bluuebunny/crossref_metadata_2025 huggingface dataset:
A Preliminary Study of Tumor Microenvironment Interleukin-4 as Promoter in Immune Escape Event in Prostate Cancer
Authors: Danarto Raden , Dwianingsih Ery Kus , Dany Yurisal Akhmad , Frannata Lucky , Argo Ibnu Widya , Soerohardjo Indrawarman
Published: December 2021

Introduction : This study aims to investigate the relationship between IL-4 expression with Apoptosis-associated gene receptors (PD-1, CTLA-4) and Programmed Death-1 Ligands (PD-L1, PD-L2) in the microenvironment of prostate cancer tissue.Methods : The samples were collected from single-center hospital in a period from 2014 to 2020. Deparaffinize formalin-fixed paraffin-embedded and RNAs extraction by manufacturer’s protocol with slight modification was performed. The RNAs expressions were investigated by using quantitative real-time polymerase chain reaction. Then we categorize them into 4 groups. The ANOVA test is used to compare mean expression between groups and followed by a correlation test using Pearson test.Result : In the BPH group sample, CTLA-4 had the highest expression level, followed by the expression of IL-4, PD-L2, then PD-1 and PD-L1. The concentration of IL-4 in prostate cancer, both metastatic and non-metastatic, is higher than in BPH, with a p-value of 0.006. the correlation between IL-4 and PD-L1 is the strongest (r=0.919), between IL-4 and PD-L2 comes the second (0.832) and between PD-1 is comes the third (r=0.626).Conclusion : In this study, we find that the expression of IL-4 and Apoptosis-Associated Gene Receptors (PD-1, CTLA-4) and Programmed Death-1 Ligands (PD-L1, PD-L2) in the prostate cancer tissue microenvironment have a significant relationship. In conclusion, it is possible that IL-4 is a promoter of the Immune Escape mechanism in prostate cancer.
A Mixed Methods Investigation of Unmet Needs And Psychological Wellbeing During Active Surveillance For Prostate Cancer
Authors: McIntosh Megan , Short Camille E , O’Callaghan Michael , Vincent Andrew D , Galvão Daniel A , Opozda Melissa J
Published: December 2021

Purpose: While prostate cancer survivors experience unmet supportive care needs (USCNs) after definitive treatments, no study has measured USCNs during active surveillance (AS). This mixed-methods study aimed to identify and explore the USCNs and psychological wellbeing of AS patients.Methods: Patients 18+ years diagnosed with prostate cancer, who had been on AS for ≥6 months, were invited to complete a survey measuring USCNs, general and prostate cancer specific anxiety, and depression. A purposefully selected subset was also interviewed to explore USCNs and how needs during AS were addressed. Semi-structured interviews were transcribed verbatim and thematically analysed. Results: One hundred and three participants (n=47 currently on AS, n=54 on/had subsequent treatment, n=2 ceased all care) completed the survey, and 33 were also interviewed. Although most USCNs were considered low/moderate, 20% of participants reported high unmet informational needs around receiving information about monitoring and their test results. USCNs related to patient care (e.g., access to services in rural areas or after hours) and sexuality were also discussed in interviews. Anxiety, depression, and prostate cancer specific anxiety were generally very low. Fear of cancer progression/recurrence was the highest scoring prostate cancer specific worry and was frequently mentioned by interview participants.Conclusions: While unmet needs, anxiety and depression were generally low, one in five patients during AS experience unmet needs in psychological, physical, patient care, information, and sexual domains. Health professionals should be aware of common USCNs and offer appropriate support to address potential needs.
Integrated Metabolomic and Transcriptomic Analysis of the Anthocyanin and Proanthocyanin Regulatory Networks in Red Walnut Natural Hybrid Progeny Leaves
Authors: Wang Lei , Li Lin , Zhao Wei , Meng Haijun , Zhang Ganggang , Wu Wenjiang , Shi Jiangli , Wu Guoliang
Published: December 2021

