bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Shen Haixiang , Liu Jin , Chen Shiming , Ma Xueyou , Ying Yufan , Li Jiangfeng , Wang Weiyu , Wang Xiao , Xie Liping
Published: April 2021

Background

Tumor-associated macrophages (TAMs) are the major immune cells in tumor microenvironment. The prognostic significance of TAMs has been confirmed in various tumors. However, whether TAMs can be prognostic factors in clear cell renal cell carcinoma (ccRCC) is unclear. In this study, we aimed to clarify the prognostic value of TAMs in ccRCC.

Methods

We searched PubMed, Embase, and the Web of Science for relevant published studies before December 19, 2020. Evidence from enrolled studies were pooled and analyzed by a meta-analysis. Hazard ratios (HRs) and odd ratios (ORs) with 95% confidence intervals (CIs) were computed to evaluate the pooled results.

Results

Both of high CD68+ TAMs and M2-TAMs were risk factors for poor prognosis in ccRCC patients. The pooled HRs indicated that elevated CD68+ TAMs correlated with poor OS and PFS (HR: 3.97, 95% CI 1.39–11.39; HR: 5.73, 95% CI 2.36–13.90, respectively). For M2-TAMs, the pooled results showed ccRCC patients with high M2-TAMs suffered a worse OS and shorter PFS, with HR 1.32 (95% CI 1.16–1.50) and 1.40 (95% CI 1.14–1.72), respectively. Also, high density of TAMs was associated with advanced clinicopathological features in ccRCC.

Conclusions

TAMs could be potential biomarkers for prognosis and novel targets for immunotherapy in ccRCC. Further researches are warranted to validate our results.
The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis
Authors: Zhang Shuajia , Han Jiahui , Fu Jing
Published: April 2021

Head and neck squamous cell carcinoma (HNSCC) refers to an epithelial malignant tumor that originates in the head and neck, and over 600,000 new cases are reported every year, However, the overall prognosis is still poor due to local recurrence and distant metastasis after surgery. The circ_0032822 has been reported upregulated in human oral squamous cell carcinoma; however, the detailed function or mechanism remains unknown. In this study, we confirmed the upregulation of circ_0032822 in HNSCC tumor tissues. Functionally, the overexpression of circ_0032822 significantly promoted the proliferation of HNSCC cell lines along with the S phase arrest and reduced apoptosis, while downregulation of circ_0032822 has the opposite effect in vitro. Mechanistic analysis showed that circ_0032822 acted as a competing endogenous RNA of miR-141 to diminish the repressive effect of miR-141 on its target E2F3. In conclusion, we demonstrated that circ_0032822 functions as a tumor oncogene in HNSCC and that its function is regulated via the miR-141/E2F3 axis.
Optimization of PhysicoChemical Parameters for Production of Cytotoxic Secondary Metabolites and Apoptosis Induction Activities in the Culture Extract of a Marine Algal–Derived Endophytic Fungus Aspergillus sp.
Authors: Taritla Sidhartha , Kumari Madhuree , Kamat Siya , Bhat Sarita G. , Jayabaskaran C.
Published: April 2021

The endophytic fungal community in the marine ecosystem has been demonstrated to be relevant source of novel and pharmacologically active secondary metabolites. The current study focused on the evaluation of cytotoxic and apoptosis induction potential in the culture extracts of endophytic fungi associated with Sargassum muticum, a marine brown alga. The cytotoxicity of the four marine endophytes, Aspergillus sp., Nigrospora sphaerica, Talaromyces purpureogenus, and Talaromyces stipitatus, was evaluated by the MTT assay on HeLa cells. Further, several physicochemical parameters, including growth curve, culture media, and organic solvents, were optimized for enhanced cytotoxic activity of the selected extract. The Aspergillus sp. ethyl acetate extract (ASE) showed maximum cytotoxicity on multiple cancer cell lines. Chemical investigation of the metabolites by gas chromatography–mass spectroscopy (GC-MS) showed the presence of several compounds, including quinoline, indole, 2,4-bis(1,1-dimethylethyl) phenol, and hexadecenoic acid, known to be cytotoxic in ASE. The ASE was then tested for cytotoxicity in vitro on a panel of six human cancer cell lines, namely, HeLa (cervical adenocarcinoma), MCF-7 (breast adenocarcinoma), Hep G2 (hepatocellular carcinoma), A-549 (lung carcinoma), A-431 (skin/epidermis carcinoma), and LN-229 (glioblastoma). HeLa cells were most vulnerable to ASE treatment with an IC50 value of 24 ± 2 μg/ml. The mechanism of cytotoxicity exhibited by the ASE was further investigated on Hela cells. The results showed that the ASE was capable of inducing apoptosis in HeLa cells through production of reactive oxygen species, depolarization of mitochondrial membrane, and activation of the caspase-3 pathway, which shows a possible activation of the intrinsic apoptosis pathway. It also arrested the HeLa cells at the G2/M phase of the cell cycle, eventually leading to apoptosis. Through this study, we add to the knowledge about the marine algae associated with fungal endophytes and report its potential for purifying specific compounds responsible for cytotoxicity.
Analysis of Time Course and Dose Effect From Metformin on Body Mass Index in Children and Adolescents
Authors: Wang Dong-Dong , Mao Yi-Zhen , He Su-Mei , Chen Xiao
Published: April 2021

