Notes

[Suggestions for the nomenclature of liver cancer].
Foveal hypoplasia is the major cause of visual loss. Here we report an isolated foveal hypoplasia patient without nystagmus. It is very rare, and its etiology is not completely understood. Using whole-exome sequencing and foveal hypoplasia-related gene filtering from a family with two generations, we identified a novel variant c.859T>C (p.S287P) and a rare non-frameshift variant c.229_230insGGG (p.Arg77_Glu78insGly) in the tyrosinase (TYR) gene that co-segregated in the affected member of this family. find more The compound heterozygous variants inherited in the proband were confirmed by Sanger sequencing and predicted from in silico studies to have an effect on protein function. In conclusion, our finding extends the spectrum of TYR variants and supports the important role of TYR in the development of eyes.Mutual exclusivity analyses provide an effective tool to identify driver genes from passenger genes for cancer studies. Various algorithms have been developed for the detection of mutual exclusivity, but controlling false positive and improving accuracy remain challenging. We propose a forward selection algorithm for identification of mutually exclusive gene sets (FSME) in this paper. The method includes an initial search of seed pair of mutually exclusive (ME) genes and subsequently including more genes into the current ME set. Simulations demonstrated that, compared to recently published approaches (i.e., CoMEt, WExT, and MEGSA), FSME could provide higher precision or recall rate to identify ME gene sets, and had superior control of false positive rates. With application to TCGA real data sets for AML, BRCA, and GBM, we confirmed that FSME can be utilized to discover cancer driver genes.Management of fluid overload is one of the most challenging problems in the care of critically ill patients with oliguric acute kidney injury. Various clinical practice guidelines support fluid removal using ultrafiltration during kidney replacement therapy. However, ultrafiltration is associated with considerable risks. Emerging evidence from observational studies suggests that both slow and fast rates of net fluid removal (that is, net ultrafiltration (UFNET)) during continuous kidney replacement therapy are associated with increased mortality compared with moderate UFNET rates. In addition, fast UFNET rates are associated with an increased risk of cardiac arrhythmias. Experimental studies in patients with kidney failure who were treated with intermittent haemodialysis suggest that fast UFNET rates are also associated with ischaemic injury to the heart, brain, kidney and gut. The UFNET rate should be prescribed based on patient body weight in millilitres per kilogramme per hour with close monitoring of patient haemodynamics and fluid balance. Dialysate cooling and sodium modelling may prevent haemodynamic instability and facilitate large volumes of fluid removal in patients with kidney failure who are treated with intermittent haemodialysis, but the effects of this strategy on organ injury are less well studied in critically ill patients treated with continuous kidney replacement therapy. Randomized trials are required to examine whether moderate UFNET rates are associated with a reduced risk of haemodynamic instability, organ injury and improved outcomes in critically ill patients.Targeting receptor proteins, such as ligand-gated ion channels and G protein-coupled receptors, has directly enabled the discovery of most drugs developed to modulate receptor signalling. However, as the search for novel and improved drugs continues, an innovative approach - targeting receptor complexes - is emerging. Receptor complexes are composed of core receptor proteins and receptor-associated proteins, which have profound effects on the overall receptor structure, function and localization. Hence, targeting key protein-protein interactions within receptor complexes provides an opportunity to develop more selective drugs with fewer side effects. In this Review, we discuss our current understanding of ligand-gated ion channel and G protein-coupled receptor complexes and discuss strategies for their pharmacological modulation. Although such strategies are still in preclinical development for most receptor complexes, they exemplify how receptor complexes can be drugged, and lay the groundwork for this nascent area of research.An essential protein of the SARS-CoV-2 virus, the envelope protein E, forms a homopentameric cation channel that is important for virus pathogenicity. Here we report a 2.1-Å structure and the drug-binding site of E's transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal α-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs.
Cancer patients undergoing radiotherapy (RT) frequently experience weight loss and changes in body composition, which negatively affect their nutritional status, lead to a poor clinical prognosis, and reduce survival rates. This study aimed to evaluate whether changes in body weight, phase angle, and standardized phase angle are associated with longer survival in cancer patients undergoing RT.

This prospective cohort study included 62 cancer patients who underwent RT between 2008 and 2009 and were followed until 2019. Anthropometric and bioelectrical impedance analysis data were assessed before and after RT. The Kaplan-Meier method was used to calculate survival, and mortality risk was assessed using the Cox proportional hazards model.

Kaplan-Meier analysis indicated no significant difference in survival time after the 10-year follow-up between patients who had weight loss during RT and those with weight maintenance or weight gain during RT. Mortality risk was associated, in the adjusted multivariate analysis, with age (p = 0.
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