and sensitivity analyses.

Results: Fifteen studies were included in our analysis. The 25-(OH)-VitD level was significantly lower immediately after surgery [stand mean difference (SMD), 0.69; 95%CI (0.1, 1.28), P = 0.023] and 24-h after surgery [0.84; (0.47, 1.21), 0.000] compared with that before surgery. A higher prevalence of 25-(OH)-VitD deficiency was recorded 24 h after surgery [RR, 0.59; 95%CI (0.47, 0.73), P = 0.00]. Pooled results demonstrated a significant relationship between the preoperative 25-(OH)-VitD level and vasoactive-inotropic score (VIS) [SMD, −3.71; 95%CI (−6.32, −1.10); P = 0.005], and patients with 25-(OH)-VitD deficiency revealed a comparatively poor prognosis and severe condition after cardiac surgery [−0.80; (−1.41, −0.19), 0.01]. However, 25-(OH)-VitD deficiency was not associated with the duration of stay in the intensive care unit.

Conclusions: Cardiac surgery would leads to deficiency of 25-(OH)-VitD. And the preoperative and postoperative levels of 25-(OH)-VitD are associated with adverse events, which is eligible to work as an indicator to demonstrate clinical outcomes.
Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Is There a Relevant Experimental Model? A Systematic Review of Preclinical Literature
Authors: Goursaud Suzanne , Martinez de Lizarrondo Sara , Grolleau François , Chagnot Audrey , Agin Véronique , Maubert Eric , Gauberti Maxime , Vivien Denis , Ali Carine , Gakuba Clément
Published: November 2021

Delayed cerebral ischemia (DCI) is one of the main prognosis factors for disability after aneurysmal subarachnoid hemorrhage (SAH). The lack of a consensual definition for DCI had limited investigation and care in human until 2010, when a multidisciplinary research expert group proposed to define DCI as the occurrence of cerebral infarction (identified on imaging or histology) associated with clinical deterioration. We performed a systematic review to assess whether preclinical models of SAH meet this definition, focusing on the combination of noninvasive imaging and neurological deficits. To this aim, we searched in PUBMED database and included all rodent SAH models that considered cerebral ischemia and/or neurological outcome and/or vasospasm. Seventy-eight publications were included. Eight different methods were performed to induce SAH, with blood injection in the cisterna magna being the most widely used (n = 39, 50%). Vasospasm was the most investigated SAH-related complication (n = 52, 67%) compared to cerebral ischemia (n = 30, 38%), which was never investigated with imaging. Neurological deficits were also explored (n = 19, 24%). This systematic review shows that no preclinical SAH model meets the 2010 clinical definition of DCI, highlighting the inconsistencies between preclinical and clinical standards. In order to enhance research and favor translation to humans, pertinent SAH animal models reproducing DCI are urgently needed.
Cardiac Involvement in Human Immunodeficiency Virus Infected Patients: An Observational Cardiac Magnetic Resonance Study
Authors: Yan Chengxi , Li Ruili , Guo Xiaojuan , Yu Huan , Li Wenhuan , Li Wenqiao , Ren Meiji , Yang Minglei , Li Hongjun
Published: November 2021

Objectives: To investigate the subclinical imaging changes in terms of myocardial inflammation and fibrosis and to explore the risk factors associated with myocardial fibrosis by cardiac magnetic resonance (CMR) approach in a Chinese HIV/AIDS cohort.

Methods: We evaluated myocardial function (cine), myocardial inflammation (T1, T2), and myocardial fibrosis (through extracellular volume fraction [ECV] and late gadolinium enhancement [LGE]) by a multiparametric CMR scan protocol in a total of 68 participants, including 47 HIV-infected individuals, who were divided into two groups: asymptomatic HIV (HIV+) (n = 30), and acquired immunodeficiency syndrome (AIDS) (n = 17), and 21 healthy controls.

Results: HIV-infected patients had lower left (55.3 ± 6.5 vs. 63.0 ± 7.9%, P < 0.001) and right ventricular systolic function (35.9 ± 15.7 vs. 50.8 ± 9.3%, P < 0.001). Radial systolic strain (30.7 ± 9.3 vs. 39.3 ± 9.4%, P = 0.001), circumferential systolic strain (−17.5 ± 2.6 vs. −19.4 ± 2.7%, P = 0.008), and longitudinal systolic strain (−9.4 ± 5.7 vs. −12.8 ± 3.1%, P = 0.012) were also decreased in HIV. Native T1 relaxation time (1,337.2 ± 70.2 vs. 1,249.5 ± 47.0 ms, P < 0.001), ECV value (33.5 ± 6.2 vs. 28.5 ± 2.9 ms, P = 0.026), and T2 relaxation time (45.2 ± 3.5 vs. 42.0 ± 2.6 ms, P = 0.001) were higher in HIV-infected patients compared with controls. Myocardial fibrosis, predominantly in the mid-inferior wall, was detected in 24.4% of the HIV-infected patients. HIV+ had a significantly lower value of ECV [29.1 (26.1, 31.8) vs. 35.2 (31.8, 41.9) %, P < 0.001] and frequency of LGE [3/25 (8%) vs. 7/16 (43.8%), P = 0.014)] compared with AIDS. AIDS was associated with myocardial fibrosis.