The purpose of this study was to analyze the time course and dose effect from metformin on body mass index (BMI) in children and adolescents by model-based meta-analysis (MBMA). Searching randomized controlled trial (RCT) studies of metformin on BMI in children and adolescents. The change rates of BMI from baseline values were used as indicator of evaluating metformin efficacy. A total of 18 RCT studies, 1,228 children and adolescents, were included for analysis, including patients with obesity, patients with type 1 diabetes mellitus, patients with nonalcoholic fatty liver, and patients with precocity. In order to achieve better effect of metformin on BMI in children and adolescents, the present study recommended that for patients with obesity, 1,000 mg/day metformin was required for at least 15.2 weeks and 60.8 weeks to achieve the plateau of metformin effect; for patients with type 1 diabetes mellitus, 1,000 mg/day metformin was required for at least 25.2 weeks and 100.8 weeks to achieve the plateau of metformin effect; for patients with nonalcoholic fatty liver, 1,000 mg/day metformin was required for at least 6.57 weeks and 26.28 weeks to achieve the plateau of metformin effect; for patients with precocity, 425 mg/day metformin was required for at least 12.4 weeks and 49.6 weeks to achieve the plateau of metformin effect. It was the first time to analyze the time course and dose effect from metformin on BMI and to recommend dosage and duration of treatment for metformin in children and adolescents with different disease types.
Novel Murine Biomarkers of Radiation Exposure Using An Aptamer-Based Proteomic Technology
Authors: Sproull Mary , Shankavaram Uma , Camphausen Kevin
Published: April 2021

Purpose: There is a need to identify new biomarkers of radiation exposure both for use in the development of biodosimetry blood diagnostics for radiation exposure and for clinical use as markers of radiation injury. In the current study, a novel high-throughput proteomics screening approach was used to identify proteomic markers of radiation exposure in the plasma of total body irradiated mice. A subset panel of significantly altered proteins was selected to build predictive models of radiation exposure and received radiation dose useful for population screening in a future radiological or nuclear event.

Methods: Female C57BL6 Mice of 8–14 weeks of age received a single total body irradiation (TBI) dose of 2, 3.5, 8 Gy or sham radiation and plasma was collected by cardiac puncture at days 1, 3, and 7 post-exposure. Plasma was then screened using the aptamer-based SOMAscan proteomic assay technology, for changes in expression of 1,310 protein analytes. A subset panel of protein biomarkers which demonstrated significant changes (p < 0.05) in expression following radiation exposure were used to build predictive models of radiation exposure and radiation dose.

Results: Detectable values were obtained for all 1,310 proteins included in the SOMAscan assay. For the Control vs. Radiation model, the top predictive proteins were immunoglobulin heavy constant mu (IGHM), mitogen-activated protein kinase 14 (MAPK14), ectodysplasin A2 receptor (EDA2R) and solute carrier family 25 member 18 (SLC25A18). For the Control vs. Dose model, the top predictive proteins were cyclin dependent kinase 2/cyclin A2 (CDK2. CCNA2), E-selectin (SELE), BCL2 associated agonist of cell death (BAD) and SLC25A18. Following model validation with a training set of samples, both models tested with a new sample cohort had overall predictive accuracies of 85% and 73% for the Control vs. Radiation and Control vs. Dose models respectively.

Conclusion: The SOMAscan proteomics platform is a useful screening tool to evaluate changes in biomarker expression. In our study we were able to identify a novel panel of radiation responsive proteins useful for predicting whether an animal had received a radiation exposure and to what dose they had received. Such diagnostic tools are needed for future medical management of radiation exposures.
Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
Authors: Liang Xiaohui , Wang Ping , Yang Chun , Huang Fei , Wu Hui , Shi Hailian , Wu Xiaojun
Published: April 2021

Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.
Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome
Authors: Huarte Eduardo , Peel Michael T. , Verbist Katherine , Fay Brittany L. , Bassett Rachel , Albeituni Sabrin , Nichols Kim E. , Smith Paul A.
Published: April 2021