BackgroundWalnuts are one of the most important dry fruit crops worldwide, typically exhibiting green leaves and yellow–brown or gray–yellow seed coats. A specific walnut type, red walnut ‘RW-1’, with red leaves and seed coats was selected as the plant material because of its higher anthocyanin and proanthocyanin (PA) contents. Anthocyanins and PAs coprise important secondary defense methods for plants to respond to biotic and abiotic stresses. However, few studies have focused on the molecular mechanism of anthocyanin biosynthesis in walnuts.ResultsFrom the results of widely targeted metabolome and anthocyanidin detection analysis, 395 substances, including 4 PAs and 26 anthocyanins, were identified from the red-leaf walnuts of RW-1 natural hybrid progenies (SR) and the green-leaf walnuts of RW-1 natural hybrid progenies (SG). Among these, all anthocyanin types in SR were significantly upregulated compared with SG. Additionally, delphinidin 3-O-galactoside, cyanidin 3-O-galactoside, delphinidin 3-O-glucoside and cyanidin 3-O-glucoside were identified as the primary components of anthocyanidins because of their higher contents. Nine anthocyanidins, malvidin 3-O-galactoside, malvidin 3-O-arabinoside, cyanidin 3-O-(6-O-malonyl-beta-D-glucoside), delphinidin 3-O-glucoside, delphinidin 3,5-O-diglucoside (Delphin), peonidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-(6-O-malonyl-beta-D-glucoside), petunidin 3-O-arabinoside and pelargonidin 3-O-(6-O-malonyl-beta-D-glucoside), were detected only in the SR walnuts. For PAs, proanthocyanin C1 was upregulated in SR compared with SG, while proanthocyanin B1 and proanthocyanin B3 were upregulated in SR-1 and SR-3 but downregulated in SR-2 compared with the controls. Furthermore, transcriptome analysis demonstrated that the expression of structural genes (C4H, F3H, F3’5’H, UFGTs, LAR and ANR), four MYBs and six WD40s in the anthocyanin and PA biosynthetic pathways were significantly higher in the SR walnut.ConclusionsOur results provide valuable information on anthocyanin and PA metabolites and candidate genes in anthocyanin and PA biosynthesis, which provides new insights into anthocyanin and PA biosynthesis in walnuts.
Prevalence and Risk Factors for Retinopathy of Prematurity in China: A Systematic Review and Meta-Analysis
Authors: Lumin Qi , Ziying Gu , Xincheng Sun
Published: December 2021

Background
The etiology of retinopathy of prematurity (ROP) is thought to be related to genetic susceptibility and environmental exposure factors. The purpose of this article was to estimate the prevalence of ROP in mainland China and to attempt to summarize the environmental risk factors for ROP in Chinese infants.
Method
We searched 9 databases for articles that were published before May 29, 2021, and studies describing the prevalence and risk factors for ROP in Chinese infants were included. The fixed-effects model and the random-effects model were applied to the effect sizes (ES) and their 95% confidence intervals (CIs) with I2≤50% and I2>50% in the heterogeneity tests, respectively.
Results
Twenty-two separate populations were included in the meta-analysis of the prevalence of ROP. The prevalence of ROP in mainland China was 9.284% (95% CI: 6.546-12.022%). It was negatively correlated with birth weight (BW) and gestational age (GA). Fifty independent meta-analyses were observed to be related to environmental exposure factors of ROP. Thirty of the 50 meta-analyses had results that were significant at p values less than 0.05. The first three risk factors with the largest combined effect size were GA≤34 w, bronchopulmonary dysplasia (BPD) and BW≤2,000 g.
Conclusions
Approximately one in ten immature infants suffered from ROP. More studies need to be included. Premature babies with diseases that cause hypoxia and irregular oxygen use should be paid more attention for ROP screening.
Understanding How Socioeconomic Inequalities Drive Inequalities In COVID-19 Infections
Authors: Laajaj Rachid , Webb Duncan , Aristizabal Danilo , Behrentz Eduardo , Bernal Raquel , Buitrago Giancarlo , Cucunuba Zulma , Hoz Fernando De la , Gaviria Alejandro , Hernandez Luis Jorge , Rios Camilo de Los , Varela Andrea Ramirez , Restrepo Silvia , Schady Norbert , Vives Martha
Published: December 2021

Background: Across the world, the COVID-19 pandemic has disproportionately affected economically disadvantaged groups. This differential impact has numerous possible explanations, each with significantly different policy implications. We examine, for the first time in a low- or middle-income country, which mechanisms best explain the disproportionate impact of the virus on the poor. Methods: We use primary data from the CoVIDA project, including the results of 59,770 RT-PCR tests in Bogotá, targeted on a mostly asymptomatic adult population June 2020 to March 3rd, 2021. This is combined with administrative data that covers all reported cases in Bogotá. We estimate a number of parameters that are likely to drive inequality in COVID-19 infection rates across socioeconomic groups, then use these estimates in an individual-level branching process model of the epidemic. We use counterfactual scenarios to estimate the relative importance of different channels for explaining inequality in infection rates. Findings: Total infections and inequalities in infections are largely driven by inequalities in the ability to work remotely and in within-home secondary attack rates. Inequalities in isolation behavior are less important but non-negligible, while access to testing and contract-tracing plays practically no role. Interventions that mitigate transmission are found to be more effective when targeted on socioeconomically disadvantaged groups.Interpretation: Socioeconomically disadvantaged groups are particularly vulnerable to COVID-19 infections, and this appears to be primarily driven by the need to work out of home, higher transmission within home, and to some extent, the ability to isolate when needed. Policies that can successfully reduce these channels of transmission among the poor are likely to have large benefits.
Long-Term Drinking Behavior Change Patterns and Its Association With Hyperuricemia in Chinese Adults: Evidence From China Health and Nutrition Survey
Authors: Zhu Bowen , Li Yang , Shi Yiqin , Song Nana , Fang Yi , Ding Xiaoqiang
Published: December 2021

