bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation and immunity connect hypertension with adverse COVID-19 outcomes
Authors: Cai Lei , He Chuan , Liu Yonglin , Sun Yanlan , He Lin , Baranova Ancha 
Published: September 2022

Objectives: To explore the connection of hypertension and severe COVID-19 outcomes.Methods: A total of 68 observational studies recording mortality and/or general severity of COVID-19 were pooled for meta-analyses of the relationship of severe COVID-19 outcomes with hypertension as well as systolic and diastolic blood pressure. Genome-wide cross-trait meta-analysis (GWCTM) was performed to explore the genes linking between hypertension and COVID-19 severity.Results: The results of meta-analysis with the random effect model indicated that pooled risk ratios of hypertension on mortality and severity of COVID-19 were 1.80 [95% confidence interval (CI) 1.54–2.1] and 1.78 (95% confidence interval 1.56–2.04), respectively, although the apparent heterogeneity of the included studies was detected. In subgroup analysis, cohorts of severe and mild patients of COVID-19 assessed in Europe had a significant pooled weighted mean difference of 6.61 mmHg (95% CI 3.66–9.55) with no heterogeneity found (p = 0.26). The genes in the shared signature of hypertension and the COVID-19 severity were mostly expressed in lungs. Analysis of molecular networks commonly affected both by hypertension and by severe COVID-19 highlighted CCR1/CCR5 and IL10RB signaling, as well as Th1 and Th2 activation pathways, and also a potential for a shared regulation with multiple sclerosis.Conclusion: Hypertension is significantly associated with the severe course of COVID-19. Genetic variants within inflammation- and immunity-related genes may affect their expression in lungs and confer liability to both elevated blood pressure and to severe COVID-19.
High FLT3 expression indicates favorable prognosis and correlates with clinicopathological parameters and immune infiltration in breast cancer
Authors: Chen Rui , Wang Xinyang , Fu Jingyue , Liang Mengdi , Xia Tiansong 
Published: September 2022

Purpose: Breast cancer is a highly heterogeneous malignancy, seriously threatening female health worldwide and inducing higher mortalities. Few have the studies evaluated Fms-like TyrosineKinase-3 (FLT3) in prognostic risk, immunotherapy or any other treatment of breast cancer. Our study focused on investigating the function of FLT3 in breast cancer.Patients and methods: Based on transcriptome and methylation data mined from The Cancer Gene Atlas (TCGA), we explored the clinical features of FLT3 expression in 1079 breast cancer samples. RT-qPCR in cell lines and tissue samples was used to verify the expression difference of FLT3. Kaplan–Meier survival analysis and cox regression models were employed for screening of FLT3 with potential prognostic capacity. Subsequently, functional analysis of the co-expressed genes was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). The correlation between FLT3 expression and tumor immune infiltration was jointly analyzed with estimate, ssGSEA, TIMER, and TISIDB. Then we employed checkpoint-related molecules, immunophenoscore (IPS), and tumor mutation burden (TMB) to assess the efficacy of immuno-checkpoint inhibitors (ICIs). Pearson correlation coefficient was employed to exam the association between DNA methylation and FLT3 expression.Results: FLT3 displays an elevated expression in breast cancer than normal pairs and is significantly associated with multiple clinical characteristics like age, menopause status, histological type, pathological stage, and molecular subtype as well as increased overall survival (OS). Additionally, FLT3 is a favorable independent prognostic factor. GO, KEGG, and GSEA suggested that FLT3 was associated with diversified immune-related features. FLT3 expression is correlated with the abundance of various immune cells namely CD4+T cell, CD8+ T cell, myeloid dendritic cell, and neutrophil as well as immune inhibitors especially CTLA4, which is positively correlated with FLT3 expression. Moreover, TMB displayed a negative correlation with FLT3 expression while IPS showed adverse tendency. Ultimately, the methylation of FLT3 downregulates the gene expression and closely binds to a few clinical parameters.Conclusion: FLT3 can be used for prognostic prediction and is relevant to immune infiltration in breast cancer. FLT3 may pave the way for future novel immunotherapies.
Transcriptomic profiles of poplar (Populus simonii × P. nigra) cuttings during adventitious root formation
Authors: Yu Yue , Meng Nan , Chen Song , Zhang Hongjiao , Liu Zhijie , Wang Yiran , Jing Yanan , Wang Yuting , Chen Su 
Published: September 2022

