The lifetime cost estimation of human papillomavirus-related diseases in China : a modeling study

Objectives: To estimate the lifetime treatment costs of patients with human papillomavirus (HPV) infection-related diseases in China and to provide cost estimates for the economic evaluation of HPV intervention strategies. Methods: We extracted real-world hospital data from 2012 to 2019 and screened for subjects who met the criteria of clinical diagnosis of HPV-related diseases to obtain country-specific inputs into a Markov decision model. The model simulated lifetime treatment costs for HPV from the perspective of a national payer. A 5% discount rate was applied. Costs were converted and inflated to 2020 US dollars (USD) Results: Using 2021 as the base year, the lifetime costs per patient for carcinoma in situ, local metastasis, and distant metastasis cervical cancer are $24,208 (95$19,562 (95%CI: 14,456-25,567), and $17,599 (95$17,593 (95%CI: 14,962-23,596), $17,120 (95$22,411 (95%CI: 12,172-22,249), respectively. The base-case lifetime cost per patient for different stages of vulvar cancer/penile cancer/anal cancer/oral cancer/oropharyngeal cancer/laryngeal cancer falls within $17,120-$58,236. Conclusions: Using real-world data, we calculated lifetime treatment costs of HPV-related cancer in China and found that the lifetime cost for patients exceeded $17,000 for various stages of disease. The national burden of HPV-related disease could be significantly reduced by eliminating HPV infection

A binary additive stream cipher based on permutations

Both stream ciphers and block ciphers can be used to provide data confidentiality service. Stream ciphers are preferred in many applications, since they can destroy statistical properties of natural languages to some extent. However, it seems hard to design a stream cipher with many proven security properties. The objective of this paper is to present a binary stream cipher which is secure with respect to a number of attacks, and has reasonable performance. The advantage of the stream cipher over existing ones is that it has more proven security properties

A simple stream cipher with proven properties

Both stream ciphers and block ciphers can be used to provide data confidentiality service. Stream ciphers are preferred in many applications, since they can destroy statistical properties of natural languages to some extent. However, it seems hard to design a stream cipher with many proven security properties. The objective of this paper is to present a binary stream cipher which is secure with respect to a number of attacks, and has reasonable performance. The advantage of the stream cipher over existing ones is that it has more proven security properties. © 2011 Springer Science + Business Media, LLC

MicroRNAs secreted by human embryos could be potential biomarkers for clinical outcomes of assisted reproductive technology

Introduction: MicroRNAs (miRNAs) are important regulators of many biological functions, including embryo implantation and development. Recently, it has been reported that miRNAs in biofluids are predictive for physiological and pathological processes. Objectives: In this study, we aim to investigate whether the miRNAs secreted by human embryos in culture medium can be used as embryonic biomarkers. Methods: The culture media were prospectively collected from embryos of patients at reproductive medicine center with informed consent. A high-throughput miRNA sequencing method was applied to detect the miRNA profiles in the human embryo culture media. After bioinformatics analysis and screening of differentially expressed miRNAs, quantitative real-time polymerase chain reaction (qRT-PCR) assay was subsequently performed to further confirm the sequencing results with mixed samples. Furthermore, we performed droplet digital PCR (ddPCR) to verify the target miRNAs at single sample level. Receiver operating characteristic (ROC) analyses were performed for differentially expressed miRNAs. Results: Compared with embryos with failed pregnancy, the embryos with successful pregnancy secreted different miRNA profiles into the culture media, which were predicted to be involved in multiple biological processes. Validated by droplet digital polymerase chain reaction (ddPCR), the expression of hsa-miR-26b-5p and hsa-miR-21-5p in the culture media of cleavage embryos with successful pregnancy was significantly lower than that of embryos with failed pregnancy. Moreover, the Receiver Operating Characteristic (ROC) curve analysis indicated that hsa-miR-26b-5p and hsa-miR-21-5p could serve as potential biomarkers for reproductive outcomes. Conclusion: Together, our findings highlight the important predictive potential of miRNAs secreted by human embryos in culture media, which is meaningful for non-invasive embryo selection in assisted reproductive technology

MethylRAD Sequencing Technology Reveals DNA Methylation Characteristics of <i>Apostichopus japonicus</i> of Different Ages

The A. japonicus industry has expanded significantly, but no research has focused on determining the age of A. japonicus during farming. Correctly estimating the age of A. japonicus can provide a decision-making basis for the breeding process and data for the protection of A. japonicus aquatic germplasm resources. DNA methylation levels in the body wall of Apostichopus japonicus at 4 months, 1 year, 2 years, and 3 years old were determined using MethylRAD-Seq, and differentially methylated genes were screened. A total of 441 and 966 differentially methylated genes were detected at the CCGG and CCWGG sites, respectively. Aspartate aminotransferase, succinate semialdehyde dehydrogenase, isocitrate dehydrogenase, the histone H2AX, heat shock protein Hsp90, aminopeptidase N, cell division cycle CDC6, Ras GTPase activating protein (RasGAP), slit guidance ligand slit1, integrin-linked kinase ILK, mechanistic target of rapamycin kinase Mtor, protein kinase A Pka, and autophagy-related 3 atg3 genes may play key roles in the growth and aging process of A. japonicus. This study provides valuable information regarding age-related genes for future research, and these candidate genes can be used to create an “epigenetic clock”

Whole-genome resequencing reveals genetic differences and the genetic basis of parapodium number in Russian and Chinese Apostichopus japonicus

Abstract Background Apostichopus japonicus is an economically important species in the global aquaculture industry. Russian A. japonicus, mainly harvested in the Vladivostok region, exhibits significant phenotypic differentiation, including in many economically important traits, compared with Chinese A. japonicus owing to differences in their habitat. However, both the genetic basis for the phenotypic divergence and the population genetic structure of Russian and Chinese A. japonicus are unknown. Result In this study, 210 individuals from seven Russian and Chinese A. japonicus populations were sampled for whole-genome resequencing. The genetic structure analysis differentiated the Russian and Chinese A. japonicus into two groups. Population genetic analyses indicated that the Russian population showed a high degree of allelic linkage and had undergone stronger positive selection compared with the Chinese populations. Gene ontology terms enriched among candidate genes with group selection analysis were mainly involved in immunity, such as inflammatory response, antimicrobial peptides, humoral immunity, and apoptosis. Genome-wide association analysis yielded eight single-nucleotide polymorphism loci significantly associated with parapodium number, and these loci are located in regions with a high degree of genomic differentiation between the Chinese and Russia populations. These SNPs were associated with five genes. Gene expression validation revealed that three of these genes were significantly differentially expressed in individuals differing in parapodium number. AJAP08772 and AJAP08773 may directly affect parapodium production by promoting endothelial cell proliferation and metabolism, whereas AJAP07248 indirectly affects parapodium production by participating in immune responses. Conclusions This study, we performed population genetic structure and GWAS analysis on Chinese and Russian A. japonicus, and found three candidate genes related to the number of parapodium. The results provide an in-depth understanding of the differences in the genetic structure of A. japonicus populations in China and Russia, and provide important information for subsequent genetic analysis and breeding of this species

Altered expression of the L-arginine/nitric oxide pathway in ovarian cancer: metabolic biomarkers and biological implications

Abstract Motivation Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. Methods A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). Results Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. Conclusion Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test