Hyperinflammatory syndromes comprise a heterogeneous group of disorders characterized by severe inflammation, multiple organ dysfunction, and potentially death. In response to antigenic stimulus (e.g., SARS-CoV-2 infection), overactivated CD8+ T-cells and macrophages produce high levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-6, and IL-12. Multiple inflammatory mediators implicated in hyperinflammatory syndromes utilize the Janus kinase–signal transducers and activators of transcription (JAK-STAT) cascade to propagate their biological function. Our findings demonstrate that oral ruxolitinib dosing designed to mimic clinically relevant JAK-STAT pathway inhibition significantly reduces the harmful consequences of immune overactivation in multiple hyperinflammatory models. In contrast to monoclonal antibody therapies targeting a single cytokine, ruxolitinib effectively downregulates the functional effect of multiple cytokines implicated in hyperinflammatory states, without broad immunosuppression.
The Traditional Uses, Phytochemistry, Pharmacology, Toxicology, and Clinical Uses of Metagentiana Rhodantha (Franch.) T.N.Ho and S.W.Liu, an Ethnomedicine in Southwest China
Authors: Chang Botao , Tang Songjiang , Chen Rong , Xiao Nan , Zhu Jingsong , Tian Mengxian , Jiang Huizhong , Li Xi , Jian Zhonglu , Han Xu , Gao Ying , Yao Qi
Published: April 2021

Background:Metagentiana rhodantha (Franch.) T.N.Ho and S.W.Liu (MR) belongs to Gentianales, and it is often called Hong-hua-long-dan in Chinese. Traditionally, it has been used to cure acute icteric hepatitis, sore throat, dysentery, acute gastritis, carbuncle, and furuncle based on traditional Chinese medicine (TCM) concepts.

Aim of Study: This review manages to provide a critical and comprehensive analysis on the traditional uses, phytochemistry, pharmacology, toxicology, and clinical uses of MR and to evaluate the therapeutic potential of this plant.

Methods: Relevant data mainly literatures on MR were selected from available database. All the papers reviewed provided evidence that the source herbs were reliably identified.

Results: The heat-clearing and removing the phlegm, and purging fire and removing toxicity of MR contribute to its dispelling jaundice, and clearing lung heat and cough. The compounds isolated from this plant include iridoids and secoiridoids, phenolic acids, ketones, triterpenoids, flavonoids, benzophenone glycosides, and others. Mangiferin (MAF) is a characteristic substance from this plant. The pharmacological studies show that some extracts and compounds from MR exhibit anti-inflammatory, antinociceptive, antibacterial, hepatoprotective, cardioprotective, and other effects which are associated with the traditional uses of this plant. The toxicological studies suggest that MAF is less toxic in mice and dogs. Nowadays, Chinese patent drugs such as Feilike Jiaonang and Kangfuling Jiaonang containing MR have been used to cure cough, asthma, chronic bronchitis, dysmenorrhea, and appendagitis.

Conclusion: Although the current studies provide related research information of MR, it is still necessary to systemically evaluate the chemistry, pharmacology, toxicity, and safety of the extracts or compounds from this plant before clinical trials in the future. In addition, except for lung infection-related diseases, analgesia, anti-tumor, and hypertriglycemia may be new and prior therapeutic scopes of this ethnomedicine in the future.
Dense Networks With Mixture Degree Distribution
Authors: Wang Xiaomin , Ma Fei , Yao Bing
Published: April 2021

Complex networks have become a powerful tool to describe the structure and evolution in a large quantity of real networks in the past few years, such as friendship networks, metabolic networks, protein–protein interaction networks, and software networks. While a variety of complex networks have been published, dense networks sharing remarkable structural properties, such as the scale-free feature, are seldom reported. Here, our goal is to construct a class of dense networks. Then, we discover that our networks follow the mixture degree distribution; that is, there is a critical point above which the cumulative degree distribution has a power-law form and below which the exponential distribution is observed. Next, we also prove the networks proposed to show the small-world property. Finally, we study random walks on our networks with a trap fixed at a vertex with the highest degree and find that the closed form for the mean first-passage time increases logarithmically with the number of vertices of our networks.
Oxidative Stress, Inflammation, and Activators of Mitochondrial Biogenesis: Tempol Targets in the Diaphragm Muscle of Exercise Trained-mdx Mice
Authors: Silva Heloina Nathalliê Mariano da , Covatti Caroline , Rocha Guilherme Luiz da , Mizobuti Daniela Sayuri , Mâncio Rafael Dias , Hermes Túlio de Almeida , Kido Larissa Akemi , Cagnon Valéria Helena Alves , Pereira Elaine Cristina Leite , Minatel Elaine
Published: April 2021

The mdx mouse phenotype aggravated by chronic exercise on a treadmill makes this murine model more reliable for the study of muscular dystrophy. Thus, to better assess the Tempol effect on dystrophic pathways, the analyses in this study were performed in the blood samples and diaphragm muscle from treadmill trained adult (7–11-weeks old) mdx animals. The mdx mice were divided into three groups: mdxSed, sedentary controls (n = 28); mdxEx, exercise-trained animals (n = 28); and mdxEx+T, exercise-trained animals with the Tempol treatment (n = 28). The results demonstrated that the Tempol treatment promoted muscle strength gain, prevented muscle damage, reduced the inflammatory process, oxidative stress, and angiogenesis regulator, and up regulated the activators of mitochondrial biogenesis. The main new findings of this study are that Tempol reduced the NF-κB and increased the PGC1-α and PPARδ levels in the exercise-trained-mdx mice, which are probably related to the ability of this antioxidant to scavenge excessive ROS. These results reinforce the use of Tempol as a potential therapeutic strategy in DMD.
Gene Expression Patterns for Proteins With Lectin Domains in Flax Stem Tissues Are Related to Deposition of Distinct Cell Wall Types
Authors: Petrova Natalia , Nazipova Alsu , Gorshkov Oleg , Mokshina Natalia , Patova Olga , Gorshkova Tatyana
Published: April 2021