The formation of adventitious roots (ARs) is vital for the vegetative propagation of poplars. However, the relevant mechanisms remain unclear. To reveal the underlying molecular mechanism, we used RNA-seq to investigate the transcriptional alterations of poplar cuttings soaked in water for 0, 2, 4, 6, 8, and 10 d; 3,798 genes were differentially expressed at all the time points, including 2,448 upregulated and 1,350 downregulated genes. Biological processes including “cell cycle,” “photosynthesis,” “regulation of hormone levels,” and “auxin transport” were enriched in the differentially expressed genes (DEGs). KEGG results showed that the common DEGs were most enriched in the pathway of “Carbon fixation in photosynthetic organisms” and “Starch and sucrose metabolism.” We further dissected 38 DEGs related to root and auxin, including two lateral root primordium 1 (LRP1), one root meristem growth factor (RGF9), one auxin-induced in the root (AIR12), three rooting-associated genes (AUR1 and AUR3), eight auxin transcription factors (ARFs and LBDs), 10 auxin respective genes (SAURs and GH3s), nine auxin transporters (PINs, ABCs, LAX2, and AUXs), and four auxin signal genes (IAAs and TIR1). We found that the rooting abilities of poplar cuttings with and without leaves are different. By applying different concentrations of IBA and sucrose to the top of cuttings without leaves, we found that 0.2 mg/ml IBA and 2 mg/ml sucrose had the best effect on promoting AR formation. The transcriptome results indicated photosynthesis may influence AR formation in poplar cuttings with leaves and revealed a potential regulatory mechanism of leafy cuttage from poplar cuttings. In addition, we provided a new perspective to resolve rooting difficulties in recalcitrant species.
Local Immunoglobulin E in nasal polyps: Role and modulation
Authors: Shen Yang , Zhang Nan , Yang Yucheng , Hong Suling , Bachert Claus 
Published: September 2022

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE’s characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen-Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-β, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.
Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy
Authors: Liu Zhaoyun , Liu Xiaohan , Shen Hongli , Xu Xintong , Zhao Xianghong , Fu Rong 
Published: September 2022

There are two figures and one table in this review, the review consists of 5823 words, without the description of figures and table, but including references.Tumor cells escape anti-tumor immune responses in various ways, including functionally shaping the microenvironment through the secretion of various chemokines and, cytokines. Adenosine is a powerful immunosuppressive metabolite, that is frequently elevated in the extracellular tumor microenvironment (TME). Thus, it has recently been proposed as a novel antitumor immunoassay for targeting adenosine- generating enzymes, such as CD39, CD73, and adenosine receptors. In recent years, the discovery of the immune checkpoints, such as programmed cell death 1(PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), has also greatly changed treatment methods and ideas for malignant tumors. Malignant tumor immunotherapy has been developed from point-to-point therapy targeting immune checkpoints, combining different points of different pathways to create a therapy based on the macroscopic immune regulatory system network. This article reviews the theoretical basis of the adenosine energy axis and immune checkpoint combined therapy for malignant tumors and the latest advances in malignant tumors.
Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers
Authors: Wang Yanni , Zou Jianling , Li Yun , Jiao Xi , Wang Yujiao , Zhuo Na , Gao Mengting , Gong Jifang , Li Jian , Zhang Xiaotian , Wang Xicheng , Peng Zhi , Qi Changsong , Wang Zhenghang , Li Jie , Li Yan , Shen Lin , Zhang Henghui , Lu Zhihao 
Published: September 2022

BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.Patients and methodsMetastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.ResultsFifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.ConclusionsSerological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy.
Predictive validity of admission criteria in predicting academic performance of medical students: A retrospective cohort study
Authors: Almarabheh Amer , Shehata Mohamed Hany , Ismaeel Abdulrahman , Atwa Hani , Jaradat Ahmed 
Published: September 2022

