bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies
Authors: Zhou Xueping , Zhang Jipeng , Ding Ying , Huang Heng , Li Yanming , Chen Wei 
Published: March 2023

Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the leading cause of blindness in developed countries. Current genome-wide association studies (GWAS) for late-stage age-related macular degeneration are mainly single-marker-based approaches, which investigate one Single-Nucleotide Polymorphism (SNP) at a time and postpone the integration of inter-marker Linkage-disequilibrium (LD) information in the downstream fine mappings. Recent studies showed that directly incorporating inter-marker connection/correlation into variants detection can help discover novel marginally weak single-nucleotide polymorphisms, which are often missed in conventional genome-wide association studies, and can also help improve disease prediction accuracy.Methods: Single-marker analysis is performed first to detect marginally strong single-nucleotide polymorphisms. Then the whole-genome linkage-disequilibrium spectrum is explored and used to search for high-linkage-disequilibrium connected single-nucleotide polymorphism clusters for each strong single-nucleotide polymorphism detected. Marginally weak single-nucleotide polymorphisms are selected via a joint linear discriminant model with the detected single-nucleotide polymorphism clusters. Prediction is made based on the selected strong and weak single-nucleotide polymorphisms.Results: Several previously identified late-stage age-related macular degeneration susceptibility genes, for example, BTBD16, C3, CFH, CFHR3, HTARA1, are confirmed. Novel genes DENND1B, PLK5, ARHGAP45, and BAG6 are discovered as marginally weak signals. Overall prediction accuracy of 76.8% and 73.2% was achieved with and without the inclusion of the identified marginally weak signals, respectively.Conclusion: Marginally weak single-nucleotide polymorphisms, detected from integrating inter-marker linkage-disequilibrium information, may have strong predictive effects on age-related macular degeneration. Detecting and integrating such marginally weak signals can help with a better understanding of the underlying disease-development mechanisms for age-related macular degeneration and more accurate prognostics.
Factors associated with knowledge and vaccination intention for human papillomavirus on trans girls by their main caregiver: A cross-sectional study
Authors: Domínguez-Riscart Jesus , Ariza-Jimenez Ana-Belen , Baez-Castillo Celia , Mateo-Gavira Isabel 
Published: March 2023

IntroductionTrans women are highly affected by the human papillomavirus (HPV) and are at risk of suffering from HPV-related diseases such as oropharyngeal, anal, penile, or neovaginal neoplasia. HPV vaccination seems to be a good strategy to reduce HPV-related diseases, mainly during the early age before the first sexual intercourse, but only cisgender girls are covered by the National Health Services, while some high-risk groups such as trans girls are not included. Achieving a high vaccination rate is important in the adolescent population, but there are many factors that could affect it, such as lack of knowledge about HPV or fear of side effects by patients and main caregivers. The aim of our study is to analyze the knowledge of trans girls’ main caregivers about HPV-related diseases in the general population and, in particular, in trans women, as well as factors associated with HPV vaccination intention.MethodsA cross-sectional study was performed with the collaboration of main caregivers of adolescent trans girls, between 9 and 16 years old, assisted in two reference centers’ multidisciplinary Gender Diversity Units. Information was requested through a self-completed questionnaire: HPV-related diseases Knowledge Transwomen questionnaire (HPV-TQ) was elaborated based on a 19-item self-administered questionnaire and score was standardized from 0 to 19 points. Percentage of correct answers was calculated and defined by the group of high scores that showed over 70% correct answers.ResultsA total of 65 main caregivers were included. Almost all main caregivers were mothers with a Caucasian ethnicity. The HPV-TQ average score was 11 (3.7) with an average correct answer of 58.1% (19.6). Only 17/65 (26.1%) of main caregivers were highly knowledgeable in HPV. Of 65 trans girls, 14 were already vaccinated (29.8% of trans girls over 12 years old); 78.5% were not vaccinated and only 21.5% had intentions to be vaccinated. The group with a high score in HPV-TQ had a longer follow-up at the transgender unit, a higher maternal vaccination rate, and a positive family history of HPV-related disease, especially in mothers.ConclusionAdolescent trans girls attended to in our units had a low rate and a low intention of vaccination against HPV. Education on and promotion and prevention of transgender HPV-related diseases should probably be implemented to achieve a higher knowledge and vaccination coverage in adolescent trans girls.
PIK3C2A is a prognostic biomarker that is linked to immune infiltrates in kidney renal clear cell carcinoma
Authors: Qin Chengdong , Liu Siyuan , Zhou Shiqi , Wang Qibo , Xia Xianghou , Hu Jiejie , Yuan Xiaohong , Wang Zongping , Yu Yang , Ma Dening 
Published: March 2023

BackgroundPhosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown.MethodsThe expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks.ResultsSignificant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC.ConclusionThese findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells.
Single-cell analyses reveal the dynamic functions of Itgb2+ microglia subclusters at different stages of cerebral ischemia-reperfusion injury in transient middle cerebral occlusion mice model
Authors: Zeng Fanning , Cao Jun , Hong Zexuan , Liu Yujun , Hao Jie , Qin Zaisheng , Zou Xin , Tao Tao 
Published: March 2023

IntroductionThe underlying pathophysiological mechanisms of cerebral ischemia reperfusion injury (CIRI) is intricate, and current studies suggest that neuron, astrocyte, microglia, endothelial cell, and pericyte all have different phenotypic changes of specific cell types after ischemic stroke. And microglia account for the largest proportion after CIRI. Previous transcriptomic studies of ischemic stroke have typically focused on the 24 hours after CIRI, obscuring the dynamics of cellular subclusters throughout the disease process. Therefore, traditional methods for identifying cell types and their subclusters may not be sufficient to fully unveil the complexity of single-cell transcriptional profile dynamics caused by an ischemic stroke.MethodsIn this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used single-cell State Transition Across-samples of RNA-seq data (scSTAR), a new bioinformatics method, to analyze the single-cell transcriptional profile of day 1, 3, and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequences and proteomics data, we found the importance of the integrin beta 2 (Itgb2) gene in post-modeling. And microglia of Itgb2+ and Itgb2- were clustered by the scSTAR method. Finally, the functions of the subpopulations were defined by Matescape, and three different time points after tMCAO were found to exhibit specific functions.ResultsOur analysis revealed a dynamic transcriptional profile of single cells in microglia after tMCAO and explored the important role of Itgb2 contributed to microglia by combined transcriptomics and proteomics analysis after modeling. Our further analysis revealed that the Itgb2+ microglia subcluster was mainly involved in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation, and repair at 1, 3, and 7 days after tMCAO, respectively.DiscussionOur results suggested that Itgb2+ microglia act as a time-specific multifunctional immunomodulatory subcluster during CIRI, and the underlying mechanisms remain to be further investigated.
Acute exercise and high-glucose ingestion elicit dynamic and individualized responses in systemic markers of redox homeostasis
Authors: Thomas Hannah J. , Ang Teddy , Morrison Dale J. , Keske Michelle A. , Parker Lewan 
Published: March 2023

