At the 2-year follow-up, more patients in the DE-CMR-guided group remained free from recurrences compared with the conventional group (70% vs. 39%, respectively, P = 0.007). In univariate Cox-regression analyses, AF pattern [persistent AF, hazard ratio (HR) 2.66 (1.27-5.46), P = 0.006] and the use of DE-CMR [HR 0.36 (0.17-0.79), P = 0.009] predicted recurrences during follow-up; both factors remained independent predictors in multivariate analyses.
The substrate characterization provided by DE-CMR facilitates the identification of anatomical veno-atrial gaps and associates with shorter procedures and better clinical outcomes in repeated AF ablation procedures.
The substrate characterization provided by DE-CMR facilitates the identification of anatomical veno-atrial gaps and associates with shorter procedures and better clinical outcomes in repeated AF ablation procedures.
To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs).
This observational, population-based cohort study enrolled 53236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC.
In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.
In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.During folliculogenesis, the gonadotrophin (GTH)-dependent phase begins at the small antral follicle stage and ends with Graafian follicles. In this study, pregnant mare's serum GTH was used to induce GTH-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. GTH-dependent folliculogenesis consisted of three phases preparation, rapid growth and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid growth phase lasted from 12 to 24 h; in this phase, granulosa cells completed their proliferation, and follicles acquired the capacity for estradiol secretion and ovulation. Meanwhile, the decelerating growth phase occurred between 24 and 48 h of GTH-dependent folliculogenesis. In this phase, the proliferation and expansion of the follicular antrum were reduced, energy metabolism was shifted to oxidative phosphorylation, and cell migration and lipid metabolism were enhanced in preparation for luteinization. We also revealed the key signaling pathways that regulate GTH-dependent folliculogenesis and elucidated the activation sequence of these pathways. A comparison of our RNA-sequencing data with that reported for humans suggested that the mechanisms involved in mouse and human folliculogenesis are evolutionarily conserved. In this study, we draw a detailed atlas of GTH-dependent folliculogenesis, thereby laying the foundation for further investigation of the regulatory mechanisms underlying this process.MicroRNA-106b-5p (miR-106b-5p) is involved in the development of many cancers including colorectal cancer (CRC), and FAT4 is correlated with regulation of growth and apoptosis of cancer cells. The present study aimed to investigate the relation between FAT4 and miR-106b-5p and the underlying mechanism of the two on the development of CRC. Quantitative real-time PCR (qRT-PCR) assay and Western blot (WB) analysis were performed to detect the expressions of messenger RNAs (mRNAs), microRNAs (miRNAs) and proteins. The viability of CRC cells was detected by cell counting kit-8 (CCK-8). Scratch test and transwell assay were performed to measure the migration and invasion of CRC cell. Tumor angiogenesis was simulated by in vitro angiogenesis experiment. Dual-luciferase reporter assay was performed to verify the targeting relation between miR-106b-5p and FAT4. The study found that the expression of FAT4 was down-regulated and that of miR-106b-5p was up-regulated in CRC tissues. Overexpression of FAT4 resulted in decreased proliferation, migration, invasion and angiogenesis of CRC cells, whereas silencing of FAT4 led to the opposite results. In rescue experiment, miR-106b-5p partially reversed the function of FAT4 in CRC cells, thus playing a carcinogenic role by targeting FAT4 in the CRC cells.
The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. In silico and in vitro studies suggest that sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2.
Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. The primary outcomes measured were clinical recovery within 14 days of randomization, time to clinical recovery and all-cause mortality. A two-step approach was used to analyse individual-level patient data. The individual trial statistics were pooled using the random-effects inverse-variance model.