IntroductionAdmission to medical school is one of the most competitive entry points in higher education. Medical school admissions committees need accurate and precise screening tools to select among well-qualified applicants. This study explores data from a cohort of graduated medical students over 6 years to offer a critical perspective on predictive validity in medical school admissions.MethodsA retrospective cohort study of 160 students was performed to identify the predictive validity of admission criteria for medical students to predict academic performance over 6 years for a cohort of all students enrolled in the medical program during the academic year 2013–2014.ResultsThe main results indicated that there was a statistically significant positive correlation between the admission criteria and Students’ performance in Year 1, Year 4, B.Sc. (Bachelor of Medical Science) exam, and Medical Doctor (MD) exam across the 6 years of the medical program, except for the English Test, which showed that there was no significant correlation with average MD exam scores for students who enrolled directly in Year 1. The results related to students who were admitted to the Foundation Program showed that there was no significant correlation between high school Grade Point Average (HSGPA) and their academic performance in Year 1, Year 4, B.Sc. exam, and MD exam. The overall results related to all study samples indicated that all predictor variables correlate significantly with all outcome variables (academic performance), and the results showed that Science test scores demonstrated 27.7, 15.0, 19.7, and 12.6% of variation in Students’ performance in Year 1, Year 4, B.Sc. exam, and MD exam, respectively.ConclusionScience test scores were found to be more predictive of academic performance compared to other predictors. Not all the admission criteria used for student selection are good indicators of their achievement in the medical program. It is recommended that other valid and reliable admission tools, such as the multiple mini-interviews and the questionnaire for a candidate’s suitability to follow a problem-based learning curriculum, should be considered.
Periodontitis induced by orthodontic wire ligature drives oral microflora dysbiosis and aggravates alveolar bone loss in an improved murine model
Authors: Ai Rongshuang , Li Dingyi , Shi Luyao , Zhang Xiaonan , Ding Zhiqiang , Zhu Yiting , He Yujuan 
Published: September 2022

AimTo assess the contribution of polymicrobial disruption of host homeostasis to periodontitis progression in orthodontic wire ligation murine model.MethodsOrthodontic wire rings were inserted between the first and second molars of mice for 18 days for the orthodontic wire ligation mouse model, and Pg injection model and Pg-LPS injection model were used as controls. Alveolar bone loss and periodontal inflammation were analyzed by micro-CT, histological staining and qRT-PCR. Further, pyrosequencing of 16S rRNA gene amplicon was used to analyze the development of oral microorganism dysbiosis in the mice.ResultsMicro-CT, TRAP staining and qRT-PCR showed that orthodontic wire ligation model led to more severe alveolar bone loss than Pg and Pg-LPS models.H&amp;E staining and qRT-PCR demonstrated that stronger inflammatory response was induced by the orthodontic wire treatment compared to the other models. In addition, pyrosequencing of 16S rRNA gene amplicons revealed that the composition of oral microbiota presented a transition as the disease progressed and significant differences emerged in oral microbiota communities between orthodontic ligature mice and healthy controls. Furthermore, antibiotic treatment decreased both inflammation and alveolar bone loss in response to microbial community dysbiosis. However, no significant difference in bacterial community composition was observed in Pg and Pg-LPS models.ConclusionsOrthodontic wire ligation drove oral microbial community transitions that mimicked polymicrobial communities characterized by polymicrobial synergy and dysbiosis. Our improved model is suitable for further study of pathogenesis of periodontitis and exploration of corresponding treatment strategies.
Serious games and eating behaviors: A systematic review of the last 5 years (2018–2022)
Authors: Limone Pierpaolo , Messina Giovanni , Toto Giusi Antonia 
Published: September 2022