Background: We aimed to explore the association between long-term drinking behavior change patterns with hyperuricemia (HUA) in Chinese community adults.Methods: This study was designed as a community-based cohort study involving 4127 adults aged between 18~75 years, derived from the China Health and Nutrition Survey (CHNS) in 1997 and 2009. We applied logistic regression models to explore the associations between drinking behavior change patterns and HUA.Results: The average age of the participants was 54.6 (±11.3) years and 47.8% were male. The overall prevalence of HUA was 15.5%. Drinking behavior change patterns of quitting (aOR 1.8; 95%CI 1.1~2.8) and continued drinking (aOR 2.0; 95%CI 1.3~3.0) were positively associated with high risks of HUA in the male participants. Early drinking behaviors such as liquor intake (aOR 1.8; 95%CI 1.4~2.5) and high consumption or frequency showed a positive correlation with HUA. Of note, heavy alcoholism (aOR 2.0; 95%CI 1.4~2.8) and daily drinking (aOR 2.5; 95% CI 1.7~3.6) had the highest risks of HUA. Furthermore, there was a significant association between early alcohol intake and HUA was more pronounced at 18 standard drinks, with a stable increasing trend. In contrast, no statistical correlation was observed between the drinking behaviors and HUA in the female participants. Conclusions: Drinking behavior change patterns of quitting and continued drinking are strongly associated with increased risks of HUA in males. The risks emanated from early drinking behaviors such as liquor drinking, high drinking frequency, and alcohol consumption. Although quitting drinking was associated with lower HUA risks compared to continued drinking, it still presented an undeniable risk for HUA.
The Association of Hepatitis B Virus Replication During Pregnancy with Perinatal Outcomes: A Retrospective Cohort Study
Authors: Jiang Pingying , Huang Yongzhu , Mao Kaiyi , Lin Yongxu , Li Dan , Chen Fenglin , Lin Na
Published: December 2021

Background
The effect of hepatitis B virus (HBV) replication during pregnancy on the outcomes of singleton pregnancies is not fully understood. In this study, we investigated the association between HBV replication and poor maternal and infant outcomes.
Methods
We retrospectively analyzed the clinical data of 836 pregnant inpatients with hepatitis B surface antigen positivity who delivered at two provincial tertiary grade A hospitals in Fujian Province from June 2016 to October 2020. The patients were divided into the HBV replication (n = 283) and non-HBV replication groups (n = 553). Chi-squared test of adverse maternal and infant outcomes was performed using SPSS 26.0 software, and univariate analysis of variance of basic clinical indexes of pregnant women and newborns was performed. P<0.05 was considered statistically significant.
Results
The incidences of perinatal outcomes of intrahepatic cholestasis of pregnancy, hypertensive syndrome complicating pregnancy, gestational diabetes mellitus, preterm birth, macrosomia, growth restriction, and vaginal infection in the HBV and non-HBV replication groups were not significantly different (P>0.05); however, there were significant differences between the two groups in the rate of cesarean section (53.8% vs. 45.0%; P=0.017) and neonatal jaundice (15.5% vs. 7.2%; P=0.000). After using propensity score analysis and multivariable modeling to adjust for glutamic pyruvic transaminase and glutamic oxaloacetic transaminase levels in the two groups, the replication group was found to have an increased risk for cesarean section (54.3% vs. 33.5%; P=0.000) and vaginal infection (3% vs. 0.4%; P=0.038), and their infants had a higher rate of newborn jaundice (16% vs.1.5%; P=0.000).
Conclusion
The findings provide further understanding of the association between maternal HBV replication status and perinatal outcomes. Pregnant women with viral replication have an increased risk of vaginal infection and cesarean section, and their infants appear to be at a higher risk for neonatal jaundice.
A Qualitative Exploration of Medical Student Empathy During the COVID-19 Pandemic
Authors: Ellison Gabriel , Pruzinsky Thomas
Published: December 2021

BackgroundThere is evidence that medical student self-reported empathy may decline as one progresses through their clinical training. Due to the unprecedented changes to both patient care and medical education caused by COVID-19, it is reasonable to assume that medical student empathy may be impacted. The goal of this July 2020 study was to qualitatively explore how the COVID-19 pandemic might affect medical students’ reported experience of empathy.MethodUsing a semi-structured interview, the authors interviewed 12 medical students, 6 second-year and 6 fourth-year. They selected these groups because of the distinct differences in their clinical experience. ResultsData analysis identified 5 major themes: 1) Expanded Perspective (e.g., a feeling of “we’re in this together”, increased awareness of patient vulnerability) 2) Moral Dilemmas (e.g., difficult decisions faced by students as a result of the pandemic such as weighing educational vs. family responsibilities, students risking their own health to provide the best possible care) 3) Confirmation of Values (e.g., Feeling reaffirmed in decision to enter medicine, feeling the pandemic was “what we signed up for” by entering medical school) 4) Shaping Priorities (e.g., changes in medical specialty or populations of interest) 5) Barriers to Empathy and Adaptive Strategies (e.g., COVID-19 created many physical, psychological, and social barriers to empathy for students, students presented many strategies for ameliorating these barriers). Five students (42%) reported increased empathy with no students reporting a decrease in empathy due to experiences during the pandemic. Conclusions Participants did not report that their personal experience of empathy for patients was negatively influenced by the COVID-19 pandemic. Many reported that their empathy increased. The observed differences in responses by pre-clinical (second-year) and clinical (fourth-year) students suggests a possible shift in how empathy is experienced and practiced as one progresses through their medical education. The overwhelmingly positive responses to the semi-structured interview, emphasizing appreciation of the opportunity to discuss topics not previously openly discussed, underscores the importance of providing explicit opportunities for students to discuss their emotional/interpersonal experiences within medical education, particularly in difficult times such as the COVID-19 pandemic.
Augmented Reality Technology As A Delivery Mechanism For Psychological Intervention In Adolescents With Asthma: A Randomised Controlled Feasibility Trial Protocol
Authors: Sharrad Kelsey , Martini Caitlin , Kopsaftis Zoe , Tai Andrew , Spurrier Nicola , Smith Ross , Esterman Adrian , Gwilt Ian , Sandford Debra , Carson-Chahhoud Kristin
Published: December 2021

