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For each patient who is over-diagnosed with breast cancer, the adverse consequences include unnecessary anxiety, financial hardships, and a small risk of morbidity and mortality from unnecessary treatments. Moreover, the over-treatment of breast cancer, as a consequence of over-diagnosis, is costly and contributes to waste in healthcare spending. In this article, we argue that there is a need to establish better endpoints in breast cancer screening trials, including quality of life and composite endpoints. Tumor-detection endpoints should be abandoned, as they may lead to the implementation of screening strategies that increase the risk of over-diagnosis.DNA cytosine methylation is central to many biological processes, including regulation of gene expression, cellular differentiation, and development. This DNA modification is conserved across animals, having been found in representatives of sponges, ctenophores, cnidarians, and bilaterians, and with very few known instances of secondary loss in animals. Myxozoans are a group of microscopic, obligate endoparasitic cnidarians that have lost many genes over the course of their evolution from free-living ancestors. Here, we investigated the evolution of the key enzymes involved in DNA cytosine methylation in 29 cnidarians and found that these enzymes were lost in an ancestor of Myxosporea (the most speciose class of Myxozoa). Additionally, using whole-genome bisulfite sequencing, we confirmed that the genomes of two distant species of myxosporeans, Ceratonova shasta and Henneguya salminicola, completely lack DNA cytosine methylation. Our results add a notable and novel taxonomic group, the Myxosporea, to the very short list of animal taxa lacking DNA cytosine methylation, further illuminating the complex evolutionary history of this epigenetic regulatory mechanism.

Systemic therapy for hepatocellular carcinoma (HCC) consisting of the tyrosine kinase inhibitor sorafenib has remained unchanged for over a decade, although results from phase III targeted therapy trials have recently emerged. This review considers available phase III evidence on the use and sequencing of targeted therapy for intermediate and advanced non-locoregional therapy (LRT) eligible HCC and discusses implications for clinical practice.

Published and presented literature on phase III data reporting on targeted therapy for advanced HCC that was not eligible for loco-regional therapies was identified using the key search terms "hepatocellular cancer" AND "advanced" AND "targeted therapy" AND "phase III" OR respective aliases (PRISMA).

Ten phase III trials assessed targeted therapy first-line and eight following sorafenib. In the first-line, atezolizumab plus bevacizumab statistically significantly improved overall survival (OS) and patient-reported outcomes (PROs) compared with sorafenib, while lengation.

Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridge this gap.

We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered MERS-CoV patients for three years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge.

Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients that suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than two fold. DNA inhibitor Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viralinfection.

This brief report aims to highlight stark mortality disparities among older Latinos that result from the novel coronavirus disease (COVID-19) pandemic.

We use recent data from the Centers for Disease Control and Prevention to compute age-specific death rates (ASDRs) for 3 causes of death deaths from COVID-19, residual deaths, and total deaths for 4 age groups (55-64, 65-74, 75-84, and 85 and older) to assess the impact of COVID-19 on older Latino mortality relative to non-Latino Whites and non-Latino Blacks and also in comparison to residual deaths. Additionally, we obtain ASDRs for all causes of deaths from 1999 to 2018 to provide a pre-pandemic context and assess the extent to which the consistently observed mortality advantage among Latinos persists during the pandemic.

Consistent with previous research, our findings show that Latinos have lower ASDRs for non-COVID-19 causes of death across all age groups compared to non-Latino Whites. However, our findings indicate that Latinos have significantly hiome available.

Several inherited arrhythmic diseases have been linked to single gene mutations in cardiac ion channels and interacting proteins. However, the mechanisms underlying most arrhythmias, are thought to involve altered regulation of the expression of multiple effectors. In this study, we aimed to examine the role of a transcription factor belonging to the Iroquois homeobox family, IRX5, in cardiac electrical function.

Using human cardiac tissues, transcriptomic correlative analyses between IRX5 and genes involved in cardiac electrical activity showed that in human ventricular compartment, IRX5 expression strongly correlated to the expression of major actors of cardiac conduction, including the sodium channel, Nav1.5, and Connexin 40 (Cx40). We then generated human induced pluripotent stem cells (hiPSCs) derived from two Hamamy Syndrome-affected patients carrying distinct homozygous loss-of-function mutations in IRX5 gene. Cardiomyocytes derived from these hiPSCs showed impaired cardiac gene expression program,RX5 in the regulation of several major players of ventricular depolarization conduction and in arrhythmogenesis. Thus, this study supports systematic screening for genetic variants in IRX5 in inherited cardiac arrhythmias.