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Objective: The hepatitis B virus (HBV)-polymerase region overlaps pre-S/S genes with high epitope density and plays an essential role in viral replication. We investigated whether genetic variation in the polymerase region determined long-term dynamics of viral load and the risk of hepatitis B progression in a population-based cohort study. Methods: We sequenced the HBV-polymerase region using baseline plasma from treatment-naïve individuals with HBV-DNA levels≥1000 copies/mL in a longitudinal viral-load study of participants with chronic HBV infection followed-up for 17 years, and obtained sequences from 575 participants (80% with HBV genotype Ba and 17% with Ce). Results: Patterns of viral sequence diversity across phases (i.e., immune-tolerant, immune-clearance, non/low replicative, and hepatitis B e antigen (HBeAg)-negative hepatitis phases) of HBV-infection, which were associated with viral and clinical features at baseline and during follow-up, were similar between HBV genotypes, despite greater diversity for genotype Ce vs. Ba. Irrespective of genotypes, however, HBeAg-negative participants had 1.5-to-2-fold higher levels of sequence diversity than HBeAg-positive participants (P<0.0001). Furthermore, levels of viral genetic divergence from the population consensus sequence, estimated by numbers of nucleotide substitutions, were inversely associated with long-term viral load even in HBeAg-negative participants. A mixed model developed through analysis of the entire HBV-polymerase region identified 153 viral load-associated single nucleotide polymorphisms in overall and 136 in HBeAg-negative participants, with distinct profiles between HBV genotypes. These polymorphisms were most evident at sites within or flanking T-cell epitopes. Seven polymorphisms revealed associations with both enhanced viral load and a more than 4-fold increased risk of hepatocellular carcinoma and/or liver cirrhosis. Conclusions: The data highlight a role of viral genetic divergence in the natural course of HBV-infection. Interindividual differences in the long-term dynamics of viral load is not only associated with accumulation of mutations in HBV-polymerase region, but differences in specific viral polymorphisms which differ between genotypes. [ABSTRACT FROM AUTHOR]

Background: The development and progression of colorectal cancer (CRC) involve a complex process of multiple genetic changes. Tumor suppressor p53 is capable of determining the fate of CRC cells. However, the role of a p53-inducible modulator, ribosomal protein S27-like (RPS27L), in CRC is unknown. Methods: Here, the differential expression of RPS27L was examined in the feces and colonic tissues of CRC patients, to explore its possible correlation with patient survival and to investigate the cellular mechanisms underlying their clinical outcomes. Eighty intermediate-stage CRC patients (42 at stage II and 38 at stage III) were divided into two groups according to their fecal RPS27L mRNA levels. The survival probabilities of the groups were estimated using the Kaplan–Meier method. The RPS27L protein in the colonic tissues of stage III patients with different prognoses was further examined immunohistochemically. RPS27L expression in LoVo cells was manipulated to examine the possible cellular responses in vitro. Results: Elevated RPS27L expression, in either feces or tissues, was related to a better prognosis. In vitro, RPS27L-expressing LoVo cells ceased DNA synthesis and apoptotic activity while the expression of their DNA repair molecules was upregulated. Conclusions: Elevated RPS27L may improve the prognoses of certain CRC patients by enhancing the DNA repair capacity of their colonic cells, and can be determined in feces. By integrating clinical, molecular, and cellular data, our study demonstrates that fecal RPS27L may be a useful index for predicting prognoses and guiding personalized therapeutic strategies, especially in patients with intermediate-stage CRC. [ABSTRACT FROM AUTHOR]

Background: The liver is the most common target organ in the metastasis of colorectal cancer (CRC). Synchronous liver metastases may confer a poorer prognosis than metachronous metastases, and genetic alterations and an inflammatory response have also been associated with a poor prognosis in cases of a liver metastasis arising from CRC. However, few studies have examined the relationship between KRAS mutations and inflammatory status in CRC, especially with respect to liver metastases. Methods: The effect of the activated mitogen-activated protein kinase pathway and another protein involved in inflammation, C-reactive protein, in liver metastases were examined. We aimed to determine the impact of the CRP-specific single nucleotide polymorphism (SNP) rs7553007 in liver metastasis on the CRC-specific survival (CSS) of patients after colorectal liver metastasectomy. Results: We found no significant differences in genotype distributions and allele frequencies at the CRP SNP rs7553007 between CRC patients with liver metastasis and the control group. CSS rates were low in the subgroup of patients with synchronous metastasis with the A-allele (A/A and A/G) at rs7553007 or mutated KRAS/BRAF in liver metastatic specimens. Furthermore, the CRP SNP rs7553007 (hazard ratio [HR] = 1.101; 95% confidence interval [CI] = 1.011–1.200; P = 0.027) and KRAS/BRAF mutations (HR = 2.377; 95% CI = 1.293–4.368; P = 0.005) remained predictive for the CSS of CRC patients with synchronous liver metastasis in multivariate analysis. Conclusions: Both the CRP SNP rs7553007 and KRAS/BRAF mutations were independent prognostic factors for CRC patients with synchronous liver metastasis. [ABSTRACT FROM AUTHOR]