BackgroundBiomarkers of oxidation-reduction (redox) homeostasis are commonly measured in human blood to assess whether certain stimuli (e.g., high-glucose ingestion or acute exercise) lead to a state of oxidative distress (detrimental to health) or oxidative eustress (beneficial to health). Emerging research indicates that redox responses are likely to be highly individualized, yet few studies report individual responses. Furthermore, the effects of complex redox stimuli (e.g., high-glucose-ingestion after exercise) on redox homeostasis remains unclear. We investigated the effect of acute exercise (oxidative eustress), high-glucose ingestion (oxidative distress), and high-glucose ingestion after exercise (both oxidative eu/distress), on commonly measured redox biomarkers in serum/plasma.MethodsIn a randomized crossover fashion, eight healthy men (age: 28 ± 4 years; BMI: 24.5 ± 1.5 kg/m2 [mean ± SD]) completed two separate testing conditions; 1) consumption of a high-glucose mixed-nutrient meal (45% carbohydrate [1.1 g glucose.kg-1], 20% protein, and 35% fat) at rest (control trial), and 2) consumption of the same meal 3 h and 24 h after 1 h of moderate-intensity cycling exercise (exercise trial). Plasma and serum were analyzed for an array of commonly studied redox biomarkers.ResultsOxidative stress and antioxidant defense markers (hydrogen peroxide, 8-isoprostanes, catalase, superoxide dismutase, and nitrate levels) increased immediately after exercise (p &lt; 0.05), whereas nitric oxide activity and thiobarbituric acid reactive substances (TBARS) remained similar to baseline (p &gt; 0.118). Nitric oxide activity and nitrate levels decreased at 3 h post-exercise compared to pre-exercise baseline levels. Depending on when the high-glucose mixed nutrient meal was ingested and the postprandial timepoint investigated, oxidative stress and antioxidant defense biomarkers either increased (hydrogen peroxide, TBARS, and superoxide dismutase), decreased (hydrogen peroxide, 8-isoprostanes, superoxide dismutase, nitric oxide activity, nitrate, and nitrite), or remained similar to pre-meal baseline levels (hydrogen peroxide, 8-isoprostanes, TBARS, catalase, superoxide dismutase and nitrite). Redox responses exhibited large inter-individual variability in the magnitude and/or direction of responses.ConclusionFindings highlight the necessity to interpret redox biomarkers in the context of the individual, biomarker measured, and stimuli observed. Individual redox responsiveness may be of physiological relevance and should be explored as a potential means to inform personalized redox intervention.
Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study
Authors: Yang Ming , Lin Shi-Qi , Liu Xiao-Yue , Tang Meng , Hu Chun-Lei , Wang Zi-Wen , Zhang Qi , Zhang Xi , Song Meng-Meng , Ruan Guo-Tian , Zhang Xiao-Wei , Liu Tong , Xie Hai-Lun , Zhang He-Yang , Liu Chen-An , Zhang Kang-Ping , Li Qin-Qin , Li Xiang-Rui , Ge Yi-Zhong , Liu Yu-Ying , Chen Yue , Zheng Xin , Shi Han-Ping 
Published: March 2023

BackgroundColorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC.MethodsThe clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage.ResultsMultivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P&lt;0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P&lt;0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P&lt;0.001) than the TNM stage.ConclusionThe CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.
Breakthrough infections due to SARS-CoV-2 Delta variant: relation to humoral and cellular vaccine responses
Authors: Buscot Matthieu , Cremoni Marion , Graça Daisy , Brglez Vesna , Courjon Johan , Allouche Jonathan , Teisseyre Maxime , Boyer Laurent , Barrière Jérôme , Chamorey Emmanuel , Carles Michel , Seitz-Polski Barbara 
Published: March 2023

IntroductionCOVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood.MethodsHere, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease.ResultsIn this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form.DiscussionKnowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters.Trial registration numbershttps://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.
Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization
Authors: Hou Tianzhichao , Dai Huajie , Wang Qi , Hou Yanan , Zhang Xiaoyun , Lin Hong , Wang Shuangyuan , Li Mian , Zhao Zhiyun , Lu Jieli , Xu Yu , Chen Yuhong , Gu Yanyun , Zheng Jie , Wang Tiange , Wang Weiqing , Bi Yufang , Ning Guang , Xu Min 
Published: March 2023

ObjectivesOur aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.MethodsWe extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.ResultsTwo taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.ConclusionsGut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.
MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla via targeting IFIT2 in apical periodontitis
Authors: Hu Jing , Huang Xia , Zheng Liwen , Zhang Yuxin , Zeng Huan , Nie Li , Pang Xiaoxiao , Zhang Hongmei 
Published: March 2023