Background: Australia has one of the highest rates of asthma prevalence worldwide, with almost one in 10 children affected. The mental health and wellbeing of asthmatic children is reported to be significantly more impacted than non-asthmatic peers; affecting both asthma management and their overall quality of life. The relationship between asthma and psychological distress is likely bi-directional, therefore requiring an intervention that addresses both psychological and physiological factors. Technology-based psychological interventions provide a potential solution that may increase engagement with treatment amongst adolescents. In particular, augmented reality (AR) is a novel technology that can be tailored to individual populations and has been proven effective in the management of other conditions. No evidence exists currently on the feasibility of AR in the management of psychological wellbeing within the asthmatic community.Methods: An 80-page workbook has been developed based on best-practice asthma guidelines and through consultation with field experts in Psychology and Paediatric Respiratory Medicine, AR tools have been developed following a needs assessment, and a bespoke smartphone app has been developed by Portal Australia. Forty (n=40) young people aged 13-17 years with persistent asthma will be recruited from the Respiratory Department at the Women’s and Children’s Hospital. Participants will be required to download a smartphone application (YOLO de-stress) and will be encouraged to use the app for a month. Participants will be required to complete the Youth Asthma-related Anxiety Scale, Paediatric Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire at baseline and one-month post-intervention. Data analysis will be descriptive, with counts and percentages for categorical data, and means and standard deviations for continuous data compared between baseline and follow-up. For continuous outcome variables mixed effects linear models will be used. For other outcome measures mixed effects generalized linear models will be used. Discussion: This study will explore the feasibility of AR tools to aid delivery of psychological intervention to manage symptoms of elevated psychological distress among young people with asthma, and inform development of a fully powered RCT. Trial registration: This project was prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12620001109998
Nanopore Long-Read Transcriptomics Profiling Reveals Gene Expression Signatures of Mouse Tumor Endothelial Cells 2H-11
Authors: Tian Yuanyuan , Zhao Jiao , Huang Ju , Zhang Haiying , Ni Fushun , Tang Rong , Shao Jing , Li Yilei , Li Wei
Published: December 2021

Background:Tumor endothelial cells (TECs) play an indispensable role in tumor growth and metastasis. Compared with normal endothelial cells (NECs), TECs exhibit unique phenotypic and functional heterogeneity in terms of metabolism, genetics, and transcriptomics. It is not only the key to coordinate tumor angiogenesis, but also an important factor of immune regulation in the tumor microenvironment. In recent years, the role of TECs in tumor metabolism and invasion has been continuously reported. However, the research on the mechanism behind the complex functions of TECs is still at the basic stage. We use Oxford Nanopore Technology (ONT) three-generation full-length transcriptome sequencing to detect all genetic structural changes in the transcriptome of mouse TECs 2H-11 and mouse NECs SVEC4-10.Results: In Tumor endothelial cells 2H-11,1847genes are up-regulated and 1202 genes are down-regulated. According to the Gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs), we found that different functional trends related to metabolic processes, developmental processes, localization, immune system processes, and locomotion are the main reasons for the differences. DEGs are mainly enriched in signal pathways related to cancer, immunity and metabolism, involving Pathways in cancer,Antigen processing and presentation , Proteoglycans in cancer, Focal adhesion, MAPK signaling pathway ,Protein digestion and absorption，ECM-receptor interaction，PI3K-Akt signaling pathway and Glutathione metabolism. We also obtained the structural variation of transcripts such as alternative splicing, gene fusion, and alternative polyadenylation and accurately quantified the expression of the transcript. Some of our results have been confirmed in other documents. But other data have not been reported yet, which is the focus of our future exploration.Conclusion: We try to use transcriptomics and bioinformatics methods to characterize tumor endothelial cell-related genes and signaling pathways.It could help better understand the molecular mechanisms of tumor endothelial cells involved in tumorigenesis and development. DEGs in key pathways may be potential diagnostic markers or therapeutic targets of TECs. Our data also provide useful genetic resources for improving the genome and transcriptome annotations of TECs and NECs.
Overall Survival Rate Analysis For Risk Factors In Women With Neuroendocrine Carcinoma of The Cervix Using Surveillance, Epidemiology, And End Results (SEER) Database
Authors: Yin Ziran , Huang Xiumin
Published: December 2021