Our search identified eight studies of which three met the inclusion criteria (n = 176 patients); two studies were randomized and one was non-randomized. Baseline characteristics were similar across treatment arms. Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms comd in larger randomized controlled trials.Least absolute shrinkage and selection operator (LASSO) regression is often applied to select the most promising set of single nucleotide polymorphisms (SNPs) associated with a molecular phenotype of interest. While the penalization parameter λ restricts the number of selected SNPs and the potential model overfitting, the least-squares loss function of standard LASSO regression translates into a strong dependence of statistical results on a small number of individuals with phenotypes or genotypes divergent from the majority of the study population-typically comprised of outliers and high-leverage observations. Robust methods have been developed to constrain the influence of divergent observations and generate statistical results that apply to the bulk of study data, but they have rarely been applied to genetic association studies. In this article, we review, for newcomers to the field of robust statistics, a novel version of standard LASSO that utilizes the Huber loss function. We conduct comprehensive simulations and analyze real protein, metabolite, mRNA expression and genotype data to compare the stability of penalization, the cross-iteration concordance of the model, the false-positive and true-positive rates and the prediction accuracy of standard and robust Huber-LASSO. Although the two methods showed controlled false-positive rates ≤2.1% and similar true-positive rates, robust Huber-LASSO outperformed standard LASSO in the accuracy of predicted protein, metabolite and gene expression levels using individual SNP data. The conducted simulations and real-data analyses show that robust Huber-LASSO represents a valuable alternative to standard LASSO in genetic studies of molecular phenotypes.Organoselenium drugs like selenourea (SeU) and selenocystine (SeC) are found to exhibit several medicinal properties and have reported roles in the field of cancer prevention. However, studies related to their interactions with the major erythroid protein, hemoglobin (HbA) are still in dearth despite being of prime importance. In view of this it was considered essential to investigate the interaction of these two anticancer drugs with Hb. Both the drugs showed significant changes in absorption spectra of Hb at wavelength of maximum absorption (λmax) 630 nm. https://www.selleckchem.com/products/tecovirimat.html SeU itself had no effect on the absorbance value at 630 nm with respect to time even with 400 µM concentration. However, it was rapidly converted to nanoselenium in presence of nitrite and there was an increase in the absorbance rate at 630 nm from 3.39 × 10-3 min-1 (without nitrite) to 8.94 × 10-3 min-1 in presence of nitrite (200 µM) owing to the generation of reactive oxygen species in the medium. Although the generation and increase in peak intensity at 630 nm in Hb generally indicates the formation and rise in the levels of methemoglobin (metHb), nanoselenium was observed to follow a different path. Instead of causing oxidation of Fe2+ to Fe3+ responsible for metHb formation, nanoselenium was found to interact with the protein part, thereby causing changes in its secondary structure which is reflected in the increasing absorbance at 630 nm. SeC, however showed a different effect. It was shown to act as a novel agent to reduce nitrite induced metHb formation in a dose dependent manner. The efficiency of SeC was again found to be less in diabetic blood samples as compared to the nondiabetic ones. For similar ratio of metHb to SeC (18), % reduction of metHb was found to be 27.46 ± 0.82 and 16.1 ± 2.4 for non-diabetic and diabetic samples respectively with a two tailed p value much less than 0.05 which implies that the data is highly significant.
Privacy-related concerns can prevent equitable participation in health research by US Indigenous communities. However, studies focused on these communities' views regarding health data privacy, including systematic reviews, are lacking.
We conducted a systematic literature review analyzing empirical, US-based studies involving American Indian/Alaska Native (AI/AN) and Native Hawaiian or other Pacific Islander (NHPI) perspectives on health data privacy, which we define as the practice of maintaining the security and confidentiality of an individual's personal health records and/or biological samples (including data derived from biological specimens, such as personal genetic information), as well as the secure and approved use of those data.
Twenty-one studies involving 3234 AI/AN and NHPI participants were eligible for review. The results of this review suggest that concerns about the privacy of health data are both prevalent and complex in AI/AN and NHPI communities. Many respondents raised concerns about the potential for misuse of their health data, including discrimination or stigma, confidentiality breaches, and undesirable or unknown uses of biological specimens.