The genomes of higher plants encode a variety of proteins with lectin domains that are able to specifically recognize certain carbohydrates. Plants are enriched in a variety of potentially complementary glycans, many of which are located in the cell wall. We performed a genome-wide search for flax proteins with lectin domains and compared the expression of the encoding genes in different stem tissues that have distinct cell wall types with different sets of major polysaccharides. Over 400 genes encoding proteins with lectin domains that belong to different families were revealed in the flax genome; three quarters of these genes were expressed in stem tissues. Hierarchical clustering of the data for all expressed lectins grouped the analyzed samples according to their characteristic cell wall type. Most lectins differentially expressed in tissues with primary, secondary, and tertiary cell walls were predicted to localize at the plasma membrane or cell wall. These lectins were from different families and had various architectural types. Three out of four flax genes for proteins with jacalin-like domains were highly upregulated in bast fibers at the stage of tertiary cell wall deposition. The dynamic changes in transcript level of many genes for lectins from various families were detected in stem tissue over the course of gravitropic response induced by plant gravistimulation. The data obtained in this study indicate a large number of lectin-mediated events in plants and provide insight into the proteins that take part in tissue specialization and reaction to abiotic stress.
Morpho-Physiological Responses and Secondary Metabolites Modulation by Preharvest Factors of Three Hydroponically Grown Genovese Basil Cultivars
Authors: Ciriello Michele , Formisano Luigi , El-Nakhel Christophe , Corrado Giandomenico , Pannico Antonio , De Pascale Stefania , Rouphael Youssef
Published: April 2021

Sweet basil (Ocimum basilicum L.) is an economically important leafy vegetable especially in Mediterranean countries. In Italian gastronomy, the large elliptical leaves of the Genovese type are mostly used for the well-known pesto sauce, and almost all (>90%) professional production is for the food industry. The growing demand for fresh leaves with standardized technological and sensory characteristics has prompted basil producers to adopt advanced cultivation methods such as the floating raft system (FRS). The aim of this study was to evaluate the productive, qualitative, and physiological performance of three Genovese basil cultivars (“Aroma 2,” “Eleonora,” and “Italiano Classico”) in two successive harvests and at two densities (159 and 317 plants m–2). Caffeic, chicoric, rosmarinic, and ferulic acid were determined through the high-performance liquid chromatography (HPLC) system, whereas the extraction and quantification of the volatile organic compounds (VOCs) were performed by solid-phase microextraction (SPME) and gas chromatography coupled to a mass spectrometer (GC/MS). “Aroma 2” showed the highest fresh yield and photosynthetic rate together with the lowest nitrate content. For all the tested cultivars, the higher density, while reducing the number of leaves per plant, resulted in higher fresh and dry production per unit area, without altering the aroma profile. Successive harvests resulted in a significant increase in both the yield (37.5%) and the total phenolic acids (75.1%) and favored Eucalyptol and 1-octen-3-ol accumulation (+25.9 and +15.1%, respectively). The here presented comprehensive and multifactorial assessment of the productive and qualitative response of basil provides evidence of the positive effects (from biomass to specialized metabolites) that can be obtained from the management of the pre-harvest factors in soilless cultivation. In addition, it also highlights the role and constraints of the genetic factor in the observed response. We also discuss the implications of our work considering the impact for the food processing industry. Future research may explore the phenolic acids accumulation as a possible fortification means to extend the pesto sauce shelf life, reducing the need of added antioxidants and thermal processing.
How to Improve the Well-Being of Youths: An Exploratory Study of the Relationships Among Coping Style, Emotion Regulation, and Subjective Well-Being Using the Random Forest Classification and Structural Equation Modeling
Authors: Jiang Xiaowei , Ji Lili , Chen Yanan , Zhou Chenghao , Ge Chunlei , Zhang Xiaolin
Published: April 2021