Background: Neuroendocrine carcinoma of the cervix is rare and aggressive disease, of which prognosis information and the effectiveness of the therapies is unclear.Methods: A retrospective study using data from the SEER database for the first diagnosed Neuroendocrine carcinoma of the cervix patients was conducted. We performed univariate and multivariate Cox models to screen for independent prognostic factors for overall survival. Subgroup analysis and sensitive analysis were performed for further study, then again univariate and multivariate analyses of Cox regression analysis were performed based on the sensitivity analysis data set.Results: A total of 250 Neuroendocrine carcinoma of the cervix cases was included, tumor subtype, age, marriage, race, number of regional lymph nodes, number of positive lymph nodes, radiotherapy, surgery, and FIGO stage were all factors affecting OS, and multivariate analysis identified FIGO staging (HR, 2.4; 95% CI, 1.505-3.828, P < 0.001) and surgery (HR, 0.467; 95% CI, 0.358-0.609, P < 0.001) treatment as independent indicators. With respect to the factors associated with treatments, we found that patients who underwent surgery (yes vs. no vs. unknown) or radiation (yes vs. no) experienced prolonged survival, both P < 0.001Conclusions: Our investigation shows that for patients with NECC surgery seems to be the effective treatment. Chemotherapy cannot improve the prognosis of NECC patients, and the effectiveness of radiation should be further verified.
Antioxidant Potentials of the Pod Extract of Caesalpinia Pulcherrima Swarta (Fabaece) and the Theoretical Evaluation of the Antioxidant Property of the Isolated Compounds
Authors: Faloye Kolade , Famuyiwa Samson , Akinwunmi Kemi , Tata Charlotte , Ayoola Marcus , Fakola Emmanuel , Akinyele Olawale , Ndinteh Derek
Published: December 2021

Various diseases associated with oxidative stress have necessitated the need to investigate plants for antioxidant agents. This study aims to investigate the antioxidant potential of the extract and fractions of C. pulcherrima and estimate the quantum chemical properties of polyphenolic compounds isolated from its most active antioxidant fraction. Methanolic extract and partition fractions of the pods of the plant were assayed for their antioxidant activity using four models: 1,1-diphenyl-2-dipicrylhydrazyl radical scavenging, ferric reducing antioxidant power, total antioxidant capacity and hydroxyl radical scavenging activity. Total phenolic and flavonoid contents of the extract and fractions were also investigated. Furthermore, the quantum chemical properties of two polyphenolic compounds were calculated to predict the antioxidant potential. The extract exhibited good antioxidant activity with IC50 = 45.63 µg/ml comparable to ascorbic acid of IC50 = 37.94 µg/ml, high reducing power with value at 376.74 ± 6.78, total antioxidant capacity obtained at ascorbic acid equivalence of 383 ± 8.16 mgAAE/g and potent hydroxyl radical scavenging activity with value at 580.97 µg/ml with ascorbic acid at 30.7 µg/ml. The total phenol and flavonoid contents values at 540.53 ± 3.71 and 347.87 ± 7.13 respectively. Furthermore, the results obtained from the quantum chemical calculations reveals polyphenolic compounds; 5(4-hydroxyphenyl)-3-hydroxy-2-methoxyphenol and 3(4-methanetriiol-2,6-dihydroxyphenoxy)-3’, 4’, 5’, 5, 7-pentahydroxyflavonol as promising antioxidant agents. The study concluded that C. pulcherrima pods have good antioxidant activity. Also, the polyphenolic compounds are among the chemical constituents responsible for the antioxidant activity obtained for the extract and ethyl acetate fraction.
Effects of BET Inhibitor JQ1 and Interleukin-6 on Breast Cancer Cells
Authors: Hoseini Atefeh Sharif , Heshmati Masoud , Soltani Amin , Shirzad Hedayatollah , Sedehi Morteza , Judd Barbi A , Jami Mohammad-Saeid , Samani Mahdi Ghatreh
Published: December 2021

Bromodomain and extra-terminal (BET) proteins are recognized acetylated lysine of histone 4 and act as scaffolds to recruit many other proteins to promoters and at enhancers of active genes, especially at the super-enhancers of key genes, driving the transcription process and have been identified as potential therapeutic targets in breast cancer. However, the efficacy of BET inhibitors such as JQ1 in breast cancer therapy is impeded by IL-6 through an as yet defined mechanism. We investigated the interplay between IL-6 and JQ1 in MCF-7 and MDA-MB-231 human breast cancer cells. Here we demonstrate that the efficacy of JQ1 on the inhibition of cell growth and apoptosis was stronger in MDA-MB-231 cells than in MCF-7 cells. Further, MCF-7 cells, but not MDA-MB-231 cells, exhibited increased expression of CXCR4 following IL-6 treatment. JQ1 significantly reduced CXCR4 surface expression in both cell lines and diminished the effects of IL-6 pre-treatment on MCF-7 cells. While IL-6 suppressed the extension of breast cancer stem cells (BCSCs) in MCF-7 cells, JQ1 impeded its inhibitory effect. In addition, in MCF-7 cells JQ1 increased the number of senescent cells in a time-dependent manner. Analysis of gene expression indicated that JQ1 and IL-6 synergistically increase SNAIL expression and decrease c-MYC expression in MCF-7 cells. So, the BET proteins are promising, novel therapeutic targets in late-stage breast cancers.
Evaluating Palin Stammering Therapy for School Children (Palin STSC 8-14): Protocol for a Feasibility Randomised Control Trial Comparing Palin STSC(8-14) with Usual Treatment
Authors: Millard Sharon K , Murphy Suzanne , Barton Garry , Lethersich Maria , Rixon Lorna , Shepstone Lee , Sims Erika , Joffe Victoria
Published: December 2021