IntroductionPeriapical alveolar bone loss is the common consequence of apical periodontitis (AP) caused by persistent local inflammation around the apical area. Human stem cells from apical papilla (hSCAPs) play a crucial role in the restoration of bone lesions during AP. Studies have recently identified the critical role of microRNAs (miRNAs) involved in AP pathogenesis, but little is known about their function and potential molecular mechanism, especially in the osteogenesis of hSCAPs during AP. Here, we investigated the role of clinical sample-based specific miRNAs in the osteogenesis of hSCAPs.MethodsDifferential expression of miRNAs were detected in the periapical tissues of normal and patients with AP via transcriptomic analysis, and the expression of miR-199a-5p was confirmed by qRT-PCR. Treatment of hSCAPs with miR-199a-5p mimics while loaded onto beta-tricalcium phosphate (β-TCP) ceramic particle scaffold to explore its effect on osteogenesis in vivo. RNA binding protein immunoprecipitation (RIP) and Luciferase reporter assay were conducted to identify the target gene of miR-199a-5p.ResultsThe expression of miR-199a-5p was decreased in the periapical tissues of AP patients, and miR-199a-5p mimics markedly enhanced cell proliferation and osteogenic differentiation of hSCAPs, while miR-199a-5p antagomir dramatically attenuated hSCAPs osteogenesis. Moreover, we identified and confirmed Interferon Induced Protein with Tetratricopeptide Repeats 2 (IFIT2) as a specific target of miR-199a-5p, and silencing endogenous IFIT2 expression alleviated the inhibitory effect of miR-199a-5p antagomir on the osteogenic differentiation of hSCAPs. Furthermore, miR-199a-5p mimics transfected hSCAPs loaded onto beta-tricalcium phosphate (β-TCP) scaffolds induced robust subcutaneous ectopic bone formation in vivo.DiscussionThese results strengthen our understanding of predictors and facilitators of the key AP miRNAs (miR-199a-5p) in bone lesion repair under periapical inflammatory conditions. And the regulatory networks will be instrumental in exploring the underlying mechanisms of AP and lay the foundation for future regenerative medicine based on dental mesenchymal stem cells.
Cytokine concentration in peripheral blood of patients with colorectal cancer
Authors: Li Wenchang , Chen Fangqian , Gao Han , Xu Zhuoqing , Zhou Yu , Wang Shenjie , Lv Zeping , Zhang Yuchen , Xu Zifeng , Huo Jianting , Zhao Jingkun , Zong Yaping , Feng Wenqing , Shen Xiaohui , Wu Zhiyuan , Lu Aiguo 
Published: March 2023

IntroductionThe role of tumour secretory cytokines and peripheral circulatory cytokines in tumour progression has received increasing attention; however, the role of tumour-related inflammatory cytokines in colorectal cancer (CRC) remains unclear. In this study, the concentrations of various cytokines in the peripheral blood of healthy controls and patients with CRC at different stages were compared.MethodsPeripheral blood samples from 4 healthy participants and 22 colorectal cancer patients were examined. Luminex beads were used to evaluate concentration levels of 40 inflammatory cytokines in peripheral blood samples.ResultsIn peripheral blood, compared with healthy controls and early stage (I + II) CRC patients, advanced CRC (III + IV) patients had increased concentrations of mononuclear/macrophage chemotactic-related proteins (CCL7, CCL8, CCL15, CCL2, and MIF), M2 polarization-related factors (IL-1β, IL-4), neutrophil chemotactic and N2 polarization-related cytokines (CXCL2, CXCL5, CXCL6, IL-8), dendritic cells (DCs) chemotactic-related proteins (CCL19, CCL20, and CCL21), Natural killer (NK) cell related cytokines (CXCL9, CXCL10), Th2 cell-related cytokines (CCL1, CCL11, CCL26), CXCL12, IL-2, CCL25, and CCL27, and decreased IFN-γ and CX3CL1 concentrations. The differential upregulation of cytokines in peripheral blood was mainly concentrated in CRC patients with distant metastasis and was related to the size of the primary tumour; however, there was no significant correlation between cytokine levels in peripheral blood and the propensity and mechanism of lymph node metastasis.DiscussionDifferent types of immune cells may share the same chemokine receptors and can co-localise in response to the same chemokines and exert synergistic pro-tumour or anti-tumour functions in the tumour microenvironment. Chemokines and cytokines affect tumour metastasis and prognosis and may be potential targets for treatment.