The relationship between coping styles and subjective well-being (SWB) has recently received considerable empirical and theoretical attention in the scientific literature. However, the mechanisms underlying this relationship have primarily remained unclear. The present research aimed to determine whether emotion regulation mediated the relationship between coping styles and subjective well-being (SWB). Our hypothesis is based on the integration of theoretical models among 1,247 Chinese college students. The SWB questionnaire, Ways of Coping Questionnaire, and Emotion Regulation Questionnaire were used to correlate SWB, emotion regulation strategies, and coping styles, respectively. The random forest method was applied to predict life satisfaction and estimate the average variable importance to life satisfaction. The results indicated that positive coping can indirectly influence life satisfaction via cognitive reappraisal and indirectly influence expression suppression via positive affect. Negative coping can indirectly influence negative affect via expression suppression. Besides, negative coping was positively associated with both expression suppression and negative affect. Cognitive reappraisal was found to be positively associated with positive affect. The findings indicated that coping style is essential for the SWB of college students. These findings provide insight into how coping styles impact SWB and have implications for developing and assessing emotion regulation-based interventions.
Shifting Listening Niches: Effects of the COVID-19 Pandemic
Authors: Hurwitz Emily Rose , Krumhansl Carol Lynne
Published: April 2021

The term “listening niche” refers to the contexts in which people listen to music including what music they are listening to, with whom, when, where, and with what media. The first experiment investigates undergraduate students’ music listening niches in the initial COVID-19 lockdown period, 4 weeks immediately after the campus shut down abruptly. The second experiment explores how returning to a hybrid semester, the “new normal,” further affected these listening habits. In both experiments, the participants provided a list of their most frequently listened-to songs during the respective period of time. From these, they identified one song that seemed most associated with this period, their “signature song,” and stated why this song seemed relevant. These reasons were coded on nine underlying themes. Three clusters were found to underlie the themes: (1) emotional responses (2) memory associations, and (3) discovery of new music. We identified songs and reasons for selecting them that represented the three clusters and related these to the lyrical content. Compared to before the pandemic, participants in both experiments report listening more in general and on Spotify, but there were no differences in listening between lockdown and the new normal. Whom they were listening with shifted overtime from family members to significant others and finally to other friends and roommates. These results demonstrate how students listen to and find new music that is meaningful to them during this unprecedented pandemic.
Public Knowledge and Practices Regarding Coronavirus Disease 2019: A Cross-Sectional Survey From Pakistan
Authors: Saqlain Muhammad , Ahmed Ali , Nabi Ijaz , Gulzar Aqsa , Naz Sahar , Munir Muhammad Muddasir , Ahmed Zaheer , Kamran Sohail
Published: April 2021

Objectives: Effective mitigation of coronavirus diseases (COVID-19) pandemic requires true adoption of precautionary measures by the masses, that primarily depends upon their knowledge and practices behaviors. The current study aimed to assess the knowledge; practices of Pakistani residents regarding COVID-19 and factors associated with adequate knowledge and positive practices.

Material and Methods: A cross-sectional online survey was conducted from 15-April 2020 to 20 May 2020 among 689 Pakistanis by using a validated self-administered questionnaire (Cronbach's alpha 0.77). The questionnaire included questions on the assessment of demographics, the source of information, knowledge, and practice of COVID-19 on google forms and shared links with the WhatsApp groups, Facebook pages and other online platforms. Regression analysis was applied to find potential predictors of knowledge and practices.

Results: Of 689 participants, 431 (62.6%) were male, 64.3% (n = 443) were aged <30 years, and\328 (47.6%) of participants were married. 48.19% (n = 332) had adequate knowledge; 81% (n = 555) had positive practices regarding COVID-19 and majority (66.62%, n = 459) seek knowledge from social media. Knowledge was significantly higher (OR > 1.00, p < 0.05) among educated and higher income participants. Positive practices were significantly (OR > 1.00, p < 0.05) related to the older age (≥50 years), higher education, higher income and good knowledge regarding COVID-19.

Conclusion: The study concluded that Pakistani residents had average knowledge and good practices toward COVID-19 yet there are gaps in specific aspects of knowledge, and practice that should be focused in future awareness and educational campaigns. The study recommends the ministry of health authorities to promote all precautionary and preventive measures of COVID-19-consisting of a better-organized approach to all strata of society: less privileged people, older ones and less educated people, in order to have equilibrium of knowledge about COVID-19; hence effective implementation of precautionary measures.
A Public Mental Health Study Among Iraqi Refugees in Sweden: Social Determinants, Resilience, Gender, and Cultural Context
Authors: Çetrez Önver A. , DeMarinis Valerie , Sundvall Maria , Fernandez-Gonzalez Manuel , Borisova Liubov , Titelman David
Published: April 2021

This public mental health study highlights the interactions among social determinants and resilience on mental health, PTSD and acculturation among Iraqi refugees in Sweden 2012-2013.

Objectives:The study aims to understand participants' health, resilience and acculturation, paying specific attention to gender differences.

Design:The study, using a convenience sampling survey design (N= 4010, 53.2% men), included measures on social determinants, general health, coping, CD-RISC, selected questions from the EMIC, PC-PTSD, and acculturation.