Background: Having a stammer can have a significant effect on a child’s social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practise. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8-14: Palin Stammering Therapy for School Children (Palin STSC(8-14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8-14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised control trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with ‘treatment as usual’ (TAU), beyond the specialist context in which it was developed.Methods: This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8-14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine: the recruitment and retention of therapists and families; the acceptability of the research processes and the therapeutic intervention; the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and six months later, including measures of: stammering severity; the impact of child’s stammering on both children and parents; child temperament, behaviour, peer relations, anxiety; quality of life; and, economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. Discussion: The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8-14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence based intervention for school age children who stammer. Trial registration: ISRCTN. ISRCTN17058884. Registered 18th December 2019. https://www.isrctn.com/ISRCTN17058884
A Spatial AMH Copula-Based Dissimilarity Measure to Cluster Variables in Panel Data
Authors: Lascio F. Marta L. Di , Menapace Andrea , Pappadà Roberta
Published: December 2021

Investigating thermal energy demand is crucial for the development of sustainable cities and efficient use of renewable sources. Despite the advances made in this field, the analysis of energy data provided by smart grids is currently a demanding challenge. In this paper, we develop a clustering methodology based on a novel dissimilarity measure to analyze a high temporal resolution panel data for district heating demand in the Italian city Bozen-Bolzano. Starting from the characteristics of this data, we explore the usefulness of the Ali-Mikhail-Haq copula in defining a new dissimilarity measure to cluster variables in a hierarchical framework. We show that our proposal is particularly sensitive to small dissimilarities based on tiny differences in the dependence level. Therefore, the proposed measure is able to better distinguish between objects with low dissimilarity than classic rank-based dissimilarity measures. Moreover, our proposal is defined in a spatial version that is able to take into account the spatial location of the compared objects. We investigate the proposed measure through Monte Carlo studies and compare it with the corresponding spatial Kendall's correlation-based dissimilarity measure. Finally, the application to real data makes it possible to find clusters of buildings homogeneous with respect to their main characteristics, such as energy efficiency and heating surface, to support the design, expansion and management of district heating systems.
Melatonin Modulates Microglia Activation in Neuro-inflammation by Regulating the ER Stress/PPARd/SIRT1 Signaling Pathway
Authors: Pan Hung-Chuan , Yang Cheng-Ning , Lee Wen-Jane , Sheehan Jason , Wu Sheng-Mao , Chen Hong-Shiu , Lin Mao-Hsun , Shen Li-Wei , Lee Shu-Hua , Shen Chin-Chang , Pan Liang-Yi , Sheu Meei-Ling
Published: December 2021

Background: Activated microglia-mediated neuro-inflammation plays a vital aspect in regulating the micromilieu of the central nervous system. Neuro-inflammation involves distinct alterations of microglial phenotypes, containing nocuous pro-inflammatory (M1) phenotype and neuroprotective anti-inflammatory (M2) phenotype. Currently, there is no effective treatment for modulating such alterations. Little evidence shows that melatonin prevents the detrimental cascade of activated microglia-mediated neuro-inflammation. Methods: The expression levels of M1/M2 marker of primary microglia influenced by Melatonin were detected via qPCR. Functional activities were explored by western blotting, luciferase activity, EMSA, and ChIP assay. Structure interaction was assessed by molecular docking and LIGPLOT analysis. ER stress detection was examined by ultrastructure TEM, calapin activity, and ERSE assay. The neurobehavioral evaluations and immunofluorescence staining in animals were used for investigation of Melatonin on the neuroinflammation in vivo. Results: Melatonin had targeted on Peroxisome Proliferator Activated Receptor Delta (PPARd) activity, boosted LPS-stimulated alterations in polarization from the M1 to the M2 phenotype, and thereby inhibited NFkB–IKKb activation in primary microglia. The PPARd agonist L-165041 or over-expression of PPARd plasmid (ov-PPARd) showed similar results. Molecular docking screening, dynamic simulation approaches, and biological studies of melatonin showed that the activated site was located at PPARd (phospho-Thr256-PPARd). Furthermore, we found that activated microglia had lowered PPARd activity as well as the downstream SIRT1 formation via enhancing ER stress. Melatonin, PPARd agonist and ov-PPARd all effectively reversed the above-mentioned effects. Melatonin blocked ER stress by regulating calapin activity and expression in LPS-activated microglia. Additionally, melatonin or L-165041 ameliorated the neurobehavioral deficits in LPS-aggravated neuroinflammatory mice through blocking microglia activities, and also promoted phenotype changes to M2-predominant microglia. Conclusions Melatonin suppressed neuro-inflammation in vitro and in vivo by tuning microglial activation through the ER stress-dependent PPARd/SIRT1 signaling cascade. We proposed that this treatment strategy is an encouraging pharmacological approach for the remedy of neuro-inflammation associated disorders.
Fracture Resistance of Primary Canines Restorations Reinforced with a Flowable or a Packable Composite Resin Posts; In- Vitro
Authors: Ansari Ghasem , javadi Fatemeh , Hanjani Kiana , Abrandabadi Ahmad Najafi , Gashtasb Mahshid , Roodgarian Romina
Published: December 2021