BackgroundSerious game intervention has emerged over the years as a popular strategy for solving the problem of unhealthy eating behavior. This has prompted several scholars to explore its significant impact on eating behaviors, identifying its positive effect on nutritional knowledge and eating behaviors. However, since this research field is yet nascent, an update in knowledge is required to further inform the real-world practice as an alternative intervention for instating healthy eating behavior. Therefore, this current research utilized a systematic review method to reveal the latest state of this concept of a serious game and eating behavior, to identify the position of the literature and shed light on under-researched and emerging areas by recommending future investigations.MethodTo achieve the object of this research, four electronic databases- Science Direct, Web of Science (WoS), APA PsyclNFO, and Emerald- were searched using predefined keywords (search string) relating to the review topic. A total of 15,107 results were retrieved from the databases. After title, abstract, and full-text screening, 15 studies were included following inclusion criteria.Key findingsThe result of this research demonstrated that various designs of serious games comprise an effective intervention for changing eating behavior in both children and adults and addressed the risks of childhood obesity and overweight. The findings also show that the design of the games is co-designed by different specialists such as a nutritionist, psychologist and developer, among others, as either single or multiple players. The effectiveness of the games was attributed to behavior techniques (BT), cognitive theories (CT), and socio-cognitive theories (SCT) of behavior change technique (BCT), incorporating an element of implicit learning in serious games. Feedback and reward were the most reported influencing strategies and self-reporting the evaluation approach.ConclusionThis research contributed significantly to the body of knowledge in the field of serious games as the most recent review of evidence in the research area. Evidence from 93.33% of the included studies confirmed the effectiveness of serious games in addressing eating behavior. This study concludes that serious games are an effective intervention for improving healthy eating behavior and decreasing unhealthy eating behavior and that various elements of behavior change techniques are essential components of implicit nutritional learning through the games. In addition, it is concluded that the risk of childhood obesity and overweight can be reduced or prevented by leveraging the strength of these games. The need for future research in this field was also pointed out by this study.
Differences in severity of cardiovascular anomalies in children with Noonan syndrome based on the causative gene
Authors: Shehade-Awwad Nagham , Yeshayahu Yonatan , Pinhas-Hamiel Orit , Katz Uriel 
Published: September 2022

BackgroundNoonan syndrome (NS) is a genetic syndrome, characterized by various dysmorphic features, cardiac anomalies, short stature, and developmental delay. NS is a leading cause of cardiovascular anomalies. The syndrome results from dysregulation in the RAS-MAPK pathway and is related to the RASopathy family syndromes. Pathogenic variants in more than 20 related genes have been identified in association with NS, and several genotype-phenotype correlations were suggested. The specific severity of the same cardiovascular anomalies has not been described as linked to a specific causative gene.MethodsFor this retrospective, single-center study, data retrieved from medical charts of a multidisciplinary NS clinic included genetic diagnosis, cardiac malformations, the need for intervention, demographics, and prenatal diagnosis. We analyzed molecular genetics and the severity of cardiac malformations.ResultsThe cohort comprised 74 children with NS. Consistent with previous studies, pathogenic variants in PTPN11 were the most common (62%). Cardiovascular anomalies presented in 57%; pulmonary stenosis (PS) was the most common (about 79% of anomalies). In children with pathogenic variants in PTPN11, PS tended to be more severe and required intervention in 53%, compared to 25% of children with PS and a variant in other genes.ConclusionThis first Israeli cohort of NS showed similar rates of cardiac malformations and genetic breakdown as previously published. Variants in PTPN11 were prone to a higher risk for severe PS that requires intervention. This finding may assist in genetic counseling and cardiac treatment decisions, and stresses the importance of genetic in addition to clinical diagnosis of NS.
Relationship between mutuality and depression in patients with chronic heart failure and caregivers in China: An actor-partner interdependence model analysis
Authors: Zhou Ting , Qu Jiling , Sun Huiping , Xue Mengxin , Liu Yongbing 
Published: September 2022

BackgroundPatients with chronic heart failure and their family caregivers may experience adverse emotional problems, such as depression. Mutuality, which refers to the relationship between caregivers and those they care for, is an important factor affecting depression in the dyads. The purpose of this study was to investigate the relationship between mutuality and depression in patients with CHF and their caregivers in China.MethodsIn this cross-sectional study, we used the Mutuality Scale and the Self-Rating Depression Scale to measure mutuality and depression of patients and caregivers. We used SPSS version 26.0 and AMOS version 21.0 to analyze the data. An APIM was established to analyze the actor-partner effects of patient-caregiver mutuality and depression.ResultsA total of 250 dyads of patients and caregivers were included in the study. There were statistically significant differences in mutuality and depression between CHF patients and caregivers. The 4 dimensions of patients’ mutuality all have the actor effect on depression. There were 3 partner effects of caregivers’ “pleasurable activities”, “shared values”, and “reciprocity” on depression. Regarding caregiver depression, we only found an actor effect of caregivers’ “shared values” on depression.ConclusionThe relationship between patients and caregivers should be evaluated in the clinical setting, and it is very important to develop intervention measures to improve the adverse emotional problems affecting both patients and their caregivers.