Results:Gender differences and reported differences between life experiences in Iraq and Sweden were strong. In Sweden, religious activity was more widespread among women, whereas activity reflecting religion and spirituality as a coping mechanism decreased significantly among men. A sense of belonging both to a Swedish and an Iraqi ethnic identity was frequent. Positive self-evaluation in personal and social areas and goals in life was strong. The strongest perceived source of social support was from parents and siblings, while support from authorities generally was perceived as low. Self-rated health was high and the incidence of PTSD was low. A clear majority identified multiple social determinants contributing to mental health problems. Social or situational and emotional or developmental explanations were the most common. In general, resilience (as measured with CD-RISC) was low, with women's scores lower than that of men.

Conclusions:Vulnerability manifested itself in unemployment after a long period in Sweden, weak social networks outside the family, unsupportive authorities, gender differences in acculturation, and women showing more mental health problems. Though low socially determined personal scores of resilience were found, we also identified a strong level of resilience, when using a culture-sensitive approach and appraising resilience as expressed in coping, meaning, and goals in life. Clinicians need to be aware of the risks of poorer mental health among refugees in general and women in particular, although mental health problems should not be presumed in the individual patient. Instead clinicians need to find ways of exploring the cultural and social worlds and needs of refugee patients. Authorities need to address the described post-migration problems and unmet needs of social support, together comprising the well-established area of the social determinants of health.
Real-Time PCR Validation for Mycobacterium tuberculosis Complex Detection Targeting IS6110 Directly From Bovine Lymph Nodes
Authors: Sánchez-Carvajal José María , Galán-Relaño Ángela , Ruedas-Torres Inés , Jurado-Martos Francisco , Larenas-Muñoz Fernanda , Vera Eduardo , Gómez-Gascón Lidia , Cardoso-Toset Fernando , Rodríguez-Gómez Irene Magdalena , Maldonado Alfonso , Carrasco Librado , Tarradas Carmen , Gómez-Laguna Jaime , Luque Inmaculada
Published: April 2021

Rapid and accurate diagnostic tools, such as Real-Time PCR (qPCR), need to be implemented as a confirmatory test in the framework of bovine tuberculosis (bTB) surveillance and control programs, shortening the turnaround time to confirm bTB infection. The present study aimed to evaluate a direct qPCR from fresh tissue samples targeting the insertion sequence IS6110 using individually homogenized bovine lymph nodes compared with microbiological culture. Retropharyngeal, tracheobronchial, and mesenteric lymph nodes fresh tissue samples (n = 687) were collected from 230 different cattle carcasses at the slaughterhouse. Only 23 of the 230 examined animals showed tuberculosis-like lesions, with 62 of 230 considered as positive. Among these 62 animals, 61 resulted as culture-positive, whereas 48 were qPCR-positive. Thus, this qPCR targeting IS6110 showed an apparent diagnostic sensitivity and specificity values of 77.1% [95% confidence interval (CI): 66.5–87.6%] and 99.4% (95% CI: 98.3–100.6%), respectively, and a positive predictive value of 97.9% (95% CI: 93.9–102.0%) and negative predictive value of 92.3% (95% CI: 88.4–96.2%). Positive and negative likelihood ratios were 130.2 and 0.2, respectively, and the agreement between microbiological culture and this qPCR was almost perfect (κ = 0.82). These results highlight this qPCR targeting IS6110 as a suitable complementary method to confirm bTB in animals with either tuberculosis-like lesions or non-tuberculosis-like lesions, decreasing the number of samples subjected to microbiological culture and, hence, its overall associated costs and the turnaround time (under 48 h) to confirm bTB infection. Besides, sampling mesenteric lymph node, which is uncommonly sampled, together with tracheobronchial and retropharyngeal ones, is advisable during postmortem inspection in bTB surveillance programs at the slaughterhouse, especially in areas with a low bTB prevalence scenario.
Multiple Loci Selection with Multi-Way Epistasis in Coalescence with Recombination
Authors: Bose Aritra , Utro Filippo , Platt Daniel E. , Parida Laxmi
Published: April 2021

As studies move into deeper characterization of the impact of selection through non-neutral mutations in whole genome population genetics, modeling for selection becomes crucial. Moreover, epistasis has long been recognized as a significant component in understanding the evolution of complex genetic systems. We present a backward coalescent model, EpiSimRA, that accommodates multiple loci selection, with multi-way (k-way) epistasis for any arbitrary k. Starting from arbitrary extant populations with epistatic sites, we trace the Ancestral Recombination Graph (ARG), sampling relevant recombination and coalescent events. Our framework allows for studying different complex evolutionary scenarios in the presence of selective sweeps, positive and negative selection with multiway epistasis. We also present a forward counterpart of the coalescent model based on a Wright-Fisher (WF) process, which we use as a validation framework, comparing the hallmarks of the ARG between the two. We provide the first framework that allows a nose-to-nose comparison of multiway epistasis in a coalescent simulator with its forward counterpart with respect to the hallmarks of the ARG. We demonstrate, through extensive experiments, that EpiSimRA is consistently superior in terms of performance (seconds vs. hours) in comparison to the forward model without compromising on its accuracy.
Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib
Authors: Colombatto Piero , Demirtas Coskun Ozer , Ricco Gabriele , Civitano Luigi , Boraschi Piero , Scalise Paola , Cavallone Daniela , Oliveri Filippo , Romagnoli Veronica , Bleve Patrizia , Coco Barbara , Salvati Antonio , Urbani Lucio , Bonino Ferruccio , Brunetto Maurizia Rossana
Published: April 2021