Aim and Background:
Restoration of severely damaged primary anterior teeth are deemed as serious challenges for pediatric dentists. The aim of this study was to evaluate the fracture resistance of primary canines restored with flowable or packable composite resin posts.
Material and Methods
This study was conducted on a group of extracted primary canines. After cutting the coronal section, standard pulpectomy was performed and root canals were filled with ZOE paste leaving 3 mm coronal root space. A liner was placed above the root canal filling as a barrier. Samples were then randomly divided into two groups of fifteen. Both groups, received etch, bond, then in group I Core Flo Composite resin placement into canal, in group II, post shaping using designated packable composite resin and inserted into the canal. Followed by Core buildup and Crown reconstruction using Z250 composite resin. Samples were mounted at 148 ° angle on the acrylic blocks and stored in de-ionized water for 72 hours. Fracture resistance was measured using Universal Testing Machine. Data analysis were performed using independent t-test. Chi- square test were also employed to assess the type of fracture within groups.
Results
The mean fracture resistance in the group I was 830.31(+/-328.69N) and 803.09(+/-326.45N) in group II. Moreover, statistical analyses of the results showed no significant difference between the mean values of the fracture resistance (p-value=0.822) of groups as well as the type of fracture (p-value=0.79) between groups.
Conclusion
The ease of use and proper adhesion of the Core Flo composite resin, seems to help its use in the reconstruction of severely destructed anterior primary teeth.
The Role of Service Provider’s Rapport Behavior on Customers’ Empathy
Authors: Jin ChangHyun , Zeng JingYun
Published: December 2021

The study is intended to explore the validity of the component system of the rapport behavior of service providers. The purpose of this study was to understand how the components of the rapport behavior of service providers affect rational and emotional empathy. This study is intended to understand the relationship between rational and emotional empathy and customer satisfaction and the effect of customer satisfaction on revisit intentions. The main purpose was to identify the moderating effect of perceived authenticity on the causal relationship between rapport behavior, empathy, and customer satisfaction and revisit intentions. The sampling method used in this study was the judgment sampling, which is a method in which the researcher selects those study subjects that are thought by the researcher to be the most suitable samples for the purpose of the study. The total questionnaire period was a total of three months, from March 15 to May 15, 2020. The total number of valid samples was 1668. Uncommonly attentive behavior, courteous behavior, information-sharing, and connecting behavior, which are components of the rapport behaviors of service providers, were found to have positive effects on rational empathy with the service provider, but common grounding behavior, which is also a component of the rapport behaviors of service providers, was found to have no statistically significant effect on rational empathy with service providers. The rapport behaviors of service providers are judged to play an important role in maintaining and developing strong ties through long-term and continuous interactions with customers.
Effects of Sarcopenia and Sarcopenic Obesity on Joint Pain and Degenerative Osteoarthritis in Postmenopausal Women
Authors: Kim Hye In , Ahn So Hyun , Kim Yup , Lee Ji Eun , Seo Seok Kyo
Published: December 2021

This study aimed to identify the prevalence of sarcopenia, obesity, and sarcopenic obesity and examine their association with radiographic knee osteoarthritis (OA) and knee pain in Korean menopausal women. This cross-sectional study utilized the data from Korean National Health and Nutrition Examination Surveys 2009–2011. The participants were categorized based on body composition. The prevalence of radiographic knee OA and knee pain was calculated. The effect of hormone therapy (HT) was also evaluated. The prevalence of radiographic knee OA, knee pain, and both were all highest in the sarcopenic obese group and lowest in the non-sarcopenic non-obese group. Without sarcopenia, obese women showed higher ratio of radiographic knee OA. With sarcopenia, the coexistence of obesity presented higher ratio of radiographic knee OA, knee pain, and both compared to sarcopenia without obesity. The use of HT for more than one year was not associated with radiographic knee OA, knee pain, or both. Obesity with sarcopenia had greater effect on knee OA compared to obesity without sarcopenia. Moreover, HT use for more than one year was not associated with the prevalence of knee OA. Therefore, more efforts should focus on reducing body fat and increasing muscle in postmenopausal women with knee OA.
Acute cardiac side effects after COVID-19 mRNA vaccination, a case series
Authors: Freise Noemi F. , Kivel Milena , Grebe Olaf , Meyer Christian , Wafaisade Bahram , Peiper Matthias , Zeus Tobias , Schmidt Jan , Neuwahl Judith , Jazmati Danny , Luedde Tom , Bölke Edwin , Feldt Torsten , Jensen Björn Erik Ole , Bode Johannes , Keitel Verena , Haussmann Jan , Tamaskovics Balint , Budach Wilfried , Fischer Johannes C. , Knoefel Wolfram Trudo , Schneider Marion , Gerber Peter Arne , Pedoto Alessia , Häussinger Dieter , Griensven Martijn , Rezazadeh Amir , Flaig Yechan , Kirchner Julian , Antoch Gerald , Schelzig Hubert , Matuschek Christiane
Published: December 2021