Conclusions: HIV-infected patients were associated with changes in myocardial function and higher rates of subclinical myocardial inflammation and fibrosis, which were more abnormal with greater severity of the disease. AIDS was associated with myocardial fibrosis, where the observations supported earlier initiation of antiretroviral therapy in the Chinese HIV/AIDS cohort.
Specialized Proresolving Mediators Facilitate the Immunomodulation of the Periodontal Ligament Stem Cells
Authors: Yu Ning , Rakian Audrey , Dean Afsah , Van Dyke Thomas E.
Published: November 2021

Recent investigations into the regulation of the inflammation in the periodontitis have revealed that chronic inflammatory diseases such as periodontitis are characterized by an imbalance in the proinflammatory and proresolution mediators and can be characterized by a failure of the resolution pathways in the late stages of the acute inflammatory response. The proresolution mediators, termed as specialized proresolving mediators (SPMs), comprise the lipoxins, resolvins, protectins, and maresins that are derived from the arachidonic acid or omega-3 polyunsaturated fatty acids. In the animal studies, treatment of the periodontitis with the topical SPMs return the inflammatory lesion to the homeostasis with the regeneration of all the components of the periodontal organ lost to the disease. In this article, the study investigates the immunomodulatory role of SPMs in the periodontal ligament stem cells (PDLSCs). Primary porcine PDLSCs (pPDLSCs) were stimulated with interleukin-1β (IL-1β) and interleukin-17 (IL-17) in vitro to simulate the periodontal inflammation in the presence or absence of SPMs. This study found that IL-1β and IL-17 synergistically activated the proinflammatory genes of pPDLSCs and altered the immune phenotype of pPDLSCs including the key signaling pathways. Addition of SPMs rescued the pPDLSCs phenotype and induced further production of the additional SPMs, which was reflected by upregulation of the requisite enzymes 12- and 15-lipoxygenase by pPDLSCs. This study interrogated the immunomodulatory actions of pPDLSCs on the monocytes/macrophages, focusing on the porcine CD14/CD16/CD163 markers by using flow cytometry. This study utilized the CD14+CD16+/CD14+CD16− ratio and CD163 on the monocytes/macrophages to differentiate between a proinflammation phenotype (lower ratio) and a resolution of the inflammation phenotype (higher ratio). This study also found that the conditioned medium from pPDLSCs treated with the cytokines and Maresin1 increased the CD14+CD16+/CD14+CD16− ratio and had the highest CD163 expression. This study concludes that in an inflammatory environment, pPDLSCs become proinflammatory and exert immunomodulatory functions. Maresin 1 resolves the inflammation by acting on pPDLSCs directly and by shifting the monocytes/macrophages phenotype to the proresolution dominance.
Multi-Scale Analysis of Geotechnical and Physicochemical Changes in Loess Caused by Nano-SiO2 Pile Migration
Authors: Kong Ran , Gao Lei , Zhao Wenqing , Zhao Bo
Published: November 2021

Understanding property changes in soil improvement using a new technique is critical for enhancing engineering activity. However, little is known about nano-SiO2pile-induced changes in soil properties due to its excellent properties as an alternative new additive material. This study aims to examine the changes in properties of loess stabilized with nano-SiO2pile after curing for 28 days. Using samples taken from four desired radii (i.e., 5, 10 15, and 20 cm), we tested their mineralogical, structural, physicochemical, and index properties and analyzed the relationship of these properties to strengthen the link between microscopic characteristics and macroscopic behaviors. We then discussed the mechanism of the changes in the treated loess properties. The test results show that nano-SiO2pile induced a physical structure modification in the treated loess and, consequently, an isotropic process with coarser particles due to crystallinity. This resulted in a solidification process in loess with nano-SiO2pile, causing a decrease in water content and void ratio as well as an increase in natural density, thereby improving its mechanical strength. Meanwhile, the specific surface area (SSA)and cation exchange capacity (CEC) of treated loess were smaller than those of original loess, and there were slight changes in chemical properties. The disintegration rate of treated loess decrease compared with the original loess. The interactional relationship of the microscopic and macroscopic observation was facilitated to better understand the mechanism of changes in nano-SiO2pile-treated loess properties. This finding reveals that nano-SiO2pile has the potential as an alternative stabilized technique in loess improvement due to its obvious performance improvement and slight chemical changes.
Mapping the Concept of Sustainable Consumption: An Analysis From the Adoption and Promotion of Pro-Environmental and Social Behaviors in University Students
Authors: Arias Claudia , Vélez-Rolón Adela M. , Méndez-Pinzón Manuel
Published: November 2021

The concept of sustainable consumption has been described in the literature from different perspectives, but few have focused on defining the consumer perspective and strategies to appropriate this knowledge and behaviors in the classroom, which becomes a major challenge in times of Covid 19 and confinement. This article proposes an approach to the concept by university students from the implementation of a pedagogical strategy, which involved the implementation of a virtual learning community and the evaluation of the understanding of this concept through the use of mind maps (pre and post). Through the mind maps, data were collected to evaluate the understanding of the concept, the analysis of semantic richness and systemic complexity. The results show the associations established by the students, proposing a categorization system arising from the data and the previous literature review. The study concludes that the students broadened their vision of sustainable consumption in terms of the actors involved, consumption decisions and the social and environmental dimensions of sustainability.