In advanced HCC, tyrosine-kinase inhibitors obtain partial responses (PR) in some patients and complete responses (CR) in a few. Better understanding of the mechanism of response could be achieved by the radiomic approach combining digital imaging and serological biomarkers (α-fetoprotein, AFP and protein induced by vitamin K absence-II, PIVKA-II) kinetics. A physic-mathematical model was developed to investigate cancer cells and vasculature dynamics in three prototype patients receiving sorafenib and/or regorafenib and applied in seven others for validation. Overall four patients showed CR, two PR, two stable-disease (SD) and two progressive-disease (PD). The rate constant of cancer cells production was higher in PD than in PR-SD and CR (median: 0.398 vs. 0.325 vs. 0.316 C × day−1). Therapy induced reduction of neo-angiogenesis was greater in CR than in PR-SD and PD (median: 83.2% vs. 29.4% and 2.0%), as the reduction of cell-proliferation (55.2% vs. 7.6% and 0.7%). An additional dose-dependent acceleration of tumor vasculature decay was also observed in CR. AFP and cancer cells followed the same kinetics, whereas PIVKA-II time/dose dependent fluctuations were influenced also by tissue ischemia. In conclusion, pending confirmation in a larger HCC cohort, modeling serological and imaging biomarkers could be a new tool for systemic therapy personalization.
Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review
Authors: Bradbury Melissa , Borràs Eva , Pérez-Benavente Assumpció , Gil-Moreno Antonio , Santamaria Anna , Sabidó Eduard
Published: April 2021

High-grade serous ovarian cancer (HGSC) remains the most common and deadly subtype of ovarian cancer. It is characterized by its late diagnosis and frequent relapse despite standardized treatment with cytoreductive surgery and platinum-based chemotherapy. The past decade has seen significant advances in the clinical management and molecular understanding of HGSC following the publication of the Cancer Genome Atlas (TCGA) researchers and the introduction of targeted therapies with anti-angiogenic drugs and poly(ADP-ribose) polymerase inhibitors in specific subgroups of patients. We provide a comprehensive review of HGSC, focusing on the most important molecular advances aimed at providing a better understanding of the disease and its response to treatment. We emphasize the role that proteomic technologies are now playing in these two aspects of the disease, through the identification of proteins and their post-translational modifications in ovarian cancer tumors. Finally, we highlight how the integration of proteomics with genomics, exemplified by the work performed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), can guide the development of new biomarkers and therapeutic targets.
Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging
Authors: Jungmann Friederike , Kaissis Georgios A. , Ziegelmayer Sebastian , Harder Felix , Schilling Clara , Yen Hsi-Yu , Steiger Katja , Weichert Wilko , Schirren Rebekka , Demir Ishan Ekin , Friess Helmut , Makowski Markus R. , Braren Rickmer F. , Lohöfer Fabian K.
Published: April 2021

Background: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. Methods: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. Results: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. Conclusion: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.
The Role of Epigenetics in the Progression of Clear Cell Renal Cell Carcinoma and the Basis for Future Epigenetic Treatments
Authors: Angulo Javier C. , Manini Claudia , López Jose I. , Pueyo Angel , Colás Begoña , Ropero Santiago
Published: April 2021

Clear cell renal cell carcinoma (ccRCC) is curable when diagnosed at an early stage, but when disease is non-confined it is the urologic cancer with worst prognosis. Antiangiogenic treatment and immune checkpoint inhibition therapy constitute a very promising combined therapy for advanced and metastatic disease. Many exploratory studies have identified epigenetic markers based on DNA methylation, histone modification, and ncRNA expression that epigenetically regulate gene expression in ccRCC. Additionally, epigenetic modifiers genes have been proposed as promising biomarkers for ccRCC. We review and discuss the current understanding of how epigenetic changes determine the main molecular pathways of ccRCC initiation and progression, and also its clinical implications. Despite the extensive research performed, candidate epigenetic biomarkers are not used in clinical practice for several reasons. However, the accumulated body of evidence of developing epigenetically-based biomarkers will likely allow the identification of ccRCC at a higher risk of progression. That will facilitate the establishment of firmer therapeutic decisions in a changing landscape and also monitor active surveillance in the aging population. What is more, a better knowledge of the activities of chromatin modifiers may serve to develop new therapeutic opportunities. Interesting clinical trials on epigenetic treatments for ccRCC associated with well established antiangiogenic treatments and immune checkpoint inhibitors are revisited.
EBUS-TBNA Cytological Samples for Comprehensive Molecular Testing in Non–Small Cell Lung Cancer
Authors: Martin-Deleon Roberto , Teixido Cristina , Lucena Carmen Mª , Martinez Daniel , Fontana Ainhoa , Reyes Roxana , García Mireia , Viñolas Nuria , Vollmer Ivan , Sanchez Marcelo , Jares Pedro , Pérez Francisco Manuel , Vega Naiara , Marin Elba , Marrades Ramón Mª , Agustí Carlos , Reguart Noemi
Published: April 2021

Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.
Intelligent Fault Identification for Rolling Bearings Fusing Average Refined Composite Multiscale Dispersion Entropy-Assisted Feature Extraction and SVM with Multi-Strategy Enhanced Swarm Optimization
Authors: Shi Huibin , Fu Wenlong , Li Bailin , Shao Kaixuan , Yang Duanhao
Published: April 2021

Rolling bearings act as key parts in many items of mechanical equipment and any abnormality will affect the normal operation of the entire apparatus. To diagnose the faults of rolling bearings effectively, a novel fault identification method is proposed by merging variational mode decomposition (VMD), average refined composite multiscale dispersion entropy (ARCMDE) and support vector machine (SVM) optimized by multistrategy enhanced swarm optimization in this paper. Firstly, the vibration signals are decomposed into different series of intrinsic mode functions (IMFs) based on VMD with the center frequency observation method. Subsequently, the proposed ARCMDE, fusing the superiorities of DE and average refined composite multiscale procedure, is employed to enhance the ability of the multiscale fault-feature extraction from the IMFs. Afterwards, grey wolf optimization (GWO), enhanced by multistrategy including levy flight, cosine factor and polynomial mutation strategies (LCPGWO), is proposed to optimize the penalty factor C and kernel parameter g of SVM. Then, the optimized SVM model is trained to identify the fault type of samples based on features extracted by ARCMDE. Finally, the application experiment and contrastive analysis verify the effectiveness of the proposed VMD-ARCMDE-LCPGWO-SVM method.
A Novel Gate Drive Circuit for Suppressing Turn-on Oscillation of Non-Kelvin Packaged SiC MOSFET
Authors: Zhao Hongyan , Chen Jiangui , Li Yan , Lin Fei
Published: April 2021

Compared with a silicon MOSFET device, the SiC MOSFET has many benefits, such as higher breakdown voltage, faster action speed and better thermal conductivity. These advantages enable the SiC MOSFET to operate at higher switching frequencies, while, as the switching frequency increases, the turn-on loss accounts for most of the loss. This characteristic severely limits the applications of the SiC MOSFET at higher switching frequencies. Accordingly, an SRD-type drive circuit for a SiC MOSFET is proposed in this paper. The proposed SRD-type drive circuit can suppress the turn-on oscillation of a non-Kelvin packaged SiC MOSFET to ensure that the SiC MOSFET can work at a faster turn-on speed with a lower turn-on loss. In this paper, the basic principle of the proposed SRD-type drive circuit is analyzed, and a double pulse platform is established. For the purpose of proof-testing the performance of the presented SRD-type drive circuit, comparisons and experimental verifications between the traditional gate driver and the proposed SRD-type drive circuit were conducted. Our experimental results finally demonstrate the feasibility and effectiveness of the proposed SRD-type drive circuit.
Genomic Features of Open Chromatin Regions (OCRs) in Wild Soybean and Their Effects on Gene Expressions
Authors: Huang Ming-Kun , Zhang Ling , Zhou Li-Meng , Yung Wai-Shing , Li Man-Wah , Lam Hon-Ming
Published: April 2021

Transcription activation is tightly associated with the openness of chromatin, which allows direct contact between transcriptional regulators, such as transcription factors, and their targeted DNA for downstream gene activation. However, the annotation of open chromatin regions (OCRs) in the wild soybean (Glycine soja) genome is limited. We performed assay for transposase-accessible chromatin using sequencing (ATAC-seq) and successfully identified 22,333 OCRs in the leaf of W05 (a wild soybean accession). These OCRs were enriched in gene transcription start sites (TSS) and were positively correlated with downstream gene expression. Several known transcription factor (TF)-binding motifs were also enriched at the OCRs. A potential regulatory network was constructed using these transcription factors and the OCR-marked genes. Furthermore, by overlapping the OCR distribution with those of histone modifications from chromatin immunoprecipitation followed by sequencing (ChIP-seq), we found that the distribution of the activation histone mark, H3K4me3, but not that of the repressive H3K27me3 mark, was closely associated with OCRs for gene activation. Several putative enhancer-like distal OCRs were also found to overlap with LincRNA-encoding loci. Moreover, our data suggest that homologous OCRs could potentially influence homologous gene expression. Hence, the duplication of OCRs might be essential for plant genome architecture as well as for regulating gene expression.