Background: Facilitating the childbirth process is a global issue. Many strategies have been developed to cope with labor pain and improve the delivery experience and satisfaction of pregnant women. The results of different types of medical intervention on women's expectant pain have been varied. Therefore, this systematic review was aimed at summarizing the body of evidence regarding the effects of various non-pharmacological coping strategies for reducing labor pain. Methods: The review was conducted according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched the articles published between 1989 and 2020 in six electronic databases: PubMed, MEDLINE, CINAHL, WOS, PsycARTICLES, and Airiti Library, and the reference lists of the Clinical Trial Registry. Twenty studies were identified, with eight eligible studies included in the Bayesian network meta-analysis. Results: Eight studies with 713 participants were included in the meta-analysis with nine different non-pharmacological strategies for reducing labor pain. The traditional meta-analysis demonstrated that the non-pharmacological coping strategies were effective in reducing labor pain. Of these interventional strategies, the ranking probabilities analysis of the network meta-analysis suggested that the Bonapace Method may be the most effective strategy in reducing labor pain, followed by acupressure. Conclusions: Non-pharmacological coping strategies can reduce labor pain while maintaining an effective and satisfactory delivery experience. This systematic review, by synthesizing the body of evidence, demonstrated that non-pharmacological coping strategies are effective in reducing labor pain. Furthermore, as demonstrated in the network meta-analysis, the Bonapace Method, modulating birth pain by involving the father, is the most effective non-pharmacological intervention for reducing labor pain. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of chronic obstructive pulmonary disease (COPD) as a comorbidity in heart failure has been well documented. However, the role of pulmonary function indices in patients with heart failure and preserved ejection fraction (HFpEF) remains to be elucidated. Methods: Subjects with HFpEF received pulmonary function tests and echocardiogram. Total lung capacity (TLC), residual volume (RV), forced expiratory flow rate between 25% and 75% of vital capacity (FEF25-75), forced expiratory volume in the 1st second (FEV1), forced vital capacity (FVC), and vital capacity (VC) were measured. Echocardiographic indices, including pulmonary artery systolic pressure (PASP), the ratio of early ventricular filling flow velocity to the septal mitral annulus tissue velocity (E/e'), and left ventricular mass (LVM), were recorded. National Death Registry was linked for the identification of mortality. Results: A total of 1194 patients (72.4±13.2 years, 59% men) were enrolled. PASP, E/e' and LVM were associated with either obstructive (RV/TLC, FEV1 and FEF25-75) or restrictive (VC and TLC) ventilatory indices. During a mean follow-up of 23.0±12.8 months, 182 patients died. Subjects with COPD had a lower survival rate than those without COPD. While VC, FVC, RV/TLC, and FEV1 were all independently associated with all-cause mortality in patients without COPD, only FEF25-75 was predictive of outcomes in those with COPD. Conclusions: The abnormalities of pulmonary function were related to the cardiac hemodynamics in patients with HFpEF. In addition, these ventilatory indices were independently associated with long-term mortality, especially in those without COPD. [ABSTRACT FROM AUTHOR]

Background: Heart failure with mid-range ejection fraction (HFmrEF) has been proposed as a new phenotype of heart failure. We therefore investigated the pulsatile hemodynamic characteristics and outcomes in patients with HFmrEF, in comparison with those with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Methods: The study was composed of two cohorts of patients hospitalized due to acute heart failure. Pulsatile hemodynamic measures, including carotid-femoral pulse wave velocity (cf-PWV), carotid pulse pressure (cPP), amplitude of the backward pressure wave (Pb) and carotid augmentation index (cAIx), were recorded on admission and before discharge in Cohort A (n = 230, mean age 69.9 ±15.4 years), and long-term follow-up was performed in Cohort B (n = 2677, mean age 76.3 ± 33.4 years). Results: In Cohort A, patients with HFmrEF had persistently greater cf-PWV, cPP, Pb, and cAI than those with HFrEF, both on admission and before discharge. In contrast, patients with HFmrEF and HFpEF had similar pulsatile hemodynamic characteristics. In cohort B, patients with HFmrEF and HFrEF had similar three-year mortality rates and both were significantly higher than that in patients with HFpEF (both P values < 0.05). Conclusions: Patients with HFmrEF were characterized by a worse left ventricular systolic function than patients with HFpEF and excessive wave reflections than patients with HFrEF. Future studies are required to confirm that the unfavorable ventriculo-arterial coupling in HFmrEF might play a role in the pathogenesis of high long-term mortality in these patients. [ABSTRACT FROM AUTHOR]

The interplay between copy number variation (CNV) and differential gene expression may be able to shed light on molecular process underlying breast cancer and lead to the discovery of cancer-related genes. In the current study, genes concurrently identified in array comparative genomic hybridization (CGH) and gene expression microarrays were used to derive gene signatures for Han Chinese breast cancers. We performed 23 array CGHs and 81 gene expression microarrays in breast cancer samples from Taiwanese women. Genes with coherent patterns of both CNV and differential gene expression were identified from the 21 samples assayed using both platforms. We used these genes to derive signatures associated with clinical ER and HER2 status and disease-free survival. Distributions of signature genes were strongly associated with chromosomal location: chromosome 16 for ER and 17 for HER2. A breast cancer risk predictive model was built based on the first supervised principal component from 16 genes (RCAN3, MCOLN2, DENND2D, RWDD3, ZMYM6, CAPZA1, GPR18, WARS2, TRIM45, SCRN1, CSNK1E, HBXIP, CSDE1, MRPL20, IKZF1, and COL20A1), and distinct survival patterns were observed between the high- and low-risk groups from the combined dataset of 408 microarrays. The risk score was significantly higher in breast cancer patients with recurrence, metastasis, or mortality than in relapse-free individuals (0.241 versus 0, P<0.001). The concurrent gene risk predictive model remained discriminative across distinct clinical ER and HER2 statuses in subgroup analysis. Prognostic comparisons with published gene expression signatures showed a better discerning ability of concurrent genes, many of which were rarely identifiable if expression data were pre-selected by phenotype correlations or variability of individual genes. We conclude that parallel analysis of CGH and microarray data, in conjunction with known gene expression patterns, can be used to identify biomarkers with prognostic values in breast cancer. [ABSTRACT FROM AUTHOR]