Background: Since development and approval of the world´s first mRNA vaccines, created under pressure of the global pandemic caused by SARS-CoV-2, potential side effects have naturally been a much-debated topic. Vaccination may be one, if not the only way out of the pandemic claiming more than 4 million deaths worldwide to date. Potential side effects from vaccination have long been controversial, and case reports of fatal side effects have been published. Therefore, data are needed to identify persons being at high risk for potential side effects. Until September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© in young adults were registered by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©).Patients and Methods: Eight patients between 13-56 years of age, vaccinated with mRNA vaccine either BNT162b2 or mRNA-1273 between January and August 2021 developed cardiac side effects shortly after either their first or second vaccination. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after onset of symptoms and investigated further in severe cases. Symptoms were defined as dyspnea, chest pain, cardiac arrhythmia as determined by electrocardiography.Results: Eight patients (five males and three females) developed cardiac symptoms compatible with myocarditis according to CDC criteria shortly after SARS-CoV-2 mRNA vaccination. Three patients (two males, one female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within seven days after symptom onset Conclusion: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.
Echinacoside Improves Cognitive Impairment by Inhibiting Aβ Deposition Through the PI3K/AKT/Nrf2/PPARγ Signaling Pathways in APP/PS1 Mice
Authors: qiu hui , liu min xue
Published: December 2021

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer’s disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice were treated with ECH in 50 mg/kg/d for 3 months. Morris water maze, nesting test and immunofluorescence staining were used to observe whether ECH could improve AD pathology. Western blot was used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/ Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress and inflammatory response in AD. Therefore, we suggest that ECH may be considered as a potential drug for AD treatment.
Vitrification Cryo-Foil for Apple Cryopreservation and the Seesaw Effect Between Shoot Recovery and Virus Eradication
Authors: Wang Min-Rui , Bao Jun-Hua , Ma Xiao-Yan , Xie Ling-Ling , Zhu Li-Ying , Liu Mei-Zi , Lu Xian , Zhang Dong , Wang Qiao-Chun
Published: December 2021

Improvements of existing cryopreservation protocols are necessary to facilitate long-term preservation of plant germplasm and the cryotherapy-effect of pathogen eradication. This study reported a vitrification (V) cryo-foil/plate methods for cryopreservation of shoot tips and cryotherapy effect in ‘Pink Lady’ apple. In V cryo-foil/plate protocols, shoot tips were first attached onto aluminum foils/plates using calcium alginate before other procedures. Shoot tips cryopreserved by V cryo-foil required 6.1 weeks to fully recover and 53% of shoot regrowth was obtained, comparable to the Dv cryopreservation. Similar regrowth levels were produced between applying V cryo-foil and Dv cryopreservation to another 4 Malus genotypes. Histological observations in shoot tips cryopreserved by Dv and V cryo-foil found only those with surviving apical dome and leaf primordia (LPs) could recover after cryopreservation. In apical meristem of shoot tips cryopreserved by Dv and V cryo-foil, higher surviving probability was detected from the V cryo-foil protocol, and the young LPs showed the highest level of surviving. Virus detection in cryo-derived plants showed apple stem grooving virus and apple chlorotic leaf spot virus were all preserved after cryopreservation, and higher eradication efficiency of apple stem pitting virus (70%) was produced by Dv than the 55% of V cryo-foil. These results supported applying V cryo-foil as an improvement to the widely applied Dv method in shoot tip cryopreservation, and also revealed a seesaw mode between shoot recovery and cryotherapy effect. Once the seesaw moves to increase the recovery after cryopreservation, the cryotherapy-effect on the other side would be decreased.
Phase Retrieval Based on Deep Learning in Grating Interferometer
Authors: Oh Ohsung , Kim Youngju , Kim Daeseung , Hussey Daniel. S. , Lee Seung Wook
Published: December 2021

Grating interferometry is a promising technique to obtain differential phase contrast images with illumination source of low intrinsic transverse coherence. However, retrieving the phase contrast image from the differential phase contrast image is difficult due to the accumulated noise and artifacts from the differential phase contrast image (DPCI) reconstruction. In this paper, we implemented a deep learning-based phase retrieval method to suppress these artifacts. Conventional deep learning based denoising requires noisy-clean image pair, but it is not feasible to obtain sufficient number of clean images for grating interferometry. In this paper, we apply a recently developed neural network called Noise2Noise (N2N) that uses noise-noise image pairs for training. We obtained many differential phase contrast images through combination of phase stepping images, and these were used as noise input/target pairs for N2N training. The application of the N2N network to simulated and measured DPCI showed that the phase contrast images were retrieved with strongly suppressed phase retrieval artifacts. These results can be used in grating interferometer applications which uses phase stepping method.