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Hepatocellular carcinoma after treatment of hepatitis C with direct-acting antivirals: a critical re-appraisal
No full textSoon after introducing direct-acting antiviral agents (DAAs) for chronic hepatitis C treatment, there began a debate over the possibility of hepatocellular carcinoma (HCC) after viral clearance. Although several reports suggested that the question has been answered negatively, other reports suggested the opposite. The present review presents data in favor and against the null hypothesis and analyzes the scientific background of the possible participation of DAAs in HCC development. The reasons for the discrepancy among studies are presented. These include heterogeneity of patient selection, the nature of the studies, and the tumors themselves are responsible for varying results. Exogenous factors like alcohol consumption or metabolic syndrome confound these findings and suggest the need for statistical adjustments. The need for careful attention to the statistical details is exemplified, and the significant points of almost universal agreements are identified. The conclusion is that the definitive study is impossible for ethical and scientific reasons, and the physician should not ignore even simple personal observations and screening of all patients with extensive fibrosis in HCC, irrespective of sustained virologic response, until a robust, reliable prognostic model can be invented
Local causal pathway discovery for single-cell RNA sequencing count data: a benchmark study
No full textAim: Recent developments in single-cell RNA sequencing (scRNAseq) and analysis have revealed regulatory behaviors not previously described using bulk analysis. scRNAseq features resolution at the level of the individual cell and provides opportunities for identifying cell type-specific gene regulatory networks. The technology promises to discover biomarkers and targeted treatments with enhanced effectiveness and reduced side effects. Pathway reverse engineering and causal algorithms have been validated in bulk sequencing transcriptomic data successfully for gene regulatory network reconstruction. In the current study, we evaluated the performance of local causal discovery algorithms for de novo reconstruction of local gene regulatory networks tailored to scRNAseq count data.Method: We benchmarked the performance of the state-of-the-art local causal discovery algorithm generalized local learning with five conditional independent tests in controlled conditions (simulated count data) and real-world single-cell RNA sequencing datasets.Results: The simulation study showed that local causal discovery methods with appropriate conditional independence tests could result in excellent discovery performance (given a sufficient sample size). As expected, various conditional independence tests possess different power-sample characteristics. The discovery performance for all tested conditional independence tests on real-world data is relatively low, potentially due to imperfect standards or deviation of simulated data distribution from real-world data.Conclusion: Our findings provide insights and practical guidance for applying causal discovery methods to single-cell RNAseq data for gene regulatory network reconstruction
A report and review of the recurrent c.811C>T variant and mutation spectrum of Kindler syndrome in East Asians: a diagnostic odyssey of 2 weeks versus 49 years
No full textKindler Syndrome (KS) is one of the rarest subtypes of epidermolysis bullosa (EB). It is characterised by congenital blistering, skin fragility, photosensitivity, and poikilodermatous skin changes. It is an autosomal recessive condition with an established disease-causing mechanism of having biallelic pathogenic variants in the FERMT1 gene. Multiple variants have been reported worldwide since the discovery in 1954. This case report describes two patients of Chinese descent with molecularly confirmed KS, one diagnosed in infancy while the other in mid-adulthood. It highlights the importance and clinical utility of diagnosing KS in children versus adults. The identification of recurrent c.811C>T variant in both patients also expedited the review of local databases and the existing mutation spectrum KS in East Asians
Ionic conductivity and mechanical properties of the solid electrolyte interphase in lithium metal batteries
No full textWith the fullness of time, metallic lithium (Li) as an anode could become highly promising for high-energy-density batteries. Theoretically, using Li metal as the negative electrode can result in higher theoretical capacity and lower oxidation voltage and density than in current commercially available batteries. During the charge/discharge process, however, metallic Li shows unavoidable drawbacks, such as dendritic growth, causing capacity degradation and a solid electrolyte interphase (SEI) layer derived from the side reactions between the Li metal anode and the electrolyte, resulting in depletion of the electrolyte. The formation of a suitable SEI is crucial to avoid the side reactions at the interface by circumventing direct contact. Unavoidable dendritic growth at the Li metal anode can be controlled by its ionic conductivity. Furthermore, the SEI is also required as a mechanical reinforcement for withstanding the volume change and suppressing dendritic growth in the Li metal anode. A limiting factor due to complex SEI formation must be considered from the perspectives of chemical and mechanical properties. To further enhance the cycling performance of Li metal batteries, an in-depth understanding of the SEI needs to be achieved to clarify these issues. In this mini review, we focus on the SEI, which consists of various deposited components, and discuss its ionic conductivity and mechanical strength for applications in electric vehicles
The role of paracrine crosstalk between myeloid and endothelial cells in myocardial angiogenesis and infarcted heart repair
No full textTrilayer PVDF nanocomposites with significantly enhanced energy density and energy efficiency using 0.55Bi0.5Na0.5TiO3-0.45(Sr0.7Bi0.2)TiO3 nanofibers
No full textThe development of dielectric capacitors with high energy density and energy efficiency is of great significance in the modern electronic components market. To reduce the high energy loss of Bi0.5Na0.5TiO3, 0.55Bi0.5Na0.5TiO3-0.45(Sr0.7Bi0.2)TiO3 (BNT-BST) nanofibers with a high aspect ratio are synthesized via electrospinning. To achieve a high energy density, the design of a symmetric trilayer nanocomposite consisting of a BNT-BST/polyvinylidene difluoride (PVDF) layer with a high dielectric constant sandwiched between two layers of pure PVDF is herein described. The trilayer structure can effectively alleviate the electric field concentration effect, resulting in a considerably enhanced breakdown strength and improved discharge energy density. The maximum discharge energy density of 17.37 J/cm3 at 580 kV/mm could be achieved in the symmetric trilayer nanocomposite with a BNT-BST/PVDF middle layer, which is 90.5% greater than that achieved using pure PVDF (9.21 J/cm3 at 450 kV/mm). This study presents a new case for developing dielectric capacitors with high energy density
Contrast-enhanced ultrasound for hepatocellular carcinoma detection and diagnosis in the context of nonalcoholic fatty liver disease
No full textThe prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide and is projected to become a major etiology of cirrhosis and hepatocellular carcinoma (HCC). HCC occurs more commonly in NAFLD patients who develop cirrhosis, though HCC is known to occur in the setting of noncirrhotic NAFLD as well. This is of particular importance given that the American College of Radiology (ACR) CT/MRI Liver Reporting and Data System (LI-RADS) algorithm may only be applied to a certain population of patients, and this population does not include those with noncirrhotic NAFLD. Conventional ultrasound (US) has long been in use for HCC surveillance, but contrast-enhanced US (CEUS) is a relatively newer modality, growing in use for assessment of liver lesions, and its use in HCC diagnosis has been formalized with CEUS LI-RADS. The use of US and CEUS in the assessment of liver lesions in NAFLD patients involves the consideration of certain particular nuances, and familiarity with these considerations will continue increasing in importance as the disease becomes more common
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