DataSheet1_Immune Classification and Immune Landscape Analysis of Triple-Negative Breast Cancer.ZIP

Background: To classify triple-negative breast cancer (TNBC) immunotyping using the public database, analyze the differences between subtypes in terms of clinical characteristics and explore the role and clinical significance of immune subtypes in TNBC immunotherapy.Methods: We downloaded TNBC data from the cBioPortal and GEO databases. The immune genes were grouped to obtain immune gene modules and annotate their biological functions. Log-rank tests and Cox regression were used to evaluate the prognosis of immune subtypes (IS). Drug sensitivity analysis was also performed for the differences among immune subtypes in immunotherapy and chemotherapy. In addition, dimension reduction analysis based on graph learning was utilized to reveal the internal structure of the immune system and visualize the distribution of patients.Results: Significant differences in prognosis were observed between subtypes (IS1, IS2, and IS3), with the best in IS3 and the worst in IS1. The sensitivity of IS3 to immunotherapy and chemotherapy was better than the other two subtypes. In addition, Immune landscape analysis found the intra-class heterogeneity of immune subtypes and further classified IS3 subtypes (IS3A and IS3B). Immune-related genes were divided into seven functional modules (The turquoise module has the worst prognosis). Five hub genes (RASSF5, CD8A, ICOS, IRF8, and CD247) were screened out as the final characteristic genes related to poor prognosis by low expression.Conclusions: The immune subtypes of TNBC were significantly different in prognosis, gene mutation, immune infiltration, drug sensitivity, and heterogeneity. We validated the independent role of immune subtypes in tumor progression and immunotherapy for TNBC. This study provides a new perspective for personalized immunotherapy and the prognosis evaluation of TNBC patients in the future.</p

Image_2_Causal Relationships Between Total Physical Activity and Ankylosing Spondylitis: A Mendelian Randomization Study.tif

BackgroundCurrently, there is little literature about the association between physical activity (PA) and the risk of ankylosing spondylitis (AS). The present study aimed to understand the causal relationships between PA and AS.MethodsWe performed two-sample Mendelian randomization (MR) using publicly released genome-wide association studies summary statistics to estimate the causal associations of PA with AS risk. The inverse variance weighted (IVW) method was utilized as primary MR analysis. Furthermore, sensitivity, pleiotropy, and heterogeneity analyses were then conducted to assess the robustness of the findings of the present study.ResultsResults of the IVW analysis suggested a protective relationship between accelerometer-based PA and AS (average acceleration, odds ratio [OR] = 0.9995, 95% CI, 0.9988–0.9999, P = 0.014). On the contrary, there was no causal relationship between accelerometer-based PA (acceleration fraction >425 mg; OR = 0.9981, 95% CI = 0.9936–1.0026, P = 0.402) and AS. Furthermore, there was no significant relationship between self-reported vigorous PA and AS (OR = 1.0005, 95% CI = 0.9875–1.0136, P = 0.943), or even between self-reported moderate-to-vigorous PA and AS (OR = 1.0000, 95% CI, 0.9947–1.0052; P = 0.990).ConclusionsThe use of genetic approach in the present study revealed that total physical activity (TPA) has a protective relationship with AS risk. Furthermore, it was evident that vigorous PA or moderate-to-vigorous physical levels are not causally associated with AS. Therefore, the present study evidently supports the hypothesis that enhancing TPA rather than PA intensity is an effective prevention strategy for AS.</p

original data for all figures

The original data for all figures in the manuscript

DataSheet_1_Causal Relationships Between Total Physical Activity and Ankylosing Spondylitis: A Mendelian Randomization Study.docx

BackgroundCurrently, there is little literature about the association between physical activity (PA) and the risk of ankylosing spondylitis (AS). The present study aimed to understand the causal relationships between PA and AS.MethodsWe performed two-sample Mendelian randomization (MR) using publicly released genome-wide association studies summary statistics to estimate the causal associations of PA with AS risk. The inverse variance weighted (IVW) method was utilized as primary MR analysis. Furthermore, sensitivity, pleiotropy, and heterogeneity analyses were then conducted to assess the robustness of the findings of the present study.ResultsResults of the IVW analysis suggested a protective relationship between accelerometer-based PA and AS (average acceleration, odds ratio [OR] = 0.9995, 95% CI, 0.9988–0.9999, P = 0.014). On the contrary, there was no causal relationship between accelerometer-based PA (acceleration fraction >425 mg; OR = 0.9981, 95% CI = 0.9936–1.0026, P = 0.402) and AS. Furthermore, there was no significant relationship between self-reported vigorous PA and AS (OR = 1.0005, 95% CI = 0.9875–1.0136, P = 0.943), or even between self-reported moderate-to-vigorous PA and AS (OR = 1.0000, 95% CI, 0.9947–1.0052; P = 0.990).ConclusionsThe use of genetic approach in the present study revealed that total physical activity (TPA) has a protective relationship with AS risk. Furthermore, it was evident that vigorous PA or moderate-to-vigorous physical levels are not causally associated with AS. Therefore, the present study evidently supports the hypothesis that enhancing TPA rather than PA intensity is an effective prevention strategy for AS.</p

Image_1_Causal Relationships Between Total Physical Activity and Ankylosing Spondylitis: A Mendelian Randomization Study.tif

BackgroundCurrently, there is little literature about the association between physical activity (PA) and the risk of ankylosing spondylitis (AS). The present study aimed to understand the causal relationships between PA and AS.MethodsWe performed two-sample Mendelian randomization (MR) using publicly released genome-wide association studies summary statistics to estimate the causal associations of PA with AS risk. The inverse variance weighted (IVW) method was utilized as primary MR analysis. Furthermore, sensitivity, pleiotropy, and heterogeneity analyses were then conducted to assess the robustness of the findings of the present study.ResultsResults of the IVW analysis suggested a protective relationship between accelerometer-based PA and AS (average acceleration, odds ratio [OR] = 0.9995, 95% CI, 0.9988–0.9999, P = 0.014). On the contrary, there was no causal relationship between accelerometer-based PA (acceleration fraction >425 mg; OR = 0.9981, 95% CI = 0.9936–1.0026, P = 0.402) and AS. Furthermore, there was no significant relationship between self-reported vigorous PA and AS (OR = 1.0005, 95% CI = 0.9875–1.0136, P = 0.943), or even between self-reported moderate-to-vigorous PA and AS (OR = 1.0000, 95% CI, 0.9947–1.0052; P = 0.990).ConclusionsThe use of genetic approach in the present study revealed that total physical activity (TPA) has a protective relationship with AS risk. Furthermore, it was evident that vigorous PA or moderate-to-vigorous physical levels are not causally associated with AS. Therefore, the present study evidently supports the hypothesis that enhancing TPA rather than PA intensity is an effective prevention strategy for AS.</p

Table_1_Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.xlsx

BackgroundThe gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored.MethodsGenome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings.ResultsFour bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333–51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333–51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033–10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096–7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148–0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125–0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020–0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037–0.769, p = 0.021).ConclusionThese findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.</p

Table_3_Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.xlsx

BackgroundThe gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored.MethodsGenome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings.ResultsFour bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333–51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333–51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033–10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096–7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148–0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125–0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020–0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037–0.769, p = 0.021).ConclusionThese findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.</p

Table_2_Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.xlsx

BackgroundThe gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored.MethodsGenome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings.ResultsFour bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333–51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333–51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033–10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096–7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148–0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125–0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020–0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037–0.769, p = 0.021).ConclusionThese findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.</p

Additional file 1 of Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer

Supplementary Fig.1. Representative images of IH

Additional file 1 of Injectable exosome-functionalized extracellular matrix hydrogel for metabolism balance and pyroptosis regulation in intervertebral disc degeneration

Additional file 1: Table S1. Comparison of dECM@exo with ECM scaffolds and exosomedelivery